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Rapid antigen tests for dengue virus serotypes and Zika virus in patient serum

By Bosch I, de Puig H, Hiley M, et al.

The recent Zika virus (ZIKV) outbreak demonstrates that cost-effective clinical diagnostics are urgently needed to detect and distinguish viral infections to improve patient care. Unlike dengue virus (DENV), ZIKV infections during pregnancy correlate with severe birth defects, including microcephaly and neurological disorders. Because ZIKV and DENV are related flaviviruses, their homologous proteins and nucleic acids can cause cross-reactions and false-positive results in molecular, antigenic, and serologic diagnostics. We report the characterization of monoclonal antibody pairs that have been translated into rapid immunochromatography tests to specifically detect the viral nonstructural 1 (NS1) protein antigen and distinguish the four DENV serotypes (DENV1–4) and ZIKV without cross-reaction. To complement visual test analysis and remove user subjectivity in reading test results, we used image processing and data analysis for data capture and test result quantification. Using a 30-μl serum sample, the sensitivity and specificity values of the DENV1–4 tests and the pan-DENV test, which detects all four dengue serotypes, ranged from 0.76 to 1.00. Sensitivity/specificity for the ZIKV rapid test was 0.81/0.86, respectively, using a 150-μl serum input. Serum ZIKV NS1 protein concentrations were about 10-fold lower than corresponding DENV NS1 concentrations in infected patients; moreover, ZIKV NS1 protein was not detected in polymerase chain reaction–positive patient urine samples. Our rapid immunochromatography approach and reagents have immediate application in differential clinical diagnosis of acute ZIKV and DENV cases, and the platform can be applied toward developing rapid antigen diagnostics for emerging viruses.

Published in: Science Translational Medicine. 2017;9(409)

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Structural investigation of C6/36 and Vero cell cultures infected with a Brazilian Zika virus

By Barreto-Vieira DF, Jacome FC, da Silva MAN, et al.

Zika virus (ZIKV) is a member of the flavivirus genus, and its genome is approximately 10.8 kilobases of positive-strand RNA enclosed in a capsid and surrounded by a membrane. Studies on the replication dynamics of ZIKV are scarce, which limits the development of antiviral agents and vaccines directed against ZIKV. In this study, Aedes albopictus mosquito lineage cells (C6/36 cells) and African green monkey kidney epithelial cells (Vero cells) were inoculated with a ZIKV sample isolated from a Brazilian patient, and the infection was characterized by immunofluorescence staining, phase contrast light microscopy, transmission electron microscopy and real-time RT-PCR. The infection was observed in both cell lineages, and ZIKV particles were observed inside lysosomes, the rough endoplasmic reticulum and viroplasm-like structures. The susceptibility of C6/36 and Vero cells to ZIKV infection was demonstrated. Moreover, this study showed that part of the replicative cycle may occur within viroplasm-like structures, which has not been previously demonstrated in other flaviviruses.

Published in: PLoS One2017;12(9):e0184397.

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Zika genomics urgently need standardized and curated reference sequences

By Theys K, Libin P, Dallmeier K, et al.

In this letter, the authors address the need for curation and standardized annotation of ZIKV reference genomes in order to guide researchers and clinicians in genomic analyses and the translation of research findings.

Published in: PLoS Pathog. 2017;13(9):e1006528

 

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Neurologic Complications Associated With the Zika Virus in Brazilian Adults

By Da Silva IRF, Frontera JA, Bispo de Filippis AM, Nascimento OJMD; RIO-GBS-ZIKV Research Group. 

There are no prospective cohort studies assessing the incidence and spectrum of neurologic manifestations secondary to Zika virus (ZIKV) infection in adults. The article reports on the observational cohort study whose objective was to evaluate the rates of acute ZIKV infection among patients hospitalized with Guillain-Barré syndrome (GBS), meningoencephalitis, or transverse myelitis.

Published in: JAMA Neurol. 2017 Aug 14.

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Antibody-based assay discriminates Zika virus infection from other flaviviruses

By Balmaseda A, Stettler K, Medialdea-Carrera R, Collado D, Jin X, Zambrana JV, Jaconi S, Cameroni E, Saborio S, Rovida F, Percivalle E, Ijaz S, Dicks S, Ushiro-Lumb I, Barzon L, Siqueira PBrown DWG, Baldanti F, Tedder R, Zambon M, de Filippis AMB, Harris E, Corti D.

Zika virus (ZIKV) is a mosquito-borne flavivirus that emerged recently as a global health threat, causing a pandemic in the Americas. ZIKV infection mostly causes mild disease, but is linked to devastating congenital birth defects and Guillain-Barré syndrome in adults. The high level of cross-reactivity among flaviviruses and their cocirculation has complicated serological approaches to differentially detect ZIKV and dengue virus (DENV) infections, accentuating the urgent need for a specific and sensitive serological test. We previously generated a ZIKV nonstructural protein 1 (NS1)-specific human monoclonal antibody, which we used to develop an NS1-based competition ELISA. Well-characterized samples from RT-PCR-confirmed patients with Zika and individuals exposed to other flavivirus infections or vaccination were used in a comprehensive analysis to determine the sensitivity and specificity of the NS1 blockade-of-binding (BOB) assay, which was established in laboratories in five countries (Nicaragua, Brazil, Italy, United Kingdom, and Switzerland). Of 158 sera/plasma from RT-PCR-confirmed ZIKV infections, 145 (91.8%) yielded greater than 50% inhibition. Of 171 patients with primary or secondary DENV infections, 152 (88.9%) scored negative. When the control group was extended to patients infected by other flaviviruses, other viruses, or healthy donors (n = 540), the specificity was 95.9%. We also analyzed longitudinal samples from DENV-immune and DENV-naive ZIKV infections and found inhibition was achieved within 10 d postonset of illness and maintained over time. Thus, the Zika NS1 BOB assay is sensitive, specific, robust, simple, low-cost, and accessible, and can detect recent and past ZIKV infections for surveillance, seroprevalence studies, and intervention trials.

Published in: Proc Natl Acad Sci U S A. 2017Aug 1;114(31):8384-8389.

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Accuracy of Zika virus disease case definition during simultaneous Dengue and Chikungunya epidemics

By Braga JU, Bressan C, Dalvi APR, Calvet GA, Daumas RP, Rodrigues N, Wakimoto M, Nogueira RMR, Nielsen-Saines K, Brito C, Bispo de Filippis AM, Brasil P

Zika is a new disease in the American continent and its surveillance is of utmost importance, especially because of its ability to cause neurological manifestations as Guillain-Barré syndrome and serious congenital malformations through vertical transmission. The detection of suspected cases by the surveillance system depends on the case definition adopted. As the laboratory diagnosis of Zika infection still relies on the use of expensive and complex molecular techniques with low sensitivity due to a narrow window of detection, most suspected cases are not confirmed by laboratory tests, mainly reserved for pregnant women and newborns. In this context, an accurate definition of a suspected Zika case is crucial in order for the surveillance system to gauge the magnitude of an epidemic.

Published in: PLoS One. 2017 Jun 26;12(6):e0179725. 

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Zika virus infection-associated acute transient polyneuritis

By Nascimento OJM, Frontera JA, Amitrano DA, Bispo de Filippis AM, Da Silva IRF; RIO-GBS-ZIKV Research Group. 

This article describes a case series of 3 patients admitted to a tertiary hospital in Rio de Janeiro during the 2016 outbreak of Zika virus infection in Brazil.

Published in: Neurology 2017 Jun 13;88(24):2330-2332.

 

 

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Trends of Microcephaly and Severe Arthrogryposis in Three Urban Hospitals following the Zika, Chikungunya and Dengue Fever Epidemics of 2016 in Jamaica

By James-Powell T., Brown Y., Christie CDC., Melbourne-Chambers R., Moore JT., Morgan O., Butler B., Swaby K., Garbutt A., Anzinger J., Pierre RB., Onyonyor A., Bryan L., Palmer PM, Mitchell P., Johnson P., Bishop K., Jaggon JR., De La Haye W. 

Jamaica experienced its maiden Zika virus (ZIKV) epidemic in 2016, while dengue (serotypes 3 and 4) and chikungunya were also circulating. In this article, we describe initial trends in microcephaly and arthrogryposis observed by the clinicians from three urban birthing facilities during late 2016 to early 2017.

Published in: West Indian Medical Journal, 2017; 66:10-19 and Epub-ahead-of-print, 12 Jun, 2017; DOI 10.7727/wimj.2017.124. 

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Achieving Elimination of Vertical Transmission of HIV in Jamaica

By Christie CDC, Palmer PM, Tomlinson J., Green-Douglas T., Hamilton M., Pierre RB.,  Hylton-Kong T., Morgan O., Barrow G., Mitchell P., Skyers N., Stevens E-J., Condell-Gibson N, Harvey KM.

Jamaica is an upper middle-income developing Caribbean island-nation, population 2.8 million, with a generalized and mixed HIV epidemic. We report progress towards achieving international validation standards for the elimination of vertical transmission of HIV and syphilis in Jamaica during 2013 through 2015.

Published in: Annals of Public Health and Research 2017:4(2);1091-9.

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Maternal Zika Virus Disease Severity, Virus Load, Prior Dengue Antibodies and their Relationship to Birth Outcomes

By Halai UA, Nielsen-Saines K, Moreira ME, Sequeira PC, Pereira Junior JP, Zin AA, Cherry JD, Gabaglia CR, Gaw SL, Adachi K, Tsui I, Pilotto JH, Ribeiro Nogueira RM, Bispo de Filippis AM, Brasil P. 

Congenital Zika virus (ZIKV) syndrome is a newly identified condition resulting from infection during pregnancy. We analyzed outcome data from a mother-infant cohort in Rio de Janeiro in order to assess whether clinical severity of maternal ZIKV infection was associated with maternal virus load, prior dengue antibodies or abnormal pregnancy/infant outcomes.

Published in: Clin Infect Dis. 2017 May 23.

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