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Updated: Jul 20, 2026

Vaccinia Virus Infection & Temporal Analysis of Virus Gene Expression: Part 1
Published on: April 8, 2009
Clinical manifestations of human monkeypox influenced by route of infection
Mary G Reynolds1, Krista L Yorita, Mathew J Kuehnert
1Centers for Disease Control and Prevention, Division of Viral and Rickettsial Diseases, Atlanta, GA 30333, USA. nzr6@cdc.gov
Background:
In April 2003, an outbreak of monkeypox occurred in the United States following the importation of monkeypox virus (MPXV)-infected animals in a consignment of exotic pets from West Africa. Transmission of the virus to non-African captive species, including prairie dogs, preceded human disease.
Methods:
We evaluated the influence of the route of infection on clinical illness for persons with confirmed and probable cases of human monkeypox. Exposures were categorized as being "noninvasive" (e.g., the person touched an infected animal, cleaned an infected animal's cage, and/or stood within 6 feet of an infected animal) or "complex" (e.g., invasive bite or scratch from an ill prairie dog plus potential noninvasive exposure), and associations between exposure, illness manifestation, and illness progression (i.e., elapsed time from first exposure to an ill prairie dog through various benchmarks of illness) were assessed.
Results:
Patients with complex exposures were more likely than patients with noninvasive exposures to have experienced pronounced signs of systemic illness (49.1% vs. 16.7%; P=.041) and to have been hospitalized during illness (68.8% vs. 10.3%; P<.001). Complex exposures were also associated with shorter incubation periods (9 days for complex exposures vs. 13 days for noninvasive exposures) and the absence of a distinct febrile prodrome.
Conclusions:
The findings of this study indicate that route of infection can influence monkeypox illness manifestations.
Insights
The route of infection significantly impacts monkeypox (MPXV) illness severity and progression. Complex exposures, like bites, lead to more severe symptoms and shorter incubation periods compared to noninvasive contact.
Area of Science:
- Zoonotic disease epidemiology
- Viral pathogenesis
Background:
- The 2003 US monkeypox outbreak originated from imported exotic pets.
- Transmission occurred from infected animals to non-African species, including prairie dogs, before human cases.
Purpose of the Study:
- To investigate how the route of infection influences the clinical presentation and progression of human monkeypox (MPXV).
Main Methods:
- Categorized human MPXV exposures as noninvasive or complex (e.g., bites).
- Assessed associations between exposure type, illness manifestation, and progression.
- Analyzed incubation periods and symptom onset relative to exposure type.
Main Results:
- Complex exposures correlated with more pronounced systemic illness (49.1% vs. 16.7%) and higher hospitalization rates (68.8% vs. 10.3%).
- Patients with complex exposures had shorter incubation periods (9 days vs. 13 days) and lacked a distinct febrile prodrome.
Conclusions:
- The route of exposure is a critical factor influencing monkeypox illness manifestations.
- Understanding exposure routes can aid in predicting disease severity and patient outcomes.
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