Monitoramento das Produções

Title: Evaluation of insecticide resistance in Aedes aegypti populations connected by roads and rivers: the case of Tocantins state in Brazil
Authors: Sá, Eric Luiz Rodrigues de; Rodovalho, Cynara de Melo; Sousa, Nilciane Pinto Ribeiro de; Sá, Ivy Luizi Rodrigues de; Bellinato, Diogo Fernandes; Dias, Luciana dos Santos; Silva, Luana Carrara da; Martins, Ademir Jesus; Lima, José Bento Pereira

Title: Dinâmica de dispersão do sorotipo 3 do virus da dengue (DENV-3) no Estado da Bahia
Authors: Melo, Paulo Roberto Santana de; Reis, Eliana; Ciuffo, Isolina Allen; Góes, M.; Blanton, Edward Ronald; Reis, Mitermayer Galvão dos

Title: 5º seminário anual científico e tecnológico: immune protection against dengue infection vaccine performance
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 professor adjunto do Departamento de Medicina da Universidade Health Science – Bethesda, Doutor Scott Halstead apresentou a palestra “Immune protection against dengue infection vaccine performance”, coordenada pelo Vice-Diretor de Desenvolvimento Tecnológico de Bio-Manguinhos, Marcos Freire.

by Nicole J. Culbert, Jeremie R. L. Gilles, Jérémy Bouyer

In genetic control programmes, including the sterile insect technique (SIT), it is crucial to release insects of the highest quality with maximum survival. It is likely that male mosquitoes will follow the trend of other insects in SIT programmes and be stored, transported and eventually released under chilled conditions. The aim of our study was to investigate the impact of different chilling temperatures on male Aedes aegypti and Ae. albopictus survival by exposing them to a range of temperatures for different durations. Ae. aegypti were found to be less sensitive to the impact of chilling, with only 6°C causing a marginal decrease in survival in comparison to non-chilled controls. Conversely, Ae. albopictus displayed a significantly reduced survival at all chilling temperatures even when exposed for a short time. In both species, longer exposure to low temperatures reduced survival. Our results uncovered that Ae. albopictus are more sensitive to chilling, regardless of the temperature, when compared to Ae. aegypti. Such results indicate differences in thermal tolerances between species and the necessity of conducting experiments on a species by species basis when determining temperature limits for any insect destined for release as part of a genetic control programme.

by Florian Miksch, Beate Jahn, Kurt Junshean Espinosa, Jagpreet Chhatwal, Uwe Siebert, Nikolas Popper

For the evaluation of infectious-diseases interventions, the transmissible nature of such diseases plays a central role. Agent-based models (ABM) allow for dynamic transmission modeling but publications are limited. We aim to provide an overview of important characteristics of ABM for decision-analytic modeling of infectious diseases. A case study of dengue epidemics illustrates model characteristics, conceptualization, calibration and model analysis. First, major characteristics of ABM are outlined and discussed based on ISPOR and ISPOR-SMDM Good Practice guidelines. Second, in our case study, we modeled a dengue outbreak in Cebu City (Philippines) to assess the impact interventions to control the relative growth of the mosquito population. Model outcomes include prevalence and incidence of infected persons. The modular ABM simulates persons and mosquitoes over an annual time horizon considering daily time steps. The model was calibrated and validated. ABM is a dynamic, individual-level modeling approach that is capable to reproduce direct and indirect effects of interventions for infectious diseases. The ability to replicate emerging behavior and to include human behavior or the behavior of other agents is a distinguishing modeling characteristic (e.g., compared to Markov models). Modeling behavior may, however, require extensive calibration and validation. The analyzed hypothetical effectiveness of dengue interventions showed that a reduced human-mosquito ratio of 1:2.5 during rainy seasons leads already to a substantial decrease of infected persons. ABM can support decision-analyses for infectious diseases including disease dynamics, emerging behavior, and providing a high level of reusability due to modularity.

by Tulika Singh, Cesar A. Lopez, Camila Giuberti, Maria L. Dennis, Hannah L. Itell, Holly J. Heimsath, Helen S. Webster, Hunter K. Roark, Paulo R. Merçon de Vargas, Allison Hall, Ralph G. Corey, Geeta K. Swamy, Reynaldo Dietze, Helen M. Lazear, Sallie R. Permar

Zika virus (ZIKV) is a newly-identified infectious cause of congenital disease. Transplacental transfer of maternal IgG to the fetus plays an important role in preventing many neonatal infections. However, antibody transfer may also have negative consequences, such as mediating enhancement of flavivirus infections in early life, or trafficking of virus immune complexes to the fetal compartment. ZIKV infection produces placental pathology which could lead to impaired IgG transfer efficiency as occurs in other maternal infections, such as HIV-1 and malaria. In this study, we asked whether ZIKV infection during pregnancy impairs transplacental transfer of IgG. We enrolled pregnant women with fever or rash in a prospective cohort in Vitoria, Brazil during the recent ZIKV epidemic. ZIKV and dengue virus (DENV)-specific IgG, ZIKV and DENV neutralizing antibodies, and routine vaccine antigen-specific IgG were measured in maternal samples collected around delivery and 20 paired cord blood samples. We concluded that 8 of these mothers were infected with ZIKV during pregnancy and 12 were ZIKV-uninfected. The magnitude of flavivirus-specific IgG, neutralizing antibody, and vaccine-elicited IgG were highly correlated between maternal plasma and infant cord blood in both ZIKV-infected and -uninfected mother-infant pairs. Moreover, there was no difference in the magnitude of plasma flavivirus-specific IgG levels between mothers and infants regardless of ZIKV infection status. Our data suggests that maternal ZIKV infection during pregnancy does not impair the efficiency of placental transfer of flavivirus-specific, functional, and vaccine-elicited IgG. These findings have implications for the neonatal outomes of maternal ZIKV infection and optimal administration of antibody-based ZIKV vaccines and therapeutics.

by Ariadna Capasso, Danielle C. Ompad, Dorice L. Vieira, Annelies Wilder-Smith, Yesim Tozan
Background A severe neurological disorder, Guillain-Barré syndrome (GBS) is the leading cause of acute flaccid paralysis. Enhanced surveillance of GBS in Latin America and the Caribbean (LAC) following the 2015–2016 Zika virus (ZIKV) epidemic presents an opportunity to estimate, for the first time, the regional incidence of GBS. Methods and findings For this systematic review and meta-analysis, we searched nine scientific databases and grey literature from January 1, 1980 to October 1, 2018. Sources with primary data on incident GBS cases in LAC within a well-defined population and timeframe, published in English, Spanish, Portuguese, or French, were included. We calculated the annual GBS incidence rates (IRs) and 95% confidence intervals (CIs) for each source based on published data. Following an assessment of heterogeneity, we used random-effects meta-analysis to calculate the pooled annual IR of GBS. The study is registered with PROSPERO, number CRD42018086659. Of the 6568 initial citation hits, 31 were eligible for inclusion. Background annual GBS IRs in Latin America ranged from 0.40 in Brazil to 2.12/100,000 in Chile. The pooled annual IR in the Caribbean was 1.64 (95% CI 1.29–2.12, I2

by Ching Hua, Regina Lee, Khairunnisa Mohamed Hussain, Justin Jang Hann Chu

Chikungunya virus (CHIKV) is a re-emerging arbovirus known to cause chronic myalgia and arthralgia with high morbidity. CHIKV is now considered endemic in many countries across Asia and Africa. In this study, the susceptibility of various human, mammalian and mosquito cell lines to CHIKV infection was evaluated. CHIKV infection was found to be cell-type dependent and virus strain-specific. Furthermore, SJCRH30 (human rhabdomyosarcoma cell line) was showed to be highly permissive to CHIKV infection, with maximum production of infectious virions observed at 12 h.p.i. Pre-infection treatment of SJCRH30 with various inhibitors of endocytosis, including monodansylcadaverine (receptor-mediated endocytic inhibitor), dynasore (clathrin-mediated endocytic inhibitor), as well as filipin (caveolin-mediated endocytosis inhibitor), resulted in minimal inhibition of CHIKV infection. In contrast, dose-dependent inhibition of CHIKV infection was observed with the treatment of macropinocytosis inhibitor, 5-(N-ethyl-N-isopropyl)amiloride (EIPA). Furthermore, siRNA-mediated knockdown of sortin nexin 9 (SNX9) a protein involved in macropinosome formation, also resulted in a significant dose-dependent reduction in viral titre. By performing a virus entry assay, CHIKV particles were also observed to colocalize with FITC-dextran, a macropinosome marker. This study shows for the first time, that the infectious entry of CHIKV into human muscle cells is mediated by macropinocytosis. Together, the data from this study may pave the way for the development of specific inhibitors that target the entry process of CHIKV into cells.

by Sheila B. Agha, David P. Tchouassi, Michael J. Turell, Armanda D. S. Bastos, Rosemary Sang

Urbanization is one of the major drivers of dengue epidemics globally. In Kenya, an intriguing pattern of urban dengue virus epidemics has been documented in which recurrent epidemics are reported from the coastal city of Mombasa, whereas no outbreaks occur in the two major inland cities of Kisumu and Nairobi. In an attempt to understand the entomological risk factors underlying the observed urban dengue epidemic pattern in Kenya, we evaluated vector density, human feeding patterns, vector genetics, and prevailing environmental temperature to establish how these may interact with one another to shape the disease transmission pattern. We determined that (i) Nairobi and Kisumu had lower vector density and human blood indices, respectively, than Mombasa, (ii) vector competence for dengue-2 virus was comparable among Ae. aegypti populations from the three cities, with no discernible association between susceptibility and vector cytochrome c oxidase subunit 1 gene variation, and (iii) vector competence was temperature-dependent. Our study suggests that lower temperature and Ae. aegypti vector density in Nairobi may be responsible for the absence of dengue outbreaks in the capital city, whereas differences in feeding behavior, but not vector competence, temperature, or vector density, contribute in part to the observed recurrent dengue epidemics in coastal Mombasa compared to Kisumu.

Title: Safety and efficacy of primary yellow fever vaccination in autoimmune disease: a prospective controlled study
Authors: Valim, Valeria; Pinto, Arthur Dalmaso; Rocha, Priscila Costa Martins; Miyamoto, Samira Tatiyama; Serrano, Érica Vieira; Duque, Ruben Horst; Gavi, Maria Bernadete Renoldi de Oliveira; Balarini, Lidia; Dinis, Valquiria Garcia; Machado, Ketty Lysie Libardi Lira; Casagrande, Thais Zanon; Gianórdoli, Ana Paula E; Gouvêa, Sônia Alves; Caser, Larissa Carvalho; Lima, Sheila Maria Barbosa de; Miranda, Emlly Hime; Trindade, Gisela Freitas; Azevedo, Ana Carolina Campi; Carvalho, Andréa Teixeira de; Pascoal, Vanessa Peruhype Magalhães; Souza, Ana Lidia Silva de; Lima, Ana Paula Neves Burian; Pinto Neto, Lauro Ferreira Da Silva; Costa, Carolina Zorzaneli; Rodrigues, Luiza Correia; Bissoli, Maria Fátima; Giovelli, Raquel Altoé; Moura, Luciana D.; Dias, João Gabriel Fragoso; Pretti, Flavia Zon; Oliveira, Karine G.; Giacomim, Maryella S.; Genelhu, Luiz Felipe F; Merlo, Daniela L.; Dias, Laiza H.; Borjaille, Brunela P; Brandão, Letícia R.; Pereira, Daniela B.; Koehlert, Ingrid O.; Moura, Bruna CM; Batista, Fernanda M; Polito, Elisandra Tl; Clemente, Thalles B.; Magalhães, Enan S.; Thebit, Marcela M.; Martins Filho, Olindo Assis

Title: Duration of Humoral and Cellular Immunity 8 Years After Administration of Reduced Doses of the 17DD-Yellow Fever Vaccine
Authors: Rocha, Ismael Artur da Costa; Azevedo, Ana Carolina Campi; Pascoal, Vanessa Peruhype Magalhães; Reis, Jordana Grazziela Coelho dos; Fradico, Jordana Rodrigues Barbosa; Lopes, Thalles Souza; Reis, Laise Rodrigues; Freire, Larissa Chaves; Pereira, Christiane Costa; Mambrini, Juliana Vaz de Melo; Maia, Maria de Lourdes de Sousa; Lima, Sheila Maria Barbosa de; Noronha, Tatiana Guimarães de; Xavier, Janaina Reis; Camacho, Luiz Antonio Bastos; Albuquerque, Elizabeth Maciel de; Farias, Roberto Henrique Guedes; Castro, Thalita da Matta de; Homma, Akira; Romano, Alessandro Pecego Martins; Domingues, Carla Magda; Martins, Reinaldo de Menezes; Carvalho, Andréa Teixeira de; Martins Filho, Olindo Assis

by Shengzhang Dong, Seokyoung Kang, George Dimopoulos

Zika virus (ZIKV), an emerging arbovirus belonging to the genus Flavivirus, is transmitted by Aedes mosquitoes. ZIKV infection can cause microcephaly of newborn babies and Guillain–Barré syndrome in adults. Because no licensed vaccine or specific antiviral treatment is available for ZIKV infection, the most commonly used approach to control the spread of ZIKV is suppression of the mosquito vector population. A novel proposed strategy to block arthropod virus (arbovirus) transmission is based on the chemical inhibition of virus infection in mosquitoes. However, only a few drugs and compounds have been tested with such properties. Here we present a comprehensive screen of 55 FDA-approved anti-flaviviral drugs for potential anti-ZIKV and mosquitocidal activity. Four drugs (auranofin, actinomycin D (Act-D), bortezomib and gemcitabine) were toxic to C6/36 cells, and two drugs (5-fluorouracil and mycophenolic acid (MPA)) significantly reduced ZIKV production in C6/36 cells at 2 μM and 0.5 μM, respectively. Three drugs (Act-D, cyclosporin A, ivermectin) exhibited a strong adulticidal activity, and six drugs (U18666A, retinoic acid p-hydroxyanilide (4-HPR), clotrimazole, bortezomib, MPA, imatinib mesylate) significantly suppressed ZIKV infection in mosquito midguts. Some of these FDA-approved drugs may have potential for use for the development of ZIKV transmission-blocking strategies.

by Balgees A. Ajlan, Maram M. Alafif, Maha M. Alawi, Naeema A. Akbar, Eman K. Aldigs, Tariq A. Madani

The objective of this study was to assess the validity of the new dengue classification proposed by the World Health Organization (WHO) in 2009 and to develop pragmatic guidelines for case triage and management. This retrospective study involved 357 laboratory-confirmed cases of dengue infection diagnosed at King Abdulaziz University Hospital, Jeddah, Saudi Arabia over a 4-year period from 2014 to 2017. The sensitivity of the new classification for identifying severe cases was limited (65%) but higher than the old one (30%). It had a higher sensitivity for identifying patients who needed advanced healthcare compared to the old one (72% versus 32%, respectively). We propose adding decompensation of chronic diseases and thrombocytopenia-related bleeding to the category of severe dengue in the new classification. This modification improves sensitivity from 72% to 98% for identifying patients who need advanced healthcare without altering specificity (97%). It also improves sensitivity in predicting severe outcomes from 32% to 88%. In conclusion, the new classification had a low sensitivity for identifying patients needing advanced care and for predicting morbidity and mortality. We propose to include decompensation of chronic diseases and thrombocytopenia-related bleeding to the category of severe dengue in the new classification to improve the sensitivity of predicting cases requiring advanced care.

by Claude Flamand, Sarah Bailly, Camille Fritzell, Sandrine Fernandes Pellerin, Alhassane Toure, Naïssa Chateau, Mona Saout, Sébastien Linares, Fabien Dubois, Laurent Filleul, Mirdad Kazanji
Background French Guiana, a French overseas department located in South America between Brazil and Surinam, is the only European territory geographically located in the Amazonian forest complex and is considered endemic for yellow fever (YF).In the context of the emergent threat of YF in Latin America, we conducted a large household cross-sectional survey from June to October 2017 to estimate vaccination coverage in the population and to determine associations with sociodemographic and geographical characteristics. Methodology/Principal findings In total, 1,415 households and 2,697 individuals were included from the 22 municipalities of French Guiana. YF vaccination coverage was estimated at 95.0% (95% CI: 93.4–96.2) in the entire territory but was spatially heterogeneous, with the lowest levels estimated in the western part of the territory along the Surinamese cross-border region, particularly in children under 16 years who were not enrolled in school, immigrant adults and disadvantaged populations with low socioeconomic indexes. Conclusions/Significance Despite the good vaccination coverage against YF in the general population of French Guiana resulting from the compulsory nature of YF vaccination for residents and travelers, there is an urgent need to improve vaccination coverage in vulnerable populations living in the northwestern part of the territory to limit the risk of transmission in the context of the emerging YF threat in South America.Despite the relative rarity of YF and the significant number of infectious and tropical diseases in French Guiana, clinicians should adopt a high index of suspicion for YF, particularly in vulnerable and at-risk populations.

by Bo Yi, Yi Chen, Xiao Ma, Jia Rui, Jing-An Cui, Haibin Wang, Jia Li, Soi-Fan Chan, Rong Wang, Keqin Ding, Lei Xie, Dongliang Zhang, Shuli Jiao, Xuying Lao, Yi-Chen Chiang, Yanhua Su, Benhua Zhao, Guozhang Xu, Tianmu Chen
Background The reported incidence of dengue fever increased dramatically in recent years in China. This study aimed to investigate and to assess the effectiveness of intervention implemented in a dengue outbreak in Ningbo City, Zhejiang Province, China. Methods Data of a dengue outbreak were collected in Ningbo City in China by a field epidemiological survey according to a strict protocol and case definition. Serum specimens of all cases were collected for diagnosis and the virological characteristics were detected by using polymerase chain reaction (PCR) and gene sequencing. Vector surveillance was implemented during the outbreak to collect the larva and adult mosquito densities to calculate the Breteau Index (BI) and human biting rate (HBR), respectively. Data of monthly BI and light-trap density in 2018 were built to calculate the seasonality of the vector. A transmission mathematical model was developed to dynamic the incidence of the disease. The parameters of the model were estimated by the data of the outbreak and vector surveillance data in 2018. The effectiveness of the interventions implemented during the outbreak was assessed by the data and the modelling. Results From 11 August to 8 September, 2018, a dengue outbreak was reported with 27 confirmed cases in a population of 5536-people community (community A) of Ningbo City. Whole E gene sequences were obtained from 24 cases and were confirmed as dengue virus type 1 (DENV-1). The transmission source of the outbreak was origin from community B where a dengue case having the same E gene sequence was onset on 30 July. Aedes albopictus was the only vector species in the area. The value of BI and HBR was 57.5 and 12 per person per hour respectively on 18 August, 2018 and decreased dramatically after interventions. The transmission model fitted well (χ2 = 6.324, P = 0.388) with the reported cases data. With no intervention, the total simulated number of the cases would be 1728 with a total attack rate (TAR) of 31.21% (95%CI: 29.99%– 32.43%). Case isolation and larva control (LC) have almost the same TAR and duration of outbreak (DO) as no intervention. Different levels of reducing HBR (rHBR) had different effectiveness with TARs ranging from 1.05% to 31.21% and DOs ranging from 27 days to 102 days. Adult vector control (AVC) had a very low TAR and DO. “LC+AVC” had a similar TAR and DO as that of AVC. “rHBR100%+LC”, “rHBR100%+AVC”, “rHBR100%+LC+AVC” and “rHBR100%+LC+AVC+Iso” had the same effectiveness. Conclusions Without intervention, DENV-1 could be transmitted rapidly within a short period of time and leads to high attack rate in community in China. AVC or rHBR should be recommended as primary interventions to control rapid transmission of the dengue virus at the early stage of an outbreak.

by Rodolphe Hamel, Pornapat Surasombatpattana, Sineewanlaya Wichit, Alexandra Dauvé, Celeste Donato, Julien Pompon, Dhanasekaran Vijaykrishna, Florian Liegeois, Ronald Morales Vargas, Natthanej Luplertlop, Dorothée Missé

Dengue fever is caused by dengue viruses (DENV) from the Flavivirus genus and is the most prevalent arboviral disease. DENV exists in four immunogenically distinct and genetically-related serotypes (DENV-1 to 4), each subdivided in genotypes. Despite the endemicity of all four DENV serotypes in Thailand, no prior study has characterized the circulation of DENV in the southern provinces of the country. To determine the genetic diversity of DENV circulating in Southern Thailand in 2015 and 2016, we investigated 46 viruses from 182 patients’ sera confirmed positive for DENV by serological and Nested RT-PCR tests. Our dataset included 2 DENV-1, 20 DENV-2, 9 DENV-3 and 15 DENV-4. Phylogenetic analysis was performed on viral envelop sequences. This revealed that part of the identified genotypes from DENV-1 and DENV-4 had been predominant in Asia (genotype I for both serotypes), while genotype II for DENV-4 and the Cosmopolitan genotype DENV-2 were also circulating. Whereas DENV-3 genotype II had been predominantly detected in South East Asia during the previous decades, we found genotype III and genotype I in Southern Thailand. All DENV genotype identified in this study were closely related to contemporary strains circulating in Southeast Asian countries, emphasizing the regional circulation of DENV. These results provide new insights into the co-circulation of all four DENV serotypes in Southern Thailand, confirming the hyperendemicity of DENV in the region. These findings also suggest a new trend of dissemination for some DENV serotypes with a possible shift in genotype distribution; as recently observed in other Asian countries.

by Lucie Danet, Guillaume Beauclair, Michèle Berthet, Gonzalo Moratorio, Ségolène Gracias, Frédéric Tangy, Valérie Choumet, Nolwenn Jouvenet
Background To be transmitted to vertebrate hosts via the saliva of their vectors, arthropod-borne viruses have to cross several barriers in the mosquito body, including the midgut infection and escape barriers. Yellow fever virus (YFV) belongs to the genus Flavivirus, which includes human viruses transmitted by Aedes mosquitoes, such as dengue and Zika viruses. The live-attenuated YFV-17D vaccine has been used safely and efficiently on a large scale since the end of World War II. Early studies have shown, using viral titration from salivary glands of infected mosquitoes, that YFV-17D can infect Aedes aegypti midgut, but does not disseminate to other tissues. Methodology/Principal findings Here, we re-visited this issue using a panel of techniques, such as RT-qPCR, Western blot, immunofluorescence and titration assays. We showed that YFV-17D replication was not efficient in Aedes aegypti midgut, as compared to the clinical isolate YFV-Dakar. Viruses that replicated in the midgut failed to disseminate to secondary organs. When injected into the thorax of mosquitoes, viruses succeeded in replicating into midgut-associated tissues, suggesting that, during natural infection, the block for YFV-17D replication occurs at the basal membrane of the midgut. Conclusions/Significance The two barriers associated with Ae. aegypti midgut prevent YFV-17D replication. Our study contributes to our basic understanding of vector–pathogen interactions and may also aid in the development of non-transmissible live virus vaccines.

Title: Introdução do vírus da dengue do sorotipo 3 no Estado da Bahia
Authors: Góes, Mônica C.; Reis, Eliana; Costa, Aida Maria S.; Ferreira, Janete; Cardoso, Fernanda Maria A.; Blanton, Ronald Edward; Reis, Mitermayer Galvão dos
Description: Trabalho inserido na Revista da Sociedade Brasileira de Medicina Tropical, p. 135, Supl. I. 2004.

by Isra Wahid, Hasanuddin Ishak, Abdul Hafid, Muhammad Fajri, Sukmawati Sidjal, Armin Nurdin, Naisyah Tun Azikin, Rusdyah Sudirman, Hajar Hasan, Muhammad Yusuf, Imam Bachtiar, William A. Hawley, Ronald Rosenberg, Neil F. Lobo

Dengue virus transmission is endemic in Makassar, Indonesia, with the majority of cases reported soon after the start of the annual rainy season. Before 2006, larval source reduction, larvaciding, and reactive routine, outdoor, insecticide fogging campaigns did not result in a reduction in seasonal dengue incidence. Beginning in 2006, village volunteers conducted comprehensive surveys for immature Aedes during the dry season, when vector populations were at their lowest. Based on this pre-season vector data, a single additional pre-emptive outdoor fogging with Malathion was conducted once annually before the rains began in villages with a pre-defined proportion of sampled houses positive for Aedes immatures. This additional procedure was associated with reduced temporal larval indices as well as an 83% reduction in reported cases during the transmission season over the 8-year period of implementation. Two cities adjacent to Makassar experienced substantial but smaller reductions in dengue incidence; while other cities further from the intervention area did not. This represents the first time an integrated intervention strategy has been coupled with substantially reduced dengue transmission in Indonesia.

Title: Apparent low gene flow of Aedes Aegypti in an urban setting base on using new microsatellite markers.
Authors: Melo, Paulo Roberto Santana de; Silva, Luciano Kalabric; Ribeiro, G.; Santos, C. G. S.; Blanton, Edward Ronald; Reis, Mitermayer Galvão dos

by Peter Haddawy, Poom Wettayakorn, Boonpakorn Nonthaleerak, Myat Su Yin, Anuwat Wiratsudakul, Johannes Schöning, Yongjua Laosiritaworn, Klestia Balla, Sirinut Euaungkanakul, Papichaya Quengdaeng, Kittipop Choknitipakin, Siripong Traivijitkhun, Benyarut Erawan, Thansuda Kraisang

Targeted environmental and ecosystem management remain crucial in control of dengue. However, providing detailed environmental information on a large scale to effectively target dengue control efforts remains a challenge. An important piece of such information is the extent of the presence of potential dengue vector breeding sites, which consist primarily of open containers such as ceramic jars, buckets, old tires, and flowerpots. In this paper we present the design and implementation of a pipeline to detect outdoor open containers which constitute potential dengue vector breeding sites from geotagged images and to create highly detailed container density maps at unprecedented scale. We implement the approach using Google Street View images which have the advantage of broad coverage and of often being two to three years old which allows correlation analyses of container counts against historical data from manual surveys. Containers comprising eight of the most common breeding sites are detected in the images using convolutional neural network transfer learning. Over a test set of images the object recognition algorithm has an accuracy of 0.91 in terms of F-score. Container density counts are generated and displayed on a decision support dashboard. Analyses of the approach are carried out over three provinces in Thailand. The container counts obtained agree well with container counts from available manual surveys. Multi-variate linear regression relating densities of the eight container types to larval survey data shows good prediction of larval index values with an R-squared of 0.674. To delineate conditions under which the container density counts are indicative of larval counts, a number of factors affecting correlation with larval survey data are analyzed. We conclude that creation of container density maps from geotagged images is a promising approach to providing detailed risk maps at large scale.

by Tyler M. Sharp, Olga Lorenzi, Brenda Torres-Velásquez, Veronica Acevedo, Janice Pérez-Padilla, Aidsa Rivera, Jorge Muñoz-Jordán, Harold S. Margolis, Stephen H. Waterman, Brad J. Biggerstaff, Gabriela Paz-Bailey, Roberto Barrera
Background Public health responses to outbreaks of dengue, chikungunya, and Zika virus have been stymied by the inability to control the primary vector, Aedes aegypti mosquitos. Consequently, the need for novel approaches to Aedes vector control is urgent. Placement of three autocidal gravid ovitraps (AGO traps) in ~85% of homes in a community was previously shown to sustainably reduce the density of female Ae. aegypti by >80%. Following the introduction of chikungunya virus (CHIKV) to Puerto Rico, we conducted a seroprevalence survey to estimate the prevalence of CHIKV infection in communities with and without AGO traps and evaluate their effect on reducing CHIKV transmission. Methods and findings Multivariate models that calculated adjusted prevalence ratios (aPR) showed that among 175 and 152 residents of communities with and without AGO traps, respectively, an estimated 26.1% and 43.8% had been infected with CHIKV (aPR = 0.50, 95% CI: 0.37–0.91). After stratification by time spent in their community, protection from CHIKV infection was strongest among residents who reported spending many or all weekly daytime hours in their community:10.3% seropositive in communities with AGO traps vs. 48.7% in communities without (PR = 0.21, 95% CI: 0.11–0.41). The age-adjusted rate of fever with arthralgia attributable to CHIKV infection was 58% (95% CI: 46–66%). The monthly number of CHIKV-infected mosquitos and symptomatic residents were diminished in communities with AGO traps compared to those without. Conclusions These findings indicate that AGO traps are an effective tool that protects humans from infection with a virus transmitted by Ae. aegypti mosquitos. Future studies should evaluate their protective effectiveness in large, urban communities.

by Debajit Dey, Shumaila Iqbal Siddiqui, Prabhudutta Mamidi, Sukanya Ghosh, Chandra Shekhar Kumar, Soma Chattopadhyay, Subhendu Ghosh, Manidipa Banerjee

Viroporins like influenza A virus M2, hepatitis C virus p7, HIV-1 Vpu and picornavirus 2B associate with host membranes, and create hydrophilic corridors, which are critical for viral entry, replication and egress. The 6K proteins from alphaviruses are conjectured to be viroporins, essential during egress of progeny viruses from host membranes, although the analogue in Chikungunya Virus (CHIKV) remains relatively uncharacterized. Using a combination of electrophysiology, confocal and electron microscopy, and molecular dynamics simulations we show for the first time that CHIKV 6K is an ion channel forming protein that primarily associates with endoplasmic reticulum (ER) membranes. The ion channel activity of 6K can be inhibited by amantadine, an antiviral developed against the M2 protein of Influenza A virus; and CHIKV infection of cultured cells can be effectively inhibited in presence of this drug. Our study provides crucial mechanistic insights into the functionality of 6K during CHIKV-host interaction and suggests that 6K is a potential therapeutic drug target, with amantadine and its derivatives being strong candidates for further development.

by Amaro Nunes Duarte-Neto, Renata Aparecida de Almeida Monteiro, Janaina Johnsson, Marielton dos Passos Cunha, Shahab Zaki Pour, Amanda Cartagenes Saraiva, Yeh-Li Ho, Luiz Fernando Ferraz da Silva, Thais Mauad, Paolo Marinho de Andrade Zanotto, Paulo Hilário Nascimento Saldiva, Ilka Regina Souza de Oliveira, Marisa Dolhnikoff
Background New strategies for collecting post-mortem tissue are necessary, particularly in areas with emerging infections. Minimally invasive autopsy (MIA) has been proposed as an alternative to conventional autopsy (CA), with promising results. Previous studies using MIA addressed the cause of death in adults and children in developing countries. However, none of these studies was conducted in areas with an undergoing infectious disease epidemic. We have recently experienced an epidemic of yellow fever (YF) in Brazil. Aiming to provide new information on low-cost post-mortem techniques that could be applied in regions at risk for infectious outbreaks, we tested the efficacy of ultrasound-guided MIA (MIA-US) in the diagnosis of patients who died during the epidemic. Methodology/principal findings In this observational study, we performed MIA-US in 20 patients with suspected or confirmed YF and compared the results with those obtained in subsequent CAs. Ultrasound-guided biopsies were used for tissue sampling of liver, kidneys, lungs, spleen, and heart. Liver samples from MIA-US and CA were submitted for RT-PCR and immunohistochemistry for detection of YF virus antigen. Of the 20 patients, 17 had YF diagnosis confirmed after autopsy by histopathological and molecular analysis. There was 100% agreement between MIA-US and CA in determining the cause of death (panlobular hepatitis with hepatic failure) and main disease (yellow fever). Further, MIA-US obtained samples with good quality for molecular studies and for the assessment of the systemic involvement of the disease. Main extrahepatic findings were pulmonary hemorrhage, pneumonia, acute tubular necrosis, and glomerulonephritis. One patient was a 24-year-old, 27-week pregnant woman; MIA-US assessed the placenta and provided adequate placental tissue for analysis. Conclusions MIA-US is a reliable tool for rapid post-mortem diagnosis of yellow fever and can be used as an alternative to conventional autopsy in regions at risk for hemorrhagic fever outbreaks with limited resources to perform complete diagnostic autopsy.

by Luisa I. Alvarado, Olga D. Lorenzi, Brenda C. Torres-Velásquez, Tyler M. Sharp, Luzeida Vargas, Jorge L. Muñoz-Jordán, Elizabeth A. Hunsperger, Janice Pérez-Padilla, Aidsa Rivera, Gladys E. González-Zeno, Renee L. Galloway, Mindy Glass Elrod, Demetrius L. Mathis, M. Steven Oberste, W. Allan Nix, Elizabeth Henderson, Jennifer McQuiston, Joseph Singleton, Cecilia Kato, Carlos García-Gubern, William Santiago-Rivera, Robert Muns-Sosa, Juan D. Ortiz-Rivera, Gerson Jiménez, Vanessa Rivera-Amill, Doris A. Andújar-Pérez, Kalanthe Horiuchi, Kay M. Tomashek

Chikungunya, a mosquito-borne viral, acute febrile illness (AFI) is associated with polyarthralgia and polyarthritis. Differentiation from other AFI is difficult due to the non-specific presentation and limited availability of diagnostics. This 3-year study identified independent clinical predictors by day post-illness onset (DPO) at presentation and age-group that distinguish chikungunya cases from two groups: other AFI and dengue. Specimens collected from participants with fever ≤7 days were tested for chikungunya, dengue viruses 1–4, and 20 other pathogens. Of 8,996 participants, 18.2% had chikungunya, and 10.8% had dengue. Chikungunya cases were more likely than other groups to be older, report a chronic condition, and present

by Rokeya Akter, Suchithra Naish, Michelle Gatton, Hilary Bambrick, Wenbiao Hu, Shilu Tong

Dengue is a public health concern in northern Queensland, Australia. This study aimed to explore spatial and temporal characteristics of dengue cases in Queensland, and to identify high-risk areas after a 2009 dengue outbreak at fine spatial scale and thereby help in planning resource allocation for dengue control measures. Notifications of dengue cases for Queensland at Statistical Local Area (SLA) level were obtained from Queensland Health for the period 2010 to 2015. Spatial and temporal analysis was performed, including plotting of seasonal distribution and decomposition of cases, using regression models and creating choropleth maps of cumulative incidence. Both the space-time scan statistic (SaTScan) and Geographical Information System (GIS) were used to identify and visualise the space-time clusters of dengue cases at SLA level. A total of 1,773 dengue cases with 632 (35.65%) autochthonous cases and 1,141 (64.35%) overseas acquired cases were satisfied for the analysis in Queensland during the study period. Both autochthonous and overseas acquired cases occurred more frequently in autumn and showed a geographically expanding trend over the study period. The most likely cluster of autochthonous cases (Relative Risk, RR = 54.52, p

Title: Caracterização fenotípica e funcional de células Natural Killer (NK) durante a monoinfecção e coinfecção pelos vírus Dengue e Zika
Authors: Guimarães, Gabriel Macedo Costa
Abstract: As arboviroses correspondem uma das principais causas de morbidade e
mortalidade humana em áreas tropicais e subtropicais do mundo. O vírus
Dengue (DENV) é o arbovírus mais importante que afeta o homem e constitui um sério problema de saúde pública no Brasil. A associação com desordens congênitas e neurológicas, tornou o vírus Zika (ZIKV) uma arbovirose de importância médica no Brasil e no mundo. Diversos fatores têm sido associados à patogênese dessas doenças, no entanto, os mecanismos envolvidos não são completamente compreendidos. As células Natural Killer (NK) são linfócitos CD3neg CD56+ que fazem parte da resposta imune inata e são fundamentais durante a fase inicial das infecções por meio de suas funções antivirais e citotóxicas contra células- alvo infectadas. Pouco se sabe sobre os mecanismos de ação das células NK durante a infecção pelo DENV ou ZIKV. Assim, o objetivo deste estudo foi avaliar o envolvimento das células NK durante a infecção e coinfecção pelos vírus DENV e ZIKV. Analisando as células de pacientes naturalmente infectados e coinfectados pelo DENV e ZIKV, observamos maior frequência de células NK em pacientes infectados pelo DENV, em comparação
com os demais grupos estudados. Além disso, demonstramos elevada
frequência de células NK CD56dim CD16+ co-expressando a proteína intracelular perforina e o marcador CD62L em pacientes monoinfectados pelo DENV em comparação com pacientes monoinfectados pelo ZIKV, coinfectados DENV e ZIKV, pacientes com outras doenças febris (ODF) e doadores saudáveis. A quantificação de citocinas demonstrou elevadas concentrações de TNF-α e IL-6 em pacientes infectados pelo DENV e também nos coinfectados. Elevadas concentrações de IFN- e de IL-15 foram detectadas nos pacientes com Dengue e nos pacientes coinfectados respectivamente. Também foi padronizado um modelo in vitro de cocultura de monócitos humanos infectados pelo DENV-2 ou ZIKV e células NK na presença de IL-2. Os resultados demonstraram um percentual mais baixo de monócitos após a infecção pelo DENV ou ZIKV comparados com a cocultura não infectada. Além disso, também observamos incremento na população de monócitos CD14+ CD16+ nas coculturas infectadas. Corroborando com nossos dados ex vivo, observamos que o subtipo CD56dim CD16+ apresentou elevada coexpressão de perforina e CD62L nas coculturas
infectadas. Esses resultados demostram que as células NK são importantes
células efetoras da resposta imune antiviral e estão relacionadas com a
imunopatogenese dessas arboviroses de importância médica no Brasil.

by Leora R. Feldstein, Esther M. Ellis, Ali Rowhani-Rahbar, Morgan J. Hennessey, J. Erin Staples, M. Elizabeth Halloran, Marcia R. Weaver

Chikungunya virus (CHIKV), an alphavirus that causes fever and severe polyarthralgia, swept through the Americas in 2014 with almost 2 million suspected or confirmed cases reported by April 2016. In this study, we estimate the direct medical costs, cost of lost wages due to absenteeism, and years lived with disability (YLD) associated with the 2014–2015 CHIKV outbreak in the U.S. Virgin Islands (USVI). For this analysis, we used surveillance data from the USVI Department of Health, medical cost data from three public hospitals in USVI, and data from two studies of laboratory-positive cases up to 12 months post illness. On average, employed case-patients missed 9 days of work in the 12 months following their disease onset, which resulted in an estimated cost of $15.5 million. Estimated direct healthcare costs were $2.9 million for the first 2 months and $0.6 million for 3–12 months following the outbreak. The total estimated cost associated with the outbreak ranged from $14.8 to $33.4 million (approximately 1% of gross domestic product), depending on the proportion of the population infected with symptomatic disease, degree of underreporting, and proportion of cases who were employed. The estimated YLDs associated with long-term sequelae from the CHIKV outbreak in the USVI ranged from 599–1,322. These findings highlight the significant economic burden of the recent CHIKV outbreak in the USVI and will aid policy-makers in making informed decisions about prevention and control measures for inevitable, future CHIKV outbreaks.

by Claudia Buhler, Volker Winkler, Silvia Runge-Ranzinger, Ross Boyce, Olaf Horstick
Background Vector control remains the primary method to prevent dengue infections. Environmental interventions represent sustainable and safe methods as there are limited risks of environmental contamination and toxicity. The objective of this study is to perform a systematic review and meta-analysis of the effectiveness of the following environmental methods for dengue vector control. Methodology/Principal findings Following the PRISMA guidelines, a systematic literature search was conducted using the databases PubMed, EMBASE, LILACS, the Cochrane Library and Google Scholar. Quality assessment was done using the CONSORT 2010 checklist. For the meta-analysis the difference-in-differences (DID) and the difference-of-endlines (DOE) were calculated according to the Schmidt-Hunter method for the Breteau index (BI) and the pupae per person index (PPI). Nineteen studies were eligible for the systematic review, sixteen contributed data to the meta-analysis. The following methods were evaluated: (a) container covers with and without insecticides, (b) waste management and clean-up campaigns, and (c) elimination of breeding sites by rendering potential mosquito breeding sites unusable or by eliminating them. Study quality was highest for container covers with insecticides, followed by waste management without direct garbage collection and elimination of breeding places. Both, systematic review and meta-analysis, showed a weak effect of the interventions on larval populations, with no obvious differences between the results of each individual method. For the meta-analysis, both, container covers without insecticides (BI: DID -7.9, DOE -5) and waste management with direct garbage collection (BI: DID -8.83, DOE -6.2) achieved the strongest reductions for the BI, whereas for the PPI results were almost opposite, with container covers with insecticides (PPI: DID -0.83, DOE 0.09) and elimination of breeding places (PPI: DID -0.95, DOE -0.83) showing the strongest effects. Conclusions Each of the investigated environmental methods showed some effectiveness in reducing larval and pupal densities of Aedes sp. mosquitoes. However, there is a need for more comparable high-quality studies at an adequate standard to strengthen this evidence.

by Alessandra Aparecida Vieira Machado, Fábio Juliano Negrão, Júlio Croda, Elias Silva de Medeiros, Maria Aparecida dos Santos Pires
Background Dengue is a public health problem, and noncompliance with World Health Organization (WHO) recommendations for blood transfusion components is frequently reported. Moreover, economic impact studies of the WHO recommendations on the use of blood transfusion are scarce. Methods We compared the cost and hospitalization time in a prospective observational study, by following hospitalised patients and analysing their medical records from 2010 and March 2016 to December 2017. We divided the patients into two groups: transfused (with or without WHO criteria for transfusion) and not transfused (with or without WHO criteria for transfusion). Generalised linear modelling was performed to identify the variable that could increase the costs and hospital stay. Results Among 323 patients, 52 were transfused, of whom 52% without criteria (n = 27), and 271 were not transfused, of which 4.4% (n = 12) with criteria. Hospitalisation costs were 41% higher in the transfused group without criteria than in those with criteria (median US$ 674.3 vs US$ 478 p = 0.293). Patients who were not transfused but met the WHO criteria for transfusion (n = 12) had longer mean hospitalisation time than did those who were not transfused (3.8±3.4 days versus 3.6±3.1 days; p = 0.022). The GLM analysis using hospital stay and costs as the dependent variable explained approximately 33.4% (R2 = 0.334) of the hospitalisation time and 79.3% (R2 = 0.793) of costs. Receiving a transfusion increased the hospitalization time by 1.29 days (p = 0.0007; IRR = 1.29), and the costs were 5.1 times higher than those without receiving blood components (IRR = 5.1; p 0.001; median US$ 504.4 vs US$ 170.7). In contrast, patients who were transfused according to WHO criteria had a reduction in costs of approximately 96% (IRR = 0.044; p