Monkeypox Zoonotic Associations: Insights From Laboratory Evaluation of Animals Associated With the Multi-State Us Outbreak

Abstract

At the onset of the 2003 US monkeypox outbreak, virologic data were unavailable regarding which animal species were involved with virus importation and/or subsequent transmission to humans and whether there was a risk for establishment of zoonotic monkeypox in North America. Similarly, it was unclear which specimens would be best for virus testing. Monkeypox DNA was detected in at least 33 animals, and virus was cultured from 22. Virus-positive animals included three African species associated with the importation event (giant pouched rats, Cricetomys spp.; rope squirrels, Funisciuris sp.; and dormice, Graphiuris sp.). Virologic evidence from North American prairie dogs (Cynomys sp.) was concordant with their suspected roles as vectors for human monkeypox. Multiple tissues were found suitable for DNA detection and/or virus isolation. These data extend the potential host range for monkeypox virus infection and supports concern regarding the potential for establishment in novel reservoir species and ecosystems.

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

“…Previous analyses demonstrated that realtime PCR detection of MPXV DNA was significantly more sensitive than detection of p.f.u. (Hutson et al, 2007). Therefore, specimens were first tested for the presence of orthopoxvirus DNA by PCR and, if positive, were subsequently evaluated for viable virus by tissue culture propagation.…”

“…Human disease associated with West African MPXV infection is less severe and associated with less human-to-human transmission compared to Congo (Arita et al, 1985;Breman et al, 1980;Meyer et al, 2002), compared with up to 40 % for smallpox (Breman & Henderson, 2002). Human monkeypox had never been reported outside of Africa until 2003, when an outbreak occurred in the USA resulting from human contact with infected prairie dogs (PDs) which were co-housed with imported African rodents (Hutson et al, 2007;Reed et al, 2004). This outbreak demonstrated the potential for MPXV importation and, together with observations of ongoing human monkeypox in Africa (Boumandouki et al, 2007;Hutin et al, 2001;Learned et al, 2005;Meyer et al, 2002;Mukinda et al, 1997;Mwanbal et al, 1997;Rimoin et al, 2007), further emphasized the importance of a more complete understanding of this serious human pathogen.…”

“…Multiple animal species have been experimentally infected with MPXV (Marennikova & Seluhina, 1976;Shchelukhina & Marennikova, 1975;Tesh et al, 2004;Zaucha et al, 2001); however, most of these models have little in common with the human disease progression, presentation or mortality from either monkeypox or smallpox. Based on observations of PDs infected during the USA outbreak (Guarner et al, 2004;Hutson et al, 2007), and previous experimentally infected PDs (Xiao et al, 2005), we believe these animals will serve as a relevant model for human monkeypox. In the Xiao et al study, only West African MPXV was used and it was administered via an intranasal and an intraperitoneal route.…”

When good vaccines go wild: Feral Orthopoxvirus in developing countries and beyond

“…The first documented episode of human monkeypox outside the African continent occurred in 2003 in the Midwestern United States [92,[136][137][138][139][140]. The infection that occurred in the USA appeared to be milder than the disease described in the DRC.…”

“…However, the possibility of reintroduction from an animal reservoir should be considered. If monkeypox virus could adapt to American native rodents such as rats, squirrels or prairie dogs, it will become a major public health concern regarding the potential for its establishment in novel reservoir species and ecosystems [78,92,138,140].…”