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      Novel Orthopoxvirus Infection in an Alaska Resident

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          Summary

          A resident of interior Alaska, was diagnosed with an Orthopoxvirus infection. Phylogenetic analysis revealed it is a novel, previously undescribed Orthopoxvirus species. Phylogenetically, the virus is sister to recognized Old World orthopoxviruses, rather than North American Orthopoxvirus species.

          Abstract

          Background.

          Human infection by orthopoxviruses is being reported with increasing frequency, attributed in part to the cessation of smallpox vaccination and concomitant waning of population-level immunity. In July 2015, a female resident of interior Alaska presented to an urgent care clinic with a dermal lesion consistent with poxvirus infection. Laboratory testing of a virus isolated from the lesion confirmed infection by an Orthopoxvirus.

          Methods.

          The virus isolate was characterized by using electron microscopy and nucleic acid sequencing. An epidemiologic investigation that included patient interviews, contact tracing, and serum testing, as well as environmental and small-mammal sampling, was conducted to identify the infection source and possible additional cases.

          Results.

          Neither signs of active infection nor evidence of recent prior infection were observed in any of the 4 patient contacts identified. The patient’s infection source was not definitively identified. Potential routes of exposure included imported fomites from Azerbaijan via the patient’s cohabiting partner or wild small mammals in or around the patient’s residence. Phylogenetic analyses demonstrated that the virus represents a distinct and previously undescribed genetic lineage of Orthopoxvirus, which is most closely related to the Old World orthopoxviruses.

          Conclusions.

          Investigation findings point to infection of the patient after exposure in or near Fairbanks. This conclusion raises questions about the geographic origins (Old World vs North American) of the genus Orthopoxvirus. Clinicians should remain vigilant for signs of poxvirus infection and alert public health officials when cases are suspected.

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          Most cited references33

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          Human monkeypox.

          Human monkeypox is a zoonotic Orthopoxvirus with a presentation similar to smallpox. Clinical differentiation of the disease from smallpox and varicella is difficult. Laboratory diagnostics are principal components to identification and surveillance of disease, and new tests are needed for a more precise and rapid diagnosis. The majority of human infections occur in Central Africa, where surveillance in rural areas with poor infrastructure is difficult but can be accomplished with evidence-guided tools and educational materials to inform public health workers of important principles. Contemporary epidemiological studies are needed now that populations do not receive routine smallpox vaccination. New therapeutics and vaccines offer hope for the treatment and prevention of monkeypox; however, more research must be done before they are ready to be deployed in an endemic setting. There is a need for more research in the epidemiology, ecology, and biology of the virus in endemic areas to better understand and prevent human infections.
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            Detection of monkeypox virus with real-time PCR assays

            Background Human monkeypox, a zoonotic disease, was first reported outside of Africa during the 2003 US outbreak. Objectives We present two real-time PCR assays critical for laboratory diagnosis of monkeypox during the 2003 US outbreak. Study design A TaqMan-based assay (E9L-NVAR) targets the orthopoxvirus DNA polymerase gene and detects Eurasian orthopoxviruses other than Variola . A hybridization assay, utilizing a MGB Eclipse™ (Epoch Biosciences) probe, targets an envelope protein gene (B6R) and specifically detects monkeypox virus (MPXV). Assays were validated using coded orthopoxvirus DNA samples and used to evaluate lesion samples from five confirmed US monkeypox cases. Results E9L-NVAR did not detect variola (48 strains), North American orthopoxviruses (2), or DNA derived from non-poxviral rash illnesses. The assay reproducibly identified various concentrations of 13 Eurasian orthopoxvirus strains and was sensitive to 12.5 vaccinia genomes. The B6R assay recognized 15 different MPXV strains, while other orthopoxvirus (9) and bacteria (15) strains did not cross-react. Of the 13 human samples tested from confirmed cases, both assays identified 100% as containing MPXV DNA. Conclusions E9L-NVAR and B6R assays demonstrate 100% specificity for non-variola Eurasian orthopoxvirus and MPXV, respectively. Using two discrete viral gene targets, these assays together provide a reliable and sensitive method for quickly confirming monkeypox infections.
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              characterization of acute-phase humoral immunity to monkeypox: use of immunoglobulin M enzyme-linked immunosorbent assay for detection of monkeypox infection during the 2003 North American outbreak.

              A monkeypox outbreak occurred in the United States in 2003. Patient's sera were sent to the Centers for Disease Control and Prevention as a part of outbreak response measures. Clinical and epidemiologic information was abstracted from the case investigation forms. Serum samples from patients were tested by using an immunoglobulin M (IgM)-capture and an IgG enzyme-linked immunosorbent assay ELISA against Orthopoxvirus antigen. The detection of antiviral IgG and IgM antibodies and the kinetics of the antiviral IgG and IgM antibody responses were evaluated. Patients were classified as confirmed, probable, or suspect cases or were excluded as cases based on laboratory test results and epidemiologic and clinical criteria. A total of 37 confirmed case patients with monkeypox were identified, and 116 patients were excluded as case patients based on molecular testing or insufficient epidemiology and clinical data to warrant classification as a suspect or probable case. Of 37 confirmed case patients, 36 had a known history (presence or absence) of smallpox vaccination. Of those, 29 of the 36 either had or developed an IgG response, while 34 of the 36 developed an IgM response, regardless of vaccination status. Serum collected > or =5 days for IgM detection or serum collected > or =8 days after rash onset for IgG detection was most efficient for the detection of monkeypox virus infection. IgM ELISA detects recent infection with orthopoxviruses and, in this case, recent infection with monkeypox virus. In addition, analysis of paired sera for IgG and IgM detected seroconversion, another indicator of recent infection. The ELISA results correlated with the virologic PCR and viral culture results, indicating its diagnostic capabilities for monkeypox and potentially other orthopoxvirus infections due to zoonotic transmission or bioterrorism events.
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                Author and article information

                Journal
                Clin Infect Dis
                Clin. Infect. Dis
                cid
                Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
                Oxford University Press (US )
                1058-4838
                1537-6591
                15 June 2017
                15 March 2017
                15 March 2017
                : 64
                : 12
                : 1737-1741
                Affiliations
                [1 ]Alaska Division of Public Health, Section of Epidemiology , Anchorage
                [2 ]Tanana Valley Clinic ,
                [3 ]University of Alaska Museum , and
                [4 ]Alaska Division of Public Health, Section of Laboratories , Fairbanks;
                [5 ]Epidemic Intelligence Service, Division of Scientific Education and Professional Development,
                [6 ]Poxvirus and Rabies Branch, and
                [7 ]Infectious Diseases Pathology Branch, Centers for Disease Control and Prevention , Atlanta, Georgia;
                [8 ]Oak Ridge Institute for Science and Education , Tennessee.
                Author notes

                Correspondence: Y. P. Springer, Epidemic Intelligence Service, Division of Scientific Education and Professional Development, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Atlanta, GA 30333 ( vkh3@ 123456cdc.gov ).

                Article
                cix219
                10.1093/cid/cix219
                5447873
                28329402
                563e5df1-bc8f-4f82-8d20-8373d76f68c8
                © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence ( http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 14 December 2016
                : 08 March 2017
                Page count
                Pages: 5
                Funding
                Funded by: state of Alaska and the US federal government
                Categories
                Major Article

                Infectious disease & Microbiology
                alaska,lesion,north america,orthopoxvirus,phylogenetics.
                Infectious disease & Microbiology
                alaska, lesion, north america, orthopoxvirus, phylogenetics.

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