Human monkeypox is a sporadic zoonotic infection first identified in 1970 from remote rural villages in central and western African rainforest countries, as smallpox disappeared. Clinically, the disease closely resembles ordinary or modified smallpox, but lymphadenopathy is a more prominent feature in many cases, and occurs in the early stage of the disease. Pleomorphism and “cropping” similar to that seen in chickenpox are observed in 20% of patients. The natural history of the disease is unclear; humans, primates and squirrels appear to be involved in the enzootic cycle. The disease affects all age groups; children under 16 have historically constituted the greatest proportion of cases. The case-fatality rate among children not vaccinated against smallpox ranges from 1% to 14%. Smallpox vaccination protects against infection in some instances, and in some others mitigates clinical manifestations; recent studies suggest the protection provided by childhood smallpox vaccination is waning in the general populations at risk since the cessation of smallpox vaccination in the 1980s. Between 1970 and 1994, over 400 cases of monkeypox were reported from western and central Africa; the Democratic Republic of the Congo (DRC; formerly Zaire) accounted for about 95% of reported cases during a 5-year surveillance period from 1981 to 1986. Poor public health infrastructure and other factors complicate accurate case reporting. In the late 1990s, a prolonged outbreak of human monkeypox was recognized in DRC: it has been postulated that lack of vaccination and an epizootic allowed multiple virus transmission events to humans across the species barrier. In 2003, a prolonged and efficient, chain of human-to-human transmission was described, also in DRC.

In the 1980s about 75% of reported cases of human monkeypox were attributable to contact with affected animals; in recent outbreaks it appears that a larger number of cases were attributable to person-to-person contact. The longest chain of person-to-person transmission was 7 reported serial cases, but serial transmission usually does not extend beyond secondary. Epidemiological data suggest a secondary attack rate of about 8%. Most cases have occurred either singly or in clusters in small remote villages, usually in tropical rainforest where the population has multiple contacts with several types of wild animals. Ecological studies in the 1980s point to squirrels (Funisciurus and Heliosciurus), abundant among the oil palms surrounding the villages, as a significant local reservoir host. Maintenance of an animal reservoir and animal contact is required to sustain the disease among humans. Thus, human infection may be controllable by education to limit contact with infected cases and potentially infected animals. A recent (2003) introduction of monkeypox in the USA, related to importation and sale of exotic animals from western Africa as pets, resulted in infection of north American prairie dogs and at least 50 probable and confirmed human cases, mainly among prairie dog owners and animal handlers. Evaluation of the species associated with the shipment of imported animals demonstrated monkeypox virus in terrestrial giant pouched Gambian rats (Cricetomys sp.), squirrels (Funisciurus but not Heliosciurus spp.) and dormice (Graphiurus spp.). A thorough investigation of this outbreak led to the understanding that at least two genetically distinct clades of monkeypox exist, with different human clinical and epidemiologic manifestations. To date, West African clade monkeypox manifests without apparent human-to-human transmission, and without human mortality; whereas the Congo Basin clade is associated with human-to-human transmission and case fatalities historically reported at an average of approximately 10% in unvaccinated persons.

Monkeypox virus is a species of the genus Orthopoxvirus, with biological properties and a genome distinct from variola virus. The 2003 outbreak in the USA clearly demonstrates potential for monkeypox to be a public health threat outside enzootic areas; and there is evidence that disease has also emerged in nature outside of historic “known” enzootic areas. Full evaluation of the ecology, epidemiology, and virology associated with monkeypox outbreaks in endemic areas will enable understanding of prevention and control measures. Currently, due to adverse event profiles and anticipated clinical and epidemiologic risk-benefit ratios, cross-protective prophylactic vaccination with “smallpox vaccine” (fully replicative vaccinia) is not routinely recommended by WHO. Smallpox (vaccinia) vaccination was, however, used as an outbreak response intervention in the USA in 2003. A WHO Technical Advisory Committee on monkeypox has recently recommended continued studies of human monkeypox—in particular, intensified prospective surveillance and ecological studies.

Source: Heymann (Ed.). (2008). Control of Communicable Diseases Manual, 19th edition. Washington, DC: American Public Health Association.

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