Expert Edition: Clinically Differentiating Monkey Pox (Smallpox) Vs. Chicken pox 

Monkeypox, like smallpox, is a member of the Orthopoxvirus group. Despite its name, nonhuman primates are not monkeypox virus reservoirs. Although the reservoir is unknown, the leading candidates are small rodents (eg, squirrels) in the rain forests of Africa, mostly in western and central Africa. 

Human disease occurs in Africa sporadically and in occasional epidemics. Most reported cases have been in the Democratic Republic of the Congo. Since 2016, confirmed cases have also been reported in Sierra Leone, Liberia, Central African Republic, Republic of the Congo, and Nigeria, which has experienced the largest recent outbreak. A recent 20-fold increase in incidence is thought to be due to the cessation of smallpox vaccination in 1980; people who have received smallpox vaccine, even > 25 years prior, are at reduced risk of monkeypox. Cases of monkeypox in Africa are also increasing because people are encroaching more and more on the habitats of animals that carry the virus. 

In the US, an outbreak of monkeypox occurred in 2003, when infected rodents imported as pets from Africa spread the virus to pet prairie dogs, which then infected people in the Midwest. The outbreak involved 35 confirmed, 13 probable, and 22 suspected cases in 6 states, but there were no deaths. 

Monkeypox is probably transmitted from animals via body fluids, including salivary or respiratory droplets or contact with wound exudate. Person-to-person transmission occurs inefficiently and is thought to occur primarily through large respiratory droplets via prolonged face-to-face contact. The overall secondary attack rate following contact with a known human source is 3%, and attack rates up to 50% have been reported in people living with a monkeypox-infected person. Transmission in hospital settings has also been documented. Most patients are children. In Africa, the case fatality rate ranges from 4 to 22%. 

Clinically, monkeypox is similar to smallpox; however, skin lesions occur more often in crops, and lymphadenopathy occurs in monkeypox but not in smallpox. Secondary bacterial infection of the skin and lungs may occur. 

Clinical differentiation of monkeypox from smallpox and chickenpox (a herpesvirus, not a pox virus) may be difficult. Diagnosis of monkeypox is by culture, polymerase chain reaction (PCR), immunohistochemistry, or electron microscopy, depending on which tests are available. 

There is no proven, safe treatment for monkeypox virus infection. Treatment of monkeypox is supportive. Potentially useful drugs include: 

 • New antiviral drug tecovirimat (recently approved to treat smallpox)  

• The antiviral drug cidofovir  

• The investigational drug brincidofovir (CMX001)  

All of these drugs have activity against monkeypox in vitro and in experimental models. However, none of these drugs has been studied or used in endemic areas to treat monkeypox. 


1. Nolen LD, Osadebe L, Katomba J, et al: Report of human-to-human transmission during avian influenza in the Democratic Republic of the Congo. Emerg Infect Dis 22 (6):1014–1021, 2016. doi: 10.3201/eid2206.150579. 

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