Development of an urban molecular xenomonitoring system for lymphatic filariasis in the Recife Metropolitan Region, Brazil.

INTRODUCTION: Molecular xenomonitoring (MX)-pathogen detection in the mosquito rather than human-is a promising tool for lymphatic filariasis (LF) surveillance. In the Recife Metropolitan Region (RMR), the last LF focus in Brazil, Culex quinquefasciatus mosquitoes have been implicated in transmitting Wuchereria bancrofti parasites. This paper presents findings on the ideal mosquito collection method, mosquito dispersion, W. bancrofti infection in mosquitoes and W. bancrofti antigen in humans to aid MX development. METHODS: Experiments occurred within two densely populated urban areas of Olinda, RMR, in July and August 2015. U.S. Centers for Disease Control and Prevention (CDC) light traps were compared to battery-powered aspirators as collection methods, and mosquito dispersion was measured by mosquito mark release recapture (MMRR). Female Cx. quinquefasciatus were tested by PCR for W. bancrofti infection, and study area residents were screened by rapid tests for W. bancrofti antigen. RESULTS: Aspirators caught 2.6 times more total Cx. quinquefasciatus, including 38 times more blood-fed and 5 times more gravid stages, than CDC light traps. They also collected 123 times more Aedes aegypti. Of the 9,644 marked mosquitoes released, only ten (0.01%) were recaptured, nine of which were < 50m (34.8m median, 85.4m maximum) from the release point. Of 9,169 unmarked mosquitoes captured in the MMR, 38.3% were unfed, 48.8% blood-fed, 5.5% semi-gravid, and 7.3% gravid. PCR on 182 pools (1,556 mosquitoes) found no evidence of W. bancrofti infection in Cx. quinquefasciatus. Rapid tests on 110 of 111 eligible residents were all negative for W. bancrofti antigen. CONCLUSIONS: Aspirators were more effective than CDC light traps at capturing Ae. aegypti and all but unfed stages of Cx. quinquefasciatus. Female Cx. quinquefasciatus traveled short (< 86m) distances in this urban area. Lack of evidence for W. bancrofti infection in mosquitoes and antigen in humans in these fine-scale studies does not indicate that LF transmission has ceased in the RMR. A MX surveillance system should consider vector-specific collection methods, mosquito dispersion, and spatial scale but also local context, environmental factors such as sanitation, and host factors such as infection prevalence and treatment history

Postintervention immunological and entomological survey of lymphatic filariasis in the City of Olinda, Brazil, 2015–2016

Lymphatic filariasis (LF) is a leading cause of disability due to infectious disease worldwide. The Recife Metropolitan Region (RMR) is the only remaining focus of LF in Brazil, where the parasite Wuchereria bancrofti is transmitted solely by the mosquito Culex quinquefasciatus. This study reports the results of transmission assessment surveys and molecular xenomonitoring in the city of Olinda, RMR, after nearly 15 years (2015–2016) of interventions for LF elimination. Participants were screened for W. bancrofti antigen via immunochromatographic card tests (ICT) in: 1) door-to-door surveys conducted for all children aged 5–7 years from 4 out of 17 intervention areas treated with at least five annual doses of mass drug administration (MDA), and 2) a two-stage cluster sampling survey of residents aged 5 years and older in non-MDA areas. Mosquitoes were collected via handheld aspirators in four MDA areas, differentiated by species, sex, and physiological status, pooled into groups of up to 10 blood-fed, semigravid, and gravid mosquitoes, and screened for W. bancrofti infection by real-time quantitative polymerase chain reaction (RT-qPCR). All 1,170 children from MDA areas and the entire population sample of 990 residents in non-MDA areas were ICT negative. In MDA areas, a total of 3,152 female Cx. quinquefasciatus mosquitoes in 277 households (range, 0–296 mosquitoes per house) were collected via aspiration. RT-qPCR of 233 pools of mosquitos were negative for W. bancrofti RNA; an independent reference laboratory confirmed these results. These results provide evidence that LF transmission has been halted in this setting

Dengue virus–specific antibodies enhance brazilian Zika vrus infection

Anti-Flavivirus antibodies are highly cross-reactive and may facilitate Zika virus (ZIKV) infection through the antibody-dependent enhancement (ADE) mechanism. We demonstrate that dengue-specific antibodies enhance the infection of a primary Brazilian ZIKV isolate in a FcγRII-expressing K562 cell line. In addition, we demonstrate that serum samples from dengue-immune pregnant women enhanced ZIKV infection. These findings highlight the need for epidemiological studies and animal models to further confirm the role of ADE in the development of congenital and neurological complications associated with ZIKV infections

Persistent detection of Zika virus RNA from an infant with severe microcephaly – a case report

Abstract Background Zika virus (ZIKV) is a recently emerged arbovirus, which infection during pregnancy is associated with a series of congenital malformations, collectively denominated Congenital Zika Syndrome (CZS). Following infection, ZIKV RNA has a median duration period of 10 days in plasma and up to 6 months in semen in immunocompetent adult individuals. Moreover, ZIKV is able to replicate and persist in fetal brains and placentas, consequently, infection is associated with pregnancy loss, albeit the pathogenic mechanisms are still unknown. Case presentation Here we report a CZS case of an infant born during the ZIKV outbreak in northeast Brazil, the child presented recurrent episodes of seizures with prolonged presence of ZIKV RNA on the central nervous system (CNS) and blood. ZIKV RNA was identified and partially sequenced from a sample of cerebrospinal fluid (CSF) obtained from the infant with 6 months of life, and later from another sample after the infant completed 17 months of life. Commonly congenital infections were discarded based on STORCH (syphilis, toxoplasmosis, rubella, cytomegalovirus and herpes simplex virus) negative laboratory results. Presence of specific ZIKV antibodies on both mother and children confirmed the association of severe microcephaly and ZIKV infection, diagnosed after birth. Conclusions Altogether, our data raise the possibility that CZS cases may result in prolonged viral presence, these findings could be useful for therapy and diagnostic recommendations

Zika virus displacement by a chikungunya outbreak in Recife, Brazil

Submitted by Raphael Belchior Rodrigues ([email protected]) on 2017-12-06T16:35:01Z No. of bitstreams: 1 ve_Tereza_Magalhaes_etal_IAM_2017.pdf: 36860113 bytes, checksum: d0b4993e51041e7d8574914348560704 (MD5)Approved for entry into archive by Raphael Belchior Rodrigues ([email protected]) on 2017-12-12T18:26:18Z (GMT) No. of bitstreams: 1 ve_Tereza_Magalhaes_etal_IAM_2017.pdf: 36860113 bytes, checksum: d0b4993e51041e7d8574914348560704 (MD5)Made available in DSpace on 2017-12-12T18:26:18Z (GMT). No. of bitstreams: 1 ve_Tereza_Magalhaes_etal_IAM_2017.pdf: 36860113 bytes, checksum: d0b4993e51041e7d8574914348560704 (MD5) Previous issue date: 2017: This study was funded by the European Union’s Seventh Framework Programme for research, technological development and demonstration (grant FP7-281803 IDAMS; http:// www.idams.eu/), where it has been designated with publication reference number IDAMS 45; the State of Pernambuco funding agency (Fundac¸ão de Amparo à Ciência e Tecnologia do Estado de Pernambuco-FACEPE; grant PPSUS APQ-0302-4.01/13); the European Union’s Horizon 2020 Research and Innovation Programme under ZIKAlliance (grant 734548); the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (grant R21AI129464); the ZikaCura (PITT-FIOCRUZ Alliance); and the Brazilian national funding agency (Conselho Nacional de Desenvolvimento Cientı´fico e Tecnolo´gico of Brazil-CNPq; grant 472360/2013-2). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscriptFundação Oswaldo Cruz. Departamento de Virologia. Recife, PE, Brasil / Arthropod-borne and infectious Diseases Laboratory (AIDL), Department of Microbiology, Immunology and Pathology, Colorado State University (CSU), Fort Collins, United States of America.Fundação Oswaldo Cruz. Departamento de Parasitologia. Recife, PE, Brasil / Instituto de Medicina Integral Professor Fernando Figueira. Recife, PE, Brasil.Fundação Oswaldo Cruz. Departamento de Virologia. Recife, PE, Brasil.Fundação Oswaldo Cruz. Laboratório de Estatística e Geoprocessamento. Recife, PE, Brasil.Fundação Oswaldo Cruz. Departamento de Virologia. Recife, PE, Brasil / Universidade de Pernambuco. Faculdade de Medicina. Recife, PE, Brasil.Unidade de Pronto Atendimento de Paulista, IMIP, Paulista, Brazil.Unidade de Pronto Atendimento de Paulista, IMIP, Paulista, Brazil.Unidade de Pronto Atendimento de Paulista, IMIP, Paulista, Brazil.Instituto de Medicina Integral Professor Fernando Figueira. Recife, PE, Brasil.Fundação Oswaldo Cruz. Departamento de Virologia. Recife, PE, Brasil.Fundação Oswaldo Cruz. Departamento de Virologia. Recife, PE, Brasil.Section Clinical Tropical Medicine, Department of Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany.Section Clinical Tropical Medicine, Department of Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany / German Centre for Infection Research , partner site Heidelberg, Heidelberg, GermanyFundação Oswaldo Cruz. Departamento de Virologia. Recife, PE, Brasil / Center for Vaccine Research, University of Pittsburgh, Pittsburgh, United States of America.Several arboviruses, including dengue virus (DENV), Zika virus (ZIKV) and chikungunya virus (CHIKV), transmitted by Aedes mosquitoes, circulate in northeast Brazil. Diseases caused by these viruses are of great public health relevance, however, their epidemiological features in areas where the three viruses co-circulate are scarce. Here, we present analyses of molecular and serological diagnostics in a prospective study of acute febrile patients recruited from May 2015 to May 2016 in Recife, Brazil

Perinatal analyses of Zika- and dengue virus-specific neutralizing antibodies: A microcephaly case-control study in an area of high dengue endemicity in Brazil.

Laboratory confirmation of Zika virus (ZIKV) infection during pregnancy is challenging due to cross-reactivity with dengue virus (DENV) and limited knowledge about the kinetics of anti-Zika antibody responses during pregnancy. We described ZIKV and DENV serological markers and the maternal-fetal transfer of antibodies among mothers and neonates after the ZIKV microcephaly outbreak in Northeast Brazil (2016). We included 89 microcephaly cases and 173 neonate controls at time of birth and their mothers. Microcephaly cases were defined as newborns with a particular head circumference (2 SD below the mean). Two controls without microcephaly were matched by the expected date of delivery and area of residence. We tested maternal serum for recent (ZIKV genome, IgM and IgG3 anti-NS1) and previous (ZIKV and DENV neutralizing antibodies [NAbs]) markers of infection. Multiple markers of recent or previous ZIKV and DENV infection in mothers were analyzed using principal component analysis (PCA). At delivery, 5.6% of microcephaly case mothers and 1.7% of control mothers were positive for ZIKV IgM. Positivity for ZIKV IgG3 anti-NS1 was 8.0% for case mothers and 3.5% for control mothers. ZIKV NAbs was slightly higher among mothers of cases (69.6%) than that of mothers of controls (57.2%; p = 0.054). DENV exposure was detected in 85.8% of all mothers. PCA discriminated two distinct components related to recent or previous ZIKV infection and DENV exposure. ZIKV NAbs were higher in newborns than in their corresponding mothers (p<0.001). We detected a high frequency of ZIKV exposure among mothers after the first wave of the ZIKV outbreak in Northeast Brazil. However, we found low sensitivity of the serological markers to recent infection (IgM and IgG3 anti-NS1) in perinatal samples of mothers of microcephaly cases. Since the neutralization test cannot precisely determine the time of infection, testing for ZIKV immune status should be performed as early as possible and throughout pregnancy to monitor acute Zika infection in endemic areas