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Title: Epidemiological profile of Zika, Dengue and Chikungunya virus infections identified by medical and molecular evaluations in Rondonia, Brazil
Authors: Vieira, Deusilene Souza; Zambenedetti, Miriam Ribas; Requião, Luciana; Borghetti, Ivo Alberto; Luna, Luciano Kleber de Souza; Santos, Alcione de Oliveira Dos; Taborda, Roger Lafontaine Mesquita; Pereira, Dhelio Batista; Krieger, Marco Aurélio; Salcedo, Juan Miguel Villalobos; Rampazzo, Rita de Cássia Pontello

Title: O impacto da Leptospirose epidêmica urbana e a detecção da dengue a nível ambulatorial em Salvador - BA
Authors: Matos, Rosan Barbosa de; Saito, Elisa Y.; Nuevo, Hector Leal; Costa, Dirceu Joaquim; Flannery, Brendan; Trocoli, Maria G.; Dias, Juarez Pereira; Reis, Mitermayer Galvão dos; Ko, Albert Icksang

by Isabelle Dusfour, John Vontas, Jean-Philippe David, David Weetman, Dina M. Fonseca, Vincent Corbel, Kamaraju Raghavendra, Mamadou B. Coulibaly, Ademir J. Martins, Shinji Kasai, Fabrice Chandre
Background The landscape of mosquito-borne disease risk has changed dramatically in recent decades, due to the emergence and reemergence of urban transmission cycles driven by invasive Aedes aegypti and Ae. albopictus. Insecticide resistance is already widespread in the yellow fever mosquito, Ae. Aegypti; is emerging in the Asian tiger mosquito Ae. Albopictus; and is now threatening the global fight against human arboviral diseases such as dengue, yellow fever, chikungunya, and Zika. Because the panel of insecticides available for public health is limited, it is of primary importance to preserve the efficacy of existing and upcoming active ingredients. Timely implementation of insecticide resistance management (IRM) is crucial to maintain the arsenal of effective public health insecticides and sustain arbovirus vector control. Methodology and principal findings This Review is one of a series being generated by the Worldwide Insecticide resistance Network (WIN) and aims at defining the principles and concepts underlying IRM, identifying the main factors affecting the evolution of resistance, and evaluating the value of existing tools for resistance monitoring. Based on the lessons taken from resistance strategies used for other vector species and agricultural pests, we propose a framework for the implementation of IRM strategies for Aedes mosquito vectors. Conclusions and significance Although IRM should be a fixture of all vector control programs, it is currently often absent from the strategic plans to control mosquito-borne diseases, especially arboviruses. Experiences from other public health disease vectors and agricultural pests underscore the need for urgent action in implementing IRM for invasive Aedes mosquitoes. Based on a plan developed for malaria vectors, here we propose some key activities to establish a global plan for IRM in Aedes spp.

by Elliott F. Miot, Fabien Aubry, Stéphanie Dabo, Ian H. Mendenhall, Sébastien Marcombe, Cheong H. Tan, Lee C. Ng, Anna-Bella Failloux, Julien Pompon, Paul T. Brey, Louis Lambrechts

The case-fatality rate of yellow fever virus (YFV) is one of the highest among arthropod-borne viruses (arboviruses). Although historically, the Asia-Pacific region has remained free of YFV, the risk of introduction has never been higher due to the increasing influx of people from endemic regions and the recent outbreaks in Africa and South America. Singapore is a global hub for trade and tourism and therefore at high risk for YFV introduction. Effective control of the main domestic mosquito vector Aedes aegypti in Singapore has failed to prevent re-emergence of dengue, chikungunya and Zika viruses in the last two decades, raising suspicions that peridomestic mosquito species untargeted by domestic vector control measures may contribute to arbovirus transmission. Here, we provide empirical evidence that the peridomestic mosquito Aedes malayensis found in Singapore can transmit YFV. Our laboratory mosquito colony recently derived from wild Ae. malayensis in Singapore was experimentally competent for YFV to a similar level as Ae. aegypti controls. In addition, we captured Ae. malayensis females in one human-baited trap during three days of collection, providing preliminary evidence that host-vector contact may occur in field conditions. Finally, we detected Ae. malayensis eggs in traps deployed in high-rise building areas of Singapore. We conclude that Ae. malayensis is a competent vector of YFV and re-emphasize that vector control methods should be extended to target peridomestic vector species.

by Ricardo Arraes de Alencar Ximenes, Demócrito de Barros Miranda-Filho, Elizabeth B. Brickley, Ulisses Ramos Montarroyos, Celina Maria Turchi Martelli, Thalia Velho Barreto de Araújo, Laura C. Rodrigues, Maria de Fatima Pessoa Militão de Albuquerque, Wayner Vieira de Souza, Priscila Mayrelle da Silva Castanha, Rafael F. O. França, Rafael Dhália, Ernesto T. A. Marques, on behalf of the Microcephaly Epidemic Research Group (MERG)

Defining cases of Zika virus (ZIKV) infection is a critical challenge for epidemiological research. Due to ZIKV’s overlapping clinical features and potential immunologic cross-reactivity with other flaviviruses and the current lack of an optimal ZIKV-specific diagnostic assay, varying approaches for identifying ZIKV infections have been employed to date. This paper presents the laboratory results and diagnostic criteria developed by the Microcephaly Epidemic Research Group for defining cases of maternal ZIKV infection in a cohort of pregnant women with rash (N = 694) recruited during the declining 2015–2017 epidemic in northeast Brazil. For this investigation, we tested maternal sera for ZIKV by quantitative reverse transcription polymerase chain reaction (qRT-PCR), Immunoglobulin (Ig) M and IgG3 enzyme-linked immunosorbent assays (ELISAs), and Plaque Reduction Neutralization Test (PRNT50). Overall, 23.8% of participants tested positive by qRT-PCR during pregnancy (range of detection: 0–72 days after rash onset). However, the inter-assay concordance was lower than expected. Among women with qRT-PCR-confirmed ZIKV and further testing, only 10.1% had positive IgM tests within 90 days of rash, and only 48.5% had ZIKV-specific PRNT50 titers ≥20 within 1 year of rash. Given the complexity of these data, we convened a panel of experts to propose an algorithm for identifying ZIKV infections in pregnancy based on all available lines of evidence. When the diagnostic algorithm was applied to the cohort, 26.9% of participants were classified as having robust evidence of a ZIKV infection during pregnancy, 4.0% as having moderate evidence, 13.3% as having limited evidence of a ZIKV infection but with uncertain timing, and 19.5% as having evidence of an unspecified flavivirus infection before or during pregnancy. Our findings suggest that integrating longitudinal data from nucleic acid and serologic testing may enhance diagnostic sensitivity and underscore the need for an on-going dialogue regarding the optimization of strategies for defining cases of ZIKV in research.

Title: Wild-Type Yellow Fever Virus RNA in Cerebrospinal Fluid of Child.
Authors: Marinho, Paula Eillanny Silva; Alvarenga, Pedro Paulo Martins; Crispim, Ana Paula Correia; Candiani, Talitah Michel Sanchez; Alvarenga, Alice Martins; Machado, Isabela Bechler; Alves, Pedro A.; Dornas, Fabio Pio; Oliveira, Danilo Bretas de; Bentes, Aline Almeida; Christo, Paulo Pereira; Kroon, Erna Geessien

by Cíntia Pereira Donateli, Ariadne Barbosa do Nascimento Einloft, André Luiz Coutinho Junior, Rosângela Minardi Mitre Cotta, Glauce Dias da Costa
Background Arboviruses pose a serious and constant threat to public health, and have demanded surveillance efforts worldwide. The prevention of arbovirus transmission depends on effective measures to control vectors and promote health. The objective of this study was to examine the factors that enhance and impair the endemic disease control agents’ field work, based on their own perspective. Methodology and main findings In 2017, 65 ACE of seven municipalities participated in a series of seven focus groups in the Zona de Mata mesoregion (Minas Gerais, Brazil). The focus groups were organized aiming to broaden and deepen the discussion and analysis of ACE perception of their performance in relation to attributions, work processes, training, continuous education, and evaluation. All the workers, irrespective of municipality, recognize their role in disease prevention and health promotion, however they suffer from a reductionist stigma associated with their profession. Also, internal and external factors such as infrastructure, resources, administrative management, and the work process affect the quality of service delivered and job satisfaction. Practice challenges include incompatible demands such as refusal by residents and high sense of insecurity related to violence. The respondents reported that success of their activities depend on the population. Conclusions/Significance The recurrence of epidemics demands effective vector control policies. Therefore, the performance of these professionals as regards surveillance needs to be reassessed. Public awareness and acknowledgement of the role of ACE in the identification of risk and health protection factors are indispensable for the improvement of this workforce.

by Pei-Ying Kobres, Jean-Paul Chretien, Michael A. Johansson, Jeffrey J. Morgan, Pai-Yei Whung, Harshini Mukundan, Sara Y. Del Valle, Brett M. Forshey, Talia M. Quandelacy, Matthew Biggerstaff, Cecile Viboud, Simon Pollett
Introduction Epidemic forecasting and prediction tools have the potential to provide actionable information in the midst of emerging epidemics. While numerous predictive studies were published during the 2016–2017 Zika Virus (ZIKV) pandemic, it remains unknown how timely, reproducible, and actionable the information produced by these studies was. Methods To improve the functional use of mathematical modeling in support of future infectious disease outbreaks, we conducted a systematic review of all ZIKV prediction studies published during the recent ZIKV pandemic using the PRISMA guidelines. Using MEDLINE, EMBASE, and grey literature review, we identified studies that forecasted, predicted, or simulated ecological or epidemiological phenomena related to the Zika pandemic that were published as of March 01, 2017. Eligible studies underwent evaluation of objectives, data sources, methods, timeliness, reproducibility, accessibility, and clarity by independent reviewers. Results 2034 studies were identified, of which n = 73 met the eligibility criteria. Spatial spread, R0 (basic reproductive number), and epidemic dynamics were most commonly predicted, with few studies predicting Guillain-Barré Syndrome burden (4%), sexual transmission risk (4%), and intervention impact (4%). Most studies specifically examined populations in the Americas (52%), with few African-specific studies (4%). Case count (67%), vector (41%), and demographic data (37%) were the most common data sources. Real-time internet data and pathogen genomic information were used in 7% and 0% of studies, respectively, and social science and behavioral data were typically absent in modeling efforts. Deterministic models were favored over stochastic approaches. Forty percent of studies made model data entirely available, 29% provided all relevant model code, 43% presented uncertainty in all predictions, and 54% provided sufficient methodological detail to allow complete reproducibility. Fifty-one percent of predictions were published after the epidemic peak in the Americas. While the use of preprints improved the accessibility of ZIKV predictions by a median of 119 days sooner than journal publication dates, they were used in only 30% of studies. Conclusions Many ZIKV predictions were published during the 2016–2017 pandemic. The accessibility, reproducibility, timeliness, and incorporation of uncertainty in these published predictions varied and indicates there is substantial room for improvement. To enhance the utility of analytical tools for outbreak response it is essential to improve the sharing of model data, code, and preprints for future outbreaks, epidemics, and pandemics.

by Fabio Antonio Venancio, Maria Eulina Quilião Bernal, Maria da Conceição de Barros Vieira Ramos, Neuma Rocha Chaves, Marcos Vinicius Hendges, Mattheus Marques Rodrigues de Souza, Márcio José de Medeiros, Cláudia Du Bocage Santos Pinto, Everton Falcão de Oliveira

Congenital Zika Syndrome (CZS) is a unique pattern of congenital abnormalities found in fetuses and neonates infected with the Zika virus (ZIKV). Here, we clinically identify and characterize infants with CZS between 2015 and 2018 in Mato Grosso do Sul, Brazil—a border area with Paraguay and Bolivia. This cross-sectional study, based on primary and secondary data, tracks the cases registered in the Brazilian Public Health Reporting System through the following stages: (1) preliminary data analysis, (2) identification of the congenital syndrome cases, (3) etiologic classification of the cases, (4) active search, and (5) clinical assessment. Of the 72 investigated cases, 16 were probable cases of CZS. Of these, it was only possible to clinically assess 11 infants. Considering the 16 probable cases of CZS, nine were classified as confirmed cases, and five as potential cases of the syndrome. Regarding clinical features, brain palsy was identified in all analyzed infants. Moreover, microcephaly and pseudobulbar syndrome were found in eight infants, and hydrocephalus was found in three individuals. In addition to these conditions, seven children were malnourished. Our study may provide significant insights for other researches that aim to elucidate CZS and its clinical and populational consequences.

Title: Impact of preexisting dengue immunity on Zika virus emergence in a dengue endemic region
Authors: Rodriguez-Barraquer, Isabel; Costa, Federico; Nascimento, Eduardo J. M.; Nery, Nivison; Castanha, Priscila M. S.; Sacramento, Gielson Almeida; Cruz, Jaqueline; Carvalho, Mayara; Olivera, Daiana de; Hagan, José E.; Adhikarla, Haritha; Wunder, Elsio A.; Coêlho, Danilo F.; Azar, Sasha R.; Rossi, Shannan L.; Vasilakis, Nikos; Weaver, Scott C.; Ribeiro, Guilherme S.; Balmaseda, Angel; Harris, Eva; Nogueira, Maurício L.; Reis, Mitermayer G.; Marques, Ernesto T. A.; Cummings, Derek A. T.; Ko, Albert I.

Title: Circulation of chikungunya virus East/Central/South African lineage in Rio de Janeiro, Brazil
Authors: Xavier, Joilson; Giovanetti, Marta; Fonseca, Vagner; Thézé, Julien; Gräf, Tiago; Fabri, Allison; Jesus, Jaqueline Goes de; Mendonça, Marcos Cesar Lima de; Rodrigues, Cintia Damasceno dos Santos; Mares-Guia, Maria Angélica; Santos, Carolina Cardoso dos; Tosta, Stephane Fraga de Oliveira; Candido, Darlan; Nogueira, Rita Maria Ribeiro; Abreu, André Luiz de; Oliveira, Wanderson Kleber; Albuquerque, Carlos F. Campelo de; Chieppe, Alexandre; Oliveira, Tulio de; Brasil, Patrícia; Calvet, Guilherme; Sequeira, Patrícia Carvalho; Faria, Nuno Rodrigues; Filippis, Ana Maria Bispo de; Alcantara, Luiz Carlos Junior

Title: Short-lived immunity after 17DD Yellow Fever single dose indicates that booster vaccination may be required to guarantee protective immunity in children
Authors: Campi-Azevedo, Ana Carolina; Reis, Laise Rodrigues; Peruhype-Magalhães, Vanessa; Reis, Jordana Grazziela Coelho dos; Antonelli, Lis Ribeiro; Fonseca, Cristina Toscano; Costa-Pereira, Christiane; Souza-Fagundes, Elaine Maria; Costa-Rocha, Ismael Artur da; Mambrini, Juliana Vaz de Melo; Lemos, Jandira Aparecida Campos; Ribeiro, José Geraldo Leite; Caldas, Iramaya Rodrigues; Camacho, Luiz Antônio Bastos; Maia, Maria de Lourdes de Sousa; Noronha, Tatiana Guimarães de; Lima, Sheila Maria Barbosa de; Simões, Marisol; Freire, Marcos da Silva; Martins, Reinaldo de Menezes; Homma, Akira; Tauil, Pedro Luiz; Vasconcelos, Pedro Fernando Costa; Romano, Alessandro Pecego Martins; Domingues, Carla Magda; Teixeira-Carvalho, Andréa; Martins Filho, Olindo Assis
Abstract: A vacinação contra a febre amarela (YF) é recomendada para pessoas que vivem em áreas endêmicas e representa a estratégia mais eficaz para reduzir o risco de infecção. Estudos anteriores alertaram que os regimes de reforço devem ser considerados para garantir a persistência a longo prazo dos componentes de memória específicos da 17DD-YF em adultos que vivem em áreas com circulação do vírus da YF. Considerando as menores taxas de soroconversão observadas em crianças (9 a 12 meses de idade) em comparação aos adultos, este estudo foi desenvolvido para acessar a duração da imunidade em crianças vacinadas em dose única em um período de 10 anos de seção transversal . Os níveis de anticorpos neutralizantes (PRNT) e o status fenotípico / de memória funcional das células T e B foram medidos no início, 30 a 45 dias, 1, 2, 4, 7 e 10 anos após a vacinação primária. Os resultados revelaram que uma dose única induziu 85% de soropositividade entre 30 e 45 dias e uma diminuição progressiva dependente do tempo foi observada em apenas 2 anos e diminui para valores críticos (abaixo de 60%) em períodos de tempo ≥ 4 anos . Além disso, a imunidade celular específica de YF de curta duração, mediada pelas células T e B de memória, também foi observada após 4 anos. A análise de probabilidade prevista e a memória resultante enfatizam que os correlatos de proteção (PRNT; células T CD8 + com memória efetiva; células B com memória não clássica) diminuem para valores críticos dentro de ≥4 anos após a vacinação primária. Juntos, esses resultados demonstram claramente o declínio da resposta da memória específica da 17DD-YF ao longo do tempo em crianças vacinadas principalmente entre 9 e 12 meses de idade e suportam a necessidade de um regime de reforço para garantir a persistência a longo prazo dos componentes da memória para crianças que vivem em áreas com alto risco de transmissão YF.

by Hannah Kuper, Maria Elisabeth Lopes Moreira, Thália Velho Barreto de Araújo, Sandra Valongueiro, Silke Fernandes, Marcia Pinto, Tereza Maciel Lyra
Background Zika virus (ZIKV) infection in pregnancy can cause microcephaly and a wide spectrum of severe adverse outcomes, collectively called “Congenital Zika Syndrome” (CZS). Parenting a child with disabilities can have adverse mental health impacts, but these associations have not been fully explored in the context of CZS in Brazil. Methodology/Principal findings A cross-sectional study was undertaken in Recife and Rio de Janeiro, including 163 caregivers of a child with CZS (cases) and 324 caregivers with an unaffected child (comparison subjects), identified from existing studies. The primary caregiver, almost always the mother, was interviewed using a structured questionnaire to collect information on: depression, anxiety, and stress (Depression, Anxiety, and Stress Scale—DASS-21), social support (Medical Outcomes Study Social Support Scale—MOS-SSS), and socio-demographic data. Data was collected May 2017-January 2018. Ethical standards were adhered to throughout the research. A high proportion of mothers reported experiencing severe or extremely severe levels of depression (18%), anxiety (27%) and stress (36%). Mothers of children with CZS were more likely to experience symptoms of depression, anxiety andstress, compared to mothers of comparison children. These associations were more apparent among mothers living in Rio de Janeiro. These differences were reduced after adjustment for socio-economic status and social support. Among mothers of children with CZS, low social support was linked to higher levels of depression, anxiety and stress, but there was no association with socio-economic status. Conclusions/Significance Depression, anxiety and stress were very common among mothers of young children in Brazil, regardless of whether they were parenting a child with disabilities. Mothers of children with CZS may be particularly vulnerable to poor mental health, and this association may be buffered through better social support.

Title: The Transcriptional and Protein Profile From Human Infected Neuroprogenitor Cells Is Strongly Correlated to Zika Virus Microcephaly Cytokines Phenotype Evidencing a Persistent Inflammation in the CNS
Authors: Lima, Morganna C.; Mendonça, Leila R. de; Rezende, Antonio M.; Carrera, Raquel M.; Silva, Conceição Elidianne Anibal; Demers, Matthew; D'Aiuto, Leonardo; Wood, Joel; Chowdari, Kodavali V; Griffiths, Michael; Araujo, Antonio R. Lucena; Barral Netto, Manoel; Azevedo, Elisa A N; Alves, Renan W; Farias, Pablo C. S.; Marques, Ernesto T. A.; Castanha, Priscila M. S.; Donald, Claire L.; Kohl, Alain; Nimgaonkar, Vishwajit L.; Franca, Rafael F. O.

Title: Revisão integrativa sobre os testes diagnósticos da febre de Chikungunya
Authors: Oliveira, Monique Mendes de
Abstract: A Febre de Chikungunya é causada pelo vírus Chikungunya (VCHIK), um arbovírus de genoma RNA, de cadeia simples, com polaridade positiva e pertencente à família Togaviridae. A transmissão ocorre pela picada da fêmea de mosquitos do gênero Aedes, sendo o A. aegypti e o A. albopictus as espécies mais comumente infectadas no Brasil. O período de incubação ocorre de 2-12 dias e dentre os acometidos há uma porcentagem que não apresenta os sintomas da doença. A infecção aguda típica em pacientes sintomáticos varia de leve a moderada com recuperação de 2 a 4 semanas. A doença é caracterizada por início repentino de febre intensa, dores intensas nas articulações (artralgia) de pés e mãos (dedos, tornozelos e pulsos) e sintomas menos evidentes como cefaleia e manchas vermelhas na pele. O Ministério da Saúde definiu como casos suspeitos da doença todos os indivíduos que apresentem febre de início súbito acima de 38,5ºC, forte artralgia e que apresentem histórico de viagem recente à áreas de circulação contínua do vírus. Até o momento, não existe um tratamento específico para a doença, sendo tratados apenas os sintomas através de medicação para a febre e para as dores articulares. O diagnóstico laboratorial da doença é realizado através de testes moleculares e de testes sorológicos, sendo realizada a pesquisa de antígenos ou de anticorpos específicos. Devido aos surtos de ampla magnitude que acometeram a população mundial nos últimos anos, foram desenvolvidos kits para o diagnóstico laboratorial da doença. O objetivo do presente trabalho foi realizar uma revisão integrativa acerca das informações disponíveis na literatura sobre os parâmetros de sensibilidade e especificidade dos kits para diagnóstico da doença comercializados nos mercados nacional e mundial. A metodologia utilizada para realizar este trabalho foi a busca em bases de dados científicos, como Medline, Scopus, Web of Science, PubMed e SciELO, constando termos chaves como: “Chikungunya diagnosis”, “Tests for diagnosis of Chikungunya fever”, “Commercially assays for Chikungunya’s diagnosis”, sendo realizada de junho de 2017 à janeiro de 2018 e selecionando ao todo 4 artigos. Como resultado, pôde-se notar uma grande diferença nos valores de sensibilidade e especificidade dos testes, variando principalmente com o tipo de metodologia adotada, sendo o RT-PCR a metodologia com melhores valores de sensibilidade e especificidade e o Teste rápido a metodologia com piores valores. Como o RT-PCR apresenta alto custo, uma opção mais econômica e que mantém o bom desempenho é a Imunofluorescência Indireta. De forma geral, os valores de sensibilidade e especificidade são baixos, concluindo-se que os kits disponíveis no mercado apresentam uma grande variação de desempenho. Espera-se que com as novas pesquisas e tecnologias, sejam desenvolvidos produtos mais sensíveis, específicos e acessíveis.

Title: Investigação de Conhecimentos sobre a dengue e o índice de adoção de um recurso preventivo (capa evidengue) no domicilio de estudantes, associados a uma ação educativa em ambiente escolar
Authors: Barros, Héliton da Silva
Abstract: A crescente incidência da dengue no Brasil requer inovações que auxiliem a prevenção da proliferação dos vetores da doença, sobretudo no domicílio e peridomicílio. Tais inovações podem envolver o uso de tecnologias associadas a programas de informação e educação. Desde que a dengue se tornou um importante problema de saúde pública, várias medidas relacionadas à informação e à educação da população vêm sendo tomadas com objetivo de controlar a doença. A despeito dessas medidas, os dados da literatura de prevenção domiciliar da dengue mostram não haver relação direta entre o aumento do conhecimento e a promoção de comportamento preventivo. No presente estudo, são descritos o método e os resultados de
uma ação educativa visando a prevenção domiciliar da dengue, realizada com alunos da 8ª série do ensino fundamental e da 1ª série do ensino médio de escola pública, em área endêmica de um distrito de Belo Horizonte, MG. Participaram quatro turmas: duas do período da manhã, uma do período da tarde e uma do período da noite. A investigação consistiu na manipulação de quatro condições experimentais de uma ação educativa em saúde constituída de três componentes: aula sobre a dengue, distribuição de capa evidengue (recurso preventivo para proteção de pratos coletores de água de vasos de planta) e de folheto informativo sobre a doença e a capa. Cada condição foi manipulada em uma das quatro turmas, separadamente. A condição experimental atribuída a cada turma foi definida por meio de sorteio, sem a presença do pesquisador que ministrou a aula sobre a dengue. Para avaliar o conhecimento dos alunos sobre a doença, uma subamostra de 40 alunos (10 de cada turma) foi selecionada para responder a um questionário escrito, antes e depois da ação educativa. O questionário constou de oito questões de respostas cursivas relativas a três aspectos primários do conhecimento do aluno sobre a doença: 1) o conceito de dengue; 2) o modo de transmissão; e 3) as formas de prevenção. Após ação educativa na escola, observadores de campo visitaram as residências de 98 alunos (85,2% da amostra) para registrar a adoção da evidengue. Definiu-se adoção como a verificação, pelos observadores, do uso proficiente da capa em um ou mais vasos de planta, em cada uma das residências visitadas. Os resultados referentes ao questionário replicam dados da literatura que revelam nível satisfatório de conhecimento sobre a dengue, principalmente sobre a prevenção da doença. A manipulação do componente aula promoveu ganhos relativos de conhecimento sobre ações de prevenção e incluiu um novo conceito no repertório verbal dos alunos: o conceito de vedar em substituição ao de tampar, mudança que pode conferir maior precisão no cuidado doméstico com recipientes coletores de água. No
cômputo geral das casas em que havia vasos de planta com prato coletor, a ação educativa resultou em índices de adoção da evidengue de 34,8% na primeira verificação e de 49,2% na segunda verificação. Um cômputo que exclui a condição de controle, em que não houve distribuição da evidengue, revelou índices de 42,1% e 63%, respectivamente. A manipulação do componente folheto apresentou-se com melhores resultados do que as demais condições estudadas para a adoção.

by Hamidou Maïga, Wadaka Mamai, Nanwintoum Séverin Bimbilé Somda, Anna Konczal, Thomas Wallner, Gustavo Salvador Herranz, Rafael Argiles Herrero, Hanano Yamada, Jeremy Bouyer
Introduction The widespread emergence of resistance to insecticides used to control adult Aedes mosquitoes has made traditional control strategies inadequate for the reduction of various vector populations. Therefore, complementary vector control methods, such as the Sterile Insect Technique, are needed to enhance existing efforts. The technique relies on the rearing and release of large numbers of sterile males, and the development of efficient and standardized mass-rearing procedures and tools is essential for its application against medically important mosquitoes. Methods In the effort to reduce the cost of the rearing process, a prototype low-cost plexiglass mass-rearing cage has been developed and tested for egg production and egg hatch rate in comparison to the current Food and Agriculture Organization/International Atomic Energy Agency (FAO/IAEA) stainless-steel cage. Additionally, an adult-index was validated and used as a proxy to estimate the mosquito survival rates by counting the number of male and female mosquitoes that were resting within each of the 6 squares at a given point of time each day in the cage. Results The study has shown that the prototype mass-rearing cage is cheap and is as efficient as the FAO/IAEA stainless-steel cage in terms of egg production, with even better overall egg hatch rate. The mean numbers of eggs per cage, after seven cycles of blood feeding and egg collection, were 969,789 ± 138,101 and 779,970 ± 123,042, corresponding to 81 ± 11 and 65 ± 10 eggs per female over her lifespan, in the prototype and the stainless-steel-mass-rearing cages, respectively. The longevity of adult male and female mosquitoes was not affected by cage type and, the adult-index could be considered as an appropriate proxy for survival. Moreover, the mass-rearing cage prototype is easy to handle and transport and improves economic and logistic efficiency. Conclusion The low-cost mass-rearing prototype cage can be recommended to produce Ae. aegypti in the context of rear and release techniques. The proposed adult-index can be used as a quick proxy of mosquito survival rates in mass-rearing settings.

by Kathryn L. Schaber, Valerie A. Paz-Soldan, Amy C. Morrison, William H. D. Elson, Alan L. Rothman, Christopher N. Mores, Helvio Astete-Vega, Thomas W. Scott, Lance A. Waller, Uriel Kitron, John P. Elder, Christopher M. Barker, T. Alex Perkins, Gonzalo M. Vazquez-Prokopec
Background Human mobility plays a central role in shaping pathogen transmission by generating spatial and/or individual variability in potential pathogen-transmitting contacts. Recent research has shown that symptomatic infection can influence human mobility and pathogen transmission dynamics. Better understanding the complex relationship between symptom severity, infectiousness, and human mobility requires quantification of movement patterns throughout infectiousness. For dengue virus (DENV), human infectiousness peaks 0–2 days after symptom onset, making it paramount to understand human movement patterns from the beginning of illness. Methodology and principal findings Through community-based febrile surveillance and RT-PCR assays, we identified a cohort of DENV+ residents of the city of Iquitos, Peru (n = 63). Using retrospective interviews, we measured the movements of these individuals when healthy and during each day of symptomatic illness. The most dramatic changes in mobility occurred during the first three days after symptom onset; individuals visited significantly fewer locations (Wilcoxon test, p = 0.017) and spent significantly more time at home (Wilcoxon test, p = 0.005), compared to when healthy. By 7–9 days after symptom onset, mobility measures had returned to healthy levels. Throughout an individual’s symptomatic period, the day of illness and their subjective sense of well-being were the most significant predictors for the number of locations and houses they visited. Conclusions/Significance Our study is one of the first to collect and analyze human mobility data at a daily scale during symptomatic infection. Accounting for the observed changes in human mobility throughout illness will improve understanding of the impact of disease on DENV transmission dynamics and the interpretation of public health-based surveillance data.

by Enny S. Paixão, Moreno S. Rodrigues, Luciana L. Cardim, Juliane F. Oliveira, Catharina L. C., Maria da Conceição N. Costa, Maurício L. Barreto, Laura C. Rodrigues, Liam Smeeth, Roberto F. S. Andrade, Wanderson K. Oliveira, Maria Glória Teixeira

This study aimed to assess the impact of the Zika epidemic on the registration of birth defects in Brazil. We used an interrupted time series analysis design to identify changes in the trends in the registration of congenital anomalies. We obtained monthly data from Brazilian Live Birth Information System and used two outcome definitions: 1) rate of congenital malformation of the brain and eye (likely to be affected by Zika and its complications) 2) rate of congenital malformation not related to the brain or eye unlikely to be causally affected by Zika. The period between maternal infection with Zika and diagnosis of congenital abnormality attributable to the infection is around six months. We therefore used September 2015 as the interruption point in the time series, six months following March 2015 when cases of Zika started to increase. For the purposes of this analysis, we considered the period from January 2010 to September 2015 to be “pre-Zika event,” and the period from just after September 2015 to December 2017 to be “post-Zika event.” We found that immediately after the interruption point, there was a great increase in the notification rate of congenital anomalies of 14.9/10,000 live births in the brain and eye group and of 5.2/10,000 live births in the group not related with brain or eye malformations. This increase in reporting was in all regions of the country (except in the South) and especially in the Northeast. In the period “post-Zika event”, unlike the brain and eye group which showed a monthly decrease, the group without brain or eye malformations showed a slow but significant increase (relative to the pre-Zika trend) of 0.2/10,000 live births. These findings suggest an overall improvement in the registration of birth malformations, including malformations that were not attributed to Zika, during and after the Zika epidemic.

by Ari Whiteman, Michael R. Desjardins, Gilberto A. Eskildsen, Jose R. Loaiza

Long term surveillance of vectors and arboviruses is an integral aspect of disease prevention and control systems in countries affected by increasing risk. Yet, little effort has been made to adjust space-time risk estimation by integrating disease case counts with vector surveillance data, which may result in inaccurate risk projection when several vector species are present, and when little is known about their likely role in local transmission. Here, we integrate 13 years of dengue case surveillance and associated Aedes occurrence data across 462 localities in 63 districts to estimate the risk of infection in the Republic of Panama. Our exploratory space-time modelling approach detected the presence of five clusters, which varied by duration, relative risk, and spatial extent after incorporating vector species as covariates. The Ae. aegypti model contained the highest number of districts with more dengue cases than would be expected given baseline population levels, followed by the model accounting for both Ae. aegypti and Ae. albopictus. This implies that arbovirus case surveillance coupled with entomological surveillance can affect cluster detection and risk estimation, potentially improving efforts to understand outbreak dynamics at national scales.

by Jessica Denis, Sarah Attoumani, Patrick Gravier, Bernard Tenebray, Annabelle Garnier, Sébastien Briolant, Franck de Laval, Véronique Chastres, Gilda Grard, Isabelle Leparc-Goffart, Bruno Coutard, Cyril Badaut
Background Zika virus (ZIKV) and Dengue virus (DENV) are often co-endemic. The high protein-sequence homology of flaviviruses renders IgG induced by and directed against them highly cross-reactive against their antigen(s), as observed on a large set of sera, leading to poorly reliable sero-diagnosis. Methods We selected Domain III of the ZIKV Envelope (ZEDIII) sequence, which is virus specific. This recombinant domain was expressed and purified for the specific detection of ZEDIII-induced IgG by ELISA from ZIKV-RT-PCR-positive, ZIKV-IgM-positive, flavivirus-positive but ZIKV-negative, or flavivirus-negative sera. We also assessed the reactivity of ZEDIII-specific human antibodies against EDIII of DENV serotype 4 (D4EDIII) as a specific control. Sera from ZEDIII-immunized mice were also tested. Results Cross-reactivity of IgG from 5,600 sera against total inactivated DENV or ZIKV was high (71.0% [69.1; 72.2]), whereas the specificity and sensitivity calculated using a representative cohort (242 sera) reached 90% [84.0; 95.8] and 92% [84.5; 99.5], respectively, using a ZEDIII-based ELISA. Moreover, purified human IgG against D2EDIII or D4EDIII did not bind to ZEDIII and we observed no D4EDIII reactivity with ZIKV-induced mouse polyclonal IgGs. Conclusions We developed a ZEDIII-based ELISA that can discriminate between past or current DENV and ZIKV infections, allowing the detection of a serological scar from other flaviviruses. This could be used to confirm exposure of pregnant women or to follow the spread of an endemic disease.

by Sarah Anne J. Guagliardo, Yoosook Lee, Amanda A. Pierce, Jacklyn Wong, Yui Yin Chu, Amy C. Morrison, Helvio Astete, Berry Brosi, Gonzalo Vazquez-Prokopec, Thomas W. Scott, Uriel Kitron, Steven T. Stoddard

In the Americas, as in much of the rest of the world, the dengue virus vector Aedes aegypti is found in close association with human habitations, often leading to high population densities of mosquitoes in urban settings. In the Peruvian Amazon, this vector has been expanding to rural communities over the last 10–15 years, but to date, the population genetic structure of Ae. aegypti in this region has not been characterized. To investigate the relationship between Ae. aegypti gene flow and human transportation networks, we characterized mosquito population structure using a panel of 8 microsatellite markers and linked results to various potential mechanisms for long-distance dispersal. Adult and immature Ae. aegypti (>20 individuals per site) were collected from Iquitos city and from six neighboring riverine communities, i.e., Nauta, Indiana, Mazan, Barrio Florida, Tamshiaco, and Aucayo. FST statistics indicate significant, but low to moderate differentiation for the majority of study site pairs. Population structure of Ae. aegypti is not correlated with the geographic distance between towns, suggesting that human transportation networks provide a reasonable explanation for the high levels of population mixing. Our results indicate that Ae. aegypti gene flow among sub-populations is greatest between locations with heavy boat traffic, such as Iquitos-Tamshiaco and Iquitos-Indiana-Mazan, and lowest between locations with little or no boat/road traffic between them such as Barrio Florida-Iquitos. Bayesian clustering analysis showed ancestral admixture among three genetic clusters; no single cluster was exclusive to any site. Our results are consistent with the hypothesis that human transportation networks, particularly riverways, are responsible for the geographic spread of Ae. aegypti in the Peruvian Amazon. Our findings are applicable to other regions of the world characterized by networks of urban islands connected by fluvial transport routes.

by Naim Mahroum, Mohammad Adawi, Kassem Sharif, Roy Waknin, Hussein Mahagna, Bishara Bisharat, Mahmud Mahamid, Arsalan Abu-Much, Howard Amital, Nicola Luigi Bragazzi, Abdulla Watad

by Juan Rivera-Correa, Isadora Cristina de Siqueira, Sabrina Mota, Mateus Santana do Rosário, Pedro Antônio Pereira de Jesus, Luiz Carlos Junior Alcantara, Joel D. Ernst, Ana Rodriguez

Zika virus infection is associated with the development of Guillain-Barré syndrome (GBS), a neurological autoimmune disorder caused by immune recognition of gangliosides and other components at nerve membranes. Using a high-throughput ELISA, we have analyzed the anti-glycolipid antibody profile, including gangliosides, of plasma samples from patients with Zika infections associated or not with GBS in Salvador, Brazil. We have observed that Zika patients that develop GBS present higher levels of anti-ganglioside antibodies when compared to Zika patients without GBS. We also observed that a broad repertoire of gangliosides was targeted by both IgM and IgG anti-self antibodies in these patients. Since Zika virus infects neurons, which contain membrane gangliosides, antigen presentation of these infected cells may trigger the observed autoimmune anti-ganglioside antibodies suggesting direct infection-induced autoantibodies as a cause leading to GBS development. Collectively, our results establish a link between anti-ganglioside antibodies and Zika-associated GBS in patients.

by Xinghua Su, Yijia Guo, Jielin Deng, Jiabao Xu, Guofa Zhou, Tengfei Zhou, Yiji Li, Daibin Zhong, Ling Kong, Xiaoming Wang, Min Liu, Kun Wu, Guiyun Yan, Xiao-Guang Chen

Dengue is one of the most serious mosquito-borne infectious diseases in the world. Aedes albopictus is the most invasive mosquito and one of the primary vectors of dengue. Vector control using insecticides is the only viable strategy to prevent dengue virus transmission. In Guangzhou, after the 2014 pandemic, massive insecticides have been implemented. Massive insecticide use may lead to the development of resistance, but few reports are available on the status of insecticide resistance in Guangzhou after 2014. In this study, Ae. albopictus were collected from four districts with varied dengue virus transmission intensity in Guangzhou from 2015 to 2017. Adult Ae. albopictus insecticide susceptibility to deltamethrin (0.03%), permethrin(0.25%), DDT(4%), malathion (0.8%) and bendiocarb (0.1%) was determined by the standard WHO tube test, and larval resistance bioassays were conducted using temephos, Bacillus thuringiensis israelensis (Bti), pyriproxyfen (PPF) and hexaflumuron. Mutations at the voltage-gated sodium channel (VGSC) gene and acetylcholinesterase (AChE) gene were analyzed. The effect of cytochrome P450s on the resistance of Ae. albopictus to deltamethrin was tested using the synergistic agent piperonyl butoxide (PBO). The results showed that Ae. albopictus populations have rapidly developed very high resistances to multiple commonly used insecticides at all study areas except malathion, Bti and hexaflumuron. We found 1534 codon mutations in the VGSC gene that were significantly correlated with the resistance to pyrethroids and DDT, and 11 synonymous mutations were also found in the gene. The resistance to deltamethrin can be significantly reduced by PBO but may generated cross-resistance to PPF. Fast emerging resistance in Ae. albopictus may affect mosquito management and threaten the prevention and control of dengue, similar to the resistance in Anopheles mosquitoes has prevented the elimination of malaria and call for timely and guided insecticide management.

by Antonio S. Lima Neto, Geziel S. Sousa, Osmar J. Nascimento, Marcia C. Castro

Title: 5º seminário anual científico e tecnológico: nanosensor para testes diagnósticos point-of-care empregando quantum dots de CdTe funcionalizados com epitopos sintéticos para dengue
Abstract: Realizado de 2 a 4 de maio de 2017, no Auditório do Novo Almoxarifado e Prédio Administrativo – NAPA, o Quinto Seminário Anual Científico e Tecnológico de Bio-Manguinhos. O seminário, que já faz parte da comemoração dos 41 anos de Bio-Manguinhos, tem por objetivo incentivar e capacitar funcionários e pesquisadores de instituições nacionais e internacionais para inovação e apresentar trabalhos sobre desenvolvimento tecnológico de vacinas, reativos para diagnósticos, biofármacos e temas relativos a gestão. No segundo dia de seminário, o assessor da Vice Diretoria de Desenvolvimento Tecnológico de Bio-Manguinhos, o Pós-Doutor Marco Medeiros, coordena a apresentação “Nanosensor para testes diagnósticos point-of-care empregando quantum dots de CdTe funcionalizados com epitopos sintéticos para Dengue”, ministrada por Isis Campos Prado, do Centro de Desenvolvimento Tecnológico em Saúde da Fiocruz.

by Sam Proesmans, Freddy Katshongo, John Milambu, Blaise Fungula, Hypolite Muhindo Mavoko, Steve Ahuka-Mundeke, Raquel Inocêncio da Luz, Marjan Van Esbroeck, Kevin K. Ariën, Lieselotte Cnops, Birgit De Smet, Pascal Lutumba, Jean-Pierre Van geertruyden, Veerle Vanlerberghe
Background Pathogens causing acute fever, with the exception of malaria, remain largely unidentified in sub-Saharan Africa, given the local unavailability of diagnostic tests and the broad differential diagnosis. Methodology We conducted a cross-sectional study including outpatient acute undifferentiated fever in both children and adults, between November 2015 and June 2016 in Kinshasa, Democratic Republic of Congo. Serological and molecular diagnostic tests for selected arboviral infections were performed on blood, including PCR, NS1-RDT, ELISA and IFA for acute, and ELISA and IFA for past infections. Results Investigation among 342 patients, aged 2 to 68 years (mean age of 21 years), with acute undifferentiated fever (having no clear focus of infection) revealed 19 (8.1%) acute dengue–caused by DENV-1 and/or DENV-2 –and 2 (0.9%) acute chikungunya infections. Furthermore, 30.2% and 26.4% of participants had been infected in the past with dengue and chikungunya, respectively. We found no evidence of acute Zika nor yellow fever virus infections. 45.3% of patients tested positive on malaria Rapid Diagnostic Test, 87.7% received antimalarial treatment and 64.3% received antibacterial treatment. Discussion Chikungunya outbreaks have been reported in the study area in the past, so the high seroprevalence is not surprising. However, scarce evidence exists on dengue transmission in Kinshasa and based on our data, circulation is more important than previously reported. Furthermore, our study shows that the prescription of antibiotics, both antibacterial and antimalarial drugs, is rampant. Studies like this one, elucidating the causes of acute fever, may lead to a more considerate and rigorous use of antibiotics. This will not only stem the ever-increasing problem of antimicrobial resistance, but will–ultimately and hopefully–improve the clinical care of outpatients in low-resource settings. Trial registration ClinicalTrials.gov NCT02656862.

by Marietta Müller, Natalie Slivinski, Eleanor J. A. A. Todd, Henna Khalid, Raymond Li, Magdalena Karwatka, Andres Merits, Jamel Mankouri, Andrew Tuplin

Chikungunya virus (CHIKV) is a re-emerging, pathogenic alphavirus that is transmitted to humans by Aedes spp. mosquitoes—causing fever and debilitating joint pain, with frequent long-term health implications and high morbidity. The CHIKV lifecycle is poorly understood and specific antiviral therapeutics or vaccines are lacking. In this study, we investigated the role of host-cell chloride (Cl-) channels on CHIKV replication.We demonstrate that specific pharmacological Cl- channel inhibitors significantly inhibit CHIKV replication in a dose-dependent manner, suggesting that Cl-channels are pro-viral factors in human cells. Further analysis of the effect of the inhibitors on CHIKV attachment, entry, viral protein expression and replicon replication demonstrated that Cl- channels are specifically required for efficient CHIKV genome replication. This was conserved in mosquito cells, where CHIKV replication and genome copy number was significantly reduced following Cl- channel inhibition. siRNA silencing identified chloride intracellular channels 1 and 4 (CLIC1 and CLIC4, respectively) as required for efficient CHIKV replication and protein affinity chromatography showed low levels of CLIC1 in complex with CHIKV nsP3, an essential component of the viral replication machinery. In summary, for the first time we demonstrate that efficient replication of the CHIKV genome depends on cellular Cl- channels, in both human and mosquito cells and identifies CLIC1 and CLIC4 as agonists of CHIKV replication in human cells. We observe a modest interaction, either direct or indirect, between CLIC1 and nsP3 and hypothesize that CLIC1 may play a role in the formation/maintenance of CHIKV replication complexes. These findings advance our molecular understanding of CHIKV replication and identify potential druggable targets for the treatment and prevention of CHIKV mediated disease.

by Roya Elaine Haghighat-Khah, Tim Harvey-Samuel, Sanjay Basu, Oliver StJohn, Sarah Scaife, Sebald Verkuijl, Erica Lovett, Luke Alphey
Background Population suppression through mass-release of Aedes aegypti males carrying dominant-lethal transgenes has been demonstrated in the field. Where population dynamics show negative density-dependence, suppression can be enhanced if lethality occurs after the density-dependent (i.e. larval) stage. Existing molecular tools have limited current examples of such Genetic Pest Management (GPM) systems to achieving this through engineering ‘cell-autonomous effectors’ i.e. where the expressed deleterious protein is restricted to the cells in which it is expressed–usually under the control of the regulatory elements (e.g. promoter regions) used to build the system. This limits the flexibility of these technologies as regulatory regions with useful spatial, temporal or sex-specific expression patterns may only be employed if the cells they direct expression in are simultaneously sensitive to existing effectors, and also precludes the targeting of extracellular regions such as cell-surface receptors. Expanding the toolset to ‘non-cell autonomous’ effectors would significantly reduce these limitations. Methodology/Principal findings We sought to engineer female-specific, late-acting lethality through employing the Ae. aegypti VitellogeninA1 promoter to drive blood-meal-inducible, fat-body specific expression of tTAV. Initial attempts using pro-apoptotic effectors gave no evident phenotype, potentially due to the lower sensitivity of terminally-differentiated fat-body cells to programmed-death signals. Subsequently, we dissociated the temporal and spatial expression of this system by engineering a novel synthetic effector (Scorpion neurotoxin–TetO-gp67.AaHIT) designed to be secreted out of the tissue in which it was expressed (fat-body) and then affect cells elsewhere (neuro-muscular junctions). This resulted in a striking, temporary-paralysis phenotype after blood-feeding. Conclusions/Significance These results are significant in demonstrating for the first time an engineered ‘action at a distance’ phenotype in a non-model pest insect. The potential to dissociate temporal and spatial expression patterns of useful endogenous regulatory elements will extend to a variety of other pest insects and effectors.