• 1

    MacNeil A, Reynolds MG, Carroll DS, Karem K, Braden Z, Lash R, Moundeli A, Mombouli JV, Jumaan AO, Schmid DS, Damon IK, 2009. Monkeypox or varicella? Lessons from a rash outbreak investigation in the Republic of the Congo. Am J Trop Med Hyg 80 :503–507.

    • Search Google Scholar
    • Export Citation
  • 2

    Parker S, Nuara A, Buller RM, Schultz DA, 2007. Human monkeypox: an emerging zoonotic disease. Future Microbiol 2 :17–34.

  • 3

    Rimoin AW, Kisalu N, Kebela-Ilunga B, Mukaba T, Wright LL, Formenty P, Wolfe ND, Shongo RL, Tshioko F, Okitolonda E, Muyembe JJ, Ryder RW, Meyer H, 2007. Endemic human monkeypox, Democratic Republic of Congo, 2001–2004. Emerg Infect Dis 13 :934–937.

    • Search Google Scholar
    • Export Citation
  • 4

    Learned LA, Reynolds MG, Wassa DW, Li Y, Olson VA, Karem K, Stempora LL, Braden ZH, Kline R, Likos A, Libama F, Moudzeo H, Bolanda JD, Tarangonia P, Boumandoki P, Formenty P, Harvey JM, Damon IK, 2005. Extended interhuman transmission of monkeypox in a hospital community in the Republic of the Congo, 2003. Am J Trop Med Hyg 73 :428–434.

    • Search Google Scholar
    • Export Citation
  • 5

    Bray M, 2006. Cross-species transmission of poxviruses. Fong C, Alibek K, eds. Emerging Pathogens of the 21st Century. New York: Springer, 127–157.

  • 6

    Ladnyj ID, Ziegler P, Kima E, 1972. A human infection caused by monkeypox virus in Basankusu Territory, Democratic Republic of the Congo. Bull World Health Organ 46 :593–597.

    • Search Google Scholar
    • Export Citation
  • 7

    Fenner F, Henderson DA, Arita I, 1988. Smallpox and Its Eradication. Geneva: World Health Organization.

  • 8

    Tesh RB, Watts DM, Sbrana E, Siirin M, Popov VL, Xiao SY, 2004. Experimental infection of ground squirrels (Spermophilus tri-decemlineatus) with monkeypox virus. Emerg Infect Dis 10 :1563–1567.

    • Search Google Scholar
    • Export Citation
  • 9

    Vorou RM, Papavassiliou VG, Pierroutsakos IN, 2008. Cowpox virus infection: an emerging health threat. Curr Opin Infect Dis 21 :153–156.

    • Search Google Scholar
    • Export Citation
  • 10

    Li Y, Carroll DS, Gardner SN, Walsh MC, Vitalis EA, Damon IK, 2007. On the origin of smallpox: correlating variola phylogenics with historical smallpox records. Proc Natl Acad Sci USA 104 :15787–15792.

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Keeping an Eye on Poxviruses

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  • 1 Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Maryland

In this issue of the American Journal of Tropical Medicine and Hygiene, MacNeil and others describe the use of serologic methods to aid in retrospectively identifying a pustular rash illness that occurred among residents of a group of villages in the Republic of the Congo in 2007.1 On the basis of descriptions of the skin lesions, there were two major candidates for the diagnosis. The first candidiate was chickenpox, which is caused by a highly contagious human-adapted herpesvirus, and is endemic in central Africa, where immunization rates are low. The second candidiate was monkeypox, a zoonosis caused by an orthopoxvirus maintained in local rodents, which usually occurs as single cases, but can also produce short chains of person-to-person transmission.

Although monkeypox has been observed with increasing frequency in the neighboring Democratic Republic of the Congo over the past four decades, it has only been reported once previously in the Republic of the Congo in a 2003 outbreak described by the same group of investigators.24 In the present instance, MacNeil and others found that serum samples from approximately 40 of the villagers showed evidence of recent chickenpox, but their test results also identified three people who may have been exposed to monkeypox virus.

This report reflects the increasing sophistication of efforts to detect the occurrence of poxviral zoonoses, which also include cowpox virus infection. Why is it important to monitor these diseases, which are barely known to most of the public health community? Their relative obscurity in part reflects the fact that, before the eradication of smallpox, vaccination with vaccinia virus largely prevented their occurrence, by cross-protecting against other members of the genus Orthopoxvirus.5 However, now that most of the world’s population has never been vaccinated, there is no longer an immune barrier to keep these agents from crossing over from their reservoir species into the human population.

Monkeypox is the disease of greatest concern because it closely resembles smallpox, but it is less contagious and has a lower case-fatality rate.2 Although it has presumably occurred in central Africa for millenia, monkeypox was only discovered in 1970 during the course of the smallpox eradication campaign in Zaire (the present Democratic Republic of the Congo), when a smallpox-like illness developed in an infant in a rural village that could not be linked to any chain of person-to-person transmission. Because all other members of her family and most of the surrounding population had been vaccinated, it was initially feared that the child had contracted smallpox directly from an animal reservoir, potentially dooming efforts to eradicate the disease. 6,7 However, the agent isolated from her skin lesions proved to be monkeypox virus, which had been discovered 12 years earlier when it caused an outbreak of smallpox-like disease in monkeys in a holding facility in Copenhagen, Denmark.

Field studies over the subsequent decade identified some 150 additional cases of human monkeypox in central and west Africa, principally in Zaire, and indicated that squirrels and perhaps other rodents were the natural reservoir. Because the disease appeared to pose little threat to the local population and none to the outside world, vaccination was halted in Zaire in 1980.7

Almost 30 years later, the incidence of monkeypox in the same region has markedly increased. 2,3 In addition to the waning of vaccine-induced immunity, this increase may reflect enhanced exposure of the local population to viral maintainence hosts because recurrent civil war has forced residents to rely more extensively on the hunting of animals for sustenance. At the same time, the potential has increased for monkeypox to become an urban disease because the movement of rural populations into vast cities lacking all but the most basic medical resources has been accompanied by a growing traffic in bush meat, which could bring infected rodents into city markets. The increasing prevalence of human immunodeficiency virus infection may also lead to more severe disease, because persons lacking cell-mediated immunity are highly susceptible to orthopoxvirus infection. As the incidence of monkeypox increases, each new infection provides the virus with a new opportunity to evolve to a more contagious variant capable of sustained person-to-person transmission.

In addition to the growing threat within its enzootic region, the unexpected monkeypox outbreak in the United States in 2003 showed that the virus is capable of spreading to new animal reservoirs outside central Africa. The epidemic was triggered when rodents imported from Ghana were co-housed with American prairie dogs. The prairie dogs became severely ill, serving as amplifying hosts from which infection spread to their human owners. American ground squirrels are also highly susceptible to the virus, which suggests that the range of New World species that could serve as reservoir hosts could be quite large.8

Another human pathogen, cowpox virus, is also maintained in rodents, across a huge area extending from England to the Ural Mountains. Even more than monkeypox, cowpox virus has demonstrated a remarkable ability to cross species barriers and cause lethal disease in a wide range of mammals from cats to elephants.5 Housecats exposed to wild rodents have been the source of fatal infection for a number of immunodeficient people in Europe over the past two decades, but person-to-person transmission has not yet been observed.9 Given its broad host range, cowpox virus might be capable of becoming established among rodent populations in Africa, Asia, or the Western Hemisphere in the way that the Seoul hantavirus has spread from its original home in East Asia to Rattus species in cities around the world.

Could monkeypox or cowpox virus emerge from its natural reservoir to become a fully human-adapted pathogen, occupying the ecologic niche vacated by the eradication of smallpox? We cannot know the answer, but doubt about the possibility should be tempered by the realization that smallpox itself must once have been a zoonosis. The disease could not have been maintained solely through person-to-person transmission before the rise of large cities, and that variola virus likely evolved from an ancestral rodent-borne agent. 7,10 The cross-species transfer of poxviruses is now a well-established phenomenon, but we are only beginning to learn what factors permit such jumps from species to species. Three decades after the eradication of smallpox, the poxviruses still deserve our close attention.

*

Address correspondence to Mike Bray, Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 1437 Porter Street, Fort Detrick, MD 21702. E-mail: mbray@niaid.nih.gov

Author’s address: Mike Bray, Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 1437 Porter Street, Fort Detrick, MD 21702, E-mail: mbray@niaid.nih.gov.

REFERENCES

  • 1

    MacNeil A, Reynolds MG, Carroll DS, Karem K, Braden Z, Lash R, Moundeli A, Mombouli JV, Jumaan AO, Schmid DS, Damon IK, 2009. Monkeypox or varicella? Lessons from a rash outbreak investigation in the Republic of the Congo. Am J Trop Med Hyg 80 :503–507.

    • Search Google Scholar
    • Export Citation
  • 2

    Parker S, Nuara A, Buller RM, Schultz DA, 2007. Human monkeypox: an emerging zoonotic disease. Future Microbiol 2 :17–34.

  • 3

    Rimoin AW, Kisalu N, Kebela-Ilunga B, Mukaba T, Wright LL, Formenty P, Wolfe ND, Shongo RL, Tshioko F, Okitolonda E, Muyembe JJ, Ryder RW, Meyer H, 2007. Endemic human monkeypox, Democratic Republic of Congo, 2001–2004. Emerg Infect Dis 13 :934–937.

    • Search Google Scholar
    • Export Citation
  • 4

    Learned LA, Reynolds MG, Wassa DW, Li Y, Olson VA, Karem K, Stempora LL, Braden ZH, Kline R, Likos A, Libama F, Moudzeo H, Bolanda JD, Tarangonia P, Boumandoki P, Formenty P, Harvey JM, Damon IK, 2005. Extended interhuman transmission of monkeypox in a hospital community in the Republic of the Congo, 2003. Am J Trop Med Hyg 73 :428–434.

    • Search Google Scholar
    • Export Citation
  • 5

    Bray M, 2006. Cross-species transmission of poxviruses. Fong C, Alibek K, eds. Emerging Pathogens of the 21st Century. New York: Springer, 127–157.

  • 6

    Ladnyj ID, Ziegler P, Kima E, 1972. A human infection caused by monkeypox virus in Basankusu Territory, Democratic Republic of the Congo. Bull World Health Organ 46 :593–597.

    • Search Google Scholar
    • Export Citation
  • 7

    Fenner F, Henderson DA, Arita I, 1988. Smallpox and Its Eradication. Geneva: World Health Organization.

  • 8

    Tesh RB, Watts DM, Sbrana E, Siirin M, Popov VL, Xiao SY, 2004. Experimental infection of ground squirrels (Spermophilus tri-decemlineatus) with monkeypox virus. Emerg Infect Dis 10 :1563–1567.

    • Search Google Scholar
    • Export Citation
  • 9

    Vorou RM, Papavassiliou VG, Pierroutsakos IN, 2008. Cowpox virus infection: an emerging health threat. Curr Opin Infect Dis 21 :153–156.

    • Search Google Scholar
    • Export Citation
  • 10

    Li Y, Carroll DS, Gardner SN, Walsh MC, Vitalis EA, Damon IK, 2007. On the origin of smallpox: correlating variola phylogenics with historical smallpox records. Proc Natl Acad Sci USA 104 :15787–15792.

    • Search Google Scholar
    • Export Citation
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