This term refers to the course that a disease would follow from its inception to its end without any external intervention. Because internal intervention will always be there in the form of immunity. It can be broadly divided into two stages—the stage of prepathogenesis and the stage of pathogenesis. The concept of prepathogenesis and pathogenesis is described below.
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PART II: Epidemiological Triad Every disease process has multiple etiology. These
multiple causes may be classified as agent, host and environmental factors. The disease itself results when the balance between the agent, host and environmental factors gets tilted in favor of the causative agent. One or more of these factors may start operating long before the disease actually manifests itself. For example, the occurrence of repeated attacks of chickenpox or measles (single attacks of which usually confer life long immunity) is determined not by the virulence of the infective agent but by the presence of agammaglobulinemia, which may be congenital.7 Keeping this long temporal spectrum in view, the total disease process can be divided into two periods, the period of prepathogenesis and the period of pathogenesis. In the above example, with reference to the occurrence of a repeat attack of measles in a person with genetically determined agammaglobulinemia, the period of prepathogenesis is the period from conception till the time of second contact with measles virus, while the period of pathogenesis is the period from repeat contact with the virus till the actual occurrence and subsidence of the second attack of measles. These concepts are further explained below.8
Prepathogenesis refers to the interaction between the potential agent, host and environmental factors which interact before man is directly involved and which ultimately determine the actual occurrence of disease in man. It starts from the time the first forces start operating to create the disease stimulus in the environment or elsewhere. An example of environmental factors as the initial force is the extreme cold in Kashmir responsible for the use of Kangari by man (the host) in whom the chronic irritation of skin by local heat (the agent) causes the Kangari cancer. An example of a disease where the agent factor constitutes the initial force during prepathogenesis would be the occurrence of gonorrhea in a person who had been given otherwise adequate doses of penicillin prophylactically and therapeutically because he is infected by a penicillin resistant strain. In this case, the development of penicillin resistance constitutes the initial prepathogenetic force referrable to the agent.
Pathogenesis refers to the course of the disorder in man from the first interaction with disease provoking stimuli till the appearance of the resultant changes in form and function or till the attainment of equilibrium or till the occurrence of recovery, defect, disability or death. In the example of gonorrhea above, the period of pathogenesis starts from the moment man comes in contact with gonococci till he gets rid of the infection and the pathological process in the body has stabilised.
The period of pathogenesis consists of the preclinical phase (before the occurrence of clinical sings and symptoms) and the clinical phase (from the time of clinical presentation onwards).
To summarize, the natural history of disease covers two processes:8 prepathogenesis (the process in the
environment) and pathogenesis (the process in man).
These processes are described below in detail. They are clarified in the accompanying Table 3.1. The description of prepathogenesis will be aimed at the agent, host and environmental factors that interact and lead to the stage of pathogenesis. The description of pathogenesis will cover the temporal profile of the period of pathogenesis in the individual and the community.
TABLE 3.1: Stages of disease in man Stage of Prepathogenesis
This is the stage at which man is not involved by the disease process.
During this stage, however, the agent, host and environment interactions bring together the agent and the host or produce a disease provoking stimulus in the human host.
Stage of Pathogenesis
• Preclinical Phase
– Agent (or stimulus) becomes established in the host and increases by multiplication.
– Changes occur in the body in response to the agent. These changes may be related to immune resistance, physiological function or tissue morphology.
• Clinical Phase
– Active clinical illness with characteristic signs and symptoms – Convalescence
– Chronic illness – Disability and defect – Recovery or death
Prepathogenesis
AGENT FACTORS
These are grouped into three categories—those inherent in the agent; those related to man; and those related to environment.
Agent Factors Inherent within the Agent
• Biological such as morphology, life cycle, motility, temperature, oxygen requirements for growth and toxin production.
• Physical, such as resistance and viability when exposed to heat, drying, ultraviolet light, chemicals and antibodies.
• Chemical, such as antigenic composition.
Agent Factors in Relation to Man
In most cases, man is the host as well as the reservoir or source of infectious agents. Many agent factors are thus related to man. These are as follows:
Infectivity: It is the ability of the biological agent to invade or enter the host and then multiply. For example, Cl. tetani and C.diphtheriae have low infectivity but high pathogenicity and virulence.
Pathogenicity and virulence: Pathogenicity is the capability of an infectious agent to cause disease in a susceptible host while virulence is the degree of
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CHAPTER 3: Epidemiological Approach in Preventive and Social Medicine
pathogenicity of an infectious agent, indicated by case fatality rate and/or its ability to invade and damage tissues of the host.8 Tubercle bacillus has got high pathogenicity but low virulence. Only about 1% of the persons who get infected develop the disease. Virulence is also low in case of pneumococcal, herpetic and fungal infections. Rabies virus, on the other hand is highly virulent. Some microorganisms throw variants after turnover of a few generations. Such variants may have altered virulence and antigenicity.
Antigenicity: It means ability of the agent to stimulate the host to produce antibodies such as agglutinins, precipitins, antitoxins, bacteriolysins, complement fixing, neutralizing and sensitizing antibodies. They provide specific protection and are helpful in diagnosis of the causative microorganism. The specific antibodies in serum are demonstrable about a week after the onset of symptoms. This fact is of value in establishing the diagnosis of diseases like enteric fever, brucellosis, leptospirosis and infectious mononucleosis. Antibodies may be demonstrable in virus infections also, but clinical identity is clear by the time diagnosis is made by this method. Helminthic antigenicity is made use of in diagnosis by allergic skin tests, such as those for trichinellosis and hydatidosis. Protozoa produce com-plement fixing antibodies. Rickettsiae usually result in lasting immunity while viruses generate varying degrees of specific immunity. High pathogenicity is often associated with high antigenicity. High infectivity and low pathogenicity produce passive carriers and mild cases, as seen in meningococcal infection.
Agent Factors in Relation to Environment
The main role of the environment is either as reservoir of infectious agents or as vehicle of transmission. Both the roles depend on the morphology and the viability of various agents.
Factors in relation to reservoir
Human reservoir: Man is an important source or reservoir in most of the infections in two ways: as a case or as a carrier. Definitions of various types of carriers have already been given. Examples of a temporary carrier are healthy contacts of cases of diphtheria, poliomyelitis, etc. Examples of an incubatory carrier are diphtheria contacts who may be carrying organisms in the incubation period. Examples of convalescent carriers are patients who have recently recovered from typhoid, dysentery, cholera and diphtheria. Examples of chronic carriers are persons who have been infected with organisms causing dysentery or typhoid and pass these organisms in stools for a long time. Such discharge may be intermittent.
Animal reservoir: Domestic animals and pets are important reservoirs. Examples are dogs (rabies), rats
(plague, leptospirosis, typhus, rat bite fever, salmo-nellosis), horse (glanders), sheep and goat (anthrax) and cow (brucellosis).
Inanimate reservoir: Soil, water and sewage form secondary reservoirs for varying lengths of time. Soil may act as reservoir for spore bearing organisms like Cl. tetani. Water and sewage may be temporary or long time sources for infections like cholera, typhoid and poliomyelitis.
Factors in relation to transmission: All types of environment—physical, biological and social—may act as vehicles of transmission. The examples of physical category are fomites and infected food and water.
Examples of biological environment as vehicle of disease are provided by the large number of vectors such as mosquito and flea. The social environment operates in case of disease requiring close human contact for transmission, such as venereal diseases (genital contact, direct transmission), leprosy (skin contact and droplet transmission) and many viral and bacterial infections such as measles, diphtheria, influenza, etc.
HOST FACTORS
These relate to the characteristics inherent in the host or man himself which make him susceptible or resistant to infectious agents. These have been described in detail in the previous chapter. Some further examples will be given here to illustrate the role of host factors in infectious disease epidemiology.
Age is a very important host factor in the context.
A child under 6 months is resistant to measles but is very susceptible to it from 6 months to 2 years. Pertussis is most dangerous to children under 2 years of age.
Communicable diseases common in childhood become rare in later life.9 Typhoid is more common from 5 to 25 years of age.
Sex differences in relation to communicable diseases may be explained differently in different instances. Thus leprosy is more common in males, but this may be because of more chances of exposure in men.10 E. coli infection of the urinary tract is more common in women because of anatomical differences and the proximity of urethral and anal orifices. AIDS is particularly common in passive homosexual men because rectal mucosa offers little resistance to the virus, as also because anal intercourse is usually associated with some bleeding from rectal mucosa.
Race differences in communicable diseases may be related to socioeconomic, geographic and ethnogenetic factors. The latter are known to influence the prevalence of malaria in different regions. It has long been known that negros in the USA had P. vivax infection rate lower than that of whites and that it was more difficult to infect them with this species. The most evident consequence of resistance to P. vivax in negros occurs in West Africa
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PART II: Epidemiological Triad where, in many regions, it cannot be found in the
indi-genous population; yet the parasite is common in the inhabitants of the Eastern Congo and East Africa.11
Genetic factors determine the occurrence of sickle cell trait, sickle cell disease and other hemoglobinopathies.
The affected individuals are more prone to infections, especially those caused by Salmonella and Pneumococci.
Osteomyelitis is also common in them and frequently leads to death.12
Personality can also influence the incidence of infec-tious diseases. Some persons are very health conscious and meticulous in their hygiene, thus minimising chances of infection. Some people seek prophylactic vaccinations and inoculations on their own, while others refuse them even when approached at their home.
Some individuals are sexually extravagant and are repeatedly exposed to venereal diseases. Thus personality traits definitely act as determinants of disease.
Various habits and customs are also important. The habit of washing hands before meals protects from diseases like cholera. The custom of easing in open fields helps in the spread of hookworm infection. General and specific defence mechanisms of the body are of crucial importance influencing the occurrence and severity of infections.
ENVIRONMENTAL FACTORS
They play an important role in favor of either the agent or the host and have been described in detail in earlier chapters. The role of environmental factors in infectious diseases will be further illustrated here by appropriate examples.
Social environment: Indiscriminate defecation increases the chances of water and soil pollution. Poverty and overcrowding lower the body resistance and increase the chances of infection. Availability of good food and nutrition and facilities for immunization increase resistance to diseases. Better economic and social environment ensures better medical and health facilities.
Physical environment: Altitude, soil, climate, rainfall, water-supply, etc. may favor growth or spread of agents and their vectors and reservoirs.
Biological environment: Arthropods, pets, livestock or beasts may act as source of infection or may transmit the same. Man lives in close contact with animals like cow, pig, goat, etc. and often, even ingests them. Thus, he is liable to contact diseases like brucellosis, hydatidosis and cysticercosis.
Pathogenesis
Everyone is potentially in a phase of prepathogenesis with respect to some diseases. However, the period of
pathogenesis starts only when the infectious agent enters the host. Once that happens, one of the following possi-bilities may occur.
• The agent fails to lodge within the body:
– It may be coughed or sneezed out, passed out in stools or washed off from the skin or mucous membrane.
– It fails to enter the skin or mucous membrane because of intactness, the first line of defence.
– It is dealt with by phagocytes or reticuloendo-thelial cells or is killed by secretions such as hydro-chloric acid in stomach, the second line of defence.
• The agent is able to lodge and multiply but fails to produce obvious disease: Examples are asymptomatic Meningococcal infection and many cases of helminthic infections, e.g. Enterobiasis and Ascariasis.
• The agent lodges, establishes and multiplies within the body producing a series of changes, which may be detectable by clinical or laboratory examination.
From a clinical point of view, pathogenesis has two distinct phases: preclinical phase (incubation period) and clinical phase.
PRECLINICAL PHASE
During this period, the parasite lodges, multiplies and starts the disease process in the host but the symptoms and signs are neither felt by the prospective patient, nor are they apparent to the doctor on clinical examination.
Incubation period may, thus, be defined as the length of time, reckoned from the point of entry of the parasite into the host, till the clinical manifestation of disease.
Incubation period varies from disease to disease.
Information about mean and range of incubation period of a disease helps in diagnosis of the disease, in tracing the source of infection and in fixing the period of quarantine.
CLINICAL PHASE
The disease becomes clinically manifested in this phase.
The severity of illness in an individual again depends on agent, host or environment factors. It may manifest in the following forms:
• Mild, missed, ambulatory or atypical case, ending in complete recovery
• Acute case ending in recovery, disability, chronicity or death.
• Chronic case ending in recovery, disability or death.
INFECTIOUS DISEASE MORBIDITY
Morbidity is measured as incidence or prevalence rates, which are expressed as the number of cases per unit population (per thousand, lakh or million). When it applies to occurrence of new cases, it is called incidence rate. When applied to both new and old cases, it is called
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CHAPTER 3: Epidemiological Approach in Preventive and Social Medicine
prevalence rate. Details are given in the chapter on vital statistics. Variation in incidence or prevalence of a disease in a given population depends on the agent, host and environmental factors and is of three types.
1. Short-term fluctuations result in an increase (or decrease) in the number of cases in a community.
Common examples are outbreaks of diarrhea, cholera and infective hepatitis, which may assume the shape of an endemic or epidemic;
2. Periodic fluctuations may be seasonal or cyclic in nature. Examples of seasonal fluctuations are the high incidence of upper respiratory infections in winter and of cholera in rainy season. Examples of cyclic fluctuations are the occurrence of influenza pandemics every 7 to 10 years, of rubella every 6 to 9 years and of measles every 2 to 3 years. Such fluctuations are probably related to herd immunity.
The proportion of susceptible individuals in the
“herd” increases year after year with the result that an outbreak occurs.
3. Secular fluctuations refer to changes in morbidity rates over a long period of time, often decades.
Examples are a decreasing trend in occurrence of diphtheria and polio.
Chance in incidence of an infective disease is best judged in relation to incidence pattern in the past as reflected in monthly incidence records for last 5 to 10 years. Mean monthly incidence for each year is calculated at first. An increase through 2 standard deviations serves as a warning and an increase through 3 standard deviation calls for active community control measures. The following terms are used to express various grades of incidence and prevalence of communicable diseases in a community.
Mild incidence: When less than 3 new cases per week are reported in 100,000 population.
Considerable incidence: When 3 to 5 new cases/
100,000/week occur.
Heavy incidence: When 5 to 10 new cases/100,000/
week are reported.
Epidemic: When the number rises to ten or more/
100,000/week.
Outbreak: When there is sudden reporting of a large number of new cases, the population having been absolutely free earlier. Food poisoning and cholera often breakout suddenly.
Endemic: When the infectious agent has taken a foothold in a population which is naturally and partially protected because of occurrence of the disease over a period. Reporting of a few new cases goes on throughout the year. Examples are typhoid, diphtheria and infective hepatitis. When the incidence rises due to changes in the agent, host or environment factors, it becomes an epidemic.
Sporadic: When only isolated cases are reported here and there, now and then. There is no tendency to spread at one place or at one time. This may happen in case of meningitis and poliomyelitis.
Pandemic: When an epidemic appears simultaneously or successively in more than one country, e.g. the influenza epidemic in 1957-58.
Epizootic and enzootic: These terms are used in animals and are comparable to ‘epidemic’ and
‘endemic’ in man. Plague may be epizootic in rats while rabies is enzootic in dogs. Zoonoses are diseases that are transmitted naturally between man and vertebrate animals.13 Examples are plague, rabies, anthrax, brucellosis, hydatid disease, kyasanur forest disease and typhus.
Exotic: This is the label given to a disease imported from outside and not present in the country earlier. For example, if cases of yellow fever occur in India one day, it will be an example of exotic disease.
An epidemiologist may be able to forecast an epidemic on the basis of known agent, host and environment factors. For example, an epidemic of malaria may be expected when there is high rainfall and humidity. An epidemic of AIDS is feared in large parts of the world at present.
SPECTRUM OF DISEASE
The spectrum of disease may be defined as the sequence of events that occur in the human host from the time of contact with the etiologic agent up to the
The spectrum of disease may be defined as the sequence of events that occur in the human host from the time of contact with the etiologic agent up to the