Monkeypox in Wisconsin!

Abstract & Commentary

Synopsis: Health officials in Wisconsin have confirmed 4 cases of monkeypox in the Milwaukee area in what is believed to be the first outbreak of the disease in the Western Hemisphere.

Source: http://www.cdc.gov/ncidod/monkeypox.

Another 18 people in Milwaukee are suspected of having monkeypox which public health authorities suspect was passed to humans by prairie dogs sold by a local pet distributor. This distributor had gotten his prairie dogs from an Illinois distributor who had housed prairie dogs with an ill Gambian rat, another popular rodent pet. A potential 33 contacts are being monitored in Illinois and Indiana. All cases had direct or close contact with a recently purchased prairie dog.

Comment by Michele Barry, MD, FACP

Monkeypox is an orthopoxvirus related to smallpox and has a clinical presentation often indistinguishable from smallpox. Onset of illness in the 4 confirmed US human cases began with prodromal fever, headache, myalgias, and drenching sweats. Roughly one-third had nonproductive cough. This prodrome was followed 1-10 days later by the development of a papular rash that went through typical stages of vesiculation, pustulation, umbilication, and crusting. All patients reported contact with prairie dogs, most of which were sick. Illness in prairie dogs was frequently reported as beginning with blepharo-conjunctivitis progressing to nodular lesions and, in some cases, death.

On the basis of these preliminary cases, CDC recommends:

1. Avoiding contact with ill prairie dogs or Gambian giant rats;

2. Physicians should consider monkeypox in persons with fever, cough, headache, rash, or lymph node enlargement after contact with prairie dogs or Gambian giant rats;

3. Using hand hygiene and infection control (N95 mask, gown, glove, eye goggles, negative pressure room) for any suspected case;

4. Submission of all specimens should follow smallpox laboratory precautions and guidelines. http://www.bt.cdc.gov/agent/smallpox/lab-testing/index.asp.

Monkeypox was first described in 1959 as a primate infection in a Danish laboratory and subsequently was determined to be the cause of 8 additional laboratory monkey outbreaks between 1958 and 1968. In 1970, the first human case was identified in a tropical rain forest village in the Democratic Republic of the Congo (formerly Zaire). Between 1970 and 1995, more than 400 human cases were detected primarily in the Democratic Republic of the Congo. The cases were scattered primarily among people who trapped or consumed ground squirrels, but in a few instances larger outbreaks in villages raised the question of human-to-human transmission. Case fatality has ranged from 2% to 10% in some of the larger outbreaks.

Among the best field studies of human cases was the 1981-1986 outbreak of 338 cases of monkeypox occurring in 17 health zones of 3 regions of then Zaire. Primary infection was mostly related to trapping, eating, or contact with ground squirrels. Secondary attack rate was studied in households. Only 10% of 431 unvaccinated household contacts who lived in poorly ventilated huts came down with disease, and almost all were children who had not received smallpox vaccination due to the discontinuation of the smallpox vaccination program. Having had smallpox vaccination was felt to have conferred an 85% protection rate. By contrast, smallpox can have a 30% mortality rate with a secondary attack rate of 70% in unvaccinated hosts. The epidemic potential of monkeypox to humans in the post-smallpox vaccination era was calculated after these field studies and felt not to be an indication for reintroducing smallpox vaccination; chains of transmission were felt to arrest themselves easily with food, hygiene, and risk reduction practices such avoiding contact with dead or diseased rodents, monkeys or ill patients.

Monkeypox, like smallpox, has an incubation period of 12 days with a range of 7-17 days. A 2-5 day period of high fever, malaise, and headache is followed by a maculopapular rash appearing first on the mucosa of the mouth, pharynx, face, and forearms with eventual spread to trunk and legs. The rash of monkeypox is indistinguishable from smallpox; however patients exhibit prominent lymphadenopathy, which is less common in smallpox. Within 1-2 days, the rash becomes vesicular and then pustular and crusts begin to form on the eighth or ninth day. Palms and soles can be involved. Crops of monkeypox like early lesions of smallpox are synchronous and always found at the same stage of development, unlike varicella lesions, which are often found at different stages of development.

The principal distinguishing characteristic of monkeypox from smallpox is the temporary enlargement of lymph nodes, which are present in 86% of unvaccinated people. This lymphadenopathy is most often generalized, but localized lymphadenopathy can also be seen. Nodes are firm and often tender. They appear shortly after the onset of prodromal fever, rarely 1-2 days after onset of rash. Secondary infection of pox lesions, abscess formation in nodes and broncho-pneumonia may cause morbidity and mortality.

The methodology for laboratory diagnosis of poxvirus often requires PCR to distinguish orthopoxvirus species since the 4 orthopoxviruses that infect humans (variola, vaccinia, cowpox, and monkeypox) cannot be readily differentiated from one another in most cell cultures. Recovered patients exhibit high titers of neutralizing hemagglutination inhibiting and complementing fixing antibodies, but cross-absorption studies are required to identify the species. Scientists in Wisconsin recovered viral isolates from a patient and a prairie dog, then demonstrated a poxvirus by electron microscopy. PCR and immunohistochemical studies done at CDC confirmed the orthopoxvirus to be monkeypox.

There is no specific treatment for monkeypox, but the antiviral drug cidofovir has been promising in laboratory studies. Smallpox vaccine has been reported to reduce the risk of monkeypox among previously vaccinated persons in Africa. CDC is assessing both a potential role for postexposure use of smallpox vaccine, as well as the therapeutic use of the antiviral cidofovir.

References

1. Fine P, et al. The transmission of potential of monkeypox virus in human populations. Int J Epidemiol. 1988;17:643-650.

2. Hutin Y, et al. Outbreak of human monkeypox, Democratic Republic of Congo, 1996-1997. Emerg Infect Dis. 2001;7(3):434-438.

3. Breman J, Henderson D. Poxvirus dilemmas—monkeypox, smallpox, and biologic terrorism. N Engl J Med. 1996;339(8):556-559.

Dr. Barry is Professor of Medicine; Co-Director, Tropical Medicine and International Travelers' Clinic, Yale University School of Medicine.