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      Emergence of Monkeypox as the Most Important Orthopoxvirus Infection in Humans

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          Abstract

          Monkeypox is an emerging zoonotic disease recognized as the most important orthopoxvirus infection in humans in the smallpox post-eradication era. The clinical presentation of monkeypox is similar to the one of smallpox. The case fatality rate of monkeypox (10%) lies between the case fatality rate of variola major (30%) and variola minor (1%). The disease is endemic in the Democratic Republic of the Congo, but other countries of Central and West Africa either reported cases of monkeypox in humans or circulation in wildlife. The disease was also imported once into the USA. The disease has always been considered rare and self-limiting, however recent sporadic reports suggest otherwise. Unfortunately, the collected data is limited, dispersed and often incomplete. Therefore, the objective of this review is to trace all reported human monkeypox outbreaks and relevant epidemiological information. The frequency and geographical spread of human monkeypox cases have increased in recent years, and there are huge gaps in our understanding of the disease's emergence, epidemiology, and ecology. The monkeypox virus is considered a high threat pathogen causing a disease of public health importance. Therefore, there is an urgent need to focus on building surveillance capacities which will provide valuable information for designing appropriate prevention, preparedness and response activities.

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          The detection of monkeypox in humans in the Western Hemisphere.

          During May and June 2003, an outbreak of febrile illness with vesiculopustular eruptions occurred among persons in the midwestern United States who had had contact with ill pet prairie dogs obtained through a common distributor. Zoonotic transmission of a bacterial or viral pathogen was suspected. We reviewed medical records, conducted interviews and examinations, and collected blood and tissue samples for analysis from 11 patients and one prairie dog. Histopathological and electron-microscopical examinations, microbiologic cultures, and molecular assays were performed to identify the etiologic agent. The initial Wisconsin cases evaluated in this outbreak occurred in five males and six females ranging in age from 3 to 43 years. All patients reported having direct contact with ill prairie dogs before experiencing a febrile illness with skin eruptions. We found immunohistochemical or ultrastructural evidence of poxvirus infection in skin-lesion tissue from four patients. Monkeypox virus was recovered in cell cultures of seven samples from patients and from the prairie dog. The virus was identified by detection of monkeypox-specific DNA sequences in tissues or isolates from six patients and the prairie dog. Epidemiologic investigation suggested that the prairie dogs had been exposed to at least one species of rodent recently imported into the United States from West Africa. Our investigation documents the isolation and identification of monkeypox virus from humans in the Western Hemisphere. Infection of humans was associated with direct contact with ill prairie dogs that were being kept or sold as pets. Copyright 2004 Massachusetts Medical Society
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            A tale of two clades: monkeypox viruses.

            Human monkeypox was first recognized outside Africa in 2003 during an outbreak in the USA that was traced to imported monkeypox virus (MPXV)-infected West African rodents. Unlike the smallpox-like disease described in the Democratic Republic of the Congo (DRC; a Congo Basin country), disease in the USA appeared milder. Here, analyses compared clinical, laboratory and epidemiological features of confirmed human monkeypox case-patients, using data from outbreaks in the USA and the Congo Basin, and the results suggested that human disease pathogenicity was associated with the viral strain. Genomic sequencing of USA, Western and Central African MPXV isolates confirmed the existence of two MPXV clades. A comparison of open reading frames between MPXV clades permitted prediction of viral proteins that could cause the observed differences in human pathogenicity between these two clades. Understanding the molecular pathogenesis and clinical and epidemiological properties of MPXV can improve monkeypox prevention and control.
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              Clinical characteristics of human monkeypox, and risk factors for severe disease.

              Human monkeypox is an emerging smallpox-like illness that was identified for the first time in the United States during an outbreak in 2003. Knowledge of the clinical manifestations of monkeypox in adults is limited, and clinical laboratory findings have been unknown. Demographic information; medical history; smallpox vaccination status; signs, symptoms, and duration of illness, and laboratory results (hematologic and serum chemistry findings) were extracted from medical records of patients with a confirmed case of monkeypox in the United States. Two-way comparisons were conducted between pediatric and adult patients and between patients with and patients without previous smallpox vaccination. Bivariate and multivariate analyses of risk factors for severe disease (fever [temperature, > or =38.3 degrees C] and the presence of rash [> or =100 lesions]), activity and duration of hospitalization, and abnormal clinical laboratory findings were performed. Of 34 patients with a confirmed case of monkeypox, 5 (15%) were defined as severely ill, and 9 (26%) were hospitalized for >48 h; no patients died. Previous smallpox vaccination was not associated with disease severity or hospitalization. Pediatric patients (age, 48 h and with having > or =3 laboratory tests with abnormal results. Monkeypox can cause a severe clinical illness, with systemic signs and symptoms and abnormal clinical laboratory findings. In the appropriate epidemiologic context, monkeypox should be included in the differential diagnosis for patients with unusual vesiculopustular exanthems, mucosal lesions, gastrointestinal symptoms, and abnormal hematologic or hepatic laboratory findings. Clinicians evaluating a rash illness consistent with possible orthopoxvirus infection should alert public health officials and consider further evaluation.
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                Author and article information

                Contributors
                Journal
                Front Public Health
                Front Public Health
                Front. Public Health
                Frontiers in Public Health
                Frontiers Media S.A.
                2296-2565
                04 September 2018
                2018
                : 6
                : 241
                Affiliations
                Laboratory of Clinical Virology, Department of Microbiology & Immunology, Rega Institute for Medical Research, KU Leuven , Leuven, Belgium
                Author notes

                Edited by: Vincent Munster, National Institutes of Health (NIH), United States

                Reviewed by: Zisis Kozlakidis, International Agency For Research On Cancer (IARC), France; Marisa Silvia Castro, Instituto de Estudios de la Inmunidad Humoral (IDEHU), Argentina

                *Correspondence: Nikola Sklenovská nikolasklenovska@ 123456gmail.com

                This article was submitted to Infectious Diseases-Surveillance, Prevention and Treatment, a section of the journal Frontiers in Public Health

                Article
                10.3389/fpubh.2018.00241
                6131633
                30234087
                a468b40c-fbe3-4ae4-b88d-5c19ccb24808
                Copyright © 2018 Sklenovská and Van Ranst.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 10 April 2018
                : 10 August 2018
                Page count
                Figures: 1, Tables: 2, Equations: 0, References: 118, Pages: 12, Words: 10178
                Categories
                Public Health
                Review

                monkeypox,orthopoxvirus,emerging infectious diseases,zoonosis,disease outbreaks,one health

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