continued.35,72 Fig. 5. Extensive papulo-pustular monkeypox rashes with crust and scar formation. (Courtesy of Nigeria Centre for Disease Control, Abuja, Nigeria.) Human Monkeypox 9 In response, the WHO supported an active surveillance program for human monkeypox from 1970 to 1986.46 It was assumed to be endemic to DRC, but other Central and West African countries also reported cases of monkeypox in humans or circulation in wildlife. At the end of the smallpox eradication campaign, the GCCSE stated that smallpox vaccination to prevent monkeypox was no longer justified, even if crossprotective immunity could not be relied on for long because of the vaccinations being discontinued. In retrospect, this resolution may have been an error. Experimental studies of monkeys have shown immunization with smallpox vaccine to give cross-protection against monkeypox.19 Several reviews have summarized human monkeypox outbreaks over the past 38 years.28,29,42 Between November 2005 and November 2007, population-based surveillance studies conducted in 9 health zones in central DRC identified 760 laboratory-confirmed human monkeypox cases. The average annual cumulative incidence across the zones was 5.53 per 10,000 (2.18–14.42). Factors associated with increased risk of infection included living in forested areas, male sex, age less than 15 years, and absence of smallpox vaccination scar. Among those vaccinated, the risk of monkeypox was found to be 5.2-fold lower than among those unvaccinated (0.78 versus 4.05 per 10,000). Compared with surveillance data from the same region recorded in the 1980s, a 20-fold increase in human monkeypox incidence was observed. Between January 2001 and December 2004, the DRC Ministry of Health surveillance program reported 2734 cases of suspected human monkeypox in 11 provinces, showing an annual upward trend: 380 cases in 2001, 545 in 2002, 783 in 2003, and 1026 in 2004. Most cases (94%) were observed in children and adults younger than 25 years.41 These patients had not been vaccinated against smallpox. Surveillance activities have been halted since 2005 because of the civil war. DIAGNOSIS: LABORATORY, VIROLOGIC, AND HISTOLOGIC FEATURES Optimal clinical specimens for laboratory analyses include specimens from skin lesions such as swabs of vesicular lesions, exudate, or crusts stored in a dry, sterile tube (no viral transport media) and kept cold. A viral culture should be obtained by an oropharyngeal or nasopharyngeal swab. Skin biopsies of vesiculopustular rash or a sample of the roof of an intact skin vesicular lesion are valuable for analyses. Reference laboratories with high containment facilities are required to make a definitive diagnosis using electron microscopy, culture and molecular analysis identification by polymerase chain reaction, and sequencing. Serologic testing requires paired acute and convalescent sera for MPXV-specific immunoglobulin M detection within 5 days of presentation, or immunoglobulin G detection after 8 days. Histology and immunohistochemistry of papular lesions may show acanthosis, individual keratinocyte necrosis, and basal vacuolization, along with a superficial and deep perivascular lymphohistiocytic infiltrate in the dermis. Vesicular lesions show spongiosis with reticular and ballooning degeneration, multinucleated epithelial giant cells with epidermal necrosis with numerous eosinophils and neutrophils, and features of vasculitis and viral inclusions in keratinocytes. Intracytoplasmic, round-to-oval inclusions with sausage-shaped structures centrally, measuring 200 to 300 mm, may be seen on electron microscopic observation. TREATMENT There is no specific treatment for monkeypox. Supportive care, symptomatic management, and treatment of secondary bacterial infections remain the main recommendations. 10 Petersen et al PREVENTION Prevention of MPXV spread in endemic areas is highly challenging, and consists of avoiding any contact with rodents and primates as well as limiting direct exposure to blood and inadequately cooked meat. Efforts to halt bushmeat trade and consumption of wild animals are extremely difficult both culturally and economically because this meat may be the only protein source available for the poorest people. Massive health education campaigns are needed to increase general awareness and to advise on proper handling of potential animal reservoir species (gloves, protective clothing, surgical mask) as well as avoiding close contact with anyone infected. Infection control measures are vital to prevention of human-to-human transmission in health care. Improved nursing (gloves, protective clothing, surgical masks) and isolation practices require education as well as adequate facilities and staffing. National health authorities should consider arranging immunization against smallpox for health care workers and those treating or exposed to patients with monkeypox or their samples. Smallpox vaccination has been estimated to provide 85% crossprotection against monkeypox infection.32 The Centers for Disease Control and Prevention (CDC) recommended smallpox vaccination within 2 weeks, ideally before 4 days, after significant, unprotected exposure to a diseased animal or a confirmed human case. During an outbreak, the spread of monkeypox