Assessing Monkeypox Virus Prevalence in Small Mammals at the Human-Animal Interface in the Democratic Republic of the Congo.

During 2012, 2013 and 2015, we collected small mammals within 25 km of the town of Boende in Tshuapa Province, the Democratic Republic of the Congo. The prevalence of monkeypox virus (MPXV) in this area is unknown; however, cases of human infection were previously confirmed near these collection sites. Samples were collected from 353 mammals (rodents, shrews, pangolins, elephant shrews, a potamogale, and a hyrax). Some rodents and shrews were captured from houses where human monkeypox cases have recently been identified, but most were trapped in forests and agricultural areas near villages. Real-time PCR and ELISA were used to assess evidence of MPXV infection and other Orthopoxvirus (OPXV) infections in these small mammals. Seven (2.0%) of these animal samples were found to be anti-orthopoxvirus immunoglobulin G (IgG) antibody positive (six rodents: two Funisciurus spp.; one Graphiurus lorraineus; one Cricetomys emini; one Heliosciurus sp.; one Oenomys hypoxanthus, and one elephant shrew Petrodromus tetradactylus); no individuals were found positive in PCR-based assays. These results suggest that a variety of animals can be infected with OPXVs, and that epidemiology studies and educational campaigns should focus on animals that people are regularly contacting, including larger rodents used as protein sources.

Comparison of West African and Congo Basin monkeypox viruses in BALB/c and C57BL/6 mice.

Although monkeypox virus (MPXV) studies in wild rodents and non-human primates have generated important knowledge regarding MPXV pathogenesis and inferences about disease transmission, it might be easier to dissect the importance of virulence factors and correlates of protection to MPXV in an inbred mouse model. Herein, we compared the two clades of MPXV via two routes of infection in the BALB/c and C57BL/6 inbred mice strains. Our studies show that similar to previous animal studies, the Congo Basin strain of MPXV was more virulent than West African MPXV in both mouse strains as evidenced by clinical signs. Although animals did not develop lesions as seen in human MPX infections, localized signs were apparent with the foot pad route of inoculation, primarily in the form of edema at the site of inoculation; while the Congo Basin intranasal route of infection led to generalized symptoms, primarily weight loss. We have determined that future studies with MPXV and laboratory mice would be very beneficial in understanding the pathogenesis of MPXV, in particular if used in in vivo imaging studies. Although this mouse model may not suffice as a model of human MPX disease, with an appropriate inbred mouse model, we can unravel many unknown aspects of MPX pathogenesis, including virulence factors, disease progression in rodent hosts, and viral shedding from infected animals. In addition, such a model can be utilized to test antivirals and the next generation of orthopoxvirus vaccines for their ability to alter the course of disease.

A prairie dog animal model of systemic orthopoxvirus disease using West African and Congo Basin strains of monkeypox virus.

Multiple monkeypox virus (MPXV) animal models have been discussed in previous studies, but no small animal models, nor most non-human primate models, demonstrated the protracted asymptomatic incubation phase seen in systemic human orthopoxvirus illness. Herein, we characterize a black-tailed prairie dog (PD) (Cynomys ludovicianus) model of infection, via intranasal and intradermal exposures, with the two MPXV clades. Daily observations of the animals were made (food consumption, general symptoms, disease presentation), while weights and virus evaluations (ocular, nasal, oropharyngeal, faeces, blood) were obtained/made every third day. Generalized rash became apparent 9-12 days post-infection for all animals. Individual animals demonstrated a range of symptoms consistent with human monkeypox disease. Measurable viraemias and excretas were similar for both clade-representative strains and persisted until at least day 21. Greater morbidity was observed in Congo Basin strain-challenged animals and mortality was observed only in the Congo Basin strain-challenged animals. The PD model is valuable for the study of strain-dependent differences in MPXV. Additionally, the model closely mimics human systemic orthopoxvirus disease and may serve as a valuable non-human surrogate for investigations of antivirals and next generation orthopoxvirus vaccines.

Transmission of monkeypox among persons exposed to infected prairie dogs in Indiana in 2003.

OBJECTIVE: To describe a cluster of human monkeypox cases associated with exposure to ill prairie dogs in a home child care. DESIGN, SETTING, PARTICIPANTS: We identified all persons exposed to 2 pet prairie dogs in County A, Indiana; performed active surveillance for symptomatic monkeypox infection; and evaluated the types of exposure that may have resulted in infection. For children who attended the child care where the animals were housed, we also measured the rate of seroconversion to monkeypox virus. MAIN OUTCOME MEASURES: Nine (13%) of 70 persons exposed to the prairie dogs reported signs and symptoms of monkeypox. Two (40%) of 5 symptomatic child care attendees reported direct contact with the prairie dogs. Two (13%) of 15 child care attendees evaluated tested positive for IgM antibodies against orthopoxvirus; both reported symptoms consistent with monkeypox. RESULTS: The risk of symptomatic infection correlated with the time and intensity of animal exposure, which was 100% (4/4) among family members with extensive direct contact, 19% (5/26) among the veterinarian and nonfamily child care attendees with moderate exposure, and 0% (0/40) among school children with limited exposure (P<.01). CONCLUSIONS: Monkeypox virus was transmitted from ill prairie dogs in a child care and veterinary facilities. The risk of symptomatic infection correlated with the amount of exposure to the prairie dogs. Although most cases of human monkeypox were associated with direct animal contact, other routes of transmission cannot be excluded.

Evaluation of human-to-human transmission of monkeypox from infected patients to health care workers.

BACKGROUND: In 2003, human monkeypox was first identified in the United States. The outbreak was associated with exposure to infected prairie dogs, but the potential for person-to-person transmission was a concern. This study examines health care worker (HCW) exposure to 3 patients with confirmed monkeypox. METHODS: Exposed HCWs, defined as HCWs who entered a 2-m radius surrounding case patients with confirmed monkeypox, were identified by infection-control practitioners. A self-administered questionnaire and analysis of paired serum specimens determined exposure status, immune response, and postexposure signs and symptoms of monkeypox. RESULTS: Of 81 exposed HCWs, 57 (70%) participated in the study. Among 57 participants, 40 (70%) had > or =1 unprotected exposure; none reported signs or symptoms consistent with monkeypox illness. One exposed HCW (2%), who had been vaccinated for smallpox within the past year, had serological evidence of recent orthopoxvirus infection; acute- and convalescent-phase serum specimens tested positive for anti-orthopoxvirus IgM. No exposed HCWs had signs and symptoms consistent with monkeypox. CONCLUSION: More than three-quarters of exposed HCWs reported at least 1 unprotected encounter with a patient who had monkeypox. One asymptomatic HCW showed laboratory evidence of recent orthopoxvirus infection, which was possibly attributable to either recent infection or smallpox vaccination. Transmission of monkeypox likely is a rare event in the health care setting.