New Findings

Tanapox infection is endemic to equatorial Africa and is extremely rare outside Africa. This year, the fifth case of tanapox infection in the United States was reported. A college student acquired the disease while working with orphaned chimpanzees in the Republic of Congo. While most cases (~78%) of tanapox involve a solitary nodule, this patient had two umbilicated nodules which left small scars at the end of the disease course. Tanapox was transmitted most probably through arthropod vectors, the major route of transmission, although direct contact with a lesion was also possible.

The recognition of tanapox is crucial, given increased international travel and the possibility of biologic terrorism. The differential diagnosis in this case included tropical ulcer, poxvirus infection, and cutaneous anthrax amongst others. An accurate diagnosis can have important public health implications, and this report demonstrates that by DNA extraction and PCR, the virus' genome can be identified promptly.

Reference: Dhar, A. "Tanapox infection in a college student" The New England Journal of Medicine 22 January 2004, 350: 361-366

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Tertiary contact vaccinia in a breastfeeding infant

A soldier experienced a primary uptake reaction at the inoculation site after receiving primary smallpox vaccination. Approximately 10 days later, his breastfeeding wife developed vesicles on the areolas of her breasts. Their infant daughter developed a papule on her philtrum two weeks after her mother developed vesicles. This is the first documented case of inadvertent contact vaccinia transmission from mother to infant through direct skin-to-skin and skin-to-mucous membrane contact. This article demonstrates that breastfeeding infants living in close contact with smallpox vaccines are at potential risk for contact vaccinia even if the vaccinee is a third person and not the breastfeeding mother. The report implies that special precautions to prevent secondary transfer to breastfeeding mothers are necessary.

Reference: Garde, V. "Tertiary contact vaccinia in a breastfeeding infant" JAMA 11 February 2004, 291 (6): 725-727

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Human monkeypox: an emerging zoonosis

Monkeypox is a rare zoonosis that can cause illness clinically indistinguishable from smallpox. In the spring of 2003, an outbreak of monkeypox occurred in central USA, thus marking the first occurrence of monkeypox in the western hemisphere. There were 81 reported cases of smallpox in the following states: Kansas, Missouri, Illinois, Indiana, Ohio, and Wisconsin. 40% of the cases were laboratory confirmed for a monkeypox infection. US health officials traced the illnesses to prairie dogs sold by a Milwaukee pet distributor. The Milwaukee distributor obtained the animals from a distributor in Illinois, who had kept the prairie dogs in close contact to infected Gambian giant rats imported from Africa. There were no secondary cases in this outbreak and no fatalities. However, as a result of this outbreak and the suspicion that Gambian rats were the source of the viral infection, the US Department of Health and Human Services (HSS) issued an embargo order on the import of rodents from Africa. HSS also prohibited the distribution, sale, and transport of prairie dogs and six other African rodent species.

Reference: Giulio, D. "Human monkeypox: an emerging zoonosis" The Lancet January 2004, 4: 15-25

Smallpox infections during pregnancy: lessons on pathogenesis

Both vaccinated and unvaccinated women who contact the variola virus during pregnancy suffer much higher mortality rates than nonpregnant women. Acute maternal smallpox is also associated with significant fetal and neonatal mortality. Although smallpox does not have a reservoir, nonpregnant animal models were used in experiments to gather more information on the pathogenesis of smallpox infections. The models revealed that T helper type 1 (TH1) cytokines promote efficient resolution of smallpox infections whereas T helper type 2 (TH2) cytokines enhance viral pathogenesis.

The data from the animal models, combined with recent studies on the immune status in pregnancy, provide insights into the increased pathogenesis of variola during pregnancy. For example, the predominance of TH2 cytokines in nonimmune pregnant women delays the early production of TH1 cytokines, which are crucial for the early control of virus replication. In addition, the TH2 cytokines provide the virus with a significant growth advantage in both the mother and the placenta. The lytic effects of the virus on the placenta and the vertical transmission of lethal quantities of virus to the placenta can lead to the death of the fetus.

References: Hassett, D. "Smallpox infections during pregnancy, lessons on pathogenesis from nonpregrannt animal models of infection" Journal of Reproductive Immunology 10 March 2003, 60: 13-24.

Evaluation of smallpox immunization in the 21st century

In January of 2003 a decision was made to reinstitute smallpox vaccination for selected groups of the US population. Certain questions about the risk of smallpox vaccination arose: was the US population going to be more vulnerable to serious adverse effects of the smallpox vaccine due to an increase in conditions affecting the immune system such as HIV and immunosuppressive drugs? This report evaluates the potential effects of smallpox vaccination on the US population by examining the effects of vaccination on the military.

1. Despite close person-to-person contact following vaccination, the rate of contact transmission was low (43 per million).

2. HIV positive individuals did not experience complications, although only 10 HIV individuals were inoculated

3. Complications differed in primary vs. revaccinated individuals: generalized vaccinia and myopericarditis cases occurred only in primary vaccinees.

Overall, the military study, in which 450,293 military personnel were vaccinated against smallpox, showed that the vaccine produced few serious adverse reactions and is basically safe. Nonetheless, the majority of health care workers declined the vaccine and very few people volunteered to be vaccinated, thus bringing the smallpox vaccination program to a halt. Most recently, the National Institute of Allergy and Infectious Diseases gave a $36.1 million grant to Chimerix to develop a pill that could be used to treat and possibly prevent smallpox infection, as an alternative to the vaccine.

Reference: Wright, M. "Smallpox immunization in the 21st century: the old and the new" JAMA 25 June 2003, 289 (24): 3306-3308