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      Human West Nile Virus Disease Outbreak in Pakistan, 2015–2016

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          Abstract

          Like most of the world, Pakistan has seen an increase in mosquito-transmitted diseases in recent years. The magnitude and distribution of these diseases are poorly understood as Pakistan does not have a nation-wide system for reporting disease. A cross-sectional study to determine which flaviviruses were causing of arboviral disease in Pakistan was instituted. West Nile virus (WNV) is a cause of seasonal fever with neurotropic findings in countries that share borders with Pakistan. Here, we describe the active and persistent circulation of WNV in humans in the southern region of Pakistan. This is the first report of WNV causing neurological disease in human patients in this country. Of 997 enrolled patients presenting with clinical features suggestive of arboviral disease, 105 were positive for WNV IgM antibodies, and 71 of these patients possessed WNV-specific neutralizing antibodies. Cross-reactivity of WNV IgM antibodies with Japanese encephalitis virus (JEV) occurred in 75 of these 105 patients. WNV co-infections with Dengue viruses were not a contributing factor for the severity of disease. Nor did prior exposure to dengue virus contribute to incidence of neurological involvement in WNV-infected patients. Patients with WNV infections were more likely to present with altered mental status, seizures, and reduced Glasgow Coma scores when compared with JEV-infected patients. Human WNV cases and vector numbers exhibited a temporal correlation with climate.

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          Most cited references37

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          Epidemiological investigation of MERS-CoV spread in a single hospital in South Korea, May to June 2015.

          In this report, we describe 37 MERS-CoV infection cases (1 primary, 25 secondary, 11 tertiary cases) in a single hospital in South Korea. The median incubation period was six days (95% CI: 4–7 days) and the duration between suspected symptom onset and laboratory confirmation was 6.5 days (95% CI: 4–9). While incubation period was two days longer, the duration from suspected symptom onset to confirmation was shorter in tertiary compared with secondary infections.
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            Flavivirus-induced antibody cross-reactivity

            Dengue viruses (DENV) cause countless human deaths each year, whilst West Nile virus (WNV) has re-emerged as an important human pathogen. There are currently no WNV or DENV vaccines licensed for human use, yet vaccines exist against other flaviviruses. To investigate flavivirus cross-reactivity, sera from a human cohort with a history of vaccination against tick-borne encephalitis virus (TBEV), Japanese encephalitis virus (JEV) and yellow fever virus (YFV) were tested for antibodies by plaque reduction neutralization test. Neutralization of louping ill virus (LIV) occurred, but no significant neutralization of Murray Valley encephalitis virus was observed. Sera from some individuals vaccinated against TBEV and JEV neutralized WNV, which was enhanced by YFV vaccination in some recipients. Similarly, some individuals neutralized DENV-2, but this was not significantly influenced by YFV vaccination. Antigenic cartography techniques were used to generate a geometric illustration of the neutralization titres of selected sera against WNV, TBEV, JEV, LIV, YFV and DENV-2. This demonstrated the individual variation in antibody responses. Most sera had detectable titres against LIV and some had titres against WNV and DENV-2. Generally, LIV titres were similar to titres against TBEV, confirming the close antigenic relationship between TBEV and LIV. JEV was also antigenically closer to TBEV than WNV, using these sera. The use of sera from individuals vaccinated against multiple pathogens is unique relative to previous applications of antigenic cartography techniques. It is evident from these data that notable differences exist between amino acid sequence identity and mapped antigenic relationships within the family Flaviviridae.
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              Mosquito Oviposition Behavior and Vector Control

              The burden of gene transfer from one mosquito generation to the next falls on the female and her eggs. The selection of an oviposition site that guarantees egg and larval survival is a critical step in the reproductive process. The dangers associated with ephemeral aquatic habitats, lengthy droughts, freezing winters, and the absence of larval nutrition makes careful oviposition site selection by a female mosquito extremely important. Mosquito species exhibit a remarkable diversity of oviposition behaviors that ensure eggs are deposited into microenvironments conducive for successful larval development and the emergence of the next mosquito generation. An understanding of mosquito oviposition behavior is necessary for the development of surveillance and control opportunities directed against specific disease vectors. For example, Aedes aegypti Linnaeus is the vector of viruses causing important human diseases including yellow fever, dengue, chikungunya, and Zika. The preference of this species to oviposit in natural and artificial containers has facilitated the development of Ae. aegypti-specific surveillance and toxic oviposition traps designed to detect and control this important vector species in and around disease foci. A better understanding of the wide diversity of mosquito oviposition behavior will allow the development of new and innovative surveillance and control devices directed against other important mosquito vectors of human and animal disease.
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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
                27 February 2018
                2018
                : 6
                : 20
                Affiliations
                [1] 1Department of Pathology and Laboratory Medicine, Aga Khan University , Karachi, Pakistan
                [2] 2Department of Comparative Diagnostic and Population Medicine, College of Veterinary Medicine, University of Florida , Gainesville, FL, United States
                [3] 3Department of Environmental and Global Health, Emerging Pathogens Institute, University of Florida , Gainesville, FL, United States
                Author notes

                Edited by: Nicola Petrosillo, Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani (IRCCS), Italy

                Reviewed by: Evandro R. Winkelmann, Columbia University, United States; Lorenzo Zammarchi, University of Florence, Italy

                *Correspondence: Kelli L. Barr, kellilbarr@ 123456ufl.edu

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

                Article
                10.3389/fpubh.2018.00020
                5835076
                29535994
                b5f23061-5b4a-4559-8f83-0df515e3ebf5
                Copyright © 2018 Khan, Barr, Farooqi, Prakoso, Abbas, Khan, Ashi, Imtiaz, Aziz, Malik, Lednicky and Long.

                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 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
                : 20 November 2017
                : 22 January 2018
                Page count
                Figures: 5, Tables: 3, Equations: 0, References: 41, Pages: 11, Words: 6949
                Funding
                Funded by: Defense Threat Reduction Agency 10.13039/100000774
                Award ID: HDTRA1-14-1-0022
                Categories
                Public Health
                Original Research

                west nile virus,dengue virus,japanese encephalitis virus,encephalitis,arboviral disease

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