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Introduction

In 1917 the American Public Health Association, (APHA), began to publish a manual dedicated to the Control of Communicable Diseases in man. The publication has been updated about every five years. The 20th edition was published in 2015 and the next edition is scheduled to come out in 2021. What follows is largely based on the 20th edition [1] though over the years the present author has looked at the manual in its 11th, 17th and 18th editions, this last in disc format. This remarkable and extremely useful document is intended primarily for Public Health practitioners and includes detailed guidance for them in relation to the steps to be taken in the event of an outbreak of any of the diseases considered. For immunologists interested in infectious disease it offers a wealth of opportunities for research and could help them to gain a better perception of the biological significance of the immune response. It also could help them better to recognise the two systems of immunity, innate and adaptive, the former an attribute of all animals with an alimentary canal and the latter found only in vertebrates. The functional relationships between the two systems of immunity are important but differ in relation to the scale of generation of immunopathological effects regulation of which is increasingly seen as important in dealing with infectious disease.

The recent outbreak of disease associated with Covid-19, the worst symptoms of which are associated with so-called cytokine storms, suggests that the simple model of thinking of immunity, as consisting of antigens originating from infectious organisms, eliciting the formation of specific antibodies which can help the rejection of the invader, needs revision. Much high quality immunological research conducted since the Second-World War has had a reductionist flavour, very sensibly, as cutting down uncontrollable variables is seen as an integral part of experimental biological research. For example, measurement of adaptive immunity has often involved analysis of antibody arrays following the introduction of highly simplified antigenic epitopes often perched on the backs of carrier proteins which are supposedly not involved actively in the specification of the reaction to the target epitope which they convey. A problem also not addressed by the immunological communities is how the immunologically responding organism deals with the complex array of epitopes capable, using analytic methodology, of eliciting a specific antibody response without overloading the responsive system. There has also often been only restricted means of following the physiological consequences of the activation of the large numbers of the cells which are part of the overall immunological processes including, importantly, non-specific activation of the innate system following the creation of dead dying and damaged cells as a consequence of infection.

Many experimental immunologists faced with the measurement of a response to an antigenic array which is increasing exponentially from the time of first contact, as happens with many infections, will be hard pushed to predict the outcome. Their experiences will often be largely concerned with non-living antigenic arrays given once or twice to demonstrate the scale of a response and that by evocation, it is argued, of various memory cells the adaptive immune response is usually more reactive on second contact with the antigens concerned. That this paradigm is useful it not to be denied as it supports the whole fabric of the vaccinologists and has led to the eradication of small pox as a highly dangerous disease world-wide and in many countries the extirpation of what can be the unpleasant consequences of contact with poliomyelitis virus. Nevertheless, it is becoming increasingly apparent that the proportion of the total array of potentially infectious organisms which cause disease, particularly viruses and bacteria, is tiny. In addition it is being argued that humans and similar triploblastic animals carry thousands of species of bacteria and an unknown multitude of viruses. Most of which these foreign organisms should probably be regarded as commensal or symbiotic though it also includes a few potential pathogens. This enormous array of organisms, which are an integral part of us, can under some circumstances do harm but, in the sense that overall they do good rather than damage, should perhaps not all be termed infections which, by definition, carries the intent to do harm. It is becoming increasingly important that we better understand the precise terms of the often stable and symptom free relationship between these foreign invaders and the host organisms.

The APHA manual, from which much can be learned, deserves more attention from the immunologists interested in infectious disease. The present paper, intending to extract from the manual generalisations and initiate explorations of the mechanisms of disease processes, will be of help to immunologists interested in the field of infectious disease. Whether it will be of help to the public health practitioners, for whom the manual is primarily intended, remains to be seen. It should be made clear that what follows is in no way intended to replace the Manual but simply to draw the attention of immunologists to read through it and to pay attention to some issues which should interest them and which, otherwise, they might not be aware of. The Manual is compiled from the writings of many specialists in relation to the 250 or so diseases that are considered in outline. Often the experts on, say, malaria know little about diseases caused by viruses and this compartmentalisation can restrict the development of useful generalisations about the processes involved in disease. What will be offered is intended for immunologists to help them, not only better to frame such generalisations and, hopefully, to better understand the complexity of their subject as a mutually reactive device acting at the interface between many living organisms and, in the broad sense, their environment.

It should be noted that all infectious organisms will be labelled parasites which often, by parasitologists is a nomenclature reserved for multicellular eukaryotic organisms. The implication is that if the host of an invader can be damaged at the expense of the host whatever the nature of the invader a state of parasitism exists. In addition it should be made clear that what follows has a large subjective element emerging from the mind of an individual who, with the support of many scientific colleagues, over the last sixty years or so, has been an experimental immunobiologist.

Methods

The APHA manual is presented in a stylised manner with diseases and groups of diseases presented alphabetically. Within each of the listed diseases or groups of diseases are given their WHO ICD 9 and ICD 10 categorisations, their names with some of the synonyms are given followed by eight sets of basic information labelled, respectively, Identification, Infectious agent, Occurrence, Reservoir, Mode of Transmission, Incubation period, Period of communicability and Susceptibility and Resistance. There follows what is often a more extensive ninth section on Methods of Control aimed primarily at Public Health workers in relation to diseases with major social impact that can be epidemic or even pandemic. The present author elected to draw out, largely from information given in sections one to eight of the diseases in the manual, a categorisation based primarily on the causal infective organisms, i.e. Bacteria, Viruses, Fungi, Protoctista/Protozoa, Trematodes, Nematodes and a Miscellaneous group with such causal ‘organisms’ as arachnids, prions and diseases in some instances where the taxonomic classification of the causal agency is not certain. For each class of infective organism tables were constructed with a matrix listing each disease in relation to the Identity of the causal organism, the Geographical location of the disease occurrence(s), the Class of Disease on the WHOICD lists of diseases, an indication of its Impact, Susceptibility, Special risk factors, Immunity, Vaccines where used, primary Reservoir, Vectors and general Comments with in some instances a brief indication of the Treatments available.

Each of the Tables 1-7 is accompanied by a short summarising statement drawing attention to items of special interest. Table 8 labelled Reconciliation, aims to enable immunologists, to gain a better outline of the scale and range of the infective diseases which, ideally, are the targets of activity their immunological discipline aspires to understand and learn how to regulate. Sheep red cells, which have been a common feature of immunological investigations in mice, do not, usually, cause disease neither do they grow exponentially in the organism to which they have been placed.

Results

Bacteria

There are sixty or so diseases written about which are associated with bacterial infection. This number does not include the often numerous related species of bacteria that cause disease in the category mainly dealt with but for all that it is clear that, although there are millions of bacterial spp. Known, only very few of them are pathogenic. Perhaps more importantly it should be noted that the microbiome array in man of several thousand species often includes only very few that become pathogenic. Selected information derived from the Manual concerning bacteria is given in Table 1.

Table 1: Bacteria.

Disease Infectious agent. Target organ if any. Location ICD 10 entry.
Impact
Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments, treatment
Actinomycosis Actinomyces israelii and others of the same genus

 

Chronic disease located in orocervical facial,, thoracic and abdominopelvic regions

Sporadic throughout the world A42

rare disease small impact

low Frequency maximal between 20 and 60 years of age. Mucosal barrier disruption caused by surgery or irradiation, and immunocompromising conditions. Not demonstrated N/A humans Reasonably common component of oral flora. Can cause problems following trauma that allows access. Prolonged administration of penicillin can be effective. No spontaneous recovery.
Anthrax, Woolsorter disease, ragpicker disease. Bacillus anthracis. Three forms depending on route if introduction. Cutaneous, inhalation, gastrointestinal occasionally among drug users. S and Central America, S and E Europe, Asia and Africa A22

Primarily a disease of herbivores

Uncertain A zoonosis. An infrequent or sporadic disease among veterinarians, wild life workers and agricultural workers. Second attacks rare. Immunisation for individuals at high risk because of their location or occupation using a cell free isolate is said to be effective. For animals and those humans at occupational risk Animals and viable spores can persist in soil for decades Widely bruited as a weapon for terrorism though it has probably not yet been deployed. Complex regimens of post exposure prophylaxis are deployed.
Bartonellosis (Oroya fever, Verruga Peruana, Carrion Disease) Bartonella bacilliformis

Either a life threatening febrile anaemia (Oroyo fever) or a benign dermal eruption (Verruga Peruana). There are many spp. Of Bartonella with much more complex patterns of infection than shown in the manual. See also Cat Scratch fever and Trench Fever.

Mountain valleys of Peru, Ecuador and Southwest Columbia between altitudes of 2000 and 9,200 feet where sand flies are present A44.0, A44.1

Mortality with untreated oroya fever can be as high as ninety per cent

General More severe in adults than in children. Most common in tourists, i.e. immunologically naïve individuals. Inapparent infections and carriers are known(up to 5% in endemic areas). Recovery from untreated Oroya fever almost invariably leads to permanent immunity though the Verruga stage may recur. Asymptomatic infections and a carrier state are known. N/A Humans, no known animal reservoir. Vector sand flies. Treatment with antibiotics can be partly successful.
Intestinal Botulism, Infant Botulism Clostridium botulinum is the source of botulinum neurotoxin that causes the disease. Other spp of the genus can be involved. Severe neuropathogenic disease. Respiratory failure common cause of death. Worldwide, sporadic, family and general outbreaks are associated with imperfect food preparation A05.1 cumulative cases world wide of which 1400 were from the USA. Nevertheless regarded as a major hazard presumably because of its high lethality. General Almost all hospitalised patients were between two weeks and one year of age. 94% were less than six months!. Adults with bowel problems or treated with antibiotics can be at special risk. The use of botulinum toxin has been associated with the development of iatrogenic disease. ? Antitoxin is administered presumably as a passively given antibody. There seems to have been no attempt at active immunisation. Spores in soil ubiquitous In effect a disease of the food industry. Most problems it is written are caused not by ingestion of preformed toxin but of bacterial spores that germinate to give rise to more organisms that secrete the toxin. Important as a potential bioterrorism tool. I.V. antitoxin
Disease Infectious agent.
Target organ if any.
Location ICD 10 entry.
Impact
Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments, treatment
Brucellosis, undulant fever, Malta fever, Mediterranean fever Brucella abortus in a variety of strains

 

A systemic disease. Very complex pattern of symptoms

Worldwide A23

Less now than heretofore. Incidence in USA 120 current cases. In other parts of the world probably unreported and undiagnosed.

Severity and duration of clinical illness subject to wide (unexplained) variation. A disease of those working with farm animals as abattoir, vets or direct contact with animals. Persons eating uncooked meat are at higher risk. Unknown None in man but active successful immunisation of cattle is practised. Cattle, swine, goats and pigs. It has been suggested that infection with Brucella was a negative indication for cancer. Equally a number of suggestions have been made that brucella antigens could help suppress cancer. The evidence so far is slender. Anti Biotics
Campylobacter enteritis, Vibrionic enteritis Campylobacter jejunis

Diarrhea.

World wide A04.514% of diarrhoea worldwide caused by these organisms. Many infections are asymptomatic Children under five and young adults are at higher risk. Immunocompromised individuals at higher risk. None Poultry and cattle mainly but many other animals. Most raw poultry meat contaminated! Common disease with considerable impact. Treatment not generally indicated! Rehydration and electrolytes.
Cat Scratch Disease, benign lymphoreticulosis Bartonella benselae

Subacute usually self limiting disease. Affecting lymphoid system and often causing fever

Worldwide but uncommon A28.1

 

Slight

unknown Immuno-compromised host most infected but some evidence that younger children and younger adults are more affected Diagnosis sometimes based on serological evidence of anti-Bartonellaantibody. None Domestic cats. There is no evidence of adverse effects on cats even when they are bacteraemic Interesting example though too little is known about it to place much weight on it. The fact that infected cats are asymptomatic is noteworthy. Antibiotics
Chancroid, ulcus molle, soft chancre

 

 

Haemophilus ducreyi

STD

Sporadic. Less in temperate regions A57

small

, no natural resistance, the circumcised are at less risk than the uncircumcised. Men who frequent prostitutes! None recorded None Humans Unpleasant condition with too little known Antibiotics
Chlamydial infections, Genital (psittacosis and respiratory disease dealt with separately) Chlamydia trachomatitis

 

STD

Common A56

Nuisance rather than major threat

General,majority of infected women are asymptomatic, up to 25% of infected males the same. None given No acquired immunity has been demonstrated repeated infections common. N/A humans Common, seems to have little if any impact on immunological mechanisms. Antibiotics can render patients non-infectious.
Disease

 

Infectious agent.
Target organ if any.
Location ICD 10 entry.
Impact
Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments, treatment
Vibrio parahemyticus infection Vibrio parahemolyticus

Enteritis

Sporadic in many parts of the world. Marine coastal environments A05.3

A disease of moderate severity. Rarely systemic or lethal

Various anterior medical conditions such as liver disease, decreased gastric acidity or immunosuppression. oysters No indication given None Marine silt Rehydration, antibiotics
Vibrio vulnificus Vibrio vulnificus.

Septicaemia commonly but other symptoms encountered.

Marine environments particularly but not exclusively in N. America. A05.3

Septicaemia fatal in 50% of casess

Characteristically in patients with chronic liver disease, alcoholism, hemochromatosis or immunosuppression. Oysters. Sea water exposure of open wounds. No indication given None Free living organism in estuarine environments. Uncooked sea food can be source of infection Rehydration, antibiotics
Cholera (serotypes other than 01 and 0139) Vibrio choleraEnteritis and otitis media, and cellulitis. 2-3% of cases of diarrhoea (including travellers) in tropical countries A05.81Small relative to the pathogenic 01 and 0139 serotypes All humans said to be susceptible Wound infections, malnutrition and immunosuppression NK N/A brackish waters where they are part of the normal flora associated with outbreaks of enteritis. Fluid replacement used.
Disease

 

Infectious agent.
Target organ if any.
Location ICD 10 entry.
Impact
Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments, treatment
Bacterial conjunctivitis, pink eye, sticky eye, and Brazilian purpuric fever. Many organisms can be involved the most important are Hemophilus influenzae and Streptococcus pneumoniae. Viral causes dealt with under Viral Disease heading.

Eyes.

 

Widespread and common A48.4

Warmer climates seasonal epidemics in the main non fatal but systemic fatal disease has been reported (Brazilian purpuric fever)

Probably general Children under five most affected. The debilitated and the aged are particularly susceptible to staph. Infection. Low grade after infection and varies with the infectious agent Clearly lack of knowledge here N/A Humans Sulfacetamide plus or minus antibiotics
Chlamydial conjunctivitis, inclusion conjunctivitis, paratrachoma Chlamydia trachomatis

Eyes. An STD

Sporadic throughout the world. A74.0

 

? Affects new born infants in particular otherwise a complication of genital infection in adults No evidence of resistance to reinfection though severity of disease is variable N/A Humans Often acquired by infants during birth process. Antibiotics
Diarrhoea caused by E. coli, Enterohaemorrhagic strains. Shiga toxin producing strains. complex of pathogens STEC initially Intestine but can create massive renal and other potentially lethal problems. Important problems in N America, Europe, S Africa, Japan Australia. A04.3 Outbreaks associated with a variety of poorly cooked foods infectious dose is very low. Little is known about susceptibility or immunity Old age, achlorhydria and infants under five.

Diabetics and infants of infected mothers.

None reported

 

none Cattle and perhaps deer, more rarely humans Fluid and electrolyte replacement. Antibiotic treatment uncertain and potentially dangerous.
Diarrhoea caused by E. coli, Enterotoxigenic strains. ETEC Primarily in developing countries A04.1A major cause of travellers diarrhoea. In developing countries multiple infections of infants occur Probably universal though it is not so stated Less frequent in adults. Children <4years of age in developing countries can have up to 32% mortality. WHO reports up to 380,000 deaths of such children annually. Contaminated food particular risk factor. Serotype specific immunity is acquired following infection. Problem is that there are so many serotypes none humans Fluid replacement, rehydration salts. Anti-microbial agents often deemed dangerous.
Disease

 

Infectious agent.
Target organ if any.
Location ICD 10 entry.
Impact
Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments, treatment
Diarrhoea caused by E. coli, Entero-invasive strains EIEC Endemic in developing countries A04.2

Cause about 1-5% of cases visiting treatment centres

NK Visitors and children in endemic regions NK None Humans Fluid replacement. Few centres treat this somewhat more rare disease.
Diarrhoea caused by E. coli, enteropathogenic strains

 

 

 

EPEC Oldest recognized form of largely infant diarrhoea, largely disappeared from the Western world.. A04.0

Still a major problem in many other places in the developing world where fatality rates can be high

Susceptibility is confined to young infants but why is not known. It could be immunity but that is not established. Experiments on adults suggest that immunity is the answer. Disease uncommon in breast fed infants. Often associated with contaminated infant formula. Outbreaks due to contaminated water or rice have been reported. Likely but not certain None Humans Fluid replacement
Intestinal E. coli infections and others EAEC,, DAEC Cause of sporadic out breaks associated with acute and persistent diarrhoea in infants. In developing and developed countries. A04.4

EAEC can be a cause of traveller’s diarrhoea in as many as 20% o cases in some reports.

DAEC in some reports more pathogenic in children but information is sparse. Contaminated food and drink. Infants in particular are susceptible. NK Likely humans possibly animals Rehydration treatment and anti-microbials are said to be useful.
Disease

 

Infectious agent.
Target organ if any.
Location ICD 10 entry.
Impact
Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments, treatment
Diphtheria Corynebacterium diphtheria

Mucous membranes of upper respiratory tract, more rarely other mucous membranes. A potent exotoxin causes the problems. Carried by some strains of Corynebacteria themselves infected with the toxin generating phage.

A disease of colder months in temperate climes A36

Major outbreaks have occurred in number of areas of the world in recent years in unvaccinated individuals

Not stated Infants born to immune mothers are protected for up to six months by passively acquired antibody. Lifelong immunity is usually but not always acquired after infection. Immunisation with toxoid also produces lifelong immunity (non toxigenic bacteria rarely cause disease) Very effective Humans Presence of a phage as is true for some other bacterial spp dictates capacity to produce a toxin that is the main cause of pathogenesis. Anti toxin + sometimes antibiotics
helicobacter pylori infection Helicobacter pylori

Causes acute and chronic gastritis.

Worldwide Said to be present in 50% of the human population K29 usually no symptoms but for some gastritis and gastric Carcinoma can follow infection Universal it is supposed. Increasing prevalence with increasing age. Not identified but supposed that there must be identifiable risk factors. Lower socioeconomic status appears to be associated with higher prevalence. None recognized None presently available Humans probably though it has been found in other primates Treatment with antibiotics can be successful in reducing gastritis stopping continuation to malignancy. Controversial antibiotics
Ehrlichiosis,
Anaplasmosis, Senetsu Fever, Neoehrlichosis
Ehrlichia sennetsu

Anaplasma cytophylum

Neorickettsia senesu,

Neoehrlichia misurensis

Acute febrile illnesses with small intracellular bacteria that survive inside a variety of phagocytic white blood cells.

Four diseases here one Sennetsu fever the other three different forms of ehrlichiosis.. Distribution mainly in north and south America, Europe, Western Japan and Malaysia A79.8

 

Range from mild illnesses to severe life threatening disease. Diagnosis tricky to differentiate it from a wide variety of viral illnesses.

General Older, debilitated or immunosuppressed people more susceptible NK Re-infection rare. implication is derived adaptive immunity. Consumption of raw fish suspected cause with Senetsu fever Not certain but a variety of vertebrate hosts are involved. Ticks can be vectors. Doxycycline
Disease

 

Infectious agent.
Target organ if any.
Location ICD 10 entry.
Impact
Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments, treatment
Gonococcal infection, (a separate category of gonococcal conjunctivitis is here ignored), clap, strain, gleet, dose, G.C. Neisseria gonorrhoeae

STD particularly in the commercial sector.

 

Common worldwide A54.0 A54.2, Rarely lethal but with many unpleasant symptoms General Not given Humoral and secretory antibodies have been demonstrated but the bacterium is antigenically heterogeneous and reinfection is common none Strictly a human disease Major STD. Antibiotics but many resistant plasmids exist.
Granuloma inguinale (Donovan osis) Calymmactobacterium granulomatis

Genitalia in 90% of cases

Rare in industrialised countries but even there small occasional epidemics are recorded. A58

Slight fortunately but cluster outbreaks have been recorded in tropical and semi-tropical countries

Most common in 20-30 year old males but known also in 1-4 year old children and it is suggested that non-sexual transmission can occur. Bought sexual activity None it appears, ie second attacks occur (presumably after treatment of the first attack) none Humans Horrid condition not easily brought under control that essentially erodes the genital regions. We are clearly short of information on the disease. Antibiotics
Legionellosis (there is also non pneumonic legionellosis, Pontiac fever, which is here ignored). Legionnaires disease Various legionellae Widespread but sporadic more common in summer and autumn A48/1

Regarded as dangerous case fatality rate can be 15%.

Age related Males more than females usually in patients over 50 years of age. Patients who smoke or who have diabetes mellitus are at special risk. immunocompromised people especially those on corticosteroids special. Infected cooling towers and warm but not hot water Iimplication is that there is an immune response in that in a few locations antibodies have been detected in 1-20% of the general population. None stated Aqueous primarily, hot water systems not properly maintained. Why is it called legionnaires disease? Some antibiotics are effective. Disinfection of suspected water supplies is effective.
Disease

 

Infectious agent.
Target organ if any.
Location ICD 10 entry.
Impact
Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments, treatment
Leprosy (two forms tuberculoid and lepromatous of which the latter is more severe), Hansen’s disease. Mycobacterium leprae

Cannot be grown in culture.

Chronic disease of the skin and peripheral nerves.

Chief endemic areas are S and S Eastern Asia, Indonesia, tropical Africa and parts of latin America. A30

Considerably over a million cases worldwide but it should be stressed that probably only a small proportion of those infected develop symptoms.

Rate of lepromin positive tests increases with age but as this can give false positives it is not clear that this represents a build up of asymptomatic infections. In childhood, rarely seen under three. (not long enough for the disease to develop?) Incubation time can be anything from nine months to twenty years! Immunity said to depend on a cell mediated response though antibodies are produced. It is argued that 95% of the population are naturally immune. In the manual this is termed innate immunity but this terminology is incorrect. BCG may have some use in this context! Humans and armadillos. Still a major disease not easily cured. Prolonged treatment with a variety of antibiotics but resistance is a problem.
Leptospirosis, Weil’s Disease, Swineherd fever, mud fever, Haemorrhagic jaundice and other names. Organisms from the genus Leptospira . Large number of serotypes.

First phase of infection can be high fever. Second phase coincident in time with development of antibodies Recovery of untreated cases can take several months.

Worldwide except polar regions. Most prevalent in tropical and sub-tropical regions. A27

Asymptomatic or mild infections are common but occasional epidemics have killed many of those infected. In general 5-10% of cases progress to severe illness.

general Case fatality rate is generally low but can reach twenty percent in those with renal damage. Largely an occupational disease for those working in sugar plantations and rice fields Often a disease of bathers and campers no particular other predilections given Serovar specific immunity arises In both workers at risk and the local domestic animals this has been attempted. The results are either not known or simply not given Wide variety of wild and domestic animals. Prompt specific, early treatment with antibiotics can be effective.
Disease

 

Infectious agent.
Target organ if any.
Location ICD 10 entry.
Impact
Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments, treatment
Listeriosis Listeria monocytogenes

Can present as an invasive disease with septicaemia and meningitis.

An uncommonly diagnosed infection in USA but frequency elsewhere in the world not given. Outbreak cases are reported associated with contaminated food. A32

Accounts for a small fraction of all blood borne diseases. Despite this it is regarded as an important cause of severe illness.

Most children and young adults are resistant Adults over the age of 40 become more sensitive and Almost all the debilitating and immunosuppressive conditions, (including pregnancy) confer heightened sensitivity NK None Solid forage water mud and silage plus domestic animals and asymptomatic human (fecal) shedders. Commonly associated with manufacture of soft cheeses of which it is part of the bacterial array. Antibiotics work
Lyme disease, Lyme borreiosis, tickborne meningopoly neuritis Borelia burgdoreferi and others

 

Distinctive skin lesions and a variety of other systemic manifestations over a long time period.

Found in many places particularly well known in USA but also in Europe, China and Japan A69.2, L90.4Difficult to say on evidence presented. Clearly an uncomfortable and chronic disease that can usually be successfully treated, Universal apparently None stated Re-infection has occurred in those treated early with antibiotics, the implication is either that immunity is not a result of infection or that antibiotic treatment prevents the development of lasting immunity. Vaccines have been developed and used with up to 76% success but this is not a clear story. Disease is maintained in an enzootic transmission cycle that involves ixodid ticks wild rodents and deer. A zoonosis Treatment with antibiotics
Disease

 

Infectious agent.
Target organ if any.
Location ICD 10 entry.
Impact
Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments, treatment
Lymphogranuloma venereum, climatic or tropical bubo Chlamydia trachomatis genotypes.

 

STD in both sexes. In men who have sex with men proctitis can develop.

Worldwide especially in the tropical and subtropical areas A55

 

Disease untreated is debilitating but not usually fatal.

General Male homosexuals Not clear None Humans often asymptomatic females. Antibiotics can be effective.
Melioidosis, Whitmore disease

Glanders

Burkholderia pseudomallei causative agent for Melioiodosis, Burkholderia mallei for Glanders.

 

Cutaneous or visceral abscesses with subsequent development of a wide range of potentially lethal systemic symptoms.

A significant cause of community acquired sepsis in the tropics. A24.1, A24.4, A24.0

In a number of largely tropical places

Problem here of definition. Disease is uncommon even in parts of the world where the infective organism exists and the (rural) population are in frequent contact with the soil in which the bacterium exists. The implication is that infection as a common disease is rare Those with abraided or burned skin who also have intimate contact with soil Not clear. Change of environment, eg development of diabetes mellitus can give recrudescence of what is probably a long term latent infection None Soil and water. A saprophyte. Various animals can become infected but there are no known vectors to which they transfer the organism but they can spread it around passively TMP-SMX is effective treatment ( a mixture of trimethoprim and sulphamethoxazole)
Meningitis, cerebrospinal fever Neisseria menigitidis various strains/serotypes exist that define different epidemics

 

Inflammation of the meninges is the defining feature of this disease and here three bacterial causes of the condition will be considered. A petechial rash often present in Europe and N. America but rarely in Africa.

Ubiquitous A39.0

Nowadays in developed country case-fatality rate is 8-15%. 5-10% of those in endemic countries may be asymptomatic carriers of whom very few progress to disease.

Susceptibility to disease is low and decreases with age. Disease is primarily of very young children and young adults. More common in males than in females. Highest burden of diseasein African meningeal belt. Splenectomy, certain complement components Group specific immunity of unknown duration follows even subclinical infection Dead vaccines are available and have been reasonably successfully applied Humans Epidemics tend to crop up in those inhabiting crowded communal quarters. A variety of antibiotics can be effective treatment.
Disease

 

Infectious agent.
Target organ if any.
Location ICD 10 entry.
Impact
Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments, treatment
Hemophilus meningitis, Hemophilus influenza In industrialised countries before widespread use of Hib conjugate, vaccines meningitis was the most common presentation, epiglottitis and bacteremia were the next most common. In developing countries lower respiratory tract infection was the most common first symptom. Pneumonia of this kind has been said to cause 480,000 deaths per year among children under five years of age. Worldwide G00.0

Most prevalent among children three months to three years. Vaccine use has cut down the disease in the USA and a higher proportion of cases is now seen in adults

Universal Age Immunity usually associated with presence of circulating anti-capsular antibodies acquired transplacentally or by immunisation. Or a prior infection Yes with polysaccharides Humans Antibiotics but resistance is now a problem.
Disease

 

Infectious agent.
Target organ if any.
Location ICD 10 entry.
Impact
Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments, treatment
Nocardiosis,

Actinomycetoma

Nocardia asteroidsand others of that ilkPulmonary infection Occasional sporadic disease in all parts of the world B47.1

Difficult to say on evidence presented

Unknown Endogenous or iatrogenic adrenal hypercorticism and probably primary alveolar proteinosis Opportunistic infection can occur in immunosuppressed individuals. Implication is that there is an immune mechanism. None A saprophyte found in soil, water and organic material. TMP-SMX depending on serotyope specificity.
Pertussis, Whooping cough

Parapertussis, a milder version of the disease

Bordetella pertussis

 

Bordetella parapertussis.

 

 

A respiratory disease with occasional systemic complications.

An endemic disease common especially young children everywhere A37.0, A37.9

A37.1Schemes of immunisation have reduced the prevalence. This disease is among the most lethal of all the childhood diseases in unimmunizd individuals. In recent years it is increasingly recognized in older children and adults even when they have been immunized as infants.

Universal among non-immunised individuals. Milder and atypical cases occur in all groups (the hundred day cough!) Malnutrition and enteric infections can be predisposing conditions. Interestingly, transplacental transfer of immunity has never been demonstrated. Note comment in Vaccines column. One attack usually confers prolonged immunity although second attacks can occur. A killed vaccine is widely used. Maternal antibodies are carried across the placenta which observation has led several countries to adopt immunisation prior to pregnancy but whether this stratagem works is not stated. Humans ? Erythromycin reduces the period of communicability but does not affect symptoms except when given very early.
Disease

 

Infectious agent.
Target organ if any.
Location ICD 10 entry.
Impact
Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments, treatment
Pinta, Carate Treponema caroteum a spirochaete. A chronic non venereal skin disease. Found only among crowded rural populations living in poor conditions in the American tropics A67

Physical disability does not occur. Organ systems are not involved Not fatal. Said to be on its way to eradication!

Not defined presumably as in other treponematoses (various syphilitic diseases in relation to which immunity can develop) Mainly a disease of children Not stated None Humans. Various biting flies are suspected of being vectors. A none venereal disease. Antibiotics fix it.
Plague, Pestis Yersinia pestis

 

Three presentations, bubonic, pneumonic and septicemic.

Almost everywhere that there are wild rodents.

Foci of infection exist in the Americas particularly in N. Eastern Brazil.

A20

Both bubonic and pneumonic forms can be lethal and in the past have been responsible for major epidemic mortality. Untreated the mortality rate is 50-60% These days it is clearly less of a problem than it was.

General None given Some immunity after recovery. Yes both living and dead. They can be efficient for about three months Wild Rats with their fleas as the vector. A potential terrorist weapon. Streptomycin is the drug of choice.. The pathogenicity is associated with a mutation. P. Unusual example of a mutation conferring increased pathogenesis.
Disease

 

Infectious agent.
Target organ if any.
Location ICD 10 entry.
Impact
Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments, treatment
Pneumonia, There are many organisms which can cause pneumonia. Here only four will be dealt with 1,pneumococcal pneumonia Streptococcus pneumoniae (twenty three capsular types account for ninety per cent of the infections that cause bacterial pneumonia in the USA)

Often sudden onset high fever with a wide variety of complications.

Essentially worldwide though increasing control was being developed. Now resistance to antibiotics is becoming a problem. J13

A major cause of death in developing countries among new born children. The disease can be associated with influenza infection.

General in the sense that I suspect the organism concerned is always present. Not general in the sense that only few get the disease! The definition of susceptibility is here strained. In young infants the mortality even using antibiotics can be 60%, malnutrition and low birth weight are contributory factors. Any harm to the lower respiratory tract is predisposing. In adults almost any co-morbidity can predispose. Serotype specific immunity can be long lasting. A vaccine with all 23 capsular types is available, it is not effective in children under the age of 2 but it can be useful Prophylaxis in the elderly Humans (many normal individuals have the organism concerned as part of their respiratory tract flora.) Splenectomy is a predisposing factor.. Antibiotic resistance now common.
Pneumonia, primary atypical pneumonia Mycoplasma pneumoniae

The taxonomic designation of this organism is uncertain being either virus or bacterium. Here it is included among the bacterial causes of the symptom.

 

Worldwide sporadic and epidemic J15.7

Fatalities rare, differential diagnosis difficult there being at least ten other infectious causes of pneumonia! Clinical disease occurs in 3-30% of infections

Susceptibility not mentioned! None given Second infections do occur. Immunity correlated with antibodies that can remain for a while None Humans Impression given is of an occasional infection that elicits only little immunity perhaps because the causal organism simply does not really like it in man. There are many species that infect domestic animals but there is no record here of zoonotic infection. Antibiotics work.
Disease

 

Infectious agent.
Target organ if any.
Location ICD 10 entry.
Impact
Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments, treatment
Pneumonia, neonatal eosinophilic pneumonia, Congenital pneumonia due to Chlamydia Chlamydia trachomatis particular immunotypes

A sub-acute pulmonary disease

 

Probably coincides with the worldwide distribution of the causative organism as a genitally transmited infection P23.1

Illness usually moderate

? Infants born to mothers who have chlamydial genital infection. Unknown. Maternal antibody is not protective None Humans Oral erythromycin.
Pneumonia

pneumonia due to Chlamydia

Chlamydia pneumoniae

An acute respiratory disease.

Presumably worldwide J16.0

Death rare in uncomplicated cases

Universal Increased likelihood of clinical disease with pre-existing chronic disease. Some suggestion of immunity after infection however second episodes of pneumonia are not unusual None Humans probably Oral tetracyclines
Psittacosis, Ornithosis, Parrot fever, Avian Chlamydiosis. Chlamydophila psittaci

An acute disease with systemic presentations and respiratory symptoms.

World wide A70

Usually mild

Universal Exposure to birds and old age Immunity after infection incomplete and transitory none Parakeets, parrots and love birds mainly. Birds that appear healthy can become shedders under conditions of stress.
Q fever, Query fever. Coxiella burnettii

An acute febrile disease. Various complications sometimes involving the liver.

Worldwide, under reported It should be noted that fatality in untreated cases can be as high as 2.4%. A78

 

General A variety of occupations particularly veterinarian and abattoir workers. are associated with this disease. Immunity probably lifelong after recovery from disease. Cell mediated immunity lasts longer than humoral (does the organismpersist?) Not commercially available but for those at high risk vaccines that are effective have been prepared. Sheep, cattle., goats and dogs. Tetracyclines for acute disease Antibiotics.
Disease

 

Infectious agent.
Target organ if any.
Location ICD 10 entry.
Impact
Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments, treatment
Relapsing fever, Borrelia recurrentis

 

Fever often recurrent.

Worldwide except Australia and New Zealand A68

Untreated case fatality can be 2-10%

general None stated Unknown but second attacks are rare. None Humans and wild rodent. There are some differences between the tick and louse borne forms of the disase. Tetracyclines
Rickettsioses, tick borne, rocky mountain spotted fever.

 

Some twelve fevers are recorded under this heading from specific geographical locations, here only two will be dealt with

Rickettsia rickettsii Throughout USA and some S American states A77

Case fatality 13-25% if not recognized and treated

general Patients older than 40 Immunity not stated in 20th Edition. In earlier editions it is stated that one attack confers life time immunity. none Maintained in nature by ticks can be transferred to for example dogs in which infection is usually subclinical tetracyclines
Rickettsioses, tick borne, Boutonneuse fever Rickettsia conori and related organisms. Widely distributed in Africa and India and Eastern Europe A77.1

Mild to severe febrile illness

General Travellers! Immunity not stated in 20th Edition. None Ticks and dogs (travellers dogs pick up infected ticks that are taken home with the owners who subsequently acquire the infection. Tetracyclines
Disease

 

Infectious agent.
Target organ if any.
Location ICD 10 entry.Impact Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments, treatment
Salmonellosis, Salmonella bongori and S enterica

 

More than 2000 serotypes are recorded.

 

Severe enteritis

Worldwide, can occur in massive epidemics AA02

 

million cases reported annually in the USA alone! Not usually fatal

General, severity of condition related to ‘dosage’ of infection. The very young, achlorhydria, AIDS patients, malnutrition and other debilitating conditions. None recorded None available Predominantly an infection of food but commonly carried by a wide variety of animals. A major disease the only causes problems in high concentrations No treatment generally indicated except rehydration. In the very young and very old antibiotics can be given. Patients with AIDS may require lifelong therapy
Shigellosis, bacillary dysentery Shigella various spp

 

Distal small intestine and colon.

 

Worldwide A03

Estimated that shigellosis causes14,000 deaths annually but mild and asymptomatic infections occur and the illness is usually self-limiting

General, infection can follow ingestion of a small no of bacteria. Very young and the elderly and debilitated patients of many kinds. Breast feeding is protective for young infant. Homosexual men where conditions are poor such as in jails. Not recorded. Secondary attack rates can be up to 40% in specific households. Vaccines with some short term efficacy have been deployed. There is a clear need for an effective long term vaccine. Humans  A major disease with far too little said about it. Particularly the issue of immunity is not addressed perhaps because there is not any although the experimental vaccines have had some success. Symptomatic treatment except in severe cases. Antibiotics can then work but there are major and complex problems with resistance.
Staphylococcal diseases in the community, boils, carbuncles,, sepsis, infected lacerations. Staphyllococcus aureus various coagulase positive strains are involved, identified

Skin

Worldwide, highest incidence of disease where standards of hygiene are lowest. L02, B95.6, B 95.8 A41.0 A 41.2

 

Universal. 20-30% of general population are nasal carriers of the relevant organisms. Auto-infection responsible for at least two thirds of infection with disease. Newborn and all sorts of generally debilitated patients Immune mechanisms said to depend on the instruments of innate immunity. None recorded Humans more rarely animals Local disease does not warrant treatment. Treatment of systematized infection with antibiotics is undertaken.
Disease

 

Infectious agent.
Target organ if any.
Location ICD 10 entry.
Impact
Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments, treatment
Staphylococcal diseases in the community, boils, carbuncles sepsis, infected lacerations. Staphyllococcus aureus various coagulase positive strains are identified.

Skin

World wide, highest incidence of disease where standards of hygiene are lowest. L02, B95.6, B 95.8 A41.0 A 41.2

 

Universal 20-30% of general population are nasal carriers of the relevant organisms. Auto-infection responsible for at least two thirds of infection with disease. Newborn and all sorts of generally debilitated patients Immune mechanisms said to depend on the instruments of innate immunity i.e. not adaptive. None recorded Humans more rarely animals Local disease does not warrant treatment. Treatment of systematized infection with antibiotics is undertaken.
Staphylococcal diseases, in hospital nurseries, impetigo neonatorum, scaled skin syndrome, abscess of the breast As above

Impetigo

 

Skin.

Worldwide exacerbated by laxity in hygiene precautions and emergence of antibiotic resistance. L 01

Big problem quantification of it is given

In the new born susceptibility seems to be universal Infected infants remain at risk for the duration of infection with a pathogenic strain. ? None As above Antibiotics for both local and systemic infections can be effective.
Staphylococcal diseases, in medical and surgical wards. As above plus the problem that 90% of the strains causing problems are antibiotic resistant (MRSA).

A wide variety of conditions including endocarditis, osteomyelitis, pneumonia, meningitis,

J15.2, M86, M00.0, 133.0.

Probably the most serious problem of hospitals that have surgery, implants and so on.

Universal? Any sick people ? None As above The organism concerned is essentially ubiquitous and seems on the face of it to elicit little or no immune response Appropriate antimicrobials with great problems of resistsnce..
Streptococcal infection, caused by group A Hemolytic streps, a large no of diseases including scarlet fever, sore throat, erysipelas, puerperal fever, rheumatic fever necrotising fasciitis and so on. Streptococcus pyogenes group A

 

A wide variety of conditions mimicking sometimes the conditions caused by Staphylococci.

The diseases concerned need separate treatment as they differ in distribution across the world. Again treatment of the diseases as one category is not easy for example rheumatic fever is much less than it was but in 1985 there were outbreaks in the USA. The highest incidence of impetigo occurs in young children in the late fall and so on. General None quoted For some of the diseases long lasting type specific immunity follows infection for others it does not. For example rheumatic disease has a significant risk of recurrence. It seems that although we are dealing with the same basic organism its many disease manifestations are relatively ill understood None Humans It seems extraordinary that such a common set of diseases should be lumped together despite clear differences between them in terms of mechanisms of disease. Antibiotics.
Disease

 

Infectious agent.
Target organ if any.
Location ICD 10 entry.
Impact
Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments, treatment
Streptococcal infection, caused by group A Hemolytic streps, a large no of diseases including scarlet fever, sore throat, erysipelas, puerperal fever, rheumatic fever necrotising fasciitis and so on. Streptococcus pyogenes group A

 

A wide variety of conditions mimicking sometimes the conditions caused by Staphylococci.

The diseases concerned need separate treatment as they differ in distribution across the world. Again treatment of the diseases as one category is not easy for example rheumatic fever is much less than it was but in 1985 there were outbreaks in the USA. The highest incidence of impetigo occurs in young children in the late fall and so on. General None quoted For some of the diseases long lasting type specific immunity follows infection for others it does not. For example rheumatic disease has a significant risk of recurrence. It seems that although we are dealing with the same basic organism its many disease manifestations are relatively ill understood None Humans It seems extraordinary that such a common set of diseases should be lumped together despite clear differences between them in terms of mechanisms of disease. Antibiotics.
Streptococcal infection, caused by group B, streptococcal sepsis of the new born. (and dental caries of the new born), baby bottle tooth decay. Streptococcus aagalacticae

Serious invasive diseases of the newborn.

 

 

Same as above except group B

P36.0

Thought to occur worldwide. Information here lacking.. Most studies from N. America and Europe

Babies born prematurely, particularly when there is rupture of the membranes more than 18 hours prior to delivery. A vaccine for pregnant women to stimulate antibody production to restrict invasivc disease is said to be under production. Hunans. Commonly found in GI and urinary tracts. Anti microbial preparations. Given particularly to infected pregnant women prior to labour.
Disease

 

Infectious agent.
Target organ if any.
Location ICD 10 entry.
Impact
Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments, treatment
Syphilis. Treponema pallidum

 

STD. Extremely complex disease with three distinct phases.

Widespread among sexually active individuals A50-52 Extremely nasty consequences can arises in untreated chronic disease although ilatency is known. Universal although only 30% of exposures result in disease.. Immunosuppression, particularly HIV Immunity to re- or further- infection usually develops in time but paradoxically it often fails to develop because of early treatment.. None available Humans Complex treatment protocols often involving penicillin
Tetanus, lockjaw, Obstretrical tetanus, tetanus neonatorum. Clostridium tetani

 

Acute disease caused by an exotoxin. A variety of disease forms can emerge after contact with the causal organism.

Worldwide A35, A 33. A.34.

Relatively uncommon in industrialised countries case fatality 2.3% for those aged under 20-39 and 18% for those over 60. Case fatality can up to 80% depending on quality of care.

General Infants and elderly at higher risk. Members of service groups such as armed forces and police and those in contact with sewage. Paradoxically recovery from infection does not guarantee immunity and there is no detectable antibody (this is somewhat of a paradox in that anti-toxin immunisation is effective for long periods of time). Active long lasting immunity is elicited by toxoid Intestines of cattle and soil in which human and or animal faeces are found. The organism is essentially everywhere. Prohylactic antibiotics in those by culture felt to obe at risk
Trachoma, Chlamydia trachomatis, specific serovars.

 

Initially conjunctivitis,

Can resolve spontaneously but repeated reinfection can lead to blindness.

Worldwide occurring as an endemic disease largely in poorer communities A71

A major cause of development of blindness over a long period of time.

General. Active disease tends not to be seen in older children and adults Poor living conditions,

Dust and fine sand may exacerbate the condition.

No evidence for immunity None successful Humans A major disease but seemingly curable. Topical tetracylines can be effective. Repositioning of eyelashes so they no longer abrade the cornea can be effective.
Disease

 

Infectious agent.
Target organ if any.
Location ICD 10 entry.
Impact
Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments, treatment
Trench fever, Quintana fever Bartonella quintana

 

A typically febrile non fatal septicaemia.

 

Scattered but in many places A79

Particularly prevalent in world war one trenches

General Immunocompormised patients have a variety of severe symptoms unknown None recorded Humans but vector is the body louse. Tetracyclines
Tuberculosis, TB

 

Mycobacterium tuberculosis and to far lesser extent M. bovis.

It is estimated that 1/3 of the world population is presently infected. Active disease can be pulmonary or extra pulmonary.

There is given in the manual a brief account of non-tuberculous mycobacterial disease. Here it is not considered.

Worldwide AA15-19

Probably the biggest single cause of mortality and disability associated with infection. Despite this it is likely that the majority (90%) of those infected enter a latent condition from which there is always a danger of reactivation.

Ostensibly risk of infection is related to degree of exposure. The first six to twelve months after infection are the most dangerous for development of full blown disease. Risk of developing disease highest under the age of 3, lowest in later childhood and high again among young adults the aged and the immunosuppressed HIV in particular. Other debilitating diseases can contribute to the likelihood of reactivation. The utility in some circumstances of BCG vaccination suggests that there is a degree if immunological control but one wonders if this is niche occupation rather than immunity per se. There is little in the text about immunity except in relation to the PPD skin testing that is usually positive in infected people. This is a very complex story BCG has been deployed but in some circumstances it seems not to work in terms of avoiding disease. The whole issue is complicated by the differences in frequency of wild type challenge in some of the regions that are being compared. Humans primarily. The argument in relation to badgers and cattle still rages. Antibimicrobials. Whether latent TB should be treated seems not to have been addressed. Also the latent status seems to be little understood
Disease

 

Infectious agent.
Target organ if any.
Location ICD 10 entry.
Impact
Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments, treatment
Tularaemia, Rabbit fever, Deer-fly fever, Ohara disease, Francis disease. Francisella tularensis

 

Skin and lymphadenopathy, or the latter without the former.

N America, former Soviet Union China and Japan A21

Complex set of diseases with a wide variety of symptoms..

All ages susceptible, and presumably all people Closely linked to occupational and recreational activities. Long term immunity follows recovery from infection. None Numerous wild animals, with a tick vector usually or, less commonly, deer fly Streptomycin.
Typhoid, paratyphoid fever, enteric fever, typhus abdominalis. Salmonella typhi Worldwide.,major diseases of which paratyphoid is the milder. A01.0,A01.4

No of cases annually estimated at 17 million cases annually with estimated 600,000! Deaths. Many mild and inapparent infections occur

General Achlorhydria, HIV infection, IN endemic areas disease is most common in children up to 19 years of age. Relative specific immunity follows infection with disease, unapparent infection or active immunisation A double vaccine is available, one part live and the other a coat polysaccharide (from paratyphus). They are not uniformly successful. Humans for typhoid, and paratyphoid. More rarely animals for paratyphoid. Some chronic carriers. Antibiotics but resistance is becoming an increasingly difficult problem.
Typhus fever, epidemic louse borne typhus fever Rickettsia prowazekii

A wide variety of systsemic symptoms with a specifically recognized (Brill-Zinser) disease occurring year after the primary attack.

In colder areas where people may live in unsanitary conditions and are infested with lice. A75,Case fatality untreated varies from 10-40%. Mild infections can occur without eruptions especially in children and those partially immunized General None stated One attack gives lifelong immunity This is stated in earlier editions of the manual but not repeated in the 20th edition. None Humans and to a limited extent flying squirrels. The vector is the body louse. Antibiotic treatment, doxycycline, usually effective.
Disease

 

Infectious agent.
Target organ if any.
Location ICD 10 entry.
Impact
Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments, treatment
Typhus fever, epidemic flea borne typhus, murine typhus, shop typhus. Rickettsia typhi

Manifestations of disease similar to those associated with louse borne disease.

Worldwide A75.22

Milder than the louse borne equivalent

General None given One attack confers immunity. None Rats mice and probably other small mammals, vector infected rat fleas. Tetracyclines
Scrub typhus, tsutsugamushi disease. Miteborne typhus fever Orientia tsutsugamushi with many serotypes. and a wide variety of symptoms often dermal initially. Central and South East Asia A75.3

Case fatality rate untreated as high as 60%

General Bigger problems with older people, occupational particularly military troops Prolonged immunity against the homologous strain. Unpredictable for heterologous challenge None successful Thrombiculid mites are the reservoir Tetracyclines
Yaws, Frambesia tropica. Treponema pallidum

Highly unpleasant skin disorders.

A disease of children in moist tropical regions A66Rarely fatal but can be very disfiguring and maiming. No evidence of natural or racial resistance More frequent in male children Infection results in immunity and sometimes resistance to other pathogenic treponemes None Humans Pencillin
Yersiniosis, Yersinia enterocolitica, Y. pseudotuberculosis

 

Typically manifest as acute febrile diarrhoea with abdominal pain.

World wide A04.6Complex pattern of susceptibility, post infection arthritis is more severe in adolescents and young adults No statement but inference is that susceptibility is universal HLa-B27 positive patients more susceptible to reactive arthritis and Reiters syndrome. Septicaemia occurs more often in those with an iron overload or with underlying immunosuppression. Nothing stated None Animals particularly the pig, ie a zoonosis Organisms are sensitive to many antibiotics but not to penicillin.

About one third of bacterial diseases are labelled chronic. Clearly there are problems of definition with this epithet. It is evident that a considerable number of diseases can either be acute with no persistence of the causal infecting organism or chronic with persistence. The issue of whether when there is no persistence of the infective organism but retention of an immunological memory will be discussed elsewhere in this paper. Sometimes when a parasite does not persist, perhaps as consequence of treatment, there is no obvious residual immunological memory (for example some Chlamydial infections, Lyme disease, listeriosis). On the other hand the diseases caused by certain Rickettsia spp seem to lead to lifelong immunity even post treatment aimed at the causal organism. Is this a clear example of persistence of immunological memory? If it is, what is the difference between, say, Listeria and Rickettsia that leads to the differences in post hoc immunological memory? In cases of salmonellosis, many of which recover spontaneously albeit with periods of discomfort in between, there seems to be no immunological memory. In fact there is no evidence given in the manual for any immune response. How was the parasite brought under control? In the instance of Salmonella infections it is clear that the initial dose of infection can determine the severity of the disease that arises. With some other bacteria, Shigella, for example, only very few organisms are required to initiate an infection the severity of which is not determined by the starting dose but by other factors. It is not clear whether Shigella activates the immune response. The manual says only that up to 40% of households show second attacks. On this basis using the standard immunological paradigms if there is immunity it is sometimes transient and relatively ineffective. Later in this paper evidence will be presented that the normal gut flora normally attracts little if any attention from the adaptive immune apparatus and this might be the situation in relation to Salmonella and Shigella which are primarily infections of the gut.

In some instances as with Meloidosis there is no evidence of immune mechanisms but it does seem that the infecting organism persists in patients infected years previously who, subsequently, have recrudescence of infection on becoming diabetic. The Streptococcal, Pneumococcal and Staphylococcal organisms are all common components of the normal flora associated with skin and upper respiratory tract. All are associated with a variety of unpleasant diseases but we are not sure in mechanistic terms why what was ostensibly a balanced equilibrium (13) between host and parasite becomes unbalanced, in favour, as it were, of the parasite and active disease ensues. All the organisms concerned are numerous in relation to the varieties they display and for none of them is there a clear immunological controlling mechanism. If, for example, illness leads to alteration of the equilibrium between host and parasite what aspect of the various immune mechanisms is affected and is there any way we can identify this and perhaps intervene purposefully?

Direct zoonotic infections are found particularly among those who, as part of their occupation or as carers of companion animals, frequently come in contact with animals. In other instances a non-human vertebrate or non-vertebrate reservoirs of infection can be the source of transfer to humans by vector organisms. The disease status or not of the vectors is of considerable interest but not often considered. Invertebrate vectors, for example, do not possess the adaptive immune mechanisms which the vertebrates do possess as a class. If the transferred organisms capable of causing disease, which is sometimes controlled by adaptive immune mechanisms, what if any is the control mechanism for the invertebrate vectors? Also the immune status of non-human vertebrate organisms that serve as reservoirs of infection after transfer to humans is worth exploration. It does seem that many organisms which can potentially cause disease in man exist in an asymptomatic state in the reservoir host animals. Could it be that the symptoms of disease in the vertebrate organisms are attributable to some facet of the adaptive immune response rather than being necessarily prevented by it?

Clearly in relation to bacterial infection there are many strategies of interaction. Rather little has been done with vaccines with bacterial infections largely for the reason that the majority, though not all, of dangerous bacterial infections can readily be controlled by antibiotics. Where vaccination against a bacterial infection has been deployed it has sometimes been against a toxoid liberated by the infecting bacterium, cholera for example, or sometimes derived from phage in the bacterium rather than a product of the parasite genome, vide diphtheria. It looks as if each organism as an infection and as a cause of disease has to be explored in detail if what is referred to as evidence-based medicine is properly to be practised.

Viruses

The absolute number of viral infections in man is of the order of two hundred the majority of which are arboviruses which reach human hosts via an arthropod vector. Taxonomically viruses are diverse and it could be advantageous to group them according to the taxons they belong to. This has not been done consistently in the Table 2 which in the main lists them alphabetically by the name of the disease or group of diseases they are responsible for.

Table 2: Viruses.

Disease

 

Infectious agent.

Target organ if any.

Location ICD 10 entry.

Impact

Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments and Treatment
 Arenoviral, Haemorrhagic fevers, Junin, Matupo, Guanarito, Sabia, chapare.(this last not ICD listed). New world.

 

 

Tachibe tribe of arenoviruses

 

Acute febrile illnesses typically lasting for up to 14 days

South America particularly Bolivia, Argentina, Venezuela and Brazil A96.0,A96.1, A96.2,A96.8,

Occasional epidemics with lethality up to 30%. Variable according to location and causal agent

All ages susceptible Largely occupational with particular reference to laboratory workers. Protective immunity of unknown duration follows infection. A live virus for the Argentinian disease Various wild rodents Sub-clinical infections occur. Immune plasma only remedy but it is effective in some instances in the Argentine form of the diseases. Ribavirin also useful across the board.
Arboviruses There are more than 100 arbovuruses which constitute the biggest single category of disease causing organisms. Their common feature is their transmission to humans by arthropod vectors, mosquitos, ticks, sandflies and biting midges. Arboviruses are variously RNA viruses largely of the families Bunyaviridae, Flaviviridae, Roeviridae, and Togaviridae Here four categories of disease will briefly be considered., Arboviral arthritis and rash., Arboviral encephalitidies, Arboviral fevers and Arboviral hemorrhagic fevers. Most arboviruses are maintained in zoonotic cycles between birds or small mammals and insect vectors. Humans tend to be infected incidentally. In many but not all instances infected individuals do not develop or sustain a high enough viraemia to infect arthropod vectors. Recovery with immunity is usual but does not always occur. No vaccines mentioned. Birds and small mammals more rarely infected humans.
Disease

­

Infectious agent.

Target organ if any.

Location ICD 10 entry.

Impact

Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments, treatment
Arbo-virus encephalitides; Mosquito borne – at least 25 separate diseases with very similar features but occurring in different localities and associated with different local strains of virus. Japanese encephalitis virus and West Nile virus are listed separately. Local viruses, alpha viruses, flaviviruses, and Bunya viruses

 

Most infections are asymptomatic or result in undifferentiated febrile illness. Many forms of later complication.

Almost anywhere that mosquitoes are found. A83.8,A83.2, A83.5,A83.4, A83.6, A84.1, A92.2, A83.1.

Hugely variable some rarely lethal others with significant mortality.

Many adults have acquired immunity Children, visitors and those new to the area tend to be most diseased. The young and the old are more susceptible. Various medical conditions predispose to severity of disease. Infection usually results in lifelong homologous immunity A variety of live and dead vaccines are used for a few of the diseases in this group. Birds, small mammals

 

 

Inapparent infections usual in younger adults. No treatment available.
Disease

 

Infectious agent.

Target organ if any.

Location ICD 10 entry.

Impact

Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments, treatment
Arboviral fevers, vectors, Mosquitos, sand flies and biting midges. 25 listed in the 20th edition. Rift Valley fever listed separately. Single stranded RNA viruses of various families primarily Flaviviridae, and Bunyaviridae or double stranded RNA viruses of the family Reoviridae

Febrile illnesses lasting a week or so rarely fatal

Global but tropical or sub tropical in the main. A92.8, A93.8, A 93.2, A93.0, A93.1, B33.8,

Rarely lethal (less than ten per cent were serious in an American outbreak)

General, mild infections and subsequent immunity occur frequently in endemic areas Children at higher risk of CNS infection.. Immunocompromised individuals at higher risk of symptomatic infection. Lifelong immunity after infection is usual No vaccines mentioned. Complex patterns of transmission. No specific treatments
Arboviral hemorrhagic fevers. 4 listed, Yellow fever and Dengue are listed separately. Causal agents Flaviviridae and Bunyaviridae. Specific regions for the different diseases. Often seasonal relating to vector prevalence. A98.0, A98.1, A98.2. serious diseases with distressing symptoms and very variable mortalities ranging from 1-30-% Often health care workers, abattoir workers owners of livestock. Occupational risks. Lifelong immunity after infection is usual Some vaccines have been developed but overall use controversial at present. Wide range of reservoirs which vary according to the specific diseases. No specific treatments
Corona Virus Respiratory Infections.,

All enveloped RNA viruses that infect a wide range of mammals and birds. In man they can cause severe and sometimes lethal respiratory disease. Single stranded positive strand RNA viruses, three reported here the first two in the 20th edition of the manual the third in 2020 the cause of a pandemic which will doubtless be reported in the 21st edition of the manual to be published in 2021.

Corona virus respiratory infections MERS, Middle East respiratory syndrome MERS –CoV

As above

All cases known are linked to the Middle East. None presently allocated. By mid 2014 that 699 laboratory confirmed cases were reported to WHO with at least 209 deaths. Sporadic human cases are considered likely to continue. Not known except for common co-morbidities and contact with infected individuals. A variety of co-morbidities such as diabetes immunosuppression and heart disease most commonly reported. ? Use of convalescent plasma has been considered. Direct contact and fomites recognised with camels found to have high titres of neutralising antibodies. No anti-virals have been deployed but with some patients prophylactic antibiotics have been used.
Disease

 

Infectious agent.

Target organ if any.

Location ICD 10 entry.

Impact

Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments, treatment
Corona virus respiratory infections Covid-19 SARS-CoV-2

Huge impact worldwide with many millions of cases and a significant mortality.

Worldwide though major differences have been found between incidences in countries. Emergency code of U07 allocated.

Massive impact on health services and great economic impact as a consequence of the steps enforced by national governments in their attempts to prevent the spread of infection.

Older ages at special risk but cases known in all ages. Age and prior health conditions. A significant proportion of those hospitalised and dying had prior bad health. Antibodies are produced in severe cases but it is recorded (ref) that asymptomatic cases do not show antibody. Many presently in preparation as the authorities are wedded to the idea that vaccines are the answer. The causal agent is said to be new. Arguments rage about where the first cases appeared. In late 2020 we are desperately short of hard information about the biology of the disease and why some 70% of those infected remain asymptomtic. Declared pandemic by WHO with subsequent enormous attempts to stop it.
Keratoconjunctivitis, adenoviral, shipyard eye. Bacterial conjunctivitis dealt with in bacterial tables. Adenoviruses types 8, 19 and 37 in the USA

Eyes.

Presumably worldwide. Outbreaks have occurred in Asia, Hawaii, North America and Europe B30.0

Unusually residual scarring appears

Not stated presumably universal Any trauma can increase the risk of infection Usually long lasting type specific immunity after infection. N/A Humans Often associated with eye clinics! Clearly a very contagious agent. No treatment during acute phase.
Adenoviral hemorrhagic conjunctivitis, Pharyngoconjunctival fever Adenoviruses and picornaviruses Summer epidemics associated with swimming pools B30.0

Usually mild but severe chronic cases with residual neurological complications are recorded.

All ages can be affected. Associated with institutional overcrowding. ? Reinfections and relapses are reported the role and duraion of immunity if any is not clear N/A Humans Swimming pool disease. no specific treatment
Disease

 

Infectious agent.

Target organ if any.

Location ICD 10 entry.

Impact

Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments, treatment
Coxsackievirus diseases, vesicular pharyngitis, vesicular stomatitis with exanthema (hand foot and mouth disease), lymphonodular pharyngitis. Not recorded in 20th edition. Various coxsackieviruses Worldwide sporadic particularly the lymphonodular pharyngitis ICD 9, 074, ICD 10, B34.

In general self limiting

Universal Not stated Type specific Immunity probably acquired by clinical or inapparent infection, duration unknown N/A Humans associated with juvenile diabetes No specific treatment
Cytomegalovirus infections adult and congenital, Human (beta) herpes virus 5 inter alia.

 

Febrile illness

Ubiquitous B25, P35.1

 

Very drastic on affected infants and many of those who are immunosuppressed

Ubiquitous Immaturity and immunopareses of many kinds. It causes enormous problems in transplant patients. It produces symptoms relatively rarely. ‘t is the classic example of the persistent in apparent infection. As many as 100% of people in developing countries have antibodies and all have the infection! None generally available Man the animal CMVs do not infect humans Transmission of the disease is by intimate contact with infected mucosal surfaces. CTX ganciclovir
Dengue fever, break bone fever Flaviviruses of specific serotypes

Acute febrile illness

Endemic in most tropical countries A90.

Rarely fatal except in instances of hemorrhagic complications

universal Children affected less than adults Serotype specific and effective immunity develops that is lifelong. None Human with mosquito vectors Although rarely lethal it can cause large scale epidemics when the virus and the vector coincide.. Supportive treatment aspirin
Disease

 

Infectious agent.

Target organ if any.

Location ICD 10 entry.

Impact

Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments, treatment
Dengue hemorrhagic fever As above Outbreaks recorded from many tropical locations A91.

Case fatality rates of up to 50% are reported in which fluid replacement has not been effected.

Universal in that susceptibility to causal viruses is universal Antibodies to heterologous infection acquired either passively or as a result of a previous attack are the major risk factors. (see comments) In this instance stimulation of the immune apparatus has a detrimental effect None As above Heterologous antibody apparently enhances uptake of newly entered virus into mononuclear cells. The consequences seem to be over secretion of cytokines.
Ebola-Marburg virus diseases, African hemorrhagic fever, Negative stranded Filoviridae. Five Ebola viruses have so far been discovered of which four cause human disease. The fifth can cause fatal hemorrhagic disease in non-human primates. Marburg virus at the moment has only one discovered Species High fever is a starting symptom with a variety of detrimental systemic conditions following Initially recognized as a zoonosis from monkeys in Europe. Subsequently has been recognized in Africa in a number of epidemics with high fatality A98.4,A98.3

Extremely nasty. With outbreaks in many centres recorded from 1976 for Ebola and from 1967 for Marburg.,

All ages susceptible Main groups at risk are patients infected with contaminated needles and care givers of in affected communities, laboratory workers processing infected specimens. People working with wild life in particular non-human primates in Central Africa and bats Antibodies have been found but it is not yet clear what their relationship is to infection by any of the relevant viruses. Watch this space. None so far Cynomolgus monkeys, bats and infected patients. The viruses are highly contagious. These viruses are highly pathogenic.. Seem often apart from monkey bites and contact with direct or indirect contact with infected patients to be spread by sexual intercourse. Clearly in relation to Ebola and Marburg disease these re early days and we are short of information.
Erythema infectiosum (fifth disease) Human parvovirus B19

 

A mild childhood exanthematous disease associated with low grade fever.

worldwide B08.3

Generally benign

Universal in those with blood group P antigen. 50-80% of adults in the USA have antibodies indicating contact with the organism. Patients with underlying anaemia particularly if they get pregnant are at higher risk, as are immunosuppressed individuals Anti-B19 virus antibodies seem to confer resistance to disease One said to be under development Humans
Exantheum subitum, sixth disease, roseola infantum Human herpes virus HHV6Usually mild like glandular fever Worldwide B08.2Slight except in immunosuppressed individuals General Restricted almost to children under the age of five but over six months Latent infection with immunity to further infection Not developed but thought about Humans with latent infection. Symptomatic care but nothing given as specific treatment.
Disease

 

Infectious agent.

Target organ if any.

Location ICD 10 entry.

Impact

Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments, treatment
Gastroenteritis acute,viral, rotaviral enteritis Reoviridae, many types involved

 

Vomiting, fever and watery diarrhea

World wide A08.0

Huge, one third of all hospitalised cases of diarrhoeal illness in infants and young children due to rotavirus. It is said to be responsible for up to 900,000 deaths of children per year!

Greatest between 6 and 24 months of age beyond that most have acquired antibody. Immunocompromised individuals at special risk for prolonged rotavirus secretion and intermittent rotaviral diarrhoea Neonatal rotavirus infections are usual in certain settings but most are asymptomatic. Immunity in most instances is complete and seems to follow (asymptomatic?) infection. One being tested presently. Much work has gone into attempt passive immunisation with food containing neutralising antibodies. Result NK. Humans One of the major diseases of the world. The virus can survive for long periods on dry surfaces and is resistant to some standard disinfectants. A major cause of nosocomial infection in infants. Symptomatic treatment only –rehydration for example.
Norovirus infection Norwalk like viruses (small RNA). Commonly known as Norovirus. Worldwide and common (in parts of the USA 60% of the population had antibodies) A08.1

 

Usually a self- limiting mild to moderate disease

widespread Adults >65 and children < 5year at special risk of developing a severe disease. Antibody levels did not correlate with resistance or susceptibility. Short lived immunity up to 14 weeks was shown in volunteers but not always thereafter none Humans Associated particularly with the consumption of raw shellfish. Fluid replacement only. Can be a nosocomial infection
Hanta virus disease, hemorrhagic fever with renal syndrome Hantaviruses of various strains. This and the, pulmonary syndrome are both Acute zoonotic diseases with a febrile prodrome, thrombocytopenia. leukocytosis and capillary leakage. widespread. A98.5

In its worst manifestation up to 15% mortality

Uniform susceptibility except perhaps those who have evidence of previous infection! Occupational risks for hospital personnel and animal handlers Yes, second attacks not documented None Field rodents, humans are an accidental host Obvious zoonosis, fluid management
Disease

 

Infectious agent.

Target organ if any.

Location ICD 10 entry.

Impact

Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments, treatment
Hanta virus disease, pulmonary syndrome As above Restricted depends on distribution of carrier rodents B33.4

 

Rare but lethality up to 50%

All susceptible without prior infection None No second cases identified, mild infections. If immunity exists its duration and strength are not known None Deer mouse Another zoonosis, symptomatic management only.
Hendra and nipah viral diseases Paramyxoviruses

 

Nipah manifests primarily as a encephalitis, Hendra as a respiratory illness or a prolonged and initially mild encephalitis.

Very restricted B33.8

 

Very rare but mortality up to 50%, subclinical infections may be common!

All ages suceptible Those in contact with swine. Or infected horses. Possibly people in contact with palms sap from trees with roosting bats. Recurrent infection known. none Fruit bats and a variety of small wild animals, horses and some companion animals. Potentially very nasty zoonosis, No specific treatment.
Viral Hepatitis Diseases

Some five recognized all affecting the liver but with some very different viruses. Collectively they have a huge global impact

Viral Hepatitis A, infectious hepatitis, Epidemic jaundice. HAV a picornavirus (RNA)

 

All the hepatidides are hepatropic and in various ways on liver function.

Worldwide (33% of adults in industrialised couuntries are said to have had contact with it.

 

B15

Usually usually mild infection which resolves in time

Case fatality low. Can reach 1.8% in adults over the age of 50.

General Number of epidemics among school children particularly. Homosexual males tend to get it. Food handlers. Those with chronic liver disease t higher risk of bad outcome if infection. Homologous immunity after infection probably life long Two inactivated vaccines are available and said to be effective Humans, more rarely chimpanzees and other animals but an animal reservoir in nature has not been recognized. A major disease but not in the same league as some of its alphabetic colleagues. Passive immunisation with Ig is used.
Viral Hepatitis B, serum hepatitis, homologous serum jaundice, Australia antigen hepatitis HBV a double stranded DNA virus

 

Fewer than 10%of children and 30-50% of adults having acute infection with HBV show icteric disease. In infants it is usually asymptomtic.

World wide.

It is written that 2 billion people are infected and that approximately 600,000 die each year of the disease with four million new cases a year.

B16

 

General though only a small proportion of cases are recognized.(by icteric disease usually) Immunosuppressed individuals tend to get the chronic disease with liver complications. It is the prime cause of hepatocellular carcinoma that is second world wide to tobacco induced lung cancer. Vaccination is widespread whether spontaneous immunity develops following a recovered infection is dependent on the quality of antibodies discovered. Very effective vaccines have been available for more than twenty years. One of these is a recombinant yeast which expresses the appropriate antigen. Humans perhaps occasionally chimpanzees. Closely related viruses from other animals do not affect humans. The goliath among diseases. Alpha interferon and lamivudine but nothing which is a guaranteed cure.
Disease

 

Infectious agent.

Target organ if any.

Location ICD 10 entry.

Impact

Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments, treatment
Viral Hepatitis C, parenterally transmitted nonA nonB hepatitis, tranfusion associated hepatitis. HCV, an enveloped RNA virus

 

Onset insidious with only 20-30% of active infections being symptomatic. 75-85% of infections become chronic.

Worldwide B17.1

Limited by the number of people who share injection equipment! For all that about 1% of the world population are infected! (ie 60 million).

General. The enormous problem here is that 90% of infections are asymptomatic. Of those infected a significant number will get cirrhosis of the liver and sometimes hepatocellular carcinoma. Both these conditions are gravely life threatening. Drug users., Those using non-sterile needles, recipients of transfused blood, unprotected sex among male homosexuals. Health care workers. None recognized None Humans. In chimpanzees experimental re-infection can be brought about. but there is no evidence that non-human primates act as reservoir of. Human infection An effective treatment with direct acting anti viral treatment is now available.(not referred to in the 20th edition of the manual but recorded widely on the web.
Viral Hepatitis D, Delta hepatitis HDV a single stranded RNA virus Worldwide B17.1 About 10million people affected worldwide always in conjunction with HBV General Severe disease can occur even in children Not stated HBV can lead immunity to HDV. Humans None given. For those with established HBV infection there are presently no methods to prevent HDV
Viral Hepatitis E, epidemic,,

nonA nonB

HEV a non- enveloped single stranded RNA worldwide B17.2

Small in comparison with A and B

Susceptibility unknown Pregnant women in the third trimester of pregnancy are particularly susceptible Not stated. None ?domestic animals including swine None recorded
Disease

 

Infectious agent.

Target organ if any.

Location ICD 10 entry.

Impact

Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments, treatment
Herpes simplex, anogenital herpesviral infections, Congenital herpes viral infection.

In addition two other herpes infections are listed which will dealt with separately below.

Herpes simplex virus 1and 2 (roughly 1 for the top end in kids and 2 for the bottom in adults, it being largely an STD)

Neurovirulence, latency and a tendency to local recurrence characterize these infections

Worldwide, 50-90% of adults possess antibodies against HSV 1 A60, B00, P35.2

Many primary infections are inapparent and the symptomatic cases vary a great deal in severity in both instances

Universal Immunosuppressed individuals Antibodies are elicited but they seem not to be affected by reactivation of latent infection (or vice versa!) None quoted Humans Remarkably contagious, Acyclovir IV seems to be reasonably effective.
Kaposi’s sarcoma KS associated herpes virus or Herpes virus 8 believed to be causal.

STD. though it is argued that non sexual means of transmission also occur

Where AIDS patients are to be found, ie worldwide. C46.0, C46.9 ? Immunosuppression Antibodies to the virus are recognised but it is not clear what their relationship is to clinical status. Associated largely with HIV infections.
Influenza, human diseases and zoonoses are recognised.

 

Three types of virus some of which are further broken down but a main characteristic of the organism is its capacity to produce new variants.

 

Infection of the respiratory tract

In pandemics in which a variable proportion of the population is affected J10, J11.

as said to have killed up to 50 million in the 1918 outbreak

Complex picture, implication is that all are susceptible except those who have had a previous encounter with the same or similar organism Again very variable. In some epidemics more than 80% of those who died were over the age of 65 but in relation to the biggest epidemic (in 1918) young adults were the most affected! Type specific immunity is strong Inactivated virus used widely and it does give protection. Humans primary reservoir but other spp aquatic birds in particular have widely been mooted as capable of initiating a pandemic. A major disease the impact of which can be lessened by vaccination. Oseltamivir and Zanamivir both associated with potential side effects
Other influenza., infections circulating in and causing diseases in animals H5N1, avian influenza virus and H9N2, swine influenza virus.

Mortality can high among humans infected with the relevant viruses from (diseased?) infected poultry are the main focus in the 20th edition of the manual.

World wide J09

All potential causes of pandemics. The influenza viruses are highly mutable and always generate antigenically new variants which greatly complicates the invention of prophylactic vaccine preparation.

Initially occupational in that close contact with infected animals is a major risk factor but pandemic spread to the general population is always regarded as a potential hazard. Potentially all ages can become diseased. Immunity post infection does occur and to a limited extent can be induced either with attenuated live vaccines or non-living vaccines against extracted components of the virus responsible. Inducible Some vaccines against H5N1 have been prepared and licensed for use. Uncertain whether migratory birds are capable of spreading pathogenic viruses either to domestic animals or to man. As above.
Disease

 

Infectious agent.

Target organ if any.

Location ICD 10 entry.

Impact

Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments, treatment
Lymphocytic chorio-meningitis virus, LCM, a viral infection of rodents mainly mice. An enveloped ambisense RNA arena virus closely related to lassa and a number of others

Variety of symptoms can be influenza like. Rarely fatal.

Not uncommon in Europe and America A87.2

Rarely serious, extremely variable in its presentation

Not stated! Implication is that susceptibility is universal Surprisingly immunosuppressed patients who become infected may often not show the usual symptoms. Though in them the disease can be fatal. Occupational risk. Human foetuses can acquire the infection vertically. recovery leads to lifelong infection. Cell mediated immune responses may play a primary role antibodies are of lesser importance none Mus musculus, the house mouse. The disease in man is a zoonosis Nude, immunologically incompetent mice become chronic high level shedders but do not show disease? Ribavirin has been proposed as treatment for humans. A fascinating disease for immunologists.
Measles, rubeola Measles virus, a member of the genus Morbillivirus. A paramyxovirus Prodromal fever and pathognomonic rash. Rarely sub acute sclerosing panencephalitis develops as late complication. Complex pattern due to successful vaccination programs. Initially it seemed to be a disease of large metropolitan aggregates with a two to three year cycle. In rural populations it was less frequent but more severe B05

Unimmunuized populations can be extremely badly effected with a high case-fatality rate. World wide it was estimated that prior tow global vaccination programs six million measles deaths occurred each year!. However it is recorded by WHO that in 2011 157,700 children died. The anti-vaccine activists should look carefully these figures.

Universal (pace immunisation) More severe in infants and adults than in children Malnutrition, vitamin A deficiency predispose to severe disease. vaccination not recommended in those with immunodeficiency disease. Lifelong immunity after illness (issue of development of SSPE as a long term outcome of measles infection is not here considered in detail) Immunisation with a live attenuated virus is very effective. Humans In the developed world essentially under control until recently when resistance to vaccination has begun to reduce those who are immune. In days gone by before vaccination more than ninety per cent of people had been infected before the age of twenty. No specific treatment.
Disease

 

Infectious agent.

Target organ if any.

Location ICD 10 entry.

Impact

Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments, treatment
Molluscum contagiosum.

 

 

Molluscipox virus a member of the Poxviridae family.

Skin.

Worldwide B08.1

More nuisance value

General but specially in children Lesions tend to disseminate in HIV patients ? none Humans No specific treatment
Epstein-Barr infections

Also associated with infection by this virus are a number of diseases of which Burkitt’s lymphoma, nasopharyngeal carcinoma, Hodgkin’s disease and various non-Hodgkins lymphomas are mentioned in the 20th edition of the manual

. Monoucleosis infectious, (glandular fever), EBV, a herpesvirus 4.

 

It affects and transforms B cells.

Worldwide very common, widespread in early childhood B27Usually mild or asymptomatic, about 50% of those infected develop symptoms. All those infected retain the virus in latent (non-lytic) form for life and the possession of the virus is associated with many malignant diseases. This issue will not be dealt with in any detail here General May recur or be extremely serious in immunodeficient patients. (particularly X-linked recessive immunoproliferative disorder) Paradoxically recurrence can be associated with the development of anti EB antibodies but not the array of heterophile antibodies that has been used as pathognomonic for the acute disease. Infection incurs a immunity, despite which the organism persists in latent form for life. None yet Humans Extraordinary capacity to infect and transform B-lymphocytes (rather as can Theileria parva in cattle). Also associated with the development of nasopharyngeal carcinoma and Burkitt’s lymphoma.

NST though the tumours, particularly Burkitt’s lymphoma can be successfully treated in most cases.

Disease

 

Infectious agent.

Target organ if any.

Location ICD 10 entry.

Impact

Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments, treatment
Mumps, infectious parotitis

 

 

 

A paramyxovirus

An acute fever and tenderness of one or more of the salivary glands.

Worldwide, about 85% of unvaccinated people have antibodies by adulthood. B26

About a third of those infected remain asymptomatic. Under the age of two infections are almost always subclinical.

Not stated but presumably universal None indicated Lifelong immunity very often as a result of inapparent /latent? infection A live attenuated virus is widely used Humans None
Enterovirus Diseases

five diseases are considered under this heading, enteroviral vesicular pharyngitis, enteroviral vesicular stomatitis with exanthema, enteroviral lymphonodular pharyngitis, myalgia epidemic and viral carditis. Other symptoms such a conjunctivitis and meningitis are mentioned as associated with the coxsackie virus infections here considered. The issue of immunity to these coxsackie/enterovirus diseases is ignored in the 20th edition of the manual but in the 17th edition there is a powerful statement that immunity to some of these diseases can be powerful either following active infection or as consequence of latent/inapparent disease. These diseases include poliomyelitis disease which is an extremely serious paralytic condition that can be largely prevented by oral vaccines and it would be surprising if this were not true for the diseases caused by the far less serious enterovirus diseases considered here in the 29th edition. Perhaps the issues is simply a matter of finance it not being worthwhile to consider immunity for the non=-polio virus diseases.

enteroviral vesicular pharyngitis,, herpangina Enterovirus A serotypes CV-A1 to 19, 18, 22 and EV-A71.

Herbangina mildly febrile illness with multiple painful mouth ulcers.

B08.5Both this and the following illness have possibility of CNS involvement with a potentially fatal outcome

 

Young children Attendance at nursery schools, day care centres, households with many young children. No mention of immunity and as recurrence is stated to be common None Humans Hygienic management
Enteroviral vesicular stomatitis with exanthema, hand foot and mouth disease  Enterovirus A serotypes, CV-A16 and EV71, less frequently with enterovirus B serotypes. Skin, lesions usually heal spontaneously without scarring Worldwide In temperate regions peak incidence is in summer and early autumn but throughout the year in the tropics. B08.4

Typically brief and mild disease however see above

Young children Attendance at nursery schools, day care centres, households with many young children. No mention of immunity. as recurrence is common None Humans Hygienic management
Disease

 

Infectious agent.

Target organ if any.

Location ICD 10 entry.

Impact

Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments, treatment
enteroviral lymphonodular pharyngitis Enterovirus A serotype CV-A10

skin

Worldwide B08.8

 

Young children The entries for the 17th and 20t edition of the manual differ lymphonodular pharyngitis though mentioned in the latter is not further considered. Whereas in the 17th edition there is come information given Furthermore the accounts of three of the diseases mentioned in 20th edition differ greatly in relation to the issue of immunity ? ? ?
Myalgia, epidemic, devil’s grippe, Bornholm’s disease

 

 

 

Group B coxsackie virus

Pleurodynia with paroxysmal pain in chest and abdomen

uncommon B33.0

Outbreaks in various parts of the world, Europe, Australia, New Zealand and N Armerica

Probably general None indicated Specific immunity presumably results from infection 17th edition, none mentioned in the 020th edition. None Humans None
Poliomyelitis, infantile paralysis Poliovirus, genus Enterovirus, types 1, 2 and 3Paralysis of varying degrees. Can occur. Infection starts in the intestinal tract with spread to regional lymph nodes and more rarely to the CNS. It was worldwide now it is becoming confined to India and to a lesser extent to parts of Africa A80 Has been a major cause of partial paralysis. About 90% of infections are unapparent or result in nonspecific fever. Universal. . High risk is for those who for various reasons are not immunized. (immigrants, refugees rural and urban poor for example and more recently those influenced by the anti-vaccine activists. Type specific lifelong immunity. Very effective Humans with inapparent infections. (also a few chronic shedder) Nearly eradicated but not quite. The neurotropism demonstrated is extraordinary. No treatment
Disease

 

Infectious agent.

Target organ if any.

Location ICD 10 entry.

Impact

Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments, treatment
Rabies, hydrophobia, Lyssa Rabies virus a rhabdovirus of the genus Lyssavirus

 

Progressive viral encephalitis almost always fatal.

World wide A82

Estimated 55,000 deaths annually almost all in developing countries. The disease is almost invariably fatal.

All mammals are susceptible though humans are less so than other animal species; in the 17th edition of the manual it is stated that only 40% of Iranians bitten by known rabid animals developed the disease. This statement is not in the 20th edition.? None recorded If it is uniformly lethal the issue of immunity does not arise. However it is possible that the virus can be carried asymptomatically by a number of animal spp. Both passive and active immunisati is practised for those at high risk. Human rabies anti immune globulin is administered after bites. Many wild and domestic canidae. There are also several spp of insectivorous bats that carry the virus. Their disease status is not stated. Control over this disease has been maintained in some countries by strict quarantine regulations for imported animals. Nowadays in some instances vaccination has allowed movement again under strict control. The lethality of the disease in man is so high that it is almost the most feared of zoonoses.

No treatment

Respiratory disease, acute viral rhinitis, the common cold, rhinitis or coryza Rhinoviruses of which there are more than 100 serotypes account for 20-40% of cases, corona viruses account for 10-15% and influenza accounts of 10-15%. The etiology of common colds has only been identified in 50% of cases! Worldwide both endemic and epidemic, seasonal J100

Many people have 1-6 colds annually, incidence highest up to five years of age then declining

Universal, inapparent and abortive infections occur Nothing indicated apart from age ? with so many known causes and roughly an equal number of unknown ones the issue of immunity is complex Specific anti-adenovirus vaccination has proved effective but there is nothing available generally Humans NST
Respiratory disease, acute febrile respiratory disease (excluding Streptococcal pharyngitis). Para-influenza virus or, more rarely RSV and a large number of other agents. Worldwide, seasonal J01-06, J1.

Nuisance except in the elderly and very young

Universal, reinfection is common Age, compromised cardiac, pulmonary or immune systems. Transient immunity in the form of circulating antibodies None recorded Humans Antibiotic treatment is to be avoided!

NST

Rubella, German measles Rubella virus.

Usually a mild fever.

Worldwide universally endemic B06.

Usually a mild febrile disease

Universal after loss of maternal antibodies Fetuses Long lasting immunity Effective Humans Important because of its capacity to elicit fetal abnormalities. NST.
Disease

 

Infectious agent.

Target organ if any.

Location ICD 10 entry.

Impact

Susceptibility Special risk factors Immunity Vaccines Primary reservoir and vectors Comments, treatment
Human Papilloma Virus Infections.

There are more than 100 species of HPV with more than 40 types that can infect the human anogenital tract in both males and females. Cancers associated with HPV are of cervix, vulvar, vaginal, penile, anal and oropharyngeal. The 20th edition does not deal with these cancers as communicable diseases and in this document they will not be further considered.

Warts, viral, common wart, verruca vulgaris HPV

Skin and mucous membranes,

 Worldwide B07A wide variety of conditions most non fatal Common Young children for flat warts, genital warts in sexually active teenagers Incidence of warts higher in immunosuppressed individuals None Humans NST, cryotherapy effective.
Yellow fever A flavivirus

Variable outcome of infection from mild fever to severe disease with jaundice and haemorrhage.

 A complex pattern of disease falling into two categories, sylvatic (jungle)and urban cycles A95

a sporadic disease with high but very variable lethality. At worst 50%. The overall fatality rate in endemic regions among native populations is 5%. Mild inapparent infections are common.

Presumably everybody, it does not say Young adult males at most occupational risk unvaccinated travellers, forest workers in endemic areas. Disease is highly communicable Single attack can confer lifelong immunity. Antibodies appear in the first week of infection. Transient passive immunity in new born infants. Extremely effective live vaccine. Humans and mosquits in urban areas in forest areas almost anything on four legs. No treatment cited.

 

Of the viruses, of which account has been taken here roughly one third lead to chronic often asymptomatic infection. The remainder generate acute infections in many instances with life-long immunity to further infection by homologous organisms. As to whether this immunity is built upon a germ free immunological memory is a matter for discussion. There are few treatments for viruses that are effective and those there are tend to have adverse side effects. On the other hand some vaccines have been deployed successfully and, in some instances, attenuated live organisms have proved superior to dead vaccines. It is interesting to speculate how, where there is long term immunity but no evidence of persistence in intact form of the infective organism concerned, the immunity is maintained. The gut bacterial flora has something of the order of one hundred times more genes than are present in the human genome and there are in addition an unknown but probably large numbers of species of viruses. It could be that material detached from the organisms in the alimentary canal does gain access to the main body of the host and offers a massive library of cross reacting antigens that can mimic or are the same as antigens on the offending parasite. Such material could serve to maintain a low level of active immunity it is not certain whether food constituents often stimulate immune responses in the gut but evidence will be presented later that this is possible. If it happens regularly this in another way, aside from persistence of a parasite, that a state low level active immunity could be maintained. Whether this speculation in time proves to have a factual basis it could be that the vaccinologists could tailor their efforts to include the maintenance of active immunity based on materials from introduced genetically manipulated micro-organisms rather than entirely on what could be a fiction that long lasting memory cells maintain long lasting adaptive immune response.

The arboviruses constitute the biggest single group of infective organisms and probably overall the least known scientifically. By definition they are transmitted by vector through skin puncture and the great majority of them can engender disease free infections with lasting immunity to superinfection and the development of active disease. In evolutionary terms these organisms must surely collectively be the most important in influencing the human condition during the millions of years that our remote ancestors were hunter-gatherers with no urbanisation. At a guess it is from the ranks of the arboviruses that the 8% of the human genome that is thought to be of viral origin was recruited [2]. The significance of this is not immediately apparent except perhaps in relation to HIV that is possibly in the process of being established in time with less pathology than is now apparently the case in the human species [3].

AIDS is regarded at present as one of the most dangerous of pathogens though in fact presently it annually kills fewer individuals than does, for example, hepatitis B virus or Mycobacterium tuberculosis. The menace of HIV derives probably from its relative newness and initially its apparent inexorability. One facet of this virus which needs attention is its presently demonstrated capacity for mutability leading to switches of antigenicity that enrage those seeking appropriate vaccines. It is tempting to wonder whether, from the viral viewpoint, switching antigenicity is not an attempt to evade what seems to be an ineffective host immune response but part of a strategy to seek rapprochement with a host that has not, presently, got the capacity to make an accommodation response that would lead to a relatively peaceful co-existence. This is not particularly helpful to those presently infected with HIV who may die before the rapprochement formula is achieved but there is little in Nature to suggest that survival of all individuals by right driven partly by the remarkable successes of our medical profession, is actually what happens in what could be termed the wild world.

When the myxomatosis virus was introduced into Australia in the 1950s, after a first failed trial, it began to kill the offending rabbits on such a massive scale that it would have been predictable that there would soon be no rabbits in Australia. In fact this is not what emerged. Although it might seem likely that the surviving rabbits had been selected for resistance to the relevant virus, those who have investigated the phenomenon have shown that it is certain that the virus that changed. It is not as pathogenic as the form that was introduced into the continent [4]. Thus in host/parasite interactions it has perhaps to be recognized that there are two life strategies involved of which mutability of the parasite is perhaps the more rapid in achieving co-existence. The immune response of the hosts in these circumstances could be seen as orchestrated by the parasite as part of an overall accommodation system between host and potential parasite rather than the development, selectively, of genetically based resistance to the virus by the host.

CMV is a rather different example of viral infection from HIV or the arboviruses. In developing countries it is usual for all the adult human population to be infected. It can cause problems in immunosuppressed individuals and one wonders why infants in utero who ostensibly, before the age of say twelve weeks of gestational age are immunologically incompetent, are not all killed by the viruses of their mothers. As it is a small proportion of infants are infected in utero and of them only a small proportion (10-15%) develop disease caused by the virus. What are the factors that lead to the harm done to a very small proportion of perinatal infants? It is likely that the mother transmits anti CMV antibodies across the placenta and that these are passively effective in preventing infection of the developing foetus. Presumably the protective effect of such antibodies in inhibiting the establishment of infection is lost as maternal antibody declines during the six months post-partum. Alternatively the relationship with CMV may under normal circumstances in the mother be such that infectious viral particles are rare. In terms of the Topley and Wilson ‘equation’ (see the text below the reconciliation document) the dynamic equilibrium in this instance usually favours the host. Whatever the answer to these conundrums it is clear that there seems to be an immune response to CMV but it is not associated with rejection of the parasite. It is intriguing to note that related CMV organisms found in animals simply are not found in man. Is it that human beings have learned how to reject these potential invaders or more simply those animal viruses simply do not have the capacity, perhaps lacking appropriate receptors to enable them to enter human cells? A comparable example would be the total incapacity of diphtheria toxin to kill mouse cells to which it cannot bind whereas human cells are acutely sensitive to the same material. It is important to consider these issues of host predilection in coming to an understanding of the interface between man and those organisms that can invade him with potentially detrimental effect. The immune response has been created by immunologists as an all-purpose reaction system capable of responding to any foreign intruders which it probably is not. But, more importantly, most ‘foreigners’ almost certainly simply do not have the capability of living in the human body. This is not an example of a host defence system but rather more a demonstration of what is self- evident that not all organisms are able to react with all other organisms.

Hepatitis C virus is an extraordinary example of menace to humans. Firstly, it is said by WHO to infect at least 1% of all living humans (i.e. 60 millions or so, cf HIV with 40 millions). Secondly, few (less than 10%) of those infected realise they are infected. Thirdly, a high proportion of those infected (80% perhaps) become chronically infected essentially for the duration of their natural lives. Fourthly, major problems in a proportion (roughly 30%) of those chronically infected take between ten and forty years to become clinically apparent. Fifthly, we know virtually nothing about the immunological interface between man and HCV. Antiviral antibodies are produced but, in the present state of our knowledge they have no significance in relation to the staging of the disease. This raises an intriguing issue as far as intervention is concerned. Most vaccines are developed in order the better to prevent infection. Whether infection is in fact prevented or whether what happens is that disease, as a consequence of infection, is prevented is an issue that needs to be argued out in relation to each host/vaccine combination. We simply have little idea how to vary an ongoing immune response. In this age of molecular biology when almost any conceivable vaccine can be produced there are, nevertheless, presently few positive leads on so called therapeutic vaccination. In terms of the Topley and Wilson ‘equation’ (see the text below the reconciliation Table 8) we have a long way to go to balance the equilibrium in favour of the host as far as HCV infections are concerned. Prevention is a possibility as HCV infections is closely correlated with poor parenteral practices in hospitals and in the back streets, essentially reuse of poorly sterilised needles. It is thus a modern and preventable disease, recognized only fifteen years ago (after a long period as non-A, non-B hepatitis virus). HCV is also, paradoxically, one of the few viral infections which is ‘cleared’ by the host for reasons that are far from apparent. Recently effective treatments for the condition using sofosbuvir or simeprevir have been applied and thus the issue of their immune status from a practical point of view is less pressing.

Before leaving the hepatitis viruses, that have no taxonomic affinities, it should be noted that before successful vaccination against HAV and HBV was started they infected roughly half the population of the world and the proportion even now will not be much less. Collectively the viral hepatitides constitute what is one of the biggest single health hazards to our global populations. A point that emerges from an overall look at viruses is that relatively few of them kill the majority of those infected. HIV presently is an example of a slow viral infection that is lethal in many instances though commonly many years after initial infection. Rabies virus is thought always to be lethal but, according to the (17th edition of) the manual, only forty per cent of those bitten by rabid dogs in Iran died as a consequence. Were the majority immune? If they were immune was this an active process involving activation of the host immune response or was it failure of the virus to grow in an environment with which it has little experience. In many animals rabies viruses exist in an asymptomatic state. Did this happen in the lucky Iranians?

Along the same lines Lassa fever viruses were seen as likely to cause the most enormous havoc when the first American cases were taken to the States. There seemed no way of stopping the virus [5]. And yet it did stop and, when those parts of the world in which the virus is endemic were looked at more carefully, it was discovered that some ninety per cent of those infected remained asymptomatic. Again the question arises as to whether the population of people concerned have been genetically selected for resistance to the virus. To my jaundiced eye this seems unlikely but, clearly, the resistance of the human populations to the viruses concerned in certain parts of Africa is greater than that of those few unfortunate Americans who initially came in contact with the virus in the USA. The mechanisms involved would merit investigation.

Protozoa

The protozoa offer a very mixed bag of chronic infections including malaria that is one of the major killers in those countries with infected mosquitoes. All the diseases seem to be treatable by chemotherapeutic attack upon the parasite though clearly those with a higher parasite burden and more complex invasion patterns are more difficult than the more superficial infections. (Leishmania, dermal and visceral indicates the contrast though there is also the issue of different species of infection being involved.). In a few instances immunity that is solid and long lasting seems to be acquired, i.e. the patients are disease free. As to whether they are chronically infected seems not actually to have been seriously addressed. In the instance of such a disease as malaria it seems likely that chronic persistent and asymptomatic infection is the usual condition among the indigenous population. Infection, it is assumed, from the prevalent sp of malaria occurs in almost all infants soon after birth and in perhaps 15% of instances proves fatal without intervention. The great majority who survive these early infections probably remain chronically infected for the remainder of their lives or are perhaps continually re-infected without usually adverse effects. Is this state held at bay or maintained by the immunological apparatus? It depends how you think about it. Is anything known about the precipitating factors in an episode of malaria among the indigenous population most of whom will be demonstrably parasitaemic throughout their lives? This seems to be the kind of question like trying to find out why individuals in more temperate climates suffer quite often from the so-called common colds. It is not that there are no answers but there are many reputed risk factors often based on totally fallacious thinking (Table 3).

Table 3: Protozoa (Protoctista).

Disease Infectious agent.

Target organ if any.

Location ICD 10 entry.

Impact

Susceptibility Special risk factors Immunity Primary reservoir and vectors Comments, treatment?
In the 0th edition of the manual two amoebic disease patterns are given the first called Amoebiasis, amoebic dysentery and the second rather different group listed below all caused by free living organisms Entomoeba histolytica

Initially gut but with chronic infection more commonly and sometimes liver abscess.

Ubiquitous more prevalent in tropical regions with poor sanitation. A06

Most infections said to be symptomatic. Problems presumably more for none indigenous populations.

General, persons of all ages are susceptible. . Conditions favouring move to heightened pathogenicity stated to exist but not specified Reinfection is rare implication is that immunity once acquired is long lasting. Man, asymptomatic cyst carriers are more frequent than cyst carriers with disease. Disease unusual in the very young Largely a disease of young adults. Most infections are asymptomatic, CTX effective.
Naegleriasis,

acanthamoebiasis and

balamuthiasis

 

Naegleria fowleri

Acanthamoeba (various spp,)and

Balamuthia mandrillari

Brain, encephalitis

Global B60.2, B60.1 NK both immunocompetent and immunodeficiet individuals have been recorded with these diseases. Swimming in warm fresh water. Individuals with contact lenses NK. No indication is given of asymptomatic infected individuals Free living Amoebae in soil and water. Diseases caused have over 90% lethality but seem to be fairly rare.
Disease Infectious agent.

Target organ if any.

Location ICD 10 entry.

Impact

Susceptibility Special risk factors Immunity Primary reservoir and vectors Comments, treatment?
Babesiosis, no synonym Babesis microtis is most common of several spp involved.

Symptoms very variable but non-specific fever common

Worldwide in scattered locations, most in USA. B60.0

Restricted largely it seems by prevalence or control of tick vectors

universal Asplenic, immunocompromised and elderly people are at highest risk. Not written about. Rodents and cattle., tick vectors. Recrudescence of symptoms after prolonged asymptomatic parasitaemia can occur. CTX but not always easy
Balantidiasis,balantidial dystentery Balantidium coli Colon with dysentery.

Symptoms very variable

WorldwideIncidence of human disease low. A07.0

 

Humans seem to have high natural resistance. Other medical conditions can predispose to fatal disease. what is the basis of the resistance. Swine and rats laboroatory pigs and non-human primates. Antibiotics of various kinds. Keep away from hog faeces!
Cryptosporidiosis Cryptosporidium himinis and C. parvum

Epithelial cells of the GI tract. Diarrhea most usual symptom

Worldwide. A07.2 Low incidence of disease but occasional epidemics General but particularly immmundeficent individuals. Children younger than 2 years. Animal handlers. Men who have sex with men. Close contacts with infected individuals None indicated. Humans and various animals. The organisms infect a large no. of spp. . Nitazoxanide can be used. For children older than one.
Disease Infectious agent.

Target organ if any.

Location ICD 10 entry.

Impact

Susceptibility Special risk factors Immunity Primary reservoir and vectors Comments, treatment?
Giardiasis, giardia enteritis Giardia lamblia

Mainly of the upper intestine.

Worldwide A07.1

Not major

Asymptomatic carrier rate is high and most infections are asymptomatic. Infections are commonly self limiting.

Infected individuals commonly have long asymptomatic periods but reactivation can occur.

Inapparent and subclinical infections are common

.

Children rather than adults. Persons with AIDS may have a more severe and prolonged infection Not mentioned! Implication from HIV association is that immunity is involved but not indication that this is adaptive or innate. Humans possibly beaver and other wild and domestic animals. Contaminated water is usual source of primary infections. Metronidazole usually works.
Leishmaniasis, Aleppo evil, Baghdad or Delhi boil Leishmania tropica and others

cutaneous mucosal here recognized.

Large number of tropical and semi-tropical locales, B55.1, B55.2, Reasonably common – about a million new cases per year reported. Not usually very dangerous Factors relating to late development of severe disease not known. Antibody levels low or nonexistent but lifelong immunity can be created that is said to have a powerful cellular component Many, humans, rodents, hyraxes, sloths. unknown host in many areas CTX usually effective.
Leishmaniasis, visceral, Kala-Azar

 

Leishmania donovanii and others Fever with a wide variety of subsequent symptoms. A rural disease occurring in foci in India and Bangladesh B55.0. Usually fatal if untreated

 

Infection can predispose to lifelong homologous immunity

 

Humans and wild and domestic dogs CTX available but it may require prolonged application.
Disease Infectious agent.

Target organ if any.

Location ICD 10 entry.

Impact

Susceptibility Special risk factors Immunity Primary reservoir and vectors Comments, treatment?
Malaria, Plasmodium spp

An acute febrile illness with a wide variety of subsequent outcomes depending mainly on the infective sp. P. falciparum in particular is usually lethal if untreated. Disease due to P. vivax, P. malariae and P. ovale are considered less dangerous.

In all tropical and some subtropical regions B50-B54

Major cause of disease where it occurs.. in 2010 99 countries report on going malaria transmission with an estimated 219m cases and 600,00 deaths mostly in young children in Africa

except in some

human beings with the sickle cell gene, in relation to P falciparum or with absence of Duffy factor (P. vivax)

None quoted Tolerance or

refractoriness to subsequent clinical disease is present in adults in endemic regions. This could mean they are immune? Are they free from infection? Certainly repeated infections are normal for many of the indigenous population.

Humans, vector mosquitoes This is a massive disease and the account given leaves many questions unanswered.
Pneumonia, immunodeficient pneumonia Pneumocystis carinii (is it a protozoan or a fungus?) Acute,sub acute condition which can be fatal All continents B59

Persists sub clinically in many instances. Can be lethal in immunosuppressed individuals

Again there is the question of whether we are talking about susceptibility to infection or disease. The infection is usual the disease is not. May be endemic and epidemic in debilitated infants. It affected 60%

of AIDS patients in the USA before prophylactic measures were instituted.

If  immunodeficiency predisposes then it must be supposed that normal control is exercised by the immune response. Humans. It is found in many animal species but this is not considered significant in relation to human disease. It is now believed that the organism is a fungus. CTX available..
Disease Infectious agent.

Target organ if any.

Location ICD 10 entry.

Impact

Susceptibility Special risk factors Immunity Primary reservoir and vectors Comments, treatment?
Toxoplasmosis,, and congenital toxoplasmosis. Toxoplasma gondii, a coccidian. Worldwide in birds and mammals, infection in humans is common. B 58 (congenital version acquired transplacentally from infected mothers P37.1)

Infections frequently asymptomatic

General Immunosuppression can lead to reactivation of infection. Immunity is readily acquired and most infections are asymptomatic. The indication is that the parasite persists Cats are the definitive host Treatment for healthy individuals not normally indicated. AIDS patients treated prophylactically.
Trichomoniasis Trichomonas vaginalis

STD

Widespread a disease of all continents and races particularly in A59

Frequently asymptomatic

Universal Frequently asymptomatic. Immunocompromised individuals at greater risk. None written of Humans

 

 

Metronidazole usually effective

 

 

Trypanosomiasis, African, sleeping sickness Trypanosoma brucei gambiensis and T Rhodesiense

 

Systemic.

Confined to regions of tropical Africa where lurks the tsetse fly B56 In endemic regions arasitaemia present in 0.1-0.2% of population but during an epidemic the figure can reach 70%. Both forms of the disease are fatal General. Though spontaneous recovery has been claimed it has not been validated. No particular risk factors given. Congenital transmissions can occur. Various manifestations of activation of the immune apparatus are in evidence but immunity does not seem to arise. Humans for gambiense but wild ungulates for Rhodesiense. Vector is various spp of Glossinia CTX available but relapses can occur. Part of the problem seems to be that the drugs used do not cross the blood brain barrier.
Disease Infectious agent.

Target organ if any.

Location ICD 10 entry.

Impact

Susceptibility Special risk factors Immunity Primary reservoir and vectors Comments, treatment?
Trypanosomiasis, American, Chagas Disease. T cruzi

systemic

S. and Central America B57No figures are given on prevalence but the disease is potentially very nasty with a whole series of complex essentially autoimmune manifestations. All ages susceptible (and all people it must be supposed) but the disease is more severe in the young. Proportion clearing the infection not quoted. Immunosuppressed individuals are said to have greater chance of severe disease Nothing said about it. Humans and 150 spp of animals. Vector for man is the cone nosed bug. In the bug the parasite persists for life. CTX available for acute disease. Nothing indicated for chronic infections.

 

Trypanosomiasis attributable to the transfer of an infectious flagellate organism from another human or animal by means of various invertebrate vectors can be a most unpleasant disease but an interesting characteristic of the organisms concerned is that many of them can vary their antigenicity [6]. The usual interpretation of this fascinating property is that the invading organism is trying to avoid the immune responses of the host and of course this is a possibility. It can however be argued that the parasite if trying to persuade the host that it can produce an immune response capable of sustaining the relationship between the host and the parasite and incidentally providing edible and nutritious antibody for the parasite to take in. Such a notion does not fit with the standard paradigm of many immunologists and clinicians who commonly suppose that the parasite is trying to harm the host rather than to seek an accommodation slip. It is worthy of note that for example T. musculi which can ostensibly live in perfect harmony with its natural host mice [7] shows no capacity for antigenic variation but it might if transferred to a host where neither of the two components of the interaction had experience of each other.

Is disease potentially an immunopathological event and if it is should we better target the immunological apparatus rather than the parasite? It depends perhaps on a comparison with side effects and what if any are the collateral effects of interference with the immunological processes. In Ian Clark’s experiments in mice [8] in which he successfully converted a potentially lethal plasmodial infection into an asymptomatic inapparent interaction by simple prior reduction in the capacity of the host to make TNF, there seemed, in the short term, to be no adverse effects. If immunopathology constitutes the major mechanism of the symptoms of diseases, as will be urged later, these tables contain interesting clues as to how inapparent infections are created and or maintained. For example in relation to amoebiasis the very young seem only rarely to be affected by disease. Do they acquire the parasite without immunopathology or can the parasite for some reason not prosper in young organisms? Whatever the answer, there is, perhaps, a clue here to symptomless host/parasite interactions.

In eight of fourteen of the protozoan diseases immunosuppression is a major risk factor in rendering disease more severe. This suggests that immunity is a major defence mechanism but this conclusion, unalloyed, must be regarded carefully. In almost all circumstances that immunosuppression occurs there are many collateral effects any one of which can have major physiological consequences that could affect host/parasite interfaces. It is intriguing to note that so far there are no vaccines available for any human protozoan disease despite the strong evidence that immune mechanisms are important in relation to the majority of protozoan parasite/host interfaces. Surely those indigenous human host populations in Africa who live with malaria all their lives are essentially ‘vaccinated’ and there only arise major problems (idiopathic tropical splenomegaly, for example) in relatively small numbers of those concerned. Of course the problem is made more complex in relation to malaria by the existence of at least three major pathogenic species but is it beyond our wit genetically to tailor a parasite having epitopes common to all three that could serve as components of a live ‘attenuated’ vaccine? The fancy methods that are being proposed to vaccinate against malaria (point of entry molecules and so on) perhaps will not succeed against such a complex organism as are protozoans with a very reactive plasma membrane capable of many changes when attacked or indeed ingestion and digestion of attached antibody molecules. Antibody can of course inactivate and kill parasites but it is not difficult to imagine scenarios where the rate of production of antibody and parasite is in balance or, as has been shown in mice infected with T. musculi, the parasite is restricted by antibody (?) to a particular region of the body [7].

Fungi

There are some fifteen main fungal diseases, all chronic with often different presentations and pathogenicity according to the organism responsible. Three of the fungal diseases (candidiasis, aspergillosis and cryptococcosis) almost only occur as secondary to other debilitating conditions all of which could be said to involve immunosuppression. The clear inference is that the immune response normally keeps the relevant invaders out or prevents them creating disease. This needs looking at on a case-by-case basis. For example, contact with cryptococcal spores occurs almost daily in those crossing Time Square in New York but cryptococcosis, the disease, is only seen in few already sick individuals. The ‘resistance’ to infection is almost certainly primarily the physical barrier of the lung mucosa that is capable of capture and exclusion, perhaps by ciliary action, of considerable numbers of the spores. Is this equivalent to resistance based on a particular capacity of the adaptive immune system? In my view it is not largely because, in normal mice, if the physical barrier is circumvented by giving very few spores as an intravenous injection, death is likely. A similar argument could be applied to the entry of Aspergillus conidia though experimental evidence in support is not, as far as I know available. A rather similar argument could be used for apparent resistance (so-called) of humans to the infective agencies of Chromomycosis and Mycetoma, ie if the physical barrier to entry is disrupted or defective by for example cuts on the feet then the fungi concerned can occasionally get a toehold and cause harm (Table 4).

Table 4: Fungi (no vaccines recorded).

Disease

 

Infectious agent. Target organ if any. Location ICD 10 entry.

Impact

Susceptibility Special risk factors Immunity Primary reservoir and Vectors Comments, treatable?
Aspergillosis Aspergillus fumigatus and A. flavus 40 spp have been reported as infectious.

Lungs, initially.

Worldwide though uncommon and sporadic B44

Naturally, slight.

. The disease is usually secondary to a primary condition. This it is claimed, in conjunction with the ubiquity of the fungal spores indicates that most individuals are resistant Immunosuppression, particularly prolonged neutropenia.

 

Contact with aflotoxins

Natural immunity claimed. There is no indication of activation of adaptive immune mechanisms. Aspergillus spp are ubiquitous in nature Invasive forms of the disease in immuno-impaired individuals become the problem.. Treatment, of Allergic disease is by prolonged corticosteroid suppression. Treatment far from simple.
Blastomycosis, Gilchrist disease Blastomyces dermatidis

 

lungs

Rare B40Sporadic in Central and Southern USA, Canada, Africa India Israel and Saudi Arabia. Untreated chronic infections often eventually lethal Unknown but rarity of the natural disease and of laboratory infections suggests most people are relatively resistant

Immunocompromised patients at higher risk of disease.

Rare in children, more common in males than in females. Disease in dogs is frequent also in such rarities as a horse as captive African Lion and a sea lion. In apparent pulmonary infections are probable. There is evidence that CMI plays a role in controlling lung infection Moist soil. Companion animals susceptible but zoonosis not recorded. Acute disease often lasts three weeks before resolving. Evolution into a chronic disease is common. CTX available
Disease

 

Infectious agent.

Target organ if any.

Location ICD 10 entry.

Impact

Susceptibility Special risk factors Immunity Primary reservoir and Vectors Comments, treatable?
Candidiasis, moniliasis, thrush. Candida albicans +other spp.

 

Skin, mucous membranes

Worldwide. Candida is a part of the normal flora, is this to be called an in apparent infection? B37Big problems in those with illness of a wide variety of kinds, diabetes mellitus therapy with broad spectrum antibiotics HIV infection and so on. Either high immunity or low level pathogenicity! Many debilitating diseases can predispose to creating candida problems. Most adults and older children have delayed type hypersentivity and humoral antibodies. humans Fascinating organism. It clearly occupies a niche probably in balance with other organisms.
Chromomycosis,

dermatitis verrucosa.

About ten species involved including Phialophora verrucosa

 

skin

World wide B43

 

Suggestion is that relative rarity indicates a degree of resistance. The absence of laboratory infections is regarded as confirmation. Associated with men aged 30-50 only rarely seen in women. Barefoot workers are at higher risk ? Rotting wood and in general decaying vegetation A minor problem except for those that get it CTX available plus sometimes surgery to remove large lesions.
Coccidioidomycosis, valley fever, San Joaquin fever, Desert fever. Coccidioides immitis

<1% of symptomatic cases becme disseminatedLung probably site of entry

Only in arid regions of Western Hemisphere B38

Important disease among archaeologists, migrant workers and military personnel from non endemic areas

Affects all ages, all races and both genders. More than half patients are between 15 and 25 years of age. Susceptibility to dissemination is greater among African Americans, Filipinos and other Asians. Pregnant women are at particular risk. AIDS is a risk factor Males more frequently affected than females (occupational exposure is suggested). Reactivation of latent infection can occur if immunosuppression arises High frequency of subclinical infections felt to be the case. Recovery from infection is associated with solid lifelong immunity Soil especially around Indian middens and rodent burrows. Infects almost any animal it seems but not transmitted from them to other animals or to man or vice versa.. Primary infection usually responds without treatment but in severe cases CTX does exist.
Disease

 

Infectious agent.

Target organ if any.

Location ICD 10 entry.

Impact

Susceptibility Special risk factors Immunity Primary reservoir and Vectors Comments, treatable?
Cryptococcosis, Torula. Cryptococcus neoformans

 

Lungs, point of entry. Secondaries in the brain can be lethal.

Sporadic infections in all parts of the world. Classic example of an organism that very rarely causes problems except in impaired individuals B45

Slight except with immunosuppressed individuals

Suggestion is that there is resistance. This is based on rarity of the disease and the ubiquity of the organism Males more than females, Immunosuppression particularly AIDS is a risk factor. Hodkins disease and sarcoidosis No immunity written of in the manual, but there are many papers published that argued both innate and adaptive immune mechanisms are active. Antibodies are however not mentioned. Pigeons and old pigeon roosts Secretes poly mannose that presents problems for recognition by macrophages via the mannose receptor. In AIDS patients can be a major problem. Indefinite treatment often the mode.
Derrnatophytosis tinea barbae and tinea capitis (ringworm). This and the following three diseases in the 20th edition are tabulated together as relatively minor fungal diseases of skin hair and nails. Various spp of microsporum and Trichophyton skin Endemic in urban areas in Eastern USA, Puerto Rico and Australia B35.0

Slight

All ages susceptible Children below the age of puberty are particularly susceptible Reinfections not recorded? Immunity? Humans and a variety of animal spp. Treatment can in time give complete recovery
Disease Infectious agent.

Target organ if any.

Location ICD 10 entry.

Impact

Susceptibility Special risk factors Immunity Primary reservoir and Vectors Comments, treatable?
Dermatophytosis, tinea cruris and tinea corporis (groin and body ringworm) As above with a few other possible spp.

Skin

worldwide B35.6

Inconvenient

Widespread, all ages affected, hot groins a starting point Males more frequently affected than females None recorded Soil and humans. The groin infection is almost exclusively male. CTX
Dermatophytosis, tinea pedis, Athletes foot Trichophyton rubrum and others

Foot skin

Worldwide B35.3

Inconvenient

Variable, infection may be inapparent Males more affected than females. Repeated attacks are frequent Humans CTX initially by local fungicides
Onchomycosis, Tinea unguium (ringworm of the nails) Various

Trichophyton spp

Nails usually of the feet

Common B35.1

Inconvenient

Variable ? Repeated attacks frequent Humans, rarely soil CTX over long periods
Disease

 

Infectious agent.

Target organ if any.

Location ICD 10 entry.

Impact

Susceptibility Special risk factors Immunity Primary reservoir and Vectors Comments, treatable?
Histoplasmosis (two diseases here of which only the more common is considered), number of causal agents but no common names given Histoplasma capsulatum can be a respiratory disease but can also present in a disseminated form.

 

Lungs

Common in particular foci, rare in Europe. In some parts of central and Eastern USA 80% of the population are histoplasmin sensitive indicative of contact with the organism. B39.5

Of varying severity. Can be lethal

Infection is common but overt clinical disease is not. Possibly opportunistic in those with immunosuppressant In apparent infections that are common seem to give increased resistance to (further?)infection Soil with undisturbed bird or bat droppings CTX, more difficult in immunosuppressed individuals.
 Eumycotic Mycetoma Devil’s grippe, Bornholm Disease. See also nocardiosis in bacterial diseases Madurella mycematomatis plus others and a set of bacteria that give comparable lesions.

skin

Rare in continental USA but common in Mexico B47.0

Nasty

Causal organism’s common but disease is relatively rare. Implication is that resistance is usual. Barefoot workers, ie infection is secondary to wounding. None recorded Soil CTX and or surgery in extreme cases.
Disease

 

Infectious agent.

Target organ if any.

Location ICD 10 entry.

Impact

Susceptibility Special risk factors Immunity Primary reservoir and Vectors Comments, treatable?
Paracoccidiomycosis, South American blastomycosis. Paracoccidioides braziliensis

 

Lungs site of primary infection

Endemic in tropical and subtropical regions of S America and to a lesser extent in Central America B41

A serious and sometimes fatal disease

Unknown ? ? Presumably soil or fungus laden dust CTX
Sporotrichosis, Sporothrix schenckii

Skin.

All parts of the world B42

An occupational disease of gardeners and horticulturists. Fatalities uncommon

unknown ? ? Soil CTX
 Mucormycosis. Zygomycosis,

A complex of diseases with a number of causal organisms.

Various zygomycete fungi including Rhizopus arrbizus Worldwide, incidence may be increasing because of longer survival of various kinds of patient such as those with diabetes mellitus, and certain blood dyscrasias B46.0

Extraordinary disease that in susceptible patients causes really nasty facial problems with erosion of many nasal structures. In the lung it can cause blood clotting and lung in farcts.

The argument put forward is that as the disease is rare but the fungi concerned are common there must be resistance to the disease. A variety of debilitating conditions predispose to the disease. What is not stated is whether it ever occurs in normal individuals. It is certainly very rare. Difficult to say. If immunosuppression predisposes to the disease it could be correctly supposed that the immune response is the basis of the resistance in non-immunosuppressed individuals. This is not the only possible explanation however. Common saprophytes. CTX and/or surgery.

 

For the other disease that occurs as secondary to a pre-existing disease condition, Candidiasis, it is less easy to point to a particular portal of entry or specific weakness related to allowing fungal proliferation. The adaptive immune response may be the main defence against Candida but the argument for any significant adaptive immunological controlling mechanism is not strong. Candidal infections for example are ubiquitous and, as is related in the manual, Candida is regarded as part of the normal skin and mucosal surfaces which any way are presumably the portal of entry of the organism. Is this normality imposed by the immune responses of the host or more simply due to failure of the infecting yeast particles to gain entry to the body except when it is in various ways debilitated? Whatever the answer it is clear that there is a point of dispute on the present evidence as to whether the adaptive immune responses maintain the normal symptom free condition.

For only one of the fungal infections, Coccidioidomycosis, is it evident that there is a powerful and long lasting immune response capable of rejecting systemic infection. In Blastomycosis the case is not made, as the evidence is incomplete as presented in the manual. In Coccidioidomycosis, infections that have no clinical consequences are common but pathological disease is rare. Further some disease arises as a consequence of reactivation of latent infection consequent upon acquired immunosuppression. Here it can be argued that the adaptive immune response is an important regulatory mechanism at the interface between the fungus and its host. But it also has to be considered that, under normal circumstances, the immune response comes to an accommodation with the invading fungus that can be stable and maintained over long periods of time. There is no evidence that the quoted long lasting immunity is associated with the rejection of the parasite. It betokens simply resistance to the development of the disease. It would be intriguing to investigate this particular fungus/host relationship to see exactly how the putative accommodation is achieved, what element of the fungus is recognized by the adaptive immune system of the host and what exactly goes wrong with it when overt disease erupts? It at least has to be considered that the fault lies not with the parasite itself, as it is difficult to see why it should have changed, but with the development of immunopathological changes consequent upon alteration of the physiological controlling mechanisms of the immunological apparatus of the host. If this is the case attack upon the fungus may not necessarily be the only or even the most satisfactory way of reducing the disease condition.

Dermatophytoses seem to cause inconvenient conditions which are not life threatening. The implication is that the potential invaders are common and that repeated contact with them often in circumstances of slight abrasion can lead to the development of largely minor infections in which it may be that the adaptive immune response is in no way implicated. The barrier to entry to the skin is keratin and under most circumstances this is enough to prevent access to any deeper tissues. In such circumstances attack upon the fungus to reduce the irritation would seem to be the right strategy. Mucormycosis is perhaps a different case. There the attack upon underlying tissues almost seems to be directly due to erosion by the fungal hyphae rather than consequent upon any immunopathology. The details given in the manual of the lesions are insufficient to make any proper comment. The evidence for any immunological control of the fungal/host interface is, as presented, weak. Attack on the fungus would seem to be reasonable and probably the only way of control of the disease.

Histoplasmosis is a relatively common condition with evidence that there is recognition by the adaptive immune response of the causal organism (80% of some individuals in endemic areas can be histoplasmin positive on testing). In the manual the phrase ‘inapparent infections are common and usually give increased resistance to infection’ is somewhat ambiguous. It could mean that there arises a state of immunity from inapparent infections that involve the adaptive immune response and this immunity inhibits the development of disease as a consequence of (further?) infection. It could perhaps mean that the mucosal surfaces are protected by, say, secreted IgA antibodies that reduce or inhibit entry to the various organs systems that can be harmfully affected by the fungus. If this is the case a specific mechanism can be postulated and searched for and, if found used to monitor susceptibility to disease or indeed used as a target for maintaining resistance, by for example transmucosal vaccination. Clearly here, as is true for paracoccidiomycosis, coccidiomycosis and sporotrichosis – we are too short of information to make any satisfactory conclusions about mechanisms of resistance.

Reasonably effective fungicides exist for most but not all of the infective fungi. What is however to be noted is that whereas with the fungal infections the word resistance is used in many instances in relation to the fungal/ host interface this is not so for the overwhelming majority of other host/parasite interfaces. It should be noted that the scientific literature presently contains many papers arguing that both innate and adaptive immune mechanism are active against fungal invaders and it may be that they contain significant truths nevertheless in experiments conducted by the present author and colleagues expert with the organisms in question, many years ago, it was possible to show that overall T-cell deficiency affected neither the speed nor final result of experimental infection of mice with either Candidaalbicans or Cryptococcus neoformans. Since those times (mid 1970s) the sophistication of immunological experiments has much improved and it may be that the more simple experimental models we adopted at the time are no longer useful.. A recent review summarises what are regarded as presently tried methods of manipulating the immune response to offset the consequences of fungal invasion [9]. Having read the review, which is thorough, it gives many indications of improvement of immunological status in sick patients which in a variety of ways have been incapable of exercise of immune functions as found in normal individuals. It is clear that it is not easy in the patients considered to define exactly how the complex immune functions are impaired and, perhaps for this reason, there are even now no clear strategies put forward for the evidence-based amelioration of the immunodeficient immune states involved. It would nevertheless be useful for those who write the Manual to look carefully at the evidence presented by Loreto and his colleagues.

Trematodes

The trematodes induce a variety of chronic diseases one of which, schistosomiasis, figures on the ‘wanted’ list of WHO. No vaccines are quoted as available as is nearly true for all the eukaryotic (and fungal) parasites of man. Effective CTX exists in most circumstances. The transfer of infection often arises due to eating habits, usually either raw fish or improperly cooked meat. Immunity if any seems a variable feast. These organisms seem to exist in the host independent of immunity with the severity of infection determined simply by the number of infective organisms that have got in. Adverse consequences in some circumstances are due to redistribution of the parasite from an adult form to larval forms that in various encysted conditions can be dangerous as space occupying lesions with the additional problems in some instances of eventual disruption with liberation of a variety of pharmacologically active substances (Table 5).

Table 5: Flat Worms, Trematodes, Including Tapeworms, Non-Segmented.

Disease

 

Infectious agent.

Target organ if any.

Location ICD 10 entry.

Impact

Susceptibility Special risk factors Immunity Primary reservoir and vectors Comments, including treatment
 

Liver fluke disease Clonorchiasis, Opisthorchiasis

Clonorchis sinensis, Opisthorchis felinensis and viverrini.

Diseases of the bile ducts, Cholangiocarcinoma can be a late side effect of infection with O. verrini.

Endemic in South East China and other parts of SE Asia. Opisthorchiasis is also frequent in the old states of the USSR. It is estimated that globally some 700m people are at risk of infection. B66.1, B66.0 (C22.1, cholangiocarcinoma) Often completely asymptomatic. Very slow chronic diseases often lasting for 30 or more years only rarely a cause of death but a major risk factor for cholangiocarcinoma Universal In endemic areas highest prevalence in adults over age of 30 None cited but fact that infection is often and probably usually asymptomatic is interesting Humans, cats, dogs, swine, rats and other animals A danger from raw or undercooked freshwater fish. Treatable with CTX. No person to person transmission
Tapeworms, in the 20th edition of the manual, following the ICD listing, considers somenine different tapeworm infections. Here only three of the most common will be considered Hymenolepis nana.

Dwarf tapeworm

Intestinal infection,

Cosmopolitan B71.0

Rarer in colder climates

Universal Children more susceptible than adults, immunosuppressed or malnourished people at particular risk Infection leads to resistance to (?further) infection Humans and possibly mice (in which it grows well under experimental circumstances) A very small addition to man!, autoinfection occurs. CTX effective.
Disease

 

Infectious agent.

Target organ if any.

Location ICD 10 entry.

Impact

Susceptibility Special risk factors Immunity Primary reservoir and Vectors Comments, treatable?
Diphyllothriasis, Broad or fish tapeworm infection Diphyllobothrium latum and several other spp. of the genus. Intestinal infection of long duration symptoms commonly trivial. Lake regions in N Hemisphere and subarctic regions where eating raw fish is practised B70.0 slight Universal None given Reinfection can occur thus immune resistance does not apparently develop Humans and a variety of animals including polar bears Another raw fish problem CTX will work.
Taeniasis (pork and beef tapeworm) and Cysticercosis Taenia solium, porkand T. saginata beef. Initially intestinal infections but development and dissemination of cysticerci can create massive later complications Worldwide wherever pork and beef are eaten insufficiently cooked and sanitary conditions allow cattle access to human faeces B68

Consequences of infection grave if cysticercosis arises

General Those living in poor and insanitary circumstances. No immunity reported though more than one tapeworm per host is rare Pigs for T. solium and cattle for T. saginata are the intermediate hosts. Humans are the definitive hosts CTX or surgery. Treatment complicated by consequences of killing cysticerci.
Echinococcosis, cystic hydatid disease. Three grades or the disease are recognized, cystic, alveolar and polycystic, here only cystic form will be considered. Echinococcus granulosus

Slowly developing disease commonly in liver or lungs but can be found elsewhere

All continents except antarctica B67.0

Not stated although note relatively high grading.

None given presumably universal Children more likely to be infected but they are also more likely to play with dogs. Really no evidence of greater susceptibility in children None written of Dogs and a variety of other animals Even multiply infected animals are often totally asymptomatic! Problems arise largely because of hydatid cysts Either surgical treatment of cysts or CTX can work
Disease Infectious agent.

Target organ if any.

Location ICD 10 entry.

Impact

Susceptibility Special risk factors Immunity Primary reservoir and Vectors Comments, treatable?
Fascioliasis, a zoonotic liver fluke Fasciola hepatica and to a lesser extent F gigantica (sheep liver fluke) Reported in various cattle rearing areas in all continents except antarctica B66.3

Accidental in man

All ages susceptible, infection persists indefinitely None given None written of Sheep cattle and snails Transfer to man commonly by consumption of aquatic plants with attached metacercariae. Nasty disease in that there is no sure fire cure!
Fasciolopsiasis, no synonyms Fasciolopsis buski (a large liver fluke up to 7cm in length) Rural Southeast Asia  B66.5

Light infections commonly asymptomatic

Universal In malnourished individuals effects of infection can be more pronounced. Severity of disease determined by number of worms None indicated Swine and humans Another aquatic plant with snail problem especially in the vicinity of pig faeces. CTX.
Disease

 

Infectious agent.

Target organ if any.

Location ICD 10 entry.

Impact

Susceptibility Special risk factors Immunity Primary reservoir and Vectors Comments, treatable?
Paragonimiasis, lung fluke disease Paragonimus westermani

And other spp. of the genus Lungs and elsewhere

Reported from various places particularly far East B66.4

Said to be 22.3 million people infected in China

General Infection may last for years and the infected person would seem well None indicated Humans and various domestic animals, fish become associated with the faeces or sputum that has been spat out Another uncooked fish disease in which the lung is affected. Often found in snails and edible crustacea. The larvae can even survive pickling! CTX indicated as successful
Schistosomiasis (bilharziasis) Schistosoma mansonii and others

A blood fluke.

Various tropical countries, Africa, China and so on. Not indigenous to N America B65

Primary disease is insignificant the consequences of chronic infection can be serious

General None given except of course for those who bath in infected waters Any immunity is variable and poorly defined Humans and all sorts of other animals. ‘Vector’ often snails. CTX treatable. No direct person to person transmission but indirect contamination can occur via eggs discharged in faeces into water. A major hazard of swimming in tropical fresh water

Nematodes

All the infections included are chronic a few of which are really nasty. Most are to be found in tropical countries, a few worldwide. Universal susceptibility seems to be the rule. In no instance is immunity recognized and quantified. Our own work on Trichinella spiralis indicated clearly that in experimental mice a T-cell dependent immune response could regulate both the number of muscle encapsulated larvae and the thickness of the capsule wall – it was much thinner without T-cells [10]. My guess is that vaccination could have an effect on some of those organisms that gain entry but that others such as pin worms that are relatively benign and remain outside the body it would be of no significance. There are some five quite serious diseases among this collection on several of which the WHO has declared war. The Onchocerciasis efforts seem to have been reasonably successful. In general there exist successful chemotherapeutic strategies of elimination. With the exception of pin worms no person to person transmission, pace strongyloidiasis in relation to which auto-infection is common. For all, except anisakiasis, reasonably effective anti-helminthic drugs are available. There seems not to exist any information on immunity or otherwise in treated patients (Table 6).

Table 6: Nematodes (Non-Segmented Round Worms).

Disease

 

Infectious agent. Target organ if any. Location  ICD 10 entry.

Impact

Susceptibility Special risk factors Immunity Primary reservoir and vectors Comments, treatment?
Anisakiasis, no synonyms quoted Anisakis and Pseudoterranova, larvae

Gastro intestinal mucosa.

Where ‘uncooked’ fish is eaten

Most cases recorded in Japan,

B81.0

slight

universal NK NK Marine mammals various intermediate hosts such as small crustaceans and a variety of fish On the increase, as eating of raw fish increases in the Western world. Surgical removal is all that is quoted by way of treatment
Ascariasis, roundworm infection Ascaris lumbricoides

 

Intestine but can give rise to symptoms I many parts of the body.

Moist tropical countries B77Common and worldwide, in many countries prevalence 50%!, complications of chronic infection can be severe, General Young children, 3-8 years in whom prevalence and intensity of infection is highest. NK Humans, often as a consequence of defaecation in soil. Ascarid eggs in soil can be viable for many years. CTX that can be complicated.
Capillariasis, intestinal capillariasis Capillaria phillipinensis Variable intestines, liver and respiratory tract Far East particularly Phillipines and Japan where it is endemic B81.1Sporadic. On Luzon some 1800 cases have been recorded. Case fatality rates of 10% have been recorded. General Perhaps males between the ages of 20 and 45 but this could be an occupational issue. ? Unknown, perhaps aquatic birds fish are intermediate hosts it is believed. Associated with eating poorly cooked fish, CTX available
Hepatic capillariasis Capillaria hepatica

 

Rare only recognized as a human disease in 1924. Worldwide but not common. B83.8

Occasionally fatal

General Malnourished children are particularly at risk, 3 years of age in particular. ? Rats but a wide variety of domestic and other animals. A liver disease about which because of its rarity little seems to be known. CTX effective.
Capillariasis,

Pulmonary capillariasis

 

C. aerophila

 

Larvae from the intestine migrate to the lungs.

Worldwide but rare. Too few cases so far for any sensible generalistions. B83.8 General Children ? Cats, dogs and other carnivorous mammals. Mebendazole, albendazole and this bendazole.
Dranunculiasis, Guinea worm infection Dranunculus medinensis

 

Subcutaneous or deeper tissues.. often initially on a foot.

Africa and in Asia, particularly in countries with dry climates B72

Prognosis generally good unless secondary bacterial infection occurs

Universal In some locales all people are infected, mainly young adults in other areas far fewer carry the organism. None recorded, multiple infections occur in the same person Humans WHO agreed to abolish the disease in 1991 but they have not yet succeeded. CTX not always effective often difficult.
Disease

 

Infectious agent. Target organ if any. Location  ICD 10 entry.

Impact

Susceptibility Special risk factors Immunity Primary reservoir and vectors Comments, treatment?
Enterobiasis, (pinworms) Enterobius vermicularis

 

Intestine.

Worldwide B80

Irritant but rarely with serious consequences

Universal Differences in severity of infection are due to different levels of exposure. Ranges from asymptomatic to recurrently symptomatic. None recorded Humans, none of the animal pinworms communicate to man One of the most common parasites of school children. Parents occasionally infected and infections in domiciliary institutions can be common. The only nematode disease that shows person to person transmission. Easily treated.
Filariasis, a variety of local or eponymous namings, eg Bancroftian filariasis, Malayan filariasis, Timorean filarisis

.

Wucheria bancrofti, Brugia malayi and Brugia timori.

 

All infections of lymphatics

Variously distributed, bancofti wide spread particularly in warm humid regions the other two more restricted B74.0, B74.1, B74.2

Repeated infections in endemic regions can lead to elephantiasis

Universal ?very long persistent condition None recorded

 

Repeated infections occur

Humans with microfilariae. Mosquitos are the vector Not easy successfully to treat. Drugs are available and have been used on a mass basis but side effects can be bad. Watch this space.
Disease

 

Infectious agent. Target organ if any. Location ICD 10 entry.

Impact

Susceptibility Special risk factors Immunity Primary reservoir and vectors Comments, treatment?
Hookworm disease, ancylostimiasis, uncinariasis, necatoriasis. Ancylostoma duodenale, A. ceylanicum, A. braziliensis, A caninum and

Necator americanus

 

Intestine.

Widely endemic in tropical and subtropical regions B76

Variable light infections are often asymptomatic

Universal None given No evidence that immunity develops with infection Humans for one two spp in cats and dogs for two others Big disease in cattle but no indication that there is any transfer to man. Note also in cattle that an irradiated vaccine was successfully developed, perhaps it was a different kind of hookworm. CTx will usually work.
Loiasis, Loa loa infection, Eye worm disease of Africa, Calabar swelling Loa loa Any body part but

Particularly nasty in the eye.

Widely distributed in the African rain forest B74.3 In some parts of central Africa ninety per cent of the population are infected Universal Chronic disease None apparent Humans, deer fly vector Treatment often complicated by hypersensitivity effects. Difficult in many ways.
Disease

 

Infectious agent. Target organ if any. Location  ICD 10 entry.

Impact

Susceptibility Special risk factors Immunity Primary reservoir and vectors Comments, treatment?
Onchercerciasis, river blindness Onchocerca volvulus

 

Skin and eye.

Restricted distribution in various tropical regions but 97% of cases in sub-saharan Africa/ B73

Situation now very different in that the Onchocerciasis control program in W Africa has proved effective but previously a major disease causing blindness among many other unpleasant symptoms

Universal None given Reinfection can occur Humans, transmitted by infected black flies of the genus simulium Has been a major disease but the use of ivermectin as a larvicide in patients and black fly control measures are achieving good control it seems. Surgery sometimes used as an adjunct treatment.
Strongyloidiasis Strongyloides stercoralis and fulleborni

 

Skin. And elsewhere.

Throughout tropical and temperate areas more usual in areas of high humidity B78

Often asymptomatic

Universal Immunosuppressed patients Acquired immunity has been demonstrated in experimental animals but not in man. Humans mainly Ivermectin, often repeated will be effective.
Creeping eruption Cutaneous larva migrans. A.       caninum. A braziliensis Dermatitis, commonly feet and buttocks. Most tropical and sub-tropical countries world wide B876.0,B876.9 ? Those who regularly come into contact with soil. Contaminated with dog or cat faeces. Commonly self limiting but no indication given of how. Dogs and cats Freezing infected areas
Disease

 

Infectious agent. Target organ if any. Location ICD 10 entry.

Impact

Susceptibility Special risk factors Immunity Primary reservoir and vectors Comments, treatment?
Toxocariasis,, visceral larva migrans Toxocara cansi and T. cati

Eosinophilia a common manifestation of disease can affect ceyes.

Worldwide B83.0

Usually relatively mild, chronic rarely fatal. In some parts of the world the majority of children are infected

Lower incidence in older people largely because of lower exposure Can be severe in children 4-14 months Reinfection can occur. Viable larvae can stay asymptomatically in tissues for many years Dogs and cats but infection often by ingestion of eggs from contaminated soil A latent infection in a female dog can result in reactivation of infection and its passage to the pups through the milk. CTX but as the text remarks effectiveness of anti-helminthics is questionable at best!
Trichinellosis, trichiniasis, trichinosis Trichinella spiralis

And other spp. of the genus

Worldwide but very variable in incidence B75Varies from inapparent infection to fulminating fatal disease depending on level of intake. General Commonly consequent upon eating poorly cooked pork. A major outbreak occurred during the first world war in a army group of whom some 1800 were killed. Partial immunity is acquired (what does this mean, I suppose that there are no active worms but the encysted organisms in tissues remain intact) A wide variety of domestic and wild animals, often in arctic regions Effective treatment is available for both the intestinal and muscle stages In mice T-cell deprivation leads to increase in worm burden and reduction of thickness of cyst walls. (10).

Miscellaneous

There is little to be said about this miscellaneous category except that it includes a disease that in cattle and in man has led in parts of the world, particularly in the UK to huge losses of money and some loss of life, largely in cattle. The disease concerned is one of four recognized prion diseases that are, ostensibly caused by accumulation of deformed protein molecules that in some way or for some reason have evaded, or overwhelmed the standard mechanisms that exist for shaping proteins in a specific and appropriate way [11]. The reason for the infectiousness of the prions is not clear although a Nobel prize has been awarded for their discovery. Prions in the sense of deformed protein molecules are common occurrences. What is less clear is why under certain, ill-defined circumstances things ‘go wrong’. The issue of immunity in relation to prions seems on the face of it sensible as deformed proteins can elicit immune responses that relate to the deformity but, so far, immunity to BSE seems not to be on the cards (Table 7).

Table 7: Diseases That Do Not Readily Fall Into The Categories Already Considered.

Disease Infectious agent, target if any Location ICD entry,

Impact

Susceptibility Special risk factors Immunity Primary reservoir and vectors Comments and Treatment?
transmissible spongiform

Encephalopathies,

Four examples are given in the 20th edition of the manual Creuzfeld-Jakob disease.

Variant CJD

Gerstmann-Straussler-Scheinker syndrome Fatal Familial insomnia

Prions

 

Nervous system

Worldwide  

 

 

 

 

 

 

A81.0

.

A81.01

A81.09

Potentially enormous

Genetic differences in susceptibility exist in families that resemble autosomal dominants NK except the genetic factors.

All the ones quoted here are sporadic and not believed to be exogenously acquired though KURU and Iatrogenic CJD are of exogenous origin.. Sometimes long incubation times.

None demonstrable either in relation to adaptive or innate immune processes. An extraordinary collection of diseases that has created great controversy particularly in relation to the human consumption of prions contained in bovine products.
Disease Infectious agent, target if any Location ICD entry,

Impact

Susceptibility Special risk factors Immunity Primary reservoir and vectors Comments

and Treatment?

Pediculosis and phthiriasis Pediculus humanus capitis (head louse) Worldwide B85Common infestation among schoolchildren everywhere Universal None given None given Humans Tends to spread in families all of whom require CTX treatment.
Scabies, sarcoptic itch. Sarcoptes scabiei a mite Widespread, endemic in many developing countries but recent epidemics in the ‘developed’ world. B86

Irritant wih intense itching

Universal In immunodeficient and senile patients can present as a general dermatitis Fewer mites succeed in establishing themselves on previously infected individuals. Hyperinfestation tends to occur in immunosuppressed individuals. Humans Usually treatable

Reconciliation

As far as distribution is concerned about half of all recognized disease causing organisms are worldwide in their distribution. In these days when travelling between continents is common this proportion may increase in time. The restrictions on distribution in part relate to differences in distribution of vectors such as mosquitoes, ticks and sand flies of particular kinds. It is also clear that many diseases are more common and rampant in tropical developing countries than in the temperate regions. The class of organism was put in for the sake of completeness and will not comment further on here except to point out the obvious fact that the more severe and dangerous diseases are largely caused by viruses or bacteria. If we were to look at domestic animals that in the tropics are ravaged by a wide variety of protozoan parasites a different story would emerge. Diseases in cattle in Africa include, on a potentially enormous scale, Trypanosome and Theilerial infections. For this table the old WHO classification which gave an indication of the reporting category to both local and global health authorities has been retained (Table 8).

Table 8: Approximate Percentage of Diseases in Various Categories.

Miscellaneous Trematodes Nematodes Fungi Protozoans Viruses Bacteria
Approximate Number of diseases in the various categories according to the taxonomic classification of the causal organisms 4 9 14 15 14 160 65
Miscellaneous Trematodes Nematodes Fungi Protozoans Viruses Bacteria
Distribution Worldwide 100 34 28 53 64 56 57
Regional 66 72 47 36 44 43
The old classes given here relate to the issue of whether an outbreak of disease has to be reported to WHO. The old classification is described in detail on pp XXJV-XXIX of the 17th edition. The new insertion of ICD listing in the 20thedition gives no indication of the severity of the diseases which to get some idea of what proportion are major threats is helpful. The severity classifications have in some instances changed over the years.
Class. 1 is most most serious, 5 least harmful. The classifications relate largely to reporting requirements. 1 2 3
1A 7 4 3
2A 7 22 12
2B 7 6 2 31
3A 6 2
3B 11 7 6 7 26 12
3C 33 7 6 50 4
4 18 7 16 21
5 100 55 72 60 28 18 8
Impact

 

 

Large 25 7 20 11
Miscellaneous Trematodes Nematodes Fungi Protozoans Viruses Bacteria
Medium 22 50 26 50 44 57
 Small 75 77 50 74 43 36 32
Primary Target organ if any. Intestine 66 57 36 8 20
Lung 20 7 8 17
Liver 22 7 7 10 2
Lymphatics and Lymph nodes 7 2 6
Lymphocytes 4
Nervous system 25 7 26 9
Skin 50 7 66 7 8 31
Eyes 14 6 6
Others including sex organs 11
Urinary tract 7
systemic 25 7 33 36 32 34
Susceptibility Universal 75 100 100

 

60 64 100 95
Resistance 25 40 14 5
Special risk factors Malnutrition 11 7 14 2 6
Miscellaneous Trematodes Nematodes Fungi Protozoans Viruses Bacteria
Immuno-Suppression 25 11 7 27 50 14 15
Pregnancy 4
Gender 8
Embryos 4
Achlorhydria 6
neonates 9
young children 25 11 14 7 18 28
Older children 4 9
Adults 7 8 14
Old people 7 4 12
Occupational 13 6 9
Other, such as diabetes general illness 7 7 2 18
Trauma

 

2 12
Prior antibiotic treatment 2
Miscellaneous Trematodes Nematodes Fungi Protozoans Viruses Bacteria
N/k 64 7 44 5
 

Immunity

N/k 25 22 57 64 16 34
Cell mediated 2 8
General immunity 25 11 14 20 36 80 38
None or adverse effect 50 66 28 2 18
Vaccines + 44 25
100 100 100 100 56 75
Point of access Skin 12 14 80 43 24 17
Anus 7
Mouth 88 78 20 50 16 25
STD 7 7 8 12
Transmission Vector to man 21 21 24 17
Animal to man 7 10 15
Man to man 75 33 36 6 20
Autoinfection 14 7 2
Food 25 88 78 7 6 23
Miscellaneous Trematodes Nematodes Fungi Protozoans Viruses Bacteria
Air 20 28 8
Soil 3
Secretions, mucosal contact except sexual, but including respiratory droplets 28 17
Water 7 21 11
Inanimate penetration 7
Syringes 2
Inapparent infection + 25 100 50 20 86 34 14
75 50 14 66
Recrudescence of latent infection. + 25 N/A N/A 7 57 6 2
75 N/A N/A 93 43 94

 

The impact classification indicates roughly how important a disease was but the one plus, two plus, three plus categories adopted are too crude and of necessity applied arbitrarily. In some instances the numbers of people dying annually are recorded but in some instances this is not stated in the Manual. The various diseases in addition to their lethality and morbidity, that impose strains on the health care services, have economic consequences on for example the labour force. There are other sources of information dealing with these issues but overall figures of economic impact would perhaps be useful for PH officials to get some idea of the import of the diseases in question. These things are not written in criticism of the Manual, that clearly is written for American practitioners primarily but, faut de mieux, there seems little else enabling a global look at communicable diseases and the Manual does not confine its approach to diseases that are only significant in N America.

The target organ category looks at in broad terms what seem to be the primary disease sites. Clearly with many of the diseases in their worst and later manifestations major organ failure will be common often starting with the lung and heart. There are one or two things that stand out, ie the neurotropicity of some viruses emerges as does the predilection of bacteria to cause skin disease. Many of the diseases are recorded as systemic in relation to protozoa, bacteria and viruses. One of the most striking things that emerged is the high frequency with which it is recorded that susceptibility is universal or widespread. With the exception of the fungi and to some extent protozoan infections almost all human hosts, as far as we know, are susceptible to invasion by all the disease causing organisms. There are very few exceptions. All the organisms to which attention is drawn cause disease in the broad sense the human species is, ipso facto, susceptible to the diseases in question. What the manual shows many times is that susceptibility to invasion is in many instances not a good indication of whether disease will develop. Nor, if disease does develop, what will be the outcome. Rabies virus, for example, in Iran it is written in the 17th edition , only caused disease in 40% of those known to have been bitten by rabid dogs. On the other hand the statement that when the disease caused by rabies virus develops it is always lethal indicates clearly the difference between being infected and developing disease. It should also be noted that a comparable statement does not exist in the 20th edition. In foxes epidemiological studies [12] showed that disease was more rampant when the fox population density was highest.. Is it ridiculous to see such organisms as rabies being part of the strategy for population density control at least in some wild animals!? There are many organisms with which we come in contact that live within us without causing disease or which do cause disease relatively rarely but not in a manner that leads suspicion to fall on a named organism? CMV is not far off such an organism nor, perhaps, is EBV. Both the organisms in question are essentially ubiquitous but only rarely cause disease.

There is a lovely statement in the 1964 Topley and Wilson, Vol 11 [13] as follows:

‘The scientist shares with Humpty Dumpty the privilege of making words mean what he/(she) likes. But if we are to avoid confusion we must at least give our words definite orders and see that they are obeyed. It happens that the state suggested by the word that we have chosen as a generic label for the phenomenon we wish to study is one about which we know very little; because the study of true immunity, in the sense of complete natural insusceptibility to infection, does little to illuminate the relations of host and parasite that are our chief concern’.

It is a minor paradox that since 1964 our understanding of the genetic basis of susceptibility to infection on the one hand and development of disease once infection has occurred seems to have evolved relatively little. (pace the nice work that has been done largely in experimental systems on the genetic basis of the quantity of immune response to certain defined antigens. As far as I know this kind of work has not been extended to the more earthy fields of parasitic disease). Perhaps the genes we are looking for are for susceptibility to infection that really does seem ubiquitous. Perhaps we should be looking for other genes or other environmental factors that make this susceptibility to infection at least occasionally hazardous as a consequence of the development of disease. In standard thinking for susceptibility to infection to be a genetic characteristic it would seem sensible to suppose that there are advantages to the organisms that will become infected. Is this an outrageous suggestion? Man, for example, is a huge conglomerate of organisms with bacterial genes in all the mitochondria and 8% of the whole genome initially of extrinsic retro-viral origin. As Todaro [2] suggested many years ago the possession of viral genetic material may be highly advantageous particularly in enabling constant replacement of epithelia, even if it carries the occasional disadvantage of making development of cancer, usually in old age, more likely. Surely we did not acquire all these other organisms that are an integral part of our make up without susceptibility to infection being genetically determined? Can it seriously be suggested that infectious disease does not have a largely negative evolutionary impact. The hackles of all the immunologists and parasitologists will rise with such an idea as the war game within which they plot their experiments and house their thinking is itself attacked as not necessarily the natural way of thinking about host/parasite interactions.

Nevertheless, as Topley and Wilson in the same introductory context go on to write ‘Our main business is with those interactions between host and parasite that are characterised by a fluctuating equilibrium, and with the factors that shift this equilibrium, so that sometimes the parasite, sometimes the host, gains the upper hand’. Special risk factors, again out of curiosity. It reveals some of the factors that shift the Topley Wilson equilibrium referred to above.

As far as immunity is concerned in some instances there are no known immune mechanisms afoot. This corresponds to what I, to my surprise, found in the experimental systems which my colleagues and I developed in the ‘70s. I also note that most but not all viruses seem to elicit immune responses. The view among many immunologists is that the adaptive immune response is all purpose and designed to respond to any antigen but this seems not to be entirely true. Not all infective organisms elicit immune responses. Perhaps the most evocative experience which justifies such an alarming statement derives from some studies fifty or so years ago which gave what we thought at the time was a totally negative result and would therefore be unlikely to be accepted for publication. In retrospect the study provides much information which is fascinating. My colleagues and I had conducted a reasonably systematic study of the histopathological consequences of stimulating, or not as the case turned out, the adaptive immune response. We used sheep red cells as tried and tested means of eliciting a response in mice and with a slightly different intent, oxazolone a powerful inducer of delayed type hypersensivity. We used pneumococcal polysaccharide as a third material as the response of T-cells to that was probably negligible. These T-cells, which we had played a large part in discovering, were, not surprisingly, a main interest for us. We discovered that there was a regular repeatable sequence of histopathologically perceptible stimulation of cells in responding lymphoid organs. Mitotic activity involving T-cells was followed by the development of germinal centres and the appearance of antibody forming cells (ref 23 leads to the published versions of this work). The picture was clear and being ambitious we elected to look at what happened when gnotobiotic mice were taken out of their bacteria proof containers and exposed to bacteria for the first time. It there was an adaptive immune response to such a huge influx of antigenic material we felt it would have spectacular consequences putting what we had found with sheep red blood cells and oxazolone to shame. We found that when put into clean boxes the retrieved gnotobiotic animals died overnight. Our microbiologist said it was due to opportunistic infection by Clostridium difficile or a similar organism. This finding offers another obvious lesson which will not be spelled out here. We then took out the gnotobiotic mice and put them into boxes that had been used by mice and which were festooned with mouse faeces. They all lived and seemed very happy in their new environment. We culled five off these mice each day for ten days using gnotobiotic and normal mice as negative and positive controls. From each mouse we retrieved the Peyer’s patches, the mesenteric lymph nodes and the spleen all of which were prepared for histopathological examination. The 450 or so sets of slides were coded and read blind by an expert in the histopathological consequences of elicitation of an adaptive immune response. The result was to us, at the time, felt to have been a total waste of , effort . Aside from a few metamyelocytes in the spleens of the ‘contaminated’ mice there was not the slightest sign of any immune activity. As a slight bonus, of which we thought nothing at the time, the germinal centres in the Peyers patches of gnotobiotic mice were the same in number as those from normal (laboratory bred) mice, We seemed to have an answer to a conundrum which had puzzled us for some time – does a mouse, or a human being for that matter, make a vigorous adaptive immune response to and keep control by such means of its gut flora. As far as we could see from our massive, properly controlled and blindly read study the answer was no. The humble earth worm that, along with the other triploblastic invertebrates, does not have an adaptive immune response, must be grateful, nevertheless, for being able to ingest, every day, a diet largely consisting of microorganisms without adverse consequences. Huge contemporary interest in the microbiome is illuminated in part from the negative outcome of our study. The signs of adaptive immunity in the gut associated lymphoid aggregates of gnotobiotic mice suggests perhaps that standard feed components play a role in the lymphoid activity in the normal GALT (gut associated lymphoid tissue). There are other indications that the immune response to introduced biochemically complex living organisms is only a pale imitation of what might have happened if responses to all the potential epitopes capable of eliciting an adaptive response had been enabled but, sadly, this is not the place to pursue such a line of thought.

As far as vaccines are concerned the lack of some of these in relation to disease is related to the fact that it is has not been a commercial proposition to produce them. I have not seriously addressed the issue of whether live or dead vaccines are to be preferred. This is an argument that needs more space than is available here. There is however something that needs to be written. Some dead vaccines lead to lifelong immunity; for example diphtheria toxoid and to a great extent tetanus toxoid. The immunologists are in the main happy with this as they suppose, perhaps rightly, that the immunological orchestra (Lancet leader 1967, 185-186) has a clear memory of the music it has played in the past. If that is true then, all the various categories of memory T and memory B cells with which the immunologists play games are secure and reasonably part of the mantras with which they punctuate their days. Also it could seem quite ridiculous to suppose that there is an ongoing response to the injected toxoid when it was administered sixty years previously.

There are nevertheless various possibilities other than the immune response, like the nervous system, possessing a long memory. For example after administration of the toxoid the immunised individual might have encountered the relevant bacterium (carrying the relevant phage that codes for the toxin) and taken it on board as a chronic asymptomatic infection in relation to which there is a continuous ongoing immune response that, under normal circumstances is stable; the fluctuating equilibrium that Topley and Wilson allude to but with no significant amplitude to the fluctuations. There is another explanation Corynebacteria are not uncommon neither are bacterial toxins. Also the host organism has an enormous library of bacterial species with which it is in continuous intimate contact. Is it impossible that, given the initial priming injection with toxoid, the response is maintained as an ongoing affair by epitopes that are found in the host but which without the priming injection will not elicit sufficient immunity to negate any marauding toxins? If this is the case can vaccinologists, as suggested previously in this document, tailor the gut microbiota to deliver the required trickle of cross reacting antigenic material? In veterinary practice the concept of trickle infections, particularly in relation to multicellular parasites, is thought to play a role in maintaining resistance to further infection.

The design of vaccines could perhaps be influenced by such considerations as these. At the moment it seems largely to be determined by the classic view of the immunologists that sterile immunity is an achievable state. The evidence in the manual suggests that it is not common nor one to which is it necessarily reasonable to aspire. As far as the point of access category it is not particularly helpful. In many instances in a parasite gains access through the skin and that at the site of introduction there is an inflammatory lesion. If I were a parasite and I wanted to creep in to the host in the dead of night and kill him or her stone dead and quickly I would not advertise my presence. I would not be antigenic. I would hide my light under a bushel (or whatever is handy). I would certainly not alert the host to my presence by bringing all his various inflammatory foot soldiers to the shore on which I had landed. Have we got it wrong? Is the parasite quite deliberately trying to persuade the host to produce a reaction that if it is successful will lead to a state, as Topley and Wilson put it, of (safe?) fluctuating equilibrium?

As an experimentalist I was much influenced by some experiments we undertook with mice some of which were variously immunologically impaired. Basically the animals concerned with either normal or T-cell deprived with all the relevant controls that I will ignore as they did not detract from our conclusions. I want to draw particular attention to some work we [7] did with Trypanosoma musculi. This is a parasite that is found in various species of small rodent. As far as I know in the wild it does little harm. In the laboratory in normal mice injection of as few as one live tryps would give substantial otherwise asymptomatic parasitaemia evident from twelve days or so and declining quite quickly twelve days later. The infected animals gained weight at the normal rate and, as far as we could tell were hale and hearty. Their spleens, unusually for laboratory mice, were replete with very healthy looking germinal centres indicative of an ongoing systemic immune response. The infected animals were solidly resistant to further challenge. For the parasitologists, with whom I was working, this was an indication that the parasite had been exterminated and that the immune response was doing what it should do. In T-cell deprived mice a different story pertained. The parasitaemia developed at the same rate but continued to grow often over many months with eventually a fulminant condition arising and death following soon afterwards. This shows clearly that without T-cells control over the growth of the parasite cannot be achieved. ‘Cell-mediated immunity in action’ mutter the immunologists sagely. But was it?

I persuaded my parasitological colleagues to look at recovered normal mice for live parasites as we had a very sensitive infectivity test. Eventually they found them in the kidney in very healthy condition and ostensibly doing no damage. The tryps would be spending their days bathed in antibody (dare it be said that this was probably their main food?). Thus in the absence of T-cells the infection eventually led to disease and death. In the presence of T-cells antibody was produced in buckets full and the parasite, albeit on a restricted scale, lived on. I found it difficult, with this example, not to suppose that the immune response functioning properly was responsible for safe retention not rejection of the parasite. It was in fact probably the most important factor in maintaining the equilibrium between host and parasite [13] without, in this instance, any obvious pathology. My hard working parasitological colleagues, for whom I should say I had and still have the greatest respect, went on to try to persuade the parasite to ‘come out’ from the kidney otherwise there would not be any continuity of infection. In ‘hyperimmune’ mice with infected kidneys they tried steroids and, post thymectomy, total body irradiation and restorative implantation of fresh syngeneic bone marrow to produce animals with few T-cells but nothing disturbed the equilibrium until, one day, in a burst of genius, they discovered that pregnancy in long term infected normal mice led to parasitaemia(personal communication). There were no adverse consequences noted of this disturbance of the equilibrium which could anyway be designed to pass the parasite to the foetuses. Sadly we did not look for this. This small example coupled with much other evidence inadvertently provided by APHA began to push me to the view that the war paradigm of sterile immunity in relation to parasites was not totally satisfactory.

The last categories in the reconciliation table show that many infections can be asymptomatic and that some can recrudesce after long periods probably of equilibrium. The immune status of organisms with latent infections is not adequately researched but such research could be helpful in enabling us to decide which patients are likely to be stable with their latent infections. It is already known in AIDS patients in which latent infections, often of Pneumocystis carini or Mycobacterium tuberculosis, are thought to become active but the exact reasons why, except to show that in the broad sense the immune mechanisms probably regulate the equilibrium, is obscure. Also, as far as Mycobacteria are concerned, it may also be that a different sp. to that of the original infection causes the later problems. The main diseases that kill many humans globally of which, incidentally, there are very few, all show the majority of the infected individuals have few if any symptoms. Particularly for tuberculosis the statement that 90% of those in regions of the world where the disease is indigenous show no symptoms when first encountering the organism but are nevertheless probably carrying the Mycobacterium which causes the disease for life illustrates what seems to be counter intuitive.

Overall Discussion

Biological Advantage

The most usual method of teaching Biology without evocation of Special Creation, which will not be done here, is to suppose that a process of evolution of living organisms has occurred. The fossil record supports such a way of proceeding and the monumental work of Darwin, on the selection of advantageous forms of life capable of better succeeding in our diverse global climate, provides a framework for the process to occur. The relatively recent discovery of the genetic apparatus in the early days of the last century [14] offered a mechanistic basis for evolution to occur by selection of genetic constructs, point mutations as they are often called, offering survival advantage to their possessors. The role of point mutations in the process of natural selection will not be queried but it will be suggested, on the basis of the survey of the APHA handbook that it is far from the only method of genetic selection that exists. Most recent biological teaching, to make sense of the tremendous morphological diversity of living organisms particularly the multicellular eukaryotes of which the human species is an example, has continually posed the questions involved in deciding on the possession of properties of biological advantage. For example, the fins of fish facilitate their movement in a liquid environment, the wings of birds enable them to move in air, the possession of chlorophyll by many plants enables them to fix solar energy, a process on which humans are presently totally reliant, and the hair of mammals helps to keep an homoiothermic organism such as Homo sapiens warm in cold climates. Students of biology have laboured over such issues ever since Darwin published his ground breaking study on diversity as the basis of biological evolution but it will be suggested that the concept of monophyletic evolution of single species should be queried and replaced by an alternative with many species of organisms working together to constitute the units for evolutionary advancement.

Communicable Diseases and Vaccination

It is in reference to such studies, exploring the biological advantage of possession of an immune response, that the present review of communicable diseases in man has been conducted. On the face of it, organisms that can invade and clearly in some instances harm humans seem to constitute a selective disadvantage and the immune response seems tailored to overcome this disadvantage. The contemporary social, disruption following the emergence and depredations made on the human species of the SARS-CoV-2 virus which can give rise to the Covid-19 severe respiratory disease, and the apparent failure of the immune mechanisms always to act protectively, underlines the importance of this manner of thinking. The standard way of getting round the problem is to evoke prophylactic vaccination, a process known in outline for centuries. Edward Jenner is often given great credit for showing, in 1798, that vaccination, in humans, using a form of small pox ‘vaccinia’ virus derived from cattle, could offer protection from the great harm that the wild type human pox virus could wreak [15]. That it took till October 1977 to extirpate the disease from human populations [16], by a combination of vaccination and contact identification using the immunisation technology invented by Jenner, inter alia, shows that highly beneficial changes in medical practice can take considerable time to become established but, nevertheless, vaccination worked. The immune response is certainly in part protective but it will be proposed that there are other aspects of its functioning. It is useful to amplify such a statement by reference to the information given in the American Public Health Association Manual of Control of Communicable Diseases which aims to review nearly all the presently known such diseases with attention to the kind of information needed by Public Health practitioners to reduce their effects when they harm humans.

The Evolutionary Perspective of the Immune Apparatus

Humans live in an increasingly sanitised world in which as far as possible micro-organisms are given short shrift as they are believed to be potentially dangerous and to be capable of causing disease. There is no doubt that there is a sound basis for such a belief in that there are some such organisms that can be pathogenic i.e. capable of causing harm in human populations. It is, nevertheless, worthwhile noting, using an evolutionary perspective, that the selective mechanisms by which the human body effects an immune response were probably put in place more than five hundred millions of years ago when vertebrates were first found in the fossil record. This is well before the advent of what we now know as the medical profession. The point about the medical profession is that the mores of the present age regard all human life to be valuable and that in those circumstances, where for medical reasons it seems to be threatened, it is the duty of the profession to do their best to reduce harm due to infection and where possible save lives. No such remediable measures were available at the time that Homo sapiens or his earlier progenitors roamed the earth. Life then, for the extant humans, was much as it is now for wild animals and plants. It can reasonably be argued that if we wish to estimate the biological significance of immune mechanisms in an evolutionary perspective it is to the ‘wild’ situation that we should look. This in no sense to argue that the medical profession are not doing a good job or that their mores are to be changed but simply to assert that the medical profession and the public health experts have moved the demographic structure of human populations massively in the last hundred or so years and that this demographic change can distort the way we think about an ancient interface system, between man and his complex environment, such as that constituted by the various facets of the immune response.

The Adaptive and the Innate Immune Responses

For historical reasons our thinking about immunity in recent years has been almost totally dominated by our pre-occupation with what immunologists call adaptive immunity. This property is possessed only by vertebrates [17] and its pursuit has largely led us to ignore the fact that the innate immune response is also an integral part of the total mechanisms of immunity. Innate immunity is not only a property of vertebrates but also functions in multicellular invertebrates [18] many of which have, in their adult forms, an exoskeleton, an alimentary canal and three basic blast layers in the early stages of their ontogenesis – so called triploblasts. The innate immune response in all such organisms has a system of cells that can become phagocytic and which, operating inside the body which contains them, in part if not exclusively, using a system of toll receptors [19], can find, ingest and destroy living invaders and act, in circumstances in which cells have been damaged or killed in the body, not necessarily as consequence of infection, to perform a clean- up operation.

The differences between adaptive and innate immunity in terms of their mechanisms and overall purpose have been dealt with extensively elsewhere [20]. Here it only needs to be said that the adaptive immune response is specific and capable of tailoring an immune response to relate to the inducing antigenic stimulus by the production of antibodies which have specific binding sites for the inducing antigen. In addition it is widely argued that specifically cytotoxic cells are produced. It must also be noted that adaptive immunity depends to a great extent on the existence and activities of two populations of lymphocytes terms T and B cells, the former of Thymic origin [21] the latter from Bone marrow. In vertebrates T-cells have a variety of ascribed functions of which one of the first to be discovered was to work synergistically to facilitate the production of antibodies by B cells [22]. These two populations of lymphocytes are often credited with a potentially long term memory of past activities perhaps comparable to memory possessed by organisms with a brain. This notion of immunological memory will be queried not as necessarily wrong but one which should be argued about.

The Adaptive Immune Response, Reject or Acceptor of Invaders

The adaptive immune response is seen by most medical practitioners, by many contemporary immunologists and often by parasitologists as primarily a defensive mechanism ideally capable of rejecting living invaders and dealing with foreign bodies of any kind. This view has been criticised [23-25] and the counter suggestion made that the adaptive immune response in evolutionary terms exists to assist accommodation of invaders. The name adaptive against this background can suggest either rejection or accommodation with, in the views of its protagonists, the latter being commonly possible and the former less often observed. These notions are not in general popular either with immunologists or parasitologists but nevertheless deserve consideration here. Probably the vertebrates appeared later in evolutionary time than the invertebrate organisms which are generally supposed to be their precursors. Accepting this view it is worth considering briefly why the adaptive immune response, characteristic of the vertebrates, was added, in response to a selective advantage, to the innate immune response of their precursors. The innate immune response has no specific memory such as is seen as a property of the adaptive response. It could be that the acquisition of a specific memory is a selective advantage. Equally as a consequence of the existence of the substantial array of isotypes of immunoglobulin antibody and their even greater array of idiotypic diversity associated with the adaptive immune response it could be seen as providing an all- purpose far more extensive protective reaction to invasion than the innate immune response alone. It seems to make good sense but it can be argued that if that were the case vertebrates would have been selected for their capacity to reject pathogenic organisms capable of reducing their viability. In fact a significant finding from the APHA manual is that humans and incidentally their domestic animals very often live for long periods of time asymptomatically with latent disease forming organisms. Also most disease causing organisms are found to be symptom free in species other than the target of interest. For example Theileria parva which can cause a disastrous and almost always lethal disease in humped cattle in East Africa is to be found in native species of asymptomatic [26] cattle (buffalo). That the great majority of viruses and bacteria do not cause disease in man could be attributed more to the organisms concerned not having a necessary biochemical affinity with hosts that they do not invade. The APHA manual makes it clear that susceptibility to the infections known to be capable of causing disease is almost universal. If such susceptibility were dangerous perhaps the all-purpose apparatus of the adaptive immune response will deal with the consequences of the ‘free’ entry of invaders. Of course there are many non-immunological barriers to entry such as mucosal membrane secretions with anti-microbial properties and physical barriers such as provided by sturdy keratinised skin but when these barriers, for whatever reason, have been by-passed successfully invasive organisms often do not cause disease symptoms or only those that can readily be dealt with by the various responsive systems possessed by the vertebrates, particularly the elements of the innate immune response which act as very effective sentries in locating and exterminating foreign organisms intent on immigration. Without doubt the adaptive immune response can control the scale of invasion which for various reasons has not been dealt with by the innate system [7] but it is not too difficult to show experimentally that long term persistence can be associated with the presence of circulating antibody specifically capable of binding to and inactivating, though not exterminating invaders [7]. It has even been argued in relation to eukaryotic single celled organisms that antibody bound by specific idiotypic ligands to their target cells could offer a high level nutritious proteinaceous diet [7]. Fie!

Recent studies on Covid-19 patients claimed that high antibody levels were present in seriously ill patients but far less frequently in the majority of infected individuals who were asymptomatic [27]. Is it totally ridiculous to argue that elements of the adaptive immune response contributed in some way to the sickness of the patients with severe disease but in those who were asymptomatic no such harmful effects were seen for the simple reason that the adaptive immune response was not so active? Alternatively the asymptomatic patients, using their adaptive system or their innate immune response, had restricted the prevalence of the invading virus and thus only a minor response in terms of inactivating circulating antibody was observed.

Invertebrate vectors which facilitate the introduction of potentially pathogenic invaders of vertebrates do not themselves seem to suffer disease symptoms or at least do not have sufficient restriction of their movements to prevent them being capable of gaining entry to the vertebrate host usually with the aim of getting a blood meal. Is the apparent general lack of suffering from disease in infected invertebrates because they do not have adaptive immune mechanisms? There are no easy ways of resolving these apparently conflicting interpretations of observations. The prevailing view is that pathogenic microbes exist to harm their hosts and must be avoided or killed. The terminology adopted by the human protagonists of this kind of approach is that used in waging wars and it is difficult not to be sympathetic but it must be pointed out that the possibility of mutual benefit as a consequence of infection should be considered. The benefit to the potential parasite is that it gets somewhere safe to live. The long term advantage to the host could be that it gains an indwelling source of genetic material. If this seems bizarre it should be remembered that two major steps in evolution, firstly the formation of eukaryotic organisms from fusion of a number of species of archaea and bacteria with subsequent simplification of the genomes involved as Lynn Margulis [28] has so elegantly pointed out, led to the emergence of the nucleated cells of which all the living organisms that not microbial are now composed. The mitochondria which are the relics of these long ago events but still retain a small fraction of genetic material known to be of microbial origin. The mitochondria are essential vital energy managing organelles of which the much simplified genetic material derived from what were initially free living organisms enacts the required energy managing function.

Is it too difficult to imagine a protracted evolutionary sequence involving contact between living organisms leading sometimes to invasion, the initial stages of which in evolutionary time could be tempestuous and dangerous, facultative parasitism it could be thought of, followed by period of accommodation, obligate parasitism, and perhaps in time genetic simplification of the invaders and total loss of their independence. The microbial flora which all triploblastic organisms possess, the acquisition of which was a major step in evolution, shows convincingly that organismal relationships can be mutually beneficial despite the massive differences in the life styles and genetic constitutions of the organisms concerned. Several billion years ago almost the first fossil organisms to be discovered, stromatolites, were complex symbiotic associations. Symbiosis is essentially a universal phenomenon and not one easily predicted by a theory of evolution only advancing by selection of advantageous point mutations. The disadvantage to host of harm or death as consequence of invasion of course exists but it can be argued that this is irrelevant in evolutionary terms however abhorrent it is to a species such as Homo sapiens which prides itself on being able to keep all the individuals of its species in good health. The innate immune response is swift and lethal. Impose on this assassin the mechanism for adoption and rehabilitation of immigrants and it can be argued that this potentially accelerates evolution by creating greater gene pools that have the capacity over time for responding to a greater degree of environmental vicissitudes than can be arrived at by monophyletic notions of evolution.

Non-Immunological Consequences of Activation of the Immune Apparatus – Inflammation

Over the years it has become apparent that immune cells of all kinds activated in vitro or in vivo produce a wide variety of proteins other than the specific antibodies, which are derived from B-cells transformed into plasma cells. The various cytokine products, in addition to antibodies, are exported into the surrounding medium whether this is a tissue culture dish or extracellular spaces. In this way activation can be, in addition to be concerned with the response to an antigenic stimulus , part of a signalling process having consequences on surrounding cells often in vivo on adjacent tissues and systemically. The secretions include what are called paracrine and autocrine hormones which by definition act locally. Wikipedia has this to say:

“When macrophages are exposed to inflammatory stimuli, they secrete cytokines such as tumor necrosis factor (TNF), IL-1, IL-6, IL-8, and IL-12. Although monocytes and macrophages are the main sources of these cytokines, they are also produced by activated lymphocytes, endothelial cells, and fibroblasts.”

The cytokine secretions from activated cells of the immunological apparatus, whilst they can also act locally in the paracrine sense, can also have systemic endocrine effects. The relationship between these cell products and the rather better known products of the endocrine organs, the thyroid, the adrenals, the pituitary and the sex organs, for example, is less well understood. There are other organs which secrete hormones such as the alimentary canal and again the relationship between these and the other secretions which can act hormonally in the sense that they have effects remote from their sites of production is far from clear though in the years to come research will sharpen up our knowledge. The cleaning operation after damage to cells in the previously whole body, referred to above, is an aspect of inflammation executed by elements of the innate immune response operating internally. This mopping up is comparable in some ways with the external debridement of wounds surfaces by the medical profession to expedite the commencement of the healing process. The clean- up operation can involve what are called pro-inflammatory constituents of the innate immune system. All being well they give way in time to anti-inflammatory components associated with the healing process. This transition often goes smoothly but if the pro-inflammatory influences do not give way in time to the next phase symptomatic problems can arise which, to those suffering from them, can be unpleasant, dangerous and potentially lethal. Presently we are not fully capable of easing the transition process but it seems likely that we can begin to identify the internal mechanisms involved. It must be made clear that the account given here is an oversimplification in that some of the cytokines identified as pro-inflammatory can be anti-inflammatory and vice versa. The whole array of inflammatory molecules is highly complex and perhaps for this reason the general analytic methods which will need to be applied to far to its control have not yet been fully discovered but a start has been made.

The Wikipedia entry summarises these issues and points particularly to a phenomenon, the secretion of TNF, tumour necrosis factor, which, as Ian Clark has pointed out for over forty years, [29] is vastly important in relation to disease symptoms including lethality. His argument based on an elegant series of experiments showed initially that the lethality of an infection of a species of Plasmodium in mice could be abolished prophylactically by reduction of the capacity of the recipient animals to produce TNF. Clark went on to show that TNF minus mice did not get sick and die, and if he injected normal animals with TNF, he could elicit disease symptoms. The issue is whether such a mechanism relates to the symptoms of some or all infectious diseases and whether it can be predicted which organisms will be most affected by the pathological effects which can derive from immune activation. Clark’s work with infection of various strains of mice with Babesia points a way forward in this respect. He found that the pathogenesis of Babesia could be predicted from a knowledge of the sensitivity of the species or subspecies strain of host animals to LPS, a bacterial product which has powerful physiological consequences due to its capacity to induce massive and dangerous inflammation [30]. Beyond such a finding if we could identify by some clinical biochemical markers those individuals most at risk from what is in fact immunopathology, lies the issue of how we can intervene to reduce such processes which, ex hypothesi, can be very harmful and should if possible be controlled.

Some of these issues are considered in a recent paper [31] summarising what I, an immunobiologist, believe is how we should think of infectious disease as a step in the evolution of a greater degree of genetic complexity. Such a message to those who die as a consequence of infection is not helpful and of course the medical profession should continue to strain to keep sick people alive but it is likely that some of their efforts are not mimicking the ways that over the ages man has emerged from the evolutionary swamp.

In summary:

  1. Genetically based resistance to disease is uncommon compared with susceptibility to invasion by potential pathogens.
  2. Immune activities are both helpful and potentially harmful to humans we should seek better to understand the mechanisms by which the harm element is brought about in addition to learning more about the general physiological benefits of immune processes.
  3. Only to think of attacking and killing invaders is to disregard the immunopathological processes that often and probably always are involved in creating the symptoms of disease.
  4. Inflammation arising from activation of immune cells occurs and it could often be better to attempt control of the host response than necessarily waging war on the invading organism. Most interaction between living systems are complex and involve activities which could be thought akin to playing table tennis i.e. the players change their activities according to the way that their partner in the game has played. An organism that can replicate in minutes rather than years and where the process of replication is prone to mutational error has a much better chance of creating advantageous genetic diversity.
  5. It should be better recognised that both adaptive and innate immunity exist in humans and the roles that each of these mechanisms both in relation in the broad sense to infection and the maintenance of good health should be taken into account.
  6. There are many problems susceptible to solution by active research by immunologists that arise from perusal of the APHA manual on Control of Communicable diseases in man.
  7. The reasons why so many diseases are more severe in those who are said to immunosuppressed or physiologically at a disadvantage , diabetic say, should be better investigated than is presently the case. In balanced ecosystems predation occurs but the loss of life due to it is easily balanced in a number of ways. Man himself is a complex example of a whole series of ecosystems and their structure and maintenance might be facilitated by better recognition of this fact.
  8. Particular attention should be given to the role that our microbiome friends play in the maintenance of health and how this property can be augmented and maintained perhaps by pro- and pre-biotics which have defined effects on the gut flora [32-34].

Acknowledgements

I wish first and foremost to thank my friend and erstwhile colleague Professor Page Faulk for bringing the APHA Manual to my attention. Over the years I was involved in active experimentation my colleagues and I published many papers and their contributions were recognized by joint authorship. I thank them here for their skill, support and enjoyment of the work we did together. As far as parasitic disease is concerned Professor Ian Clark offered an insight into the significance of Innate Immune mechanisms with his powerful studies of TNF and I thank him for his work and continued support. Prof Michael Doenhoff initiated me into the arcane world of Schistsome infections. I thank him for scientific discussions and the great fun we had together. I am grateful to Prof Lee Nelson who told me of the phenomenon of Microchimaerism which offers the possibility of all humans to have beneficial activity of immunological mechanisms they contain which they acquired following movement of cells from their mother during pregnancy. Cells acquired in this way offer generational continuity over and above the standard Weissman model of inheritance entirely through the genetic apparatus of the zygote. The importance of microchimaerism is probably presently understated. Professors Pierre Viens and Geoff Target produced results of experiments which revolutionised my understanding of adaptive immune responses and I thank them for their patience, friendship and collaboration. Professor Max Murray and his colleagues in the Veterinary College of Glasgow University led me gently into the world of parasite disease in cattle and from them I learned and continue to learn a great deal. More recently Dr Chris Owens and Professor Bruce Reid have had considerable influence on my way of thinking and I thank them for that. Dr Aamir Ahmed is a top rate physiologist with expertise in the electrophysiology of cell membranes, His regular discussions with me have both encouraged me to think and offered methodological insight which has been most valuable. My friend and wife, Agneta Lando has been unstinting in her support, checking manuscripts and offering encouragement to continue. She has been throughout invaluable.

References

  1. APHA handbook 20th Edition (2015) Editor Daniel L Heymann, APHA Press.
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Article Type

Perspective

Publication history

Received: September17, 2020
Accepted: September 24, 2020
Published: September 30, 2020

Citation

Davies AJS (2020) Communicable Diseases in Homo sapiens for Immunologists. Integr Gyn Obstet Volume 3(2): 1–48.

Corresponding author

AJS Davies
Emeritus Professor,
University of London,
POLYREM Ltd,
81 Queens Road,
Wimbledon,
London,
England