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      Sero-prevalence of arthropod-borne viral infections among Lukanga swamp residents in Zambia

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          Abstract

          Introduction

          The re-emergence of vector borne diseases affecting millions of people in recent years has drawn attention to arboviruses globally. Here, we report on the sero-prevalence of chikungunya virus (CHIKV), dengue virus (DENV), mayaro virus (MAYV) and zika virus (ZIKV) in a swamp community in Zambia.

          Methods

          We collected blood and saliva samples from residents of Lukanga swamps in 2016 during a mass-cholera vaccination campaign. Over 10,000 residents were vaccinated with two doses of Shanchol during this period. The biological samples were collected prior to vaccination (baseline) and at specified time points after vaccination. We tested a total of 214 baseline stored serum samples for IgG antibodies against NS1 of DENV and ZIKV and E2 of CHIKV and MAYV on ELISA. We defined sero-prevalence as the proportion of participants with optical density (OD) values above a defined cut-off value, determined using a finite mixture model.

          Results

          Of the 214 participants, 79 (36.9%; 95% CI 30.5–43.8) were sero-positive for Chikungunya; 23 (10.8%; 95% CI 6.9–15.7) for Zika, 36 (16.8%; 95% CI 12.1–22.5) for Dengue and 42 (19.6%; 95% CI 14.5–25.6) for Mayaro. Older participants were more likely to have Zika virus whilst those involved with fishing activities were at greater risk of contracting Chikungunya virus. Among all the antigens tested, we also found that Chikungunya saliva antibody titres correlated with baseline serum titres (Spearman’s correlation coefficient = 0.222; p = 0.03).

          Conclusion

          Arbovirus transmission is occurring in Zambia. This requires proper screening tools as well as surveillance data to accurately report on disease burden in Zambia.

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          Most cited references 36

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          Zika Virus Infection as a Cause of Congenital Brain Abnormalities and Guillain–Barré Syndrome: Systematic Review

          Background The World Health Organization (WHO) stated in March 2016 that there was scientific consensus that the mosquito-borne Zika virus was a cause of the neurological disorder Guillain–Barré syndrome (GBS) and of microcephaly and other congenital brain abnormalities based on rapid evidence assessments. Decisions about causality require systematic assessment to guide public health actions. The objectives of this study were to update and reassess the evidence for causality through a rapid and systematic review about links between Zika virus infection and (a) congenital brain abnormalities, including microcephaly, in the foetuses and offspring of pregnant women and (b) GBS in any population, and to describe the process and outcomes of an expert assessment of the evidence about causality. Methods and Findings The study had three linked components. First, in February 2016, we developed a causality framework that defined questions about the relationship between Zika virus infection and each of the two clinical outcomes in ten dimensions: temporality, biological plausibility, strength of association, alternative explanations, cessation, dose–response relationship, animal experiments, analogy, specificity, and consistency. Second, we did a systematic review (protocol number CRD42016036693). We searched multiple online sources up to May 30, 2016 to find studies that directly addressed either outcome and any causality dimension, used methods to expedite study selection, data extraction, and quality assessment, and summarised evidence descriptively. Third, WHO convened a multidisciplinary panel of experts who assessed the review findings and reached consensus statements to update the WHO position on causality. We found 1,091 unique items up to May 30, 2016. For congenital brain abnormalities, including microcephaly, we included 72 items; for eight of ten causality dimensions (all except dose–response relationship and specificity), we found that more than half the relevant studies supported a causal association with Zika virus infection. For GBS, we included 36 items, of which more than half the relevant studies supported a causal association in seven of ten dimensions (all except dose–response relationship, specificity, and animal experimental evidence). Articles identified nonsystematically from May 30 to July 29, 2016 strengthened the review findings. The expert panel concluded that (a) the most likely explanation of available evidence from outbreaks of Zika virus infection and clusters of microcephaly is that Zika virus infection during pregnancy is a cause of congenital brain abnormalities including microcephaly, and (b) the most likely explanation of available evidence from outbreaks of Zika virus infection and GBS is that Zika virus infection is a trigger of GBS. The expert panel recognised that Zika virus alone may not be sufficient to cause either congenital brain abnormalities or GBS but agreed that the evidence was sufficient to recommend increased public health measures. Weaknesses are the limited assessment of the role of dengue virus and other possible cofactors, the small number of comparative epidemiological studies, and the difficulty in keeping the review up to date with the pace of publication of new research. Conclusions Rapid and systematic reviews with frequent updating and open dissemination are now needed both for appraisal of the evidence about Zika virus infection and for the next public health threats that will emerge. This systematic review found sufficient evidence to say that Zika virus is a cause of congenital abnormalities and is a trigger of GBS.
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            Zika virus and microcephaly: why is this situation a PHEIC?

            When the Director-General of WHO declared, on Feb 1, 2016, that recently reported clusters of microcephaly and other neurological disorders are a Public Health Emergency of International Concern (PHEIC), 1 it was on the advice of an Emergency Committee of the International Health Regulations and of other experts whom she had previously consulted. We are the members of the Emergency Committee, and we were identified by the Director-General from rosters of experts that had been submitted by WHO Member States. Our advice to declare a PHEIC was not made on the basis of what is currently known about Zika virus infection. During our discussions it became clear that infection with the Zika virus, unlike other arbovirus infections including dengue and chikungunya, causes a fairly mild disease with fever, malaise, and at times a maculopapular rash, conjunctivitis, or both. 2 Additional information from previous outbreaks suggested that about 20% of people infected with Zika virus develop these symptoms, and that the rest are asymptomatic. 2 Fatality from Zika virus infection is thought to be rare. 2 Our advice to declare a PHEIC was rather made on the basis of what is not known about the clusters of microcephaly, Guillain-Barré syndrome, and possibly other neurological defects reported by country representatives from Brazil and retrospectively from French Polynesia that are associated in time and place with outbreaks of Zika infection.3, 4 The Emergency Committee meeting was convened rapidly by WHO. We were contacted by the Director-General 4 days before the Emergency Committee meeting, and by the time we met WHO had thoroughly prepared the meeting. At the start of the meeting, the WHO legal counsel provided three criteria to help the Emergency Committee decide whether the present situation was a PHEIC. A PHEIC must: (1) constitute a health risk to other countries through international spread; (2) potentially require a coordinated response because it is unexpected, serious, or unusual; and (3) have implications beyond the affected country that could require immediate action. Representatives from four countries (Brazil, El Salvador, France, and the USA) that have had either outbreaks or importations of Zika virus, and a group of arbovirus specialists, took part in the meeting. Some of them had been working for the past months with the WHO Regional Office in the Americas on the Zika virus outbreaks, and before that on those caused by the dengue and chikungunya viruses. During one country representative's account of Zika virus in French Polynesia, robust and convincing retrospective data were presented about an increase in neurological disorders during the period when there was an outbreak of Zika virus. Other presentations described current clusters of microcephaly and limited information about Zika virus identified in fetuses or infants, pointing out the temporal association with circulation of the Zika virus. After these country presentations, and comments by the assembled arbovirologists, we were able to discern as a committee, and then agree unanimously in an initial poll, that the clusters of microcephaly and neurological disorders, and their possible association with the Zika virus, constituted a PHEIC. Upon further discussion, it became clear that there was no standard surveillance case definition for microcephaly. The first recommendation of the PHEIC was to call for standardised and enhanced surveillance of microcephaly in areas of known Zika virus transmission. Such surveillance is not only important in countries where there are current and recent outbreaks, but is also retrospectively relevant in African and Asian countries where outbreaks have been occurring since the Zika virus was first identified in 1947.5, 6 Further, we felt that surveillance data should become available within months. © 2016 Fabrice Coffrini 2016 Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. Our second recommendation under the PHEIC is for increased research into the aetiology of confirmed clusters of microcephaly and neurological disorders to determine whether there is a causative link to Zika virus, other factors, and cofactors. Neurological fetal defects occur with other viral infections such as rubella, which are preventable by vaccine, 7 and could also be caused by factors such as exposure to chemicals or toxins and other environmental factors.8, 9 We understood that this PHEIC recommendation will take much longer to implement than surveillance, and will require accumulation of scientific evidence from post-mortem analyses, case-control studies, and other studies as recommended by experts in microcephaly, obstetric and neonatal medicine, and public health. Part of our discussion also included the need for development of an animal model, and of the possibility of eventually proving Koch's postulates. After our discussion on the PHEIC, there was unanimous agreement to make recommendations for precautionary measures to prevent arboviral infection. In addition to being good public health practice, which would be intensified should the clusters of microcephaly and other neurological disorders be linked to the Zika virus, they should also result in the prevention of chikungunya and dengue outbreaks.10, 11, 12 Among those recommendations were the need for: stronger surveillance of Zika virus infection with the rapid development and sharing of diagnostics suitable for seroprevalence studies and that do not require antigen presence; improved communication about the risks of outbreaks of Zika and other arboviruses; implementation of vector control measures to decrease exposure to bites from the Aedes aegypti mosquito; and guidance to be available to pregnant women so that they better understand the present situation and are empowered to make a decision about personal protection and pregnancy. We also provided longer-term advice to the Director-General to continue discussions with vaccine developers and regulatory agencies that WHO had already begun, to provide regular and clear guidance on risks associated with travel, and to ensure that all countries share data as they work with WHO to address the recommendations of the PHEIC. Since the Emergency Committee meeting we have continued to communicate among ourselves, and our hope is that WHO will work in the way that successfully led to control of the outbreak of severe acute respiratory syndrome (SARS) in 2003 when WHO established virtual networks of experts around the world who worked by telephone and the internet to collaborate in surveillance, clinical management, and research.13, 14, 15 The networks established during the SARS outbreak worked in environments that provided the confidentiality and security necessary to freely share data used for improving public health. With policies recently developed by The Lancet and other medical journals to accept for publication data that may have previously been shared openly for better outbreak prevention and control, we believe that there should be no excuse for not creating such an environment for sharing of data collected under the PHEIC.16, 17 Since the Director-General declared the PHEIC on microcephaly and neurological disorders, many of us have had questions about how our recommendation relates to the PHEIC called by the Director-General for the 2014 Ebola outbreaks in west Africa based on the recommendation of a different Emergency Committee. The answer to us is clear. The Director-General declared the Ebola outbreaks a PHEIC because of what science knew about the Ebola virus from many years of research during outbreaks in the past, whereas she declared the current PHEIC because of what is not known about the current increase in reported clusters of microcephaly and other disorders, and how this might relate to concurrent Zika outbreaks. We were told by the Director-General that she would convene us again within 3 months to reassess the situation, as required under the International Health Regulations. We are confident that virtual meetings will allow us to review global collective action and to learn from WHO about progress in understanding the present situation of microcephaly and neurological disorders and progress in implementation of the precautionary and preparatory measures related to Zika.
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              Increase in Reported Prevalence of Microcephaly in Infants Born to Women Living in Areas with Confirmed Zika Virus Transmission During the First Trimester of Pregnancy - Brazil, 2015.

              Widespread transmission of Zika virus by Aedes mosquitoes has been recognized in Brazil since late 2014, and in October 2015, an increase in the number of reported cases of microcephaly was reported to the Brazil Ministry of Health.* By January 2016, a total of 3,530 suspected microcephaly cases had been reported, many of which occurred in infants born to women who lived in or had visited areas where Zika virus transmission was occurring. Microcephaly surveillance was enhanced in late 2015 by implementing a more sensitive case definition. Based on the peak number of reported cases of microcephaly, and assuming an average estimated pregnancy duration of 38 weeks in Brazil (1), the first trimester of pregnancy coincided with reports of cases of febrile rash illness compatible with Zika virus disease in pregnant women in Bahia, Paraíba, and Pernambuco states, supporting an association between Zika virus infection during early pregnancy and the occurrence of microcephaly. Pregnant women in areas where Zika virus transmission is occurring should take steps to avoid mosquito bites. Additional studies are needed to further elucidate the relationship between Zika virus infection in pregnancy and microcephaly.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Writing – review & editing
                Role: Data curationRole: Writing – review & editing
                Role: Formal analysisRole: Writing – review & editing
                Role: Writing – review & editing
                Role: ConceptualizationRole: ResourcesRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: ResourcesRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                1 July 2020
                2020
                : 15
                : 7
                Affiliations
                [1 ] Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia
                [2 ] Department of Biostatistics, School of Public Health, University of Ghana, Accra
                [3 ] The Jenner Institute, University of Oxford, The Henry Wellcome Building for Molecular Physiology, Oxford, England, United Kingdom
                Faculty of Science, Ain Shams University (ASU), EGYPT
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Article
                PONE-D-20-08037
                10.1371/journal.pone.0235322
                7329080
                32609784
                © 2020 Chisenga et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Page count
                Figures: 4, Tables: 1, Pages: 13
                Product
                Funding
                The study sample collection was funded by The European & Developing Countries Clinical Trials Partnership (Grant # TMA2016CDF-1550). Laboratory reagents and related supplies were donated by The Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom.
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                Custom metadata
                Data will be made available to any interested researchers upon request. The CIDRZ Ethics and Compliance Committee is responsible for approving such request. To request data access, one must write to the Committee chair/Chief Scientific Officer, Dr. Roma Chilengi, ( Roma.Chilengi@ 123456cidrz.org ) or the Secretary to the Committee/Head of Research Operations, Ms. Hope Mwanyungwi ( Hope.Mwanyungwi@ 123456cidrz.org ) through the corresponding author (Samuel Bosomprah, PhD) mentioning the intended use for the data. The corresponding author will then facilitate express authorisation to release the data as requested. Dataset request must include contact information, a research project title, and a description of the analysis being proposed as well as the format it is expected. The requested data should only be used for the purposes related to the original research or study. The CIDRZ Ethics and Compliance Committee will normally review all data requests within 48-72 hrs (Monday- Friday), and provide notification if access has been granted or additional project information is needed, before access can be granted.

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