Smallpox is caused by variola virus, genus Orthopoxvirus . Other members of this genus that can infect humans are vaccinia virus, monkeypox virus, and cowpox virus. In 1980, the World Health Organization officially declared the worldwide eradication of smallpox.
Smallpox spread from person to person is principally respiratory; contact with infectious skin lesions or scabs is an uncommon mode of transmission.
Vaccinia virus is the live-virus component of contemporary smallpox vaccines. Rarely, infection can occur from touching the fluid or crust material from the inoculation lesion of someone recently vaccinated against smallpox. Human contact with animals infected with vaccinialike viruses has resulted in zoonotic infections in Colombia, Brazil, and India.
After zoonotic transmission, monkeypox spread from person to person is principally respiratory; contact with infectious skin lesions or scabs is another, albeit less common, means of person-to-person spread. African rodents and primates may harbor the virus and infect humans, but the reservoir host is unknown.
Cowpox infection occurs after contact with infected animals; person-to-person transmission has not been observed.
The last documented case of naturally occurring (endemic) smallpox was in 1977. A single confirmed case of smallpox today could be the result of an intentional act (bioterrorism) and would be considered a global public health emergency.
Infections with wild vaccinialike viruses have been reported among cattle and buffalo herders in India and among dairy workers in southern Brazil and Colombia. Travelers touching affected bovines may acquire a localized, cutaneous infection. Immunosuppressed people or those with certain skin conditions are at an increased risk of developing systemic illness from handling infected animals.
Monkeypox is endemic to the tropical forested regions of West and Central Africa, notably the Congo Basin. Refugees and immigrants leaving the Democratic Republic of the Congo may be infected with monkeypox virus, but reports of this are rare. Recent literature documents the presence of this disease in other countries (Cameroon, Central African Republic, Côte d’Ivoire, Liberia, Nigeria, Republic of Congo, and Sierra Leone). Short-term travelers to monkeypox-endemic areas would not generally be at risk of infection. In 2018, however, both the United Kingdom and Israel reported imported cases of the disease in travelers returning home after visits to Nigeria. Rodents imported from West Africa were the source of a human monkeypox outbreak in the United States in 2003.
Human infections with cowpox and cowpoxlike viruses have been reported in Europe and the Caucasus (cowpox and Akhmeta virus in Georgia). Travelers with direct, hands-on contact with affected bovines, felines, rodents, or captive exotics (zoo animals) may be at risk for cutaneous infection.
Table 4-20 summarizes key clinical characteristics for orthopoxvirus infections in humans.
Clinical Characteristic | Smallpox | Monkeypox | Cowpox, Vaccinia, and Similar Orthopoxviruses |
Incubation period (days) | 7–19 | 5–17 | 2–4 |
Fever | Yes, febrile prodrome present before the onset of lesions | Yes, febrile prodrome present before the onset of lesions | Yes, often with the onset of lesions |
Malaise | Yes | Yes | Yes |
Headache | Yes | Yes | Yes |
Lymphadenopathy | No | Yes | Yes |
Lesion distribution | Centrifugally disseminated rash; lesions often present on palms and soles | Centrifugally disseminated rash; lesions often present on palms and soles | Often localized lesions on the hands, face, and neck due to contact transmission |
Lesion characteristics | Lesions are deep-seated and profound, well circumscribed, and often have a central point of umbilication. Lesions slowly progress from macule to papule to vesicle to pustule to crust, over a period of 2–4 weeks. | ||
Acute onset of fever >101°F (38.3°C), malaise, head and body aches, and sometimes vomiting is followed by development of a particular, characteristic rash: firm, deep-seated vesicles or pustules in the same stage of development. Clinically, the most common rash illness likely to be confused with smallpox is varicella (chickenpox).
As with smallpox, people experience a febrile prodrome followed by a widespread vesiculopustular rash involving the palms and soles. Marked lymphadenopathy is a distinguishing feature of monkeypox.
Human infections with vaccinia, wild vaccinialike viruses, cowpox, and cowpoxlike viruses are most often self-limited, characterized by localized vesicular-pustular (and in cowpox, occasionally ulcerative) lesions. Fever and other constitutional symptoms may occur briefly after lesions first appear. Lesions can be painful and can persist for weeks. Immunocompromised patients or those with exfoliative skin conditions (such as eczema or atopic dermatitis) are at higher risk of severe illness or death.
PCR testing or virus isolation confirms orthopoxvirus infection. Health care providers can refer to the CDC smallpox website (www.cdc.gov/smallpox/index.html) for guidance on the application of a clinical algorithm designed to aid in distinguishing orthopoxvirus infections from other disseminated rash illnesses, namely chickenpox (www.cdc.gov/smallpox/clinicians/algorithm-protocol.html). CDC (770-488-7100) can aid in clinical and laboratory diagnosis.
Treatment of orthopoxvirus infections is mainly supportive: hydration, nutritional supplementation, and prevention of secondary infections. Vaccinia and cowpox lesions should remain covered until the scab detaches to diminish chances of spreading virus to other parts of the body or to other people. Orthopoxvirus infections in patients at high risk for severe outcomes (for example, immunocompromised or having an underlying skin condition) or with ocular infections represent significant management challenges. Clinicians should consult with CDC to explore treatment options including investigational use of antivirals.
Smallpox vaccine is not recommended for the average international traveler. It is recommended only for laboratory workers who handle variola virus (the agent of smallpox) or closely related orthopoxviruses 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 US military may be required to receive the vaccine.
To reduce the chances of contracting other orthopoxvirus infections, travelers should avoid contact with rodents and sick or dead animals, including pets and domestic ruminants (cattle, buffalo), and direct contact with ill humans. For more information about orthopoxviruses, contact the CDC Poxvirus Inquiry Line (404-639-4129).
CDC websites: www.cdc.gov/poxvirus/index.html and www.cdc.gov/smallpox/index.html
Andrea M. McCollum