Perpetuation of a virus in nature depends on the maintenance of serial infections, that is, a chain of transmission; the occurrence of disease is neither required nor necessarily advantageous. Indeed, although clinical cases may be somewhat more productive sources of infectious virus than inapparent infections, the latter are generally more numerous and do not restrict the movement of infectious individuals, and thus provide a major mechanism of viral dissemination. As our knowledge of the different features of the pathogenesis, species susceptibility, routes of transmission, and resistance of viruses to the environment has increased, epidemiologists have been able to recognize four different mechanisms (or cycles) by which viruses maintain serial transmission in their host(s): acute self-limiting infections, persistent infections, vertical transmission, and arthropod transmission.
Most viruses have a principal mechanism for survival, but if this mechanism is interrupted, for example, by a sudden decline in population of the host species due to another disease or a short-term climate change, other mechanisms, previously less apparent, may emerge. This should be remembered when relating the epidemiology of a specific disease to particular mechanisms of survival, as proposed in Table 14-3.
An appreciation of the mechanisms for viral perpetuation is valuable in designing and implementing control programs. For example, knowledge that variola virus caused an acute self-limiting infection in which the vast majority produced clinical disease, and that it had no animal host, was important in the successful eradication of smallpox.
The majority of human viral infections fall into the category of acute self-limiting infections. They lack the survival advantages of persistence, vertical transmission, or multiple host species, with or without arthropod transmission. Although optimum transmissibility is crucial, the perpetuation of viruses that cause systemic infections with lifelong immunity is possible only in
Factors Influencing Survival of Viruses in Nature"
Virus family Example
Human parvovirus Human papillomaviruses Human adenoviruses Herpes simplex virus Molluscum contagiosum virus Human enteroviruses Norwalk virus Ross River virus Rubella virus
Dengue viruses Human coronaviruses Mumps virus Rabies virus Influenza A virus Rift Valley fever virus Hantaan virus
Lymphocytic choriomeningitis virus
Large population, virus stable Persistent in chronic legions, virus stable Persistent infection; virus stable Persistent infection; recurrent infectivity Persistent in chronic lesions, virus stable Large population; ?antigenic drift Large population; virus stable Zoonosis; arthropod-borne Large population, virus persistent after congenital infection
Large population'', arthiopod-borne Large population Large population
Zoonosis, dead-end infection in humans Large population, antigenic drift and shift Zoonosis; aithropod-borne Zoonosis; persistent in rodents Zoonosis, persistent in rodents Large population, 'antigenic shift Persistent, recurrent infectivity; vertical transmission
Unless they produce persistent infections, all nonzoonotic viruses require large human populations, peipetition is also favored by heat stability of the virion
'n rural Aftrica, may also persist in small human populations, as a zoonotic disease, with monkeys as reservoir hosts large, relatively dense populations. Viruses that cause superticial mucosal infections with short-lived immunity may survive in somewhat smaller populations, and their capacity to survive may be enhanced by antigenic drift (see below).
Several factors contribute to optimal transmission of viruses. Some relate to properties of the virion itself, others to the extent and nature of shedding from the body, and others to social interactions. Enveloped viruses infecting mucosal surfaces bud from the apical surface of epithelial cells to maximize shedding into the outside world. Obviously, human-to-human transmission will be enhanced by shedding of high liters of virus containing a high proportion of infectious virions. Respiratory viruses tend to be shed over a relatively brief period (a few days) but are expelled in high concentration as an aerosol generated by explosive sneezing or coughing, thus ensuring transmission to dose contacts. Enteric viruses are also shed in large numbers but usually for a longer period (a week or more) in feces, which may contaminate hands, fomites, food, and water. Enveloped respiratory viruses are relatively labile, especially during summer or in the tropics year-round. In contrast, most enteric viruses are nonenveloped and may survive for several days or weeks in water or dust, or on fomites, as may poxviruses, adenoviruses, papillomaviruses, and hepatitis viruses.
Many viral infections show pronounced seasonal variations in incidence. In temperate climates, arbovirus infections transmitted by mosquitoes or sandflies occur mainly during the summer months, when vectors are most numerous and active. Infections transmitted by ticks occur most commonly during the spring and early summer months. More interesting, but also more difficult to explain, are the variations in seasonal incidence of infections in which humans are the only host animals.
Table 14-4 shows the season of maximal incidence of several human respiratory, enteric, and generalized infections. In temperate climates most respiratory infections are most prevalent in winter or to a lesser extent in spring or autumn. Annual winter outbreaks of severe respiratory syncytial virus infections in infants are a feature of communities in temperate climates, the major impact of each epidemic lasting for only 2 or 3 months (see Fig. 14-1); epidemics of influenza also occur almost exclusively in the winter, but they vary greatly in extent from year to year (see Fig. 31-2). Many of the exanthemata of childhood transmitted by the respiratory route peak in the spring. Among enteric viruses, infections with enteroviruses (like most enteric bacterial infections) are maximal in the summer, but caliciviruses show no regular seasonal patterns, rotaviruses tend to be more prevalent in winter. Infections with the herpesviruses HSV, cytomegalovirus, and EB virus, which are transmitted by intimate contact with saliva and other bodily secretions, show no seasonal variations in incidence, nor do other sexually transmitted diseases. The patterns shown in Table 14-4 are found in both the northern and southern hemispheres Different factors probably affect seasonality in the tropics, where wet and dry seasons tend to replace summer and winter. The peak incidence of
Season of Maxima) Incidence of Specifically Human Viral Infections m Temperate Climates"
Type ol infection
Respiratory Adenoviruses Rhinoviruses Influenza Coronaviruses Respiratory syncytial virus Parainfluenza 1 and 2 Parainfluenza 3 Enteric Enteroviruses Rotaviruses Caliciviruses Generalized Rubella Measles Mumps Varicella Hepatitis B
Herpes simplex I and 2 Cy tomega lo v irus Epstein-Barr virus Most arboviruses
" Seasonality is often different in tropical climates, whre there is little temperature fluctuation between summer and winter, but the occurrence of some infectious diseases is influenced by "wet" and "dry" seasons.
measles and chickenpox is lafe in the dry season, with an abrupt fall when the rainy season begins, whereas influenza and rhinovirus infections reach a peak during the rainy season.
Both biological and sociological factors may play a role in these seasonal variations. Measles, influenza, and vaccinia viruses survive in air better at low rather than high humidity, whereas polioviruses, rhinoviruses, and adenoviruses survive better at high humidity All survive better, in aerosols, at lower temperatures. These situations correspond with conditions prevalent during the seasons when infections due to these viruses are most prevalent. It has also been suggested that there may be seasonal changes in the susceptibility of the host, perhaps associated with changes in nasal and oropharyngeal mucous membranes, such as drying as a result of smoke, central heating, or air conditioning.
Seasonal differences in social activities may also markedly influence the opportunities for transmission of viruses, especially by the respiratory route. Although experience in the Arctic and Antarctic show that cold weather alone is not enough to cause "colds" and other respiratory infections, the crowding into restricted areas and ill-ventilated vehicles and buildings that occurs in temperate climates in winter promotes the exchange of respiratory viruses. In places subject to monsoonal rains, the onset of the rains early in summer is accompanied by greatly reduced movement of people, both in daily affairs and to lairs and festivals. While this may reduce the opportunity for exchange of viruses with those from other villages, confinement to smoke-filled huts maximizes the opportunity for transfer of respiratory viruses within family groups.
Population size and density play a role in perpetuation that depends in the main on whether the virus produces acute self-limiting or persistent infections. fn general, survival of viruses that produce acute self-limiting infections requires that the susceptible host population should be large and relatively dense. Such viruses may disappear from a population because they exhaust the potential supply of susceptible hosts as they acquire immunity to reinfection. Persistent viruses, on the other hand, may survive in very small populations, sometimes by spanning generations. Depending on the duration of immunity and the pattern of virus shedding, the critical community size varies considerably with different viruses. The principle can be exemplified by two common infections of children, measles and chickenpox.
Measles is a cosmopolitan disease that is characteristic in this respect of the generalized viral infections of childhood, like rubella, mumps, and poliomyelitis. Persistence of the virus in a community depends on a continuous supply of susceptible subjects. With an incubation period of about 12 days, maximum viral excretion for the next 6 days, and solid immunity to reinfection, between 20 and 30 susceptible individuals would need to be infected in series to maintain transmission for a year. Because, for a variety of reasons, nothing like such precise one-to-one transmission occurs, many more than 30 susceptible persons are needed to maintain endemicity. Analyses of the incidence of measles in large cities and in island communities have shown that a population of about 500,000 persons is needed to ensure a large enough annual input of new susceptibles, provided by the annual incidence of births, to maintain measles indefinitely as an endemic disease.
Because infection depends on close contact, the duration of epidemics of measles is correlated inversely with population density. If a population is dispersed over a large area, the rate of spread is reduced and the epidemic will last longer, so that the number of susceptible persons needed to maintain endemicity is reduced. On the other hand, in such a situation a break in the transmission cycle is much more likely. If a large proportion of the population is initially susceptible, the intensity of the epidemic builds very quickly. Attack rates were almost 100% in an epidemic of measles in southern Greenland in 1951, which ran through the entire population in about 40 days before running out of susceptibles and disappearing completely. Such virgin-soil epidemics in isolated communities may have devastating consequences, due rather to lack of medical care and the disruption of social life than to a higher level of genetic susceptibility or abnormal virulence o( the virus.
The peak age incidence of measles depends on local conditions of population density and the chance of exposure. In large urban communities, before the days of vaccination, epidemics occurred every 2-3 years, exhausting most of the currently available susceptible persons, and epidemics on a continental scale used to occur annually in the United States. Although newborns provide the input of susceptibles each year, the age distribution of cases in unvac-cinated communities is primarily that ol children just entering school, with a peak of secondary cases (family contacts) about 2 years old. The cyclic nature of measles outbreaks is determined by several variables, including the buildup of susceptibles, introduction of the virus, and environmental conditions that promote viral spread. Both the seasonality of infectivity (Table 14-4 and the occurrence of school holidays affect the epidemic pattern. Following the widespread introduction of immunization programs the epidemiology of measles has changed dramatically (see Chapter 28).
Although chickenpox is also an acute exanthema in which infection is followed by lifelong immunity to reinfection, it requires a dramatically smaller critical community size for indefinite persistence of the disease: less than 1000, compared with 500,000 for measles. This is explained by the fact that varicella virus, after being latent for decades, may be reactivated and cause zoster (see Chapter 10). Although zoster is not as infectious as chickenpox itself (secondary attack rates of 15%, compared with 70% for varicella), it can, in turn, produce chickenpox in susceptible children and grandchildren.
Immunity acquired from prior infection or from vaccination plays a vital role in the epidemiology of viral diseases. In most generalized infections, acquired immunity, attributable largely to circulating IgG antibody, appears to be lifelong. This occurs even in the absence of repeated subclinical infections, as evidenced by studies of measles and poliomyelitis in isolated populations. In a paper on measles in the Faroe Islands written in 1847, Panum demonstrated that the attack rate was almost 100% among exposed susceptibles, but that immunity conferred by an attack of measles experienced during an epidemic 65 years earlier remained solid in spite of no further introduction of the virus to the islands in the interim.
The situation is different with viral infections that are localized to mucosal surfaces such as the respiratory tract, since mucosal immunity is relatively short-lived. A large number of serotypes of rhinoviruses and a few serotypes of corona viruses and enteroviruses can produce superficial infections of the mucous membrane of the upper respiratory tract. The seemingly endless succession of common colds suffered by urban communities reflects a series of minor epidemics, each caused by a different serotype of one of these viruses. Protection against reinfection is due mainly to antibodies in the nasal secretions, primarily IgA. Although short-lived type-specific immunity does occur, there is no intertypic cross-immunity, hence the convalescent individual is still susceptible to all other rhinoviruses and coronaviruses Most persons contract between two and four colds each year.
In urban communities young children appear to be particularly important as the persons who introduce rhinoviruses into families, mainly because they bring back viruses from school and from neighbors' children and partly because they often shed larger amounts ol virus than adults. A feature of rhino-virus infection that had not been observed previously emerged from family studies, namely, prolonged shedding of virus for up to 3 weeks, long after the acute symptoms have subsided. The epidemiology of coronaviruses, another important cause of colds, is rather similar; however, there are only a few serotypes, and they tend to produce colds in winter, and in adults rather than children.
Epidemiologic observations on isolated human communities illustrate the need for a constant supply of susceptible subjects or antigenically novel viral serotypes to maintain respiratory diseases in nature, and the importance of repeated (often subclinical) infections in maintaining herd immunity. Explorers, for example, are notably free of respiratory illness during their sojourn in the Arctic and Antarctica, despite the freezing weather, but invariably contract severe colds when they again establish contact with other humans.
In influenza, respiratory tract immunity due to IgA selects for mutants displaying antigenic variation in the hemagglutinin (antigenic drift), leading to the emergence of new strains that can infect individuals immune to infection with previous strains of that subtype, as discussed in Chapter 4. Antigenic drift may also account for the evolution of the numerous antigenic types of rhinoviruses, enteroviruses, and other viruses that cause superficial infections confined largely to mucosal surfaces.
The more radical changes known as antigenic shift, and attributable to genetic reassortment in influenza A virus, occur much less frequently but constitute a major antigenic change that may cause widespread epidemics in a world population with no immunity (Chapters 4 and 31). As genetic reassortment can also occur in rotaviruses and there are rotaviruses affecting several animal hosts, antigenic shift may also occur with these viruses, although this has yet to be demonstrated under natural conditions.
Persistent viral infections (see Chapter 10), whether or not associated with episodes of clinical disease, play an important role in the perpetuation of many viruses. Infection with members of certain viral families is characteristically associated with continuous or intermittent shedding (Table 14-5). In the extreme case, shedding by a persistently infected person can reintroduce
Viral Infections of Humans Associated with Persistent Viral Excretion family
Ht'r/windue Epstein-Barr virus, cytomegalovirus,
Intermittent shedding in saliva, genital secretions, milk
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