John Bartlett, MD

Disclosures

July 23, 2003

In This Article

Monkeypox Review

Monkeypox was initially described as a poxvirus in monkeys in 1958, and it was first described as a human pathogen in 1970. Ground squirrels and rodents are the principal natural hosts. This virus may cause a mild disease in monkeys, but the name is now viewed as a misnomer. The disease in humans and the animal reservoir has been restricted to West and Central Africa until May 16, 2003, when the first case was noted in a 3-year-old child in Wisconsin. This case was traced to a recently purchased prairie dog that apparently had acquired the infection from animals purchased from Ghana in April by a Texas importer, who sold prairie dogs and Gambian giant rats to a distributor in Illinois. Through June 18, 2003, there were 93 cases of monkeypox in the United States including Wisconsin (44 cases), Indiana (24), Illinois (19), Ohio (4), Kansas (1), Missouri (1), and New Jersey (1).[27] Analysis of the first 53 cases showed all 50 had contact with prairie dogs that were purchased from Phil's Pocket Pets of Villa Park, Illinois. Records from this dealer indicate 200 prairie dogs were purchased, 63 were sold to identified customers, 70 were euthanized, and 67 are as yet not accounted for.[28] The implicated shipment to the Texas importer included 800 small mammals representing 9 species.[29]

On Mother's Day (May 11, 2003), a 28-year-old woman from Wisconsin received 2 prairie dogs at a pet swap meet to add to her pet menagerie that included 13 cats, 7 horses, 4 goats, and 3 donkeys. On May 13, one of the prairie dogs bit her daughter on a right finger and left palm. On May 15, the prairie dog was sick with skin lesions and drainage from the nose and eyes. On May 16, the 3-year-old daughter developed fever. On May 20, the bite sites were whitish, she had a cough, and then developed a diffuse vesicular rash with ocular drainage. She was hospitalized on May 22 and noted to have the above findings and an enlarged submandibular gland. On May 27, the 28-year-old mother developed a vesicular lesion at a cat scratch site on the right hand and then developed disseminated lesions. On May 31, the father developed sweats, multiple skin lesions, and axillary adenopathy. On June 5, the family was seen in the Marshfield Clinic and all were then well. Orthopoxvirus was seen on biopsy of the skin lesion in the mother, the submandibular gland in the daughter, and from necropsy specimens from the prairie dog; cultures from these specimens were also positive for an orthopoxvirus. In tracing the epidemiology, it appears that monkeypox-infected Gambian giant rats were imported in Texas, sold to an animal distributor in Illinois, and distributed through 1 or 2 pet stores and pet swap meets in Wisconsin.

Monkeypox is a member of the orthopoxvirus group that includes smallpox virus, vaccinia, and cowpox. As noted, it has been identified exclusively in Central and West Africa until these recent cases in the United States.

  • Source: The usual source is a bite or direct contact with an infected mammal, with transmission via blood, body fluid, or lesions; less common is person-to-person (see below).

  • Incubation period: The range is 7-17 days and the average is 12 days.

  • Symptoms: The initial symptoms are fever, chills, sore throat, cough, headache, myalgias, blepharoconjunctivitis, and adenopathy. After 1-3 days, there is the onset of the rash that is often initially on the face and then becomes generalized, including involvement of palms and soles. The rash evolves like smallpox, with papules, vesicles, pustules, and then scabs that evolve over 2-4 weeks. The disease is reportedly fatal in 1% to 10% as encountered in Africa, and children seem to be at greatest risk for lethal outcome.

  • Distinction from smallpox: The key elements are the animal contact and physical exam showing pronounced adenopathy.

The usual source is bite or contact with an infected animal via blood, body fluids, or lesions. The usual animal source is small mammals, especially prairie dogs or Gambian giant rats. There also appears to be person-to-person spread, although this is much less common and usually involves large respiratory droplets with prolonged face-to-face contact or contact with lesions. Another potential source is contact with contaminated sources, including bedding and clothes. Investigation of the first 53 US cases showed 51 had contact with prairie dogs, 1 had contact with a Gambian giant rant, and 1 had contact with a rabbit that was sick after prior contact with a prairie dog. Two patients had contact with lesions or ocular drainage from other patients. At least 1 case involves a healthcare worker without animal contact.[30]

  • Clinical: The typical clinical features are fever, cough, headache, myalgias, the characteristic rash, and adenopathy with onset within 3 weeks of contact with an infected animal or patient source.

  • Virologic diagnosis: Specimens are the same as those used to detect smallpox or vaccinia (see www.bt.cdc.gov/agent/ smallpox/lab-testing). The poxvirus may be detected by culture, PCR, serology, electron microscopy, and by immunohistochemistry.

www.cdc.gov/ncidod/monkeypox/casedefinition.htm
) and Wisconsin Division of Public Health

  • Clinical description: Includes (1) fever; (2) other clinical features including chills, sweats, headache, backache, adenopathy, sore throat, dyspnea, cough, and rash that is macular, papular, vesicular, or pustular; localized or diffuse; discrete or confluent.

  • Laboratory diagnosis: (1) Isolation of the virus in culture; (2) demonstration of monkeypox DNA by PCR; (3) demonstration of characteristic orthopox virus by electron microscope without exposure to alternative orthopox virus; or (4) demonstration of orthopoxvirus by immunohistochemical test.

  • Epidemiologic criteria (CDC): (1) Exposure to exotic or wild mammalian pet (prairie dog, Gambian giant rat, or rope squirrel) obtained after April 15, 2003 with clinical signs of illness (conjunctivitis, respiratory symptoms, rash); (2) exposure to wild mammalian pet that has been contact source of monkeypox in a mammalian pet or person; or (3) exposure (skin-skin or face-face) with suspected or confirmed case.

  • Epidemiologic criteria (Wisconsin Division of Public Health): Contact with prairie dog or Gambian giant rat originally obtained on or after April 1, 2003 from SK Exotics or Phil's Pocket Pets or contact with an animal housed with these animals at the designated sources or contact (skin-skin or face-face) with human case.

  • Public health: Importation of all rodents from Africa is banned. Within the United States, the sale, distribution, or release of the following is prohibited: prairie dogs, Gambian giant pouched rats, bush-tailed porcupines, striped mice, tree squirrels, rope squirrels, and doormice.

  • Public: Avoid contact with prairie dog or with Gambian giant rats that appear ill, especially with the characteristic clinical features of missing fur, visible rash, or nasal/eye drainage. Use proper hand hygiene if contact occurs.

  • Pet owners: Separate suspect animals from people, wear gloves and mask for any contact, and notify the health department. Contact a veterinarian for advice about transport. Clean surfaces with standard disinfectant. (See www.cdc.gov/ ncidod/monkeypox.)

  • Infection control: Suspected cases should be managed with standard contact and airborne isolation, meaning hand hygiene, gowns and gloves with goggles for possible ocular exposure, N95 mask (if not available use surgical mask), and negative pressure room (or private room if negative pressure is not available).

  • Contacts: (1) Surveillance for 21 days postexposure with concern for fever, rash, or respiratory symptoms; (2) may continue daily activities -- work, school, etc.; (3) monitor temperatures twice daily.

  • Smallpox vaccination: Prior studies show ≥ 85% protection with pre-exposure vaccination.[31] Smallpox vaccination is recommended by American College of International Physicians for laboratory and healthcare workers who are occupationally exposed to nonvariola orthopoxviruses.[32] The efficacy of postexposure smallpox vaccination is not known, but the experience with smallpox suggests efficacy. Caution needs to be advised based on the previous concerns with smallpox vaccination and its potential consequences, noting that the mortality with monkeypox is substantially lower than with smallpox, 1% to 10% in prior reports from Africa and none in the 53 cases reported to date in the US.

  • Persons investigating suspected human or animal monkeypox: Preference is for personnel with prior smallpox vaccinations, preferably within 1-3 years. Unvaccinated investigators should be vaccinated, preferably within 4 days of exposure.

  • Healthcare workers (HCWs): Preference is for HCWs with prior smallpox vaccination; if not available, vaccinate prior to clinical care. If HCW is already caring for suspected or established case, vaccinate as soon as possible after exposure; vaccine is recommended if given within 4 days of initial exposure and should be considered if within 2 weeks.

  • Contacts: Persons with direct or close contact (≤ 3 feet for ≥ 3 hours) with a sick prairie dog acquired after April 15, 2003 should receive smallpox vaccination within 4 days of exposure; this vaccination should be considered if contact is up to 2 weeks previously.

  • The standard contraindications to smallpox vaccination apply. (This includes HIV infection, but here the CDC specifies those with a CD4 count < 200 cells/microL).

  • Treatment (CDC): Smallpox vaccination may presumably be given during early in the course of monkeypox in a fashion analogous to its use in smallpox. Cidofovir is active in vitro, but there is no clinical experience to date with its use for prophylaxis or treatment. The same applies to vaccinia immune globulin (VIG).

  • Reporting: All established or suspected cases of monkeypox in people or pets should be reported to the state health department.

[Data for monkeypox and smallpox sections collated from: ProMed 6/7, 6/10, 6/11, 6/12, 2003: Authorities account for most imported Gambian rats. Texas Department of Health. June 11, 2003. News Release; Monkeypox infections in animals: updated interim guidance for veterinarians. CDC. June 27, 2003; Altman LK. As monkeypox rises, smallpox vaccines will be offered. New York Times. June 11, 2003; Snowbeck C. Monkeypox cases rise to about 40 in Midwest. Post Gazette Online. June 10, 2003; 9 new cases of monkeypox suspected in Midwest. The Sun Online. June 10, 2003; Marshfield Clinic Web site, available at
http://research.marshfieldclinic.org/crc/monkeypox.asp; Multistate outbreak of monkeypox - Illinois, Indiana, and Wisconsin, 2003. MMWR Morb Mortal Wkly Rep. 2003;52:537-540; and Marchione M. U.S. urges smallpox shots in monkeypox investigation. Milwaukee Journal Sentinel. June 11, 2003.]

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