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ABSTRACT: Monkeypox virus (MPXV) is endemic within Africa where it sporadically is reported to cause outbreaks of human disease. In 2003, an outbreak of human MPXV occurred in the US after the importation of infected African rodents. Since the eradication of smallpox (caused by an orthopoxvirus (OPXV) related to MPXV) and cessation of routine smallpox vaccination (with the live OPXV vaccinia), there is an increasing population of people susceptible to OPXV diseases. Previous studies have shown that the prairie dog MPXV model is a functional animal model for the study of systemic human OPXV illness. Studies with this model have demonstrated that infected animals are able to transmit the virus to naive animals through multiple routes of exposure causing subsequent infection, but were not able to prove that infected animals could transmit the virus exclusively via the respiratory route. Herein we used the model system to evaluate the hypothesis that the Congo Basin clade of MPXV is more easily transmitted, via respiratory route, than the West African clade. Using a small number of test animals, we show that transmission of viruses from each of the MPXV clade was minimal via respiratory transmission. However, transmissibility of the Congo Basin clade was slightly greater than West African MXPV clade (16.7% and 0% respectively). Based on these findings, respiratory transmission appears to be less efficient than those of previous studies assessing contact as a mechanism of transmission within the prairie dog MPXV animal model.
PLoS ONE 01/2013; 8(2):e55488. · 4.09 Impact Factor
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ABSTRACT: The commercially available Orthopox BioThreat(®) Alert assay for orthopoxvirus (OPV) detection is piloted. This antibody-based lateral-flow assay labels and captures OPV viral agents to detect their presence. Serial dilutions of cultured Vaccinia virus (VACV) and Monkeypox virus (MPXV) were used to evaluate the sensitivity of the Tetracore assay by visual and quantitative determinations; specificity was assessed using a small but diverse set of diagnostically relevant blinded samples from viral lesions submitted for routine OPV diagnostic testing. The BioThreat(®) Alert assay reproducibly detected samples at concentrations of 10(7)pfu/ml for VACV and MPXV and positively identified samples containing 10(6)pfu/ml in 4 of 7 independent experiments. The assay correctly identified 9 of 11 OPV clinical samples and had only one false positive when testing 11 non-OPV samples. Results suggest applicability for use of the BioThreat(®) Alert assay as a rapid screening assay and point of care diagnosis for suspect human monkeypox cases.
Journal of virological methods 09/2012; · 2.13 Impact Factor
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ABSTRACT: Maps of disease occurrences and GIS-based models of disease transmission risk are increasingly common, and both rely on georeferenced diseases data. Automated methods for georeferencing disease data have been widely studied for developed countries with rich sources of geographic referenced data. However, the transferability of these methods to countries without comparable geographic reference data, particularly when working with historical disease data, has not been as widely studied. Historically, precise geographic information about where individual cases occur has been collected and stored verbally, identifying specific locations using place names. Georeferencing historic data is challenging however, because it is difficult to find appropriate geographic reference data to match the place names to. Here, we assess the degree of care and research invested in converting textual descriptions of disease occurrence locations to numerical grid coordinates (latitude and longitude). Specifically, we develop three datasets from the same, original monkeypox disease occurrence data, with varying levels of care and effort: the first based on an automated web-service, the second improving on the first by reference to additional maps and digital gazetteers, and the third improving still more based on extensive consultation of legacy surveillance records that provided considerable additional information about each case. To illustrate the implications of these seemingly subtle improvements in data quality, we develop ecological niche models and predictive maps of monkeypox transmission risk based on each of the three occurrence data sets.
We found macrogeographic variations in ecological niche models depending on the type of georeferencing method used. Less-careful georeferencing identified much smaller areas as having potential for monkeypox transmission in the Sahel region, as well as around the rim of the Congo Basin. These results have implications for mapping efforts, as each higher level of georeferencing precision required considerably greater time investment.
The importance of careful georeferencing cannot be overlooked, despite it being a time- and labor-intensive process. Investment in archival storage of primary disease-occurrence data is merited, and improved digital gazetteers are needed to support public health mapping activities, particularly in developing countries, where maps and geographic information may be sparse.
International Journal of Health Geographics 06/2012; 11:23. · 2.62 Impact Factor
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Christine M Hughes,
Frances K Newman,
Whitni B Davidson,
Victoria A Olson,
Scott K Smith,
Robert C Holman,
Lihan Yan,
Sharon E Frey,
Robert B Belshe,
Kevin L Karem,
Inger K Damon
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ABSTRACT: Possible smallpox reemergence drives research for third-generation vaccines that effectively neutralize variola virus. A comparison of neutralization assays using different substrates, variola and vaccinia (Dryvax and modified vaccinia Ankara [MVA]), showed significantly different 90% neutralization titers; Dryvax underestimated while MVA overestimated variola neutralization. Third-generation vaccines may rely upon neutralization as a correlate of protection.
Clinical and vaccine immunology: CVI 05/2012; 19(7):1116-8. · 2.37 Impact Factor
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ABSTRACT: The prevalence of North American orthopoxviruses in nature is unknown and may be more difficult to ascertain due to wide spread use of vaccinia virus recombinant vaccines in the wild. A real time PCR assay was developed to allow for highly sensitive and specific detection of North American orthopoxvirus DNA in animal tissues and bodily fluids. This method is based on the amplification of a 156 bp sequence within a myristylated protein, highly conserved within the North American orthopoxviruses but distinct from orthologous genes present in other orthopoxviruses. The analytical sensitivity was 1.1 fg for Volepox virus DNA, 1.99 fg for Skunkpox virus DNA, and 6.4 fg for Raccoonpox virus DNA with a 95% confidence interval. Our assay did not cross-react with other orthopoxviruses or ten diverse representatives of the Chordopoxvirinae subfamily. This new assay showed more sensitivity than tissue culture tests, and was capable of differentiating North American orthopoxviruses from other members of Orthopoxvirus. Thus, our assay is a promising tool for highly sensitive and specific detection of North American orthopoxviruses in the United States and abroad.
Virology Journal 06/2011; 8:313. · 2.34 Impact Factor
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Christine M Hughes,
David Blythe,
Yu Li,
Ramani Reddy,
Carol Jordan,
Cindy Edwards,
Celia Adams,
Holly Conners,
Catherine Rasa,
Sue Wilby, [......],
Christopher Allen,
Mike Frace,
Ginny Emerson,
Victoria A Olson,
Scott K Smith,
Zachary Braden,
Jason Abel,
Whitni Davidson,
Mary Reynolds,
Inger K Damon
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ABSTRACT: Vaccinia virus is an orthopoxvirus used in the live vaccine against smallpox. Vaccinia virus infections can be transmissible and can cause severe complications in those with weakened immune systems. We report on a cluster of 4 cases of vaccinia virus infection in Maryland, USA, likely acquired at a martial arts gym.
Emerging Infectious Diseases 04/2011; 17(4):730-3. · 6.79 Impact Factor
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Christina L Hutson,
Darin S Carroll,
Nadia Gallardo-Romero,
Sonja Weiss,
Cody Clemmons, Christine M Hughes,
Johanna S Salzer,
Victoria A Olson,
Jason Abel,
Kevin L Karem,
Inger K Damon
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ABSTRACT: Monkeypox virus (MPXV) is considered the most significant human public health threat in the genus Orthopoxvirus since the eradication of variola virus (the causative agent of smallpox). MPXV is a zoonotic agent endemic to forested areas of Central and Western Africa. In 2003, MPXV caused an outbreak in the United States due to the importation of infected African rodents, and subsequent sequential infection of North American prairie dogs (Cynomys ludovicianus) and humans. In previous studies, the prairie dog MPXV model has successfully shown to be very useful for understanding MPXV since the model emulates key characteristics of human monkeypox disease. In humans, percutaneous exposure to animals has been documented but the primary method of human-to-human MPXV transmission is postulated to be by respiratory route. Only a few animal model studies of MPXV transmission have been reported. Herein, we show that MPXV infected prairie dogs are able to transmit the virus to naive animals through multiple transmission routes. All secondarily exposed animals were infected with MPXV during the course of the study. Notably, animals secondarily exposed appeared to manifest more severe disease; however, the disease course was very similar to those of experimentally challenged animals including inappetence leading to weight loss, development of lesions, production of orthopoxvirus antibodies and shedding of similar levels or in some instances higher levels of MPXV from the oral cavity. Disease was transmitted via exposure to contaminated bedding, co-housing, or respiratory secretions/nasal mucous (we could not definitively say that transmission occurred via respiratory route exclusively). Future use of the model will allow us to evaluate infection control measures, vaccines and antiviral strategies to decrease disease transmission.
PLoS ONE 01/2011; 6(12):e28295. · 4.09 Impact Factor
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Christina L Hutson,
Darin S Carroll,
Joshua Self,
Sonja Weiss, Christine M Hughes,
Zachary Braden,
Victoria A Olson,
Scott K Smith,
Kevin L Karem,
Russell L Regnery,
Inger K Damon
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ABSTRACT: The prairie dog is valuable for the study of monkeypox virus (MPXV) virulence and closely resembles human systemic orthopoxvirus disease. Herein, we utilize a variable dose intranasal challenge with approximately 10(3), 10(4), 10(5), and 10(6)PFU for each clade to further characterize virulence differences between the two MPXV clades. A trend of increased morbidity and mortality as well as greater viral shedding was observed with increasing viral challenge dose. Additionally, there appeared to be a delay in onset of disease for animals challenged with lower dosages of virus. Mathematical calculations were used to determine LD(50) values and based on these calculations, Congo Basin MPXV had approximately a hundred times lower LD(50) value than the West African clade (5.9x10(3) and 1.29x10(5) respectively); reinforcing previous findings that Congo Basin MPXV is more virulent.
Virology 04/2010; 402(1):72-82. · 3.35 Impact Factor
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ABSTRACT: In order to determine how best to tailor outreach messages about poxvirus diagnosis and infection control for health practitioners, we surveyed infectious disease physicians in the Infectious Diseases Society of America's Emerging Infections Network.
Surveys consisting of two unknown case scenarios designed to raise suspicion for monkeypox and orf were distributed to the 1,080 members of the EIN. The surveys contained questions pertaining to which diagnostic tests, points of contact, and transmission precautions they would likely utilize during patient evaluation. Basic response rates and frequencies of responses were calculated. Comparisons of the survey responses were made using the chi-square test. Of the 212 members who responded (20% response rate), significantly more respondents indicated that they would request diagnostic testing in the context of the monkeypox case scenario as compared to the orf case scenario. A significantly higher number of respondents indicated they would institute droplet or airborne precautions for the monkeypox case as opposed to the orf case scenario.
This survey provided an opportunity for public health practitioners to gain insight into physician approaches to evaluation, diagnosis and reporting of suspected poxvirus-associated infections. This survey identified key areas in which public health practitioners can better serve physicians by focusing on education. As a result we were able to identify potential knowledge gaps and deficits in the availability of useful resources to facilitate accurate case identification and management.
BMC Research Notes 02/2010; 3:46.
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Christina L Hutson,
Jason A Abel,
Darin S Carroll,
Victoria A Olson,
Zachary H Braden, Christine M Hughes,
Michael Dillon,
Consuelo Hopkins,
Kevin L Karem,
Inger K Damon,
Jorge E Osorio
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ABSTRACT: 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.
PLoS ONE 01/2010; 5(1):e8912. · 4.09 Impact Factor
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Inger K Damon,
Whitni B Davidson, Christine M Hughes,
Victoria A Olson,
Scott K Smith,
Robert C Holman,
Sharon E Frey,
Frances Newman,
Robert B Belshe,
Lihan Yan,
Kevin Karem
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ABSTRACT: The search for a 'third'-generation smallpox vaccine has resulted in the development and characterization of several vaccine candidates. A significant barrier to acceptance is the absence of challenge models showing induction of correlates of protective immunity against variola virus. In this light, virus neutralization provides one of few experimental methods to show specific 'in vitro' activity of vaccines against variola virus. Here, we provide characterization of the ability of a modified vaccinia virus Ankara vaccine to induce variola virus-neutralizing antibodies, and we provide comparison with the neutralization elicited by standard Dryvax vaccination.
Journal of General Virology 05/2009; 90(Pt 8):1962-6. · 3.36 Impact Factor
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ABSTRACT: Smallpox (infection with Orthopoxvirus variola) remains a feared illness more than 25 years after its eradication. Historically, case-fatality rates (CFRs) varied between outbreaks (<1 to approximately 40 %), the reasons for which are incompletely understood. The extracellular enveloped virus (EEV) form of orthopoxvirus progeny is hypothesized to disseminate infection. Investigations with the closely related Orthopoxvirus vaccinia have associated increased comet formation (EEV production) with increased mouse mortality (pathogenicity). Other vaccinia virus genetic manipulations which affect EEV production inconsistently support this association. However, antisera against vaccinia virus envelope protect mice from lethal challenge, further supporting a critical role for EEV in pathogenicity. Here, we show that the increased comet formation phenotypes of a diverse collection of variola viruses associate with strain phylogeny and geographical origin, but not with increased outbreak-related CFRs; within clades, there may be an association of plaque size with CFR. The mechanisms for variola virus pathogenicity probably involves multiple host and pathogen factors.
Journal of General Virology 04/2009; 90(Pt 4):792-8. · 3.36 Impact Factor
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Christina L Hutson,
Victoria A Olson,
Darin S Carroll,
Jason A Abel, Christine M Hughes,
Zachary H Braden,
Sonja Weiss,
Joshua Self,
Jorge E Osorio,
Paul N Hudson,
Michael Dillon,
Kevin L Karem,
Inger K Damon,
Russell L Regnery
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ABSTRACT: 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.
Journal of General Virology 03/2009; 90(Pt 2):323-33. · 3.36 Impact Factor
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Edith Lederman,
Roque Miramontes,
John Openshaw,
Victoria A Olson,
Kevin L Karem,
John Marcinak,
Rodrigo Panares,
Wayne Staggs,
Donna Allen,
Stephen G Weber,
Surabhi Vora,
Susan I Gerber, Christine M Hughes,
Russell Regnery,
Limone Collins,
Pamela S Diaz,
Mary G Reynolds,
Inger Damon
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ABSTRACT: On March 3, 2007, a 2-year-old boy was hospitalized with eczema vaccinatum. His two siblings, one with eczema, were subsequently removed from the home. Swabs of household items obtained on March 13th were analyzed for orthopoxvirus DNA signatures with real-time PCR. Virus culture was attempted on positive specimens. Eight of 25 household samples were positive by PCR for orthopoxvirus; of these, three yielded viable vaccinia virus in culture. Both siblings were found to have serologic evidence of orthopoxvirus exposure. These findings have implications for smallpox preparedness, especially in situations where some household members are not candidates for vaccination.
Vaccine 12/2008; 27(3):375-7. · 3.77 Impact Factor
