Ryan, Edward, T. et al. Hunter’s Tropical Medicine and Emerging Infectious Diseases E-Book. Available from: Elsevier eBooks+, (10th Edition). Elsevier – OHCE, 2019.
Natural History and Pathogenesis
Monkeypox begins with infection of either the dermis (after transmission from infected animals) or the respiratory epithelium (after transmission from an infected person). The virus disseminates through the lymphatic system, resulting in primary viremia and systemic infection. A secondary viremia results in infection of the epithelium, producing skin and mucosal lesions. As a consequence of replication in mucosal surfaces the virus can be transmitted through oropharyngeal secretions to close contacts. The risk of transmission likely depends on the density of oropharyngeal lesions, the proximity and duration of contact, and virus survival, despite host immune responses. Monkeypox virus, like other poxviruses, has evolved mechanisms to evade host immune responses. Monkeypox virus is likely to be stable on fomites, and the number of virions required for infection is thought to be low based on potential similarities with variola virus. Strain differences may exist—monkeypox strains circulating in western Africa appear to be more attenuated and less transmissible than those in the Congo basin. 21
The incubation period from exposure to the onset of clinical symptoms and signs is 10 to 14 days. Patients are infectious during the first week of rash and should be isolated. 13 Most people infected with monkeypox virus are symptomatic, but sub-clinical infection can occur. Serologic studies of household contacts of acutely infected cases in the Democratic Republic of Congo suggest that approximately 28% of all monkeypox infections are sub-clinical. More recently, immunologic evidence of exposure to monkeypox virus was identified in several asymptomatic contacts of infected people in the United States.22,23
HIV and other conditions that suppress cell-mediated immunity may alter the natural history of disease. No data exist for monkeypox, but other poxvirus infections, specifically vaccinia and molluscum contagiosum viruses, are more severe in those who are infected with HIV.
The clinical features of monkeypox resemble those of smallpox (variola) ( Table 32.2.3). Symptoms begin with a prodromal illness of fever and malaise lasting 1 to 3 days, followed by the characteristic rash. In contrast to smallpox, prominent sub-mandibular, cervical, post-auricular, axillary, or inguinal lymphadenopathy occurs in many infected persons 1 to 2 days before rash onset. Lymphadenopathy is not a typical feature of smallpox and can serve to clinically distinguish monkeypox from smallpox ( Fig. 32.2.2; see Table 32.2.3). As with smallpox, lesions develop concurrently and progress at a similar rate over 2 to 4 weeks, depending on the disease severity. The rash begins as small, 2- to 5-mm papules and progresses through vesicular, pustular, and crusted stages over 2 to 3 weeks ( Fig. 32.2.3). Like smallpox, it tends to be more severe on the head and extremities, including the palms and soles, and less intense on the trunk. The scabs slough off during recovery, leaving de-pigmented scars. Complications of monkeypox include secondary bacterial infection of the skin lesions, pneumonitis, and eye involvement. Death occurs during the second week of illness in approximately 10% of cases. Prior vaccination with vaccinia virus (smallpox vaccine) results in milder disease with fewer skin lesions, less lymphadenopathy, and significantly lower mortality. 24