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June 13, 2003 / 52(23);537-540
Multistate Outbreak of Monkeypox --- Illinois, Indiana, and Wisconsin, 2003

CDC has received reports of patients with a febrile rash illness who had close contact with pet prairie dogs and other animals. The Marshfield Clinic, Marshfield, Wisconsin, identified a virus morphologically consistent with a poxvirus by electron microscopy of skin lesion tissue from a patient, lymph node tissue from the patient's pet prairie dog, and isolates of virus from culture of these tissues. Additional laboratory testing at CDC indicated that the causative agent is a monkeypox virus, a member of the orthopoxvirus group. This report summarizes initial descriptive epidemiologic, clinical, and laboratory data, interim infection-control guidance, and new animal import regulations.

As of June 10, a total of 53 cases had been investigated in Illinois, Indiana, and Wisconsin. Of these, 29 (49%) cases were among males; the median age was 26 years (range: 4--53 years). Data were unavailable for sex and age for two and 14 patients, respectively. A total of 14 (26%) patients have been hospitalized, including a child aged <10 years with encephalitis.

Detailed clinical information was available for 30 cases reported in Illinois and Wisconsin. Among these, the earliest reported onset of illness was on May 15 (Figure 1). For the majority of patients (22 [73%]), a febrile illness has either preceded or accompanied the onset of a papular rash (Figure 2); respiratory symptoms (16 [64%]), lymphadenopathy (14 [47%]), and sore throat (10 [33%]) also were prominent signs and symptoms (Table). The rash typically progressed through stages of vesiculation, pustulation, umbilication, and encrustation. Early lesions became ulcerated in some patients. Rash distribution and lesions have occurred on the head, trunk, and extremities; many patients had initial and satellite lesions on palms, soles, and extremities. Rashes were generalized in some patients.

All patients have had contact with animals; however, at least two patients also reported contact with another patient's lesions or ocular drainage. A total of 51 patients reported direct or close contact with prairie dogs (Cynomys sp.), and one patient reported contact with a Gambian giant rat (Cricetomys sp.). One patient had contact with a rabbit (Family Leporidae) that became ill after exposure to an ill prairie dog at a veterinary clinic. Traceback investigations have been initiated to identify the source of monkeypox virus introduced into the United States and have identified a common distributor where prairie dogs and Gambian giant rats were housed together in Illinois. A search of imported animal records revealed that Gambian giant rats were shipped from Ghana in April to a wildlife importer in Texas and subsequently were sold to the Illinois distributor. The shipment contained approximately 800 small mammals of nine different species that might have been the actual source of introduction of monkeypox.

As of June 9, specimens obtained from 10 patients in Illinois, Indiana, and Wisconsin had been forwarded to CDC for testing; nine patients with skin lesions had DNA sequence signatures specific for monkeypox. No skin lesions were observed in one patient who tested negative by polymerase chain reaction. Skin biopsies were available for five patients; four showed orthopox viral antigens by immunohistochemical testing. Skin lesions from four of the 10 patients were evaluated by negative stain electron microscopy, and pox viral particles were found in three patients. Monkeypox specific DNA signatures also were found in a viral isolate derived from lymphoid tissue of a patient's ill prairie dog.

Reported by: J Melski, MD, K Reed, MD, E Stratman, MD, Marshfield Clinic and Marshfield Laboratories, Marshfield; MB Graham, MD, J Fairley, MD, C Edmiston, PhD, KS Kehl, PhD, Medical College of Wisconsin; SL Foldy, MD, GR Swain, MD, P Biedrzycki, MPH, D Gieryn, Milwaukee Health Dept; K Ernst, MPH, Milwaukee-Waukesha Consortium for Emergency Public Health Preparedness, Milwaukee; D Schier, Oak Creek Health Dept, Oak Creek; C Tomasello, Shorewood/Whitefish Bay Health Dept, Shorewood; J Ove, South Milwaukee Health Dept, South Milwaukee; D Rausch, MS, N Healy-Haney, PhD, Waukesha County Health Dept, Waukesha; N Kreuser, PhD, Wauwatosa Health Dept, Wauwatosa; MV Wegner, MD, JJ Kazmierczak, DVM, C Williams, DVM, DR Croft, MD, HH Bostrom, JP Davis, MD, Wisconsin Dept of Health and Family Svcs; R Ehlenfeldt, DVM, Wisconsin Dept of Agriculture, Trade and Consumer Protection; C Kirk, Wisconsin State Laboratory of Hygiene. M Dworkin, MD, C Conover, MD, Illinois Dept of Public Health. R Teclaw, MD, H Messersmith, MD, Indiana State Dept of Health. Monkeypox Investigation Team; MJ Sotir, PhD, G Huhn, MD, AT Fleischauer, PhD, EIS officers, CDC.

Editorial Note:

In 1970, human monkeypox was first identified in the Democratic Republic of the Congo (DRC) in a region where smallpox had been eradicated in 1968 (1). Monkeypox is caused by an orthopoxvirus that clinically resembles smallpox virus but differs both biologically and epidemiologically (2--5). After an incubation period of 7--17 days, the disease is characterized by the onset of a prodrome of fever, headache, backache, and fatigue. The monkeypox rash includes macules, papules, vesicles, pustules, and crusts that evolve in the same stage over 14--21 days, similar to smallpox (6). A major clinical difference between monkeypox and smallpox is pronounced lymphadenopathy in a majority of patients with monkeypox (6). Relatively inefficient person-to-person transmission has been documented for monkeypox, and the case-fatality rate has been approximately 1%--10% in Africa, with higher death rates among young children (2,5,6).

Preliminary findings from these investigations indicate that the primary route of transmission to humans is from close contact with infected mammalian pets. However, the possibility of human-to-human transmission cannot be excluded. CDC has issued interim guidance for infection control, exposure management, monitoring of exposed persons, and duration of isolation procedures in health-care and community settings for patients with suspected monkeypox (http://www.cdc.gov/ncidod/monkeypox/infectioncontrol.htm). Persons seeking medical care with unexplained fever, rash, or prominent lymphadenopathy should be asked about exposure to unusual or exotic pets, especially small mammals such as prairie dogs or Gambian giant rats. If monkeypox infection is suspected, standard, contact, and airborne precautions should be applied in all health-care settings (http://www.cdc.gov/ncidod/hip/ISOLAT/Isolat.htm). Interim guidance for veterinarians and pet owners also are available at http://www.cdc.gov/ncidod/monkeypox/animalguidance.htm. These recommendations are modeled after human infection-control guidelines, with modifications appropriate for veterinary and home settings where airborne precautions might not be feasible. In addition, these guidelines outline the appropriate management of exposed or ill pets to help prevent further transmission of monkeypox among animals.

Introduction of exotic species, such as rodents from Africa, poses a serious public health threat because of the potential of monkeypox virus infection and other nonindigenous pathogens. Serosurveys of various healthy rodents (and nonhuman primates), including Cricetomys emini, captured wild in Africa, have demonstrated orthopoxvirus antibodies (7). Monkeypox virus also has been isolated from a rope squirrel (Funisciurus anerythrus) found with skin lesions in the vicinity of monkeypox cases in DRC (8). Accordingly, pursuant to 42 CFR 71.32(b), CDC is implementing an immediate embargo on the importation of all rodents from Africa (Order Rodentia). In addition, CDC and the Food and Drug Administration, pursuant to 42 CFR 70.2 and 21 CFR 1240.30, are prohibiting the transportation or offering for transportation in interstate commerce, or the sale, offering for sale, or offering for any other type of commercial or public distribution, including release into the environment of prairie dogs and the following rodents from Africa: tree squirrels (Heliosciurus sp.), rope squirrels (Funisciurus sp.), dormice (Graphiurus sp.), Gambian giant pouched rats (Cricetomys sp.), brush-tailed porcupines (Atherurus sp.), and striped mice (Hybomys sp.). States can elect to enact measures to prohibit the importation, sale, distribution, or display of animals that could result in transmission of infectious agents (9,10).

Health-care providers, veterinarians, and public health officials who suspect monkeypox in animals or humans should report such cases to their state and local health departments. CDC requests that reports of suspect cases from state health departments be directed to the CDC Emergency Operations Center, telephone 770-488-7100. Additional information about monkeypox, including an interim case definition, is available at http://www.cdc.gov/ncidod/monkeypox and http://www.cdc.gov/ncidod/monkeypox/casedefinition.htm, respectively.

References

1. Landyl ID, Ziegler P, Kima A. A human infection caused by monkeypox virus in Basankusu Territory, Democratic Republic of the Congo (DRC). Bull WHO 1972;46:593--7.
2. Breman JG. Monkeypox: an emerging infection for humans? In: Scheld WM, Craig WA, Hughes JM, eds. Emerging Infections 4. Washington, DC: ASM Press, 2000:45--76.
3. Shchelkunov SN, Totmenin AV, Babkin IV, et al. Human monkeypox and smallpox viruses: genomic comparison. FEBS Lett 2001;509:66--70.
4. Shchelkunov SN, Totmenin AV, Safronov PF, et al. Analysis of the monkeypox genome. Virol 2002;297:172--94.
5. World Health Organization. Technical Advisory Group on Human Monkeypox: report of a WHO meeting. Geneva, Switzerland, January 11--12, 1999.
6. Jezek ZM, Scczeniowski KM, Paluku M, Putombo M, Grab B. Human monkeypox: clinical features of 282 patients. J Infect Dis 1987;156:293--8.
7. Hutin YJF, Williams RJ, Malfait P, et al. Outbreak of human monkeypox, Democratic Republic of Congo, 1996--1997. Emerg Infect Dis 2001;7:434--8.
8. Khodakevich L, Jezek Z, Kinzana K. 1986 Isolation of monkeypox from a wild squirrel. Lancet 1986;1:98--9.
9. State of Wisconsin, Department of Health and Family Services. Emergency order. Available at http://www.dhfs.state.wi.us/dph_bcd/monkeypox/Response.htm.
10. State of Illinois. Executive order in response to orthopox outbreak. Available at http://www.idph.state.il.us/pdf/ExecutiveOrder14.pdf.

Acknowledgments

This report is based on data contributed by P Wilson, B Grahn, Froedtert Hospital, Milwaukee; PH Hunter, MD, Covenant Medical Group, South Milwaukee; N Sawhney, MD, St. Francis Hospital, Milwaukee; JW Van Dijk, T Wittkopf, Marathon County Health Dept, Wausau; S Coffaro, B Baker, Milwaukee Health Dept; Milwaukee; P Krug, Taylor County Health Dept, Medford; C Quest, Watertown Dept of Public Health, Watertown; R Schroeder Waukesha County Health Dept, Waukesha; S Ahrabi-Fard, MS, T Haupt, MS, Wisconsin Dept of Health and Family Svcs; E Hooker, DVM, S Molina, DVM, HG Smith, DVM, Wisconsin Dept of Agriculture, Trade and Consumer Protection; E Reisdorf, P Shult, PhD, Wisconsin State Laboratory of Hygiene.

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