Noelle A. Benzekri, Mary G. Reynolds

Infectious Agent

Smallpox is caused by variola virus, a member of the Poxvirus family, genus orthopoxvirus. Other members of this genus known to cause infection in humans are vaccinia virus, cowpox virus, and monkeypox virus.

As a result of the Smallpox Eradication Program (1967–1980), smallpox was declared eradicated by the WHO in 1980.

Mode of Transmission

• Infection with vaccinia virus is a rare adverse event that can occur among social contacts of persons recently vaccinated for smallpox
• Other orthopoxvirus infections result largely from zoonotic exposures.
• Monkeypox virus infection can occur following contact with infected animals or from persons who are currently ill with monkeypox.
  • Multiple species of African rodents and primates are known to carry the virus, although the precise reservoir host for monkeypox virus remains unknown.
  • Human-to-human transmission occurs by way of large respiratory droplets and contact with lesions or infected materials.

Occurrence

• The last reported case of endemic smallpox occurred in Somalia in 1977, and the last reported case of laboratory-acquired smallpox occurred in the United Kingdom in 1978.
• Infections with wild vaccinia-like viruses have been reported among dairy workers in Brazil.
• Human infections with cowpox virus have been reported in Europe.
• Monkeypox virus is endemic in tropical forested regions of Africa, notably the Congo Basin.

Risk for Travelers

• Smallpox is not considered a risk for international travelers.
• International travelers may be at risk of infection with other orthopoxviruses.
  • Both infections with wild, vaccinia-like viruses and human infections with cowpox virus are rare, although those who are immunocompromised may have a higher risk.

Clinical Presentation

• Infections with wild vaccinia-like viruses and human infections with cowpox virus are most often self-limited, characterized by localized lesions.
• Monkeypox virus causes illness clinically identical to smallpox.
  • Results in fever, marked lymphadenopathy, and widespread vesiculopustular rash involving the palms and soles.
  • Monkeypox case-fatality rate is approximately 10%.

Diagnosis

Orthopoxvirus infection is confirmed by PCR or virus isolation.

Treatment

• Treatment is mainly supportive, to include prevention of secondary infections.
• To prevent human-to-human transmission, patients should be isolated and cared for by someone who has received the smallpox vaccine.

Preventive Measures for Travelers

• Smallpox vaccine is not recommended for international travelers.
  • Live vaccinia virus is the main component of the smallpox vaccine.
  • Because of the elimination of smallpox, routine smallpox vaccination ceased worldwide in 1980.
  • Smallpox vaccination is recommended only for laboratory workers who handle variola virus (the agent of smallpox) or viruses closely related to variola virus, and health-care and public health officials who would be designated first-responders in the event of an intentional release of variola virus. In addition, members of the U.S. military may be required to receive the vaccine.
• Travelers are advised to avoid contact with rodents and sick or dead animals.
• No vaccines for other orthopoxviruses are available for travelers.
• No drugs for preventing infection are available.

For more information about monkeypox and other orthopoxviruses, contact the CDC Poxvirus Inquiry Line: 404-639-4129.

References

1. Rotz LD, Dotson DA, Damon IK. Vaccinia (smallpox) vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2001. MMWR Recomm Rep. 2001;50(RR-10):1–25.
2. Nagasse-Sugahara TK, Kisielius JJ, Ueda-Ito M., et al. Human vaccinia-like virus outbreaks in São Paulo and Goiás States, Brazil: virus detection, isolation and identification. Rev Inst Med Trop São Paulo. 2004;46(6):315–22.
3. Vorou RM, Papavassiliou VG, Pierroutsakos IN. Cowpox virus infection: an emerging health threat. Curr Opin Infect Dis. 2008;21(2):153–6.
4. CDC. Human monkeypox—Kasai Oriental, Democratic Republic of Congo, February 1996–October 1997. MMWR Morb Mortal Wkly Rep. 1997;46:1168–71.
5. Learned LA, Reynolds MG, Wassa DW, et al. Extended interhuman transmission of monkeypox in a hospital community in the Republic of Congo, 2003. Am J Trop Med Hyg. 2005;73:428–34.
6. Reynolds mg, Davidson WB, Curns AT, et al. Spectrum of infection and risk factors for human monkeypox, United States, 2003. Emerg Infect Dis. 2007;13:1332–9.
7. Damon IK, Roth CE, Chowdhary V. Discovery of monkeypox in Sudan. N Engl J Med. 2006;355(9):962–3.
8. Levine RS, Peterson AT, Yorita KL, et al. Ecological niche and geographic distribution of human monkeypox in Africa. PLoS ONE. 2007;2(1):e176.