Monitoramento das Produções

by Yosra Bedoui, Claude Giry, Marie-Christine Jaffar-Bandjee, Jimmy Selambarom, Pascale Guiraud, Philippe Gasque

Chikungunya virus (CHIKV) is a mosquito-transmitted RNA alphavirus causing major outbreaks of infectious chronic inflammatory rheumatisms (CIR). Recently, methotrexate (MTX), a disease modifying anti-rheumatic drug has been used successfully to treat patients suffering from rheumatoid-like arthritis post-CHIK but its immunomodulatory activity in the context of viral persistence has been a matter of concerns. We herein used a model of primary human synovial fibroblasts (HSF) and the synthetic molecule polyriboinosinic:polyribocytidylic acid (PIC) to mimic chronic infectious settings in the joints of CHIKV infected patients. The innate antiviral immune and inflammatory responses were investigated in response to MTX used at the therapeutic concentration of 1 μM. We found that MTX did not affect cellular viability as indicated by the LDH release assay. By quantitative RT-PCR, we observed that HSF responded robustly to PIC by increasing ISG15 and IFNβ mRNA levels. Furthermore, PIC upregulated the mRNA expression of two of the major pattern recognition receptors, RIG-I and MDA5 involved in the innate immune detection of viral RNA. MTX did not impact the antiviral response of PIC on ISG15, IFNβ, RIG-I and MDA5 mRNA expressions. MTX alone or combined with PIC did not affect the expression of proinflammatory CCL2 and CXCL8 chemokines. PIC strongly upregulated the mRNA and protein expression of osteoclastogenic factors (IL-6, GM-CSF but not RANKL). Critically, MTX treatment alone or combined with PIC did not affect the expression of all three tested osteoclastogenic cytokines. We found that MTX alone did not increase the capacity of CHIKV to infect and replicate in HSF. In conclusion, our study argues for a beneficial effect of MTX to treat CIR post-CHIKV given that it does not critically impact the antiviral, the proinflammatory and the bone tissue remodeling responses of synovial cells.

by Erin M. McDonald, Nisha K. Duggal, Jana M. Ritter, Aaron C. Brault

While primarily a mosquito-borne virus, Zika virus (ZIKV; genus Flavivirus in the Flaviviridae family) is capable of being sexually transmitted. Thirty to fifty percent of men with confirmed ZIKV infection shed ZIKV RNA in their semen, and prolonged viral RNA shedding in semen can occur for more than 6 months. The cellular reservoir of ZIKV in semen is unknown, although spermatozoa have been shown to contain ZIKV RNA and antigen. Yet, spermatozoa are not a requisite for sexual transmission, as at least one case of ZIKV sexual transmission involved a vasectomized man. To determine the cellular reservoirs of ZIKV in semen, an established animal model of sexual transmission was used. The majority of virus detected in the seminal fluid of infected mice during the peak timing of sexual transmission was from the supernatant fraction, suggesting cell-free ZIKV may be largely responsible for sexual transmission. However, some ZIKV RNA was cell-associated. In the testes and epididymides of infected mice, intracellular staining of ZIKV RNA was more pronounced in spermatogenic precursors (spermatocytes and spermatogonia) than in spermatids. Visualization of intracellular negative strand ZIKV RNA demonstrated ZIKV replication intermediates in leukocytes, immature spermatids and epididymal epithelial cells in the male urogenital tract. Epididymal epithelial cells were the principal source of negative-strand ZIKV RNA during the peak timing of sexual transmission potential, indicating these cells may be the predominant source of infectious cell-free ZIKV in seminal fluid. These data promote a more complete understanding of sexual transmission of ZIKV and will inform further model development for future studies on persistent ZIKV RNA shedding.

Title: Zika e Aedes aegypti: antigos e novos desafios
Authors: Bueno, Flávia Thedim Costa; Garcia, Mónica; Moya, José; Löwy, Ilana; Benchimol, Jaime L.; Cerqueira, Roberta C.; Cueto, Marcos
Abstract: A infecção por zika teve grande impacto não somente nas grávidas e
nos recém-nascidos, mas também na saúde pública, nas ideias populares
sobre o Aedes aegypti e no respeito dos direitos sociais das mulheres. O
objetivo deste texto é identificar esse impacto e as mudanças históricas,
sociais e sanitárias da doença e o legado do vírus zika. As intervenções
de pesquisadores de diferentes disciplinas propiciam condições para
investigações mais abrangentes sobre futuras ameaças epidêmicas no Brasil
e na América Latina. Este diálogo ocorreu após o seminário “Aedes aegypti:
antigas e novas emergências sanitárias”, organizado pela Casa de Oswaldo
Cruz, quando conversamos com alguns palestrantes e outros destacados
pesquisadores sobre a história e os desafios do Aedes aegypti e do zika.

by Jing Jin, Michael B. Sherman, Daniel Chafets, Nuntana Dinglasan, Kai Lu, Tzong-Hae Lee, Lars-Anders Carlson, Marcus O. Muench, Graham Simmons
Background Chikungunya virus (CHIKV) is the most common alphavirus infecting humans worldwide, causing acute and chronically debilitating arthralgia at a great economic expense. Methodology/Principal findings To facilitate our study of CHIKV, we generated a mCherry tagged replication-competent chimeric virus, CHIKV 37997-mCherry. Single particle cryoEM demonstrated icosahedral organization of the chimeric virus and the display of mCherry proteins on virus surface. CHIKV 37997-mCherry is attenuated in both IFNαR knockout and wild-type mice. Strong anti-CHIKV and anti-mCherry antibody responses were induced in CHIKV 37997-mCherry infected mice. Conclusions/Significance Our work suggests that chimeric alphaviruses displaying foreign antigen can serve as vaccines against both aphaviruses and other pathogens and diseases.

by Charuai Suwanbamrung, Chanchuri Thoutong, Thidarat Eksirinimit, Supapon Tongjan, Kanapot Thongkew

Background: Dengue has been spreading in Thailand for more than 50 years, and the community prevention of dengue transmission is an important strategy to help reduce outbreaks. The larval indices surveillance system is one of the most significant prevention methods at the household and district levels. Objective: This study sought to develop a larval indices surveillance system based on a specific community context. Method: Community participation action research (CPAR) studies represent a new approach to studying the high-risk dengue area of Lansaka district, Nakhon Si Thammarat province, Thailand. This study was conducted for 2 years (from 2013 to 2015) and applied the integrated concepts of 1) community capacity building, 2) epidemiology, 3) research design for health development, and 4) an online computer program. The method included five phases: 1) community preparation, 2) situation assessment, 3) the development of the surveillance system, 4) implementation, and 5) evaluation. Results: The model was designed in partnership with all the stakeholders from 44 villages across 5 sub-districts. The surveillance system consisted of seven steps at the household level based on primary care surveillance centers (PCSCs), as well as four components at the district level based on district surveillance centers (DSCs). The dengue morbidity rate decreased from 164, 151, and 135 cases/100,000 people in 2014, 2015, and 2016, respectively. Moreover, knowledge of both dengue and larval indices among village health volunteers (VHVs) increased significantly (p .01). Conclusions: The results from the new system showed a decrease in both the larval indices level and morbidity rate; however, the levels remained higher than the standard. The active surveillance system requires continuous monitoring at both the household and district levels.

Title: Pregnant women co-infected with HIV and Zika: Outcomes and birth defects in infants according to maternal symptomatology
Authors: João, Esaú C.; Ferreira, Orlando da C.; Gouvêa, Maria Isabel; Teixeira, Maria de Lourdes B.; Tanuri, Amilcar; Higa, Luiza M.; Costa, Deise A.; Mohana-Borges, Ronaldo; Arruda, Mônica B.; Matos, Haroldo J.; Cruz, Maria Leticia; Mendes-Silva, Wallace; Read, Jennifer S.

Title: Wolbachia significantly impacts the vector competence of Aedes aegypti for Mayaro virus
Authors: Pereira, Thiago Nunes; Rocha, Marcele Neves; Sucupira, Pedro Henrique Ferreira; Carvalho, Fabiano Duarte; Moreira, Luciano Andrade

Title: Persistence of Yellow fever virus outside the Amazon Basin, causing epidemics in Southeast Brazil, from2016 to 2018
Authors: Rezende, Izabela Maurıcio de; Sacchetto, Lıvia; Mello, Erica Munhoz de; Alves, Pedro Augusto; Iani, Felipe Campos de Melo; Adelino, Talita Emile Ribeiro; Duarte, Myrian Morato; Cury, Ana Luısa Furtado; Bernardes, Andre Felipe Leal; Santos, Tayrine Araujo; Pereira, Leonardo Soares; Dutra, Maria Rita Teixeira; Ramalho, Dario Brock; Thoisy, Benoit de; Kroon, Erna Geessien; Trindade, Giliane de Souza; Drumond, Betania Paiva

by Yi Tan, Brett E. Pickett, Susmita Shrivastava, Lionel Gresh, Angel Balmaseda, Paolo Amedeo, Lihui Hu, Vinita Puri, Nadia B. Fedorova, Rebecca A. Halpin, Matthew P. LaPointe, Marshall R. Cone, Lea Heberlein-Larson, Laura D. Kramer, Alexander T. Ciota, Aubree Gordon, Reed S. Shabman, Suman R. Das, Eva Harris

Chikungunya virus (CHIKV) has been detected sporadically since the 1950s and includes three distinct co-circulating genotypes. In late 2013, the Asian genotype of CHIKV was responsible for the Caribbean outbreak (CO) that rapidly became an epidemic throughout the Americas. There is a limited understanding of the molecular evolution of CHIKV in the Americas during this epidemic. We sequenced 185 complete CHIKV genomes collected mainly from Nicaragua in Central America and Florida in the United States during the 2014–2015 Caribbean/Americas epidemic. Our comprehensive phylogenetic analyses estimated the epidemic history of the Asian genotype and the recent Caribbean outbreak (CO) clade, revealed considerable genetic diversity within the CO clade, and described different epidemiological dynamics of CHIKV in the Americas. Specifically, we identified multiple introductions in both Nicaragua and Florida, with rapid local spread of viruses in Nicaragua but limited autochthonous transmission in Florida in the US. Our phylogenetic analysis also showed phylogeographic clustering of the CO clade. In addition, we identified the significant amino acid substitutions that were observed across the entire Asian genotype during its evolution and examined amino acid changes that were specific to the CO clade. Deep sequencing analysis identified specific minor variants present in clinical specimens below-consensus levels. Finally, we investigated the association between viral phylogeny and geographic/clinical metadata in Nicaragua. To date, this study represents the largest single collection of CHIKV complete genomes during the Caribbean/Americas epidemic and significantly expands our understanding of the emergence and evolution of CHIKV CO clade in the Americas.

by Ling Xue, Xin Fang, James M. Hyman

Once Aedes aegypti and Aedes albopictus mosquitoes that spread Chikungunya virus, dengue virus, and Zika virus are infected with Wolbachia, they have reduced egg laying rates, reduced transmission abilities, and shorter lifespans. Since most infected mosquitoes are only infectious in the last few days of their lives, shortening a mosquito’s lifespan by a day or two can greatly reduce their abilities to spread mosquito-borne viral diseases, such as Chikungunya, dengue fever, and Zika. We developed a mathematical model to compare the effectiveness of the wMel and wAlbB strains of Wolbachia for controlling the spread of these viruses. The differences among the diseases, mosquitoes, and Wolbachia strains are captured by the model parameters for the mosquito-human transmission cycle. Moreover, the model accounts for the behavior changes of infectious population created by differences in the malaise caused by these viruses. We derived the effective and basic reproduction numbers for the model that are used to estimate the number of secondary infections from the infectious populations. In the same density of Wolbachia-free Aedes aegypti or Aedes albopictus mosquitoes, we observed that wMel and wAlbB strains of Wolbachia can reduce the transmission rates of these diseases effectively.

Title: Differential Vector Competency of Aedes albopictus Populations from the Americas for Zika Virus
Authors: Azar, Sasha R; Roundy, Christopher M; Rossi, Shannan L; Huang, Jing H; Leal, Grace; Yun, Ruimei; Fernandez-Salas, Ildefonso; Vitek, Christopher J; Paploski, Igor Adolfho Dexheimer; Stark, Pamela M; Vela, Jeremy; Debboun, Mustapha; Reyna, Martin; Kitron, Uriel; Ribeiro, Guilherme de Sousa; Hanley, Kathryn A; Vasilakis, Nikos; Weaver, Scott C

by Anne C. Wheeler, Camila V. Ventura, Ty Ridenour, Danielle Toth, Lucélia Lima Nobrega, Lana Claudia Silva de Souza Dantas, Camilla Rocha, Donald B. Bailey Jr., Liana O. Ventura

The recent Zika outbreak and its link to microcephaly and other birth defects in infants exposed in utero have garnered widespread international attention. Based on the severity of birth defects the extent of impairment in these infants is expected to be profound; however, virtually nothing is known regarding the developmental and behavioral sequela of congenital Zika syndrome. This pilot study collected parent-reported patterns of development and sleep in 47 infants with confirmed congenital Zika syndrome who are being followed for clinical services at the Altino Ventura Foundation (FAV) in Recife, Brazil. With assistance from clinicians at FAV, caregivers completed Brazilian Portuguese versions of the Ages and Stages Questionnaire, 3rd edition (ASQ-3) and the Brief Infant Sleep Questionnaire (BISQ). All infants were between 13–22 months of age at the time of the assessment. At 16 months of age, none of the children displayed age appropriate developmental skills. Most (~ 75%) mastered some communication and gross motor skills at around a 6–8-month level. Communication and gross motor skills were relative strengths for the sample, while problem-solving and fine motor skills were relative weaknesses. Sleep was noted to be a problem for around 18% of the sample. In utero exposure to the Zika virus will have lifelong consequences for affected children and their families. Understanding the developmental and behavioral trajectories of affected infants will help identify appropriate family supports to improve quality of life.

by Zahra Meghani, Christophe Boëte

by Min Li, Lingzhai Zhao, Chao Zhang, Xin Wang, Wenxin Hong, Jin Sun, Ran Liu, Lei Yu, Jianhua Wang, Fuchun Zhang, Xia Jin

Antibody dependent enhancement (ADE) has most often been associated with dengue virus (DENV). Studies using leukemia cell lines suggest that DENV specific antibodies can enhance Zika virus (ZIKV) infectivity, and vice versa. To examine the mechanisms of ADE of ZIKV infection in primary human cells, we assessed 40 serum samples obtained from convalescent DENV-1 or DENV-3 infected subjects. All sera tested exhibited high binding potency, while modest or none neutralization activities against ZIKV. Primary CD14+ monocytes, rather than B and T cells in peripheral blood mononuclear cells (PBMCs), were found to be the mediators of the enhancement of ZIKV infectivity by DENV immune sera. Monocyte-derived immature dendritic cells (DCs), but not mature DCs were highly permissive to ZIKV infection, whereas neither immature nor mature DCs could mediate enhanced ZIKV infection in the presence of DENV immune sera. In addition, antibody blocking of either FcγRI (CD64), or FcγRII (CD32), or FcγRIII (CD16) resulted in diminished ADE of ZIKV infection. Our findings provide an improved understanding of the pathogenesis of ZIKV infection, and inform rational vaccine design.

by Joseph Mazar, Yujia Li, Amy Rosado, Peter Phelan, Kritika Kedarinath, Griffith D. Parks, Kenneth A. Alexander, Tamarah J. Westmoreland

Neuroblastoma is the second most common childhood tumor. Survival is poor even with intensive therapy. In a search for therapies to neuroblastoma, we assessed the oncolytic potential of Zika virus. Zika virus is an emerging mosquito-borne pathogen unique among flaviviruses because of its association with congenital defects. Recent studies have shown that neuronal progenitor cells are likely the human target of Zika virus. Neuroblastoma has been shown to be responsive to infection. In this study, we show that neuroblastoma cells are widely permissive to Zika infection, revealing extensive cytopathic effects (CPE) and producing high titers of virus. However, a single cell line appeared poorly responsive to infection, producing undetectable levels of non-structural protein 1 (NS1), limited CPE, and low virus titers. A comparison of these poorly permissive cells to highly permissive neuroblastoma cells revealed a dramatic loss in the expression of the cell surface glycoprotein CD24 in poorly permissive cells. Complementation of CD24 expression in these cells led to the production of detectable levels of NS1 expression after infection with Zika, as well as dramatic increases in viral titers and CPE. Complementary studies using the Zika virus index strain and a north African isolate confirmed these phenotypes. These results suggest a possible role for CD24 in host cell specificity by Zika virus and offer a potential therapeutic target for its treatment. In addition, Zika viral therapy can serve as an adjunctive treatment for neuroblastoma by targeting tumor cells that can lead to recurrent disease and treatment failure.

by Françoise Mathieu-Daudé, Aurore Claverie, Catherine Plichart, Denis Boulanger, Fingani A. Mphande, Hervé C. Bossin
Background Aedes mosquitoes severely affect the health and wellbeing of human populations by transmitting infectious diseases. In French Polynesia, Aedes aegypti is the main vector of dengue, chikungunya and Zika, and Aedes polynesiensis the primary vector of Bancroftian filariasis and a secondary vector of arboviruses. Tools for assessing the risk of disease transmission or for measuring the efficacy of vector control programmes are scarce. A promising approach to quantify the human-vector contact relies on the detection and the quantification of antibodies directed against mosquito salivary proteins. Methodology/Principal findings An ELISA test was developed to detect and quantify the presence of immunoglobulin G (IgG) directed against proteins from salivary gland extracts (SGE) of Ae. aegypti and Ae. polynesiensis in human populations exposed to either species, through a cross-sectional study. In Tahiti and Moorea islands where Ae. aegypti and Ae. polynesiensis are present, the test revealed that 98% and 68% of individuals have developed IgG directed against Ae. aegypti and Ae. polynesiensis SGE, respectively. By comparison, ELISA tests conducted on a cohort of people from metropolitan France, not exposed to these Aedes mosquitoes, indicated that 97% of individuals had no IgG directed against SGE of either mosquito species. The analysis of additional cohorts representing different entomological Aedes contexts showed no ELISA IgG cross-reactivity between Ae. aegypti and Ae. polynesiensis SGE. Conclusions/Significance The IgG response to salivary gland extracts seems to be a valid and specific biomarker of human exposure to the bites of Ae. aegypti and Ae. polynesiensis. This new immuno-epidemiological tool will enhance our understanding of people exposure to mosquito bites, facilitate the identification of areas where disease transmission risk is high and permit to evaluate the efficacy of novel vector control strategies in Pacific islands and other tropical settings.

by Jui-Hung Kao, Chaur-Dong Chen, Zheng-Rong Tiger Li, Ta-Chien Chan, Tsung-Hwa Tung, Ying-Hsia Chu, Hau-Yuan Cheng, Jien-Wei Liu, Fuh-Yuan Shih, Pei-Yun Shu, Chien-Chou Lin, Wu-Hsiung Tsai, Chia-Chi Ku, Chi-Kung Ho, Chwan-Chuen King

by Roberto de Andrade Medronho, Volney de Magalhães Câmara, Leonardo Macrini
Introduction This paper discusses the presence of Aedes aegypti pupae in different types of containers considering: volume, pH of the container, among other variables. Methods A nonlinear method for selection was applied, based on Mutual Information, by placing in order of importance the most appropriate variables for identifying containers with and without Aedes aegypti pupae. Such variables were used for input into a Neural Network in layers for classification. Results Among the experiments carried out, the best result obtained used the first eight variables selected by order of importance. The percentage of hits for containers which had no Aedes aegypti pupae was 73.3%, and 80.9% for those which did have Aedes aegypti pupae in the containers. This Neural Network method, a model with the capacity to emulate non-linear data, got better results in comparison with the discriminant power of the Logistic Regression model. Thus, the outcomes of using the Neural Networks method achieved better separability in classifying the containers with pupae and those with no pupae. Conclusion This type of analysis will aid in the efforts to design an efficient program to control Aedes aegypti that can concentrate principally on containers which present the greatest productivity.

by Molly Duman-Scheel, Kathleen K. Eggleson, Nicole L. Achee, John P. Grieco, Limb K. Hapairai

The tourist-based economy of Belize, a tropical hub for eco-tourism, is at high risk to be disproportionately impacted by established and emerging mosquito-borne diseases such as Zika. An online survey was used to probe economic stakeholders working in the Belize tourism industry about their mosquito control practices and perceptions. Responses demonstrated that the respondents have good working knowledge of mosquitoes and mosquito-borne illnesses. Most businesses surveyed engage in some means of mosquito control, either through larval source reduction or use of insecticides on the premises. Larvicide use was significantly correlated with a general willingness to use insecticides, as well as belief that treatment of water will reduce mosquito densities and disease transmission. A majority of the respondents agreed that they would be interested in buying a new larvicide to be used on the business premises if it were shown to be safe and effective. The safety of mosquito control products for humans, animals, plants, and the environment in general, followed by product effectiveness, are the most critical determinants of mosquito control purchasing decisions. A majority of respondents agreed that control of mosquitoes and mosquito-borne illnesses is central to the success of their tourist-based industry. Respondents expressed significant concern that the Zika epidemic was over-sensationalized by the media, and that this negatively impacted their livelihoods. The respondents, many of whom are associated with eco/sustainable businesses, also voiced concerns that chemical pesticides could have a negative impact on human health and the environment and expressed a desire for balance between effective mosquito control and preservation of the rich biodiversity of Belize. This study provided a framework for further engagement activities in Belize and other Caribbean nations, uncovered both concerns and support for emerging mosquito control technologies, and revealed opportunities for further debate and educational outreach efforts.

by Victoria Phooi Khei Tan, Chin Fang Ngim, Erika Ziyan Lee, Amutha Ramadas, Lian Yih Pong, Joo Ing Ng, Sharifah Syed Hassan, Xuan Ye Ng, Amreeta Dhanoa

Both obesity and DENV infections are growing public health concerns that have far-ranging socioeconomic effects, especially in developing countries. Despite the increasing prevalence of these conditions, there is a scarcity of data investigating the potential relationships between these two entities. Our study aims to examine the influence of obesity on various clinical and laboratory parameters amongst patients with DENV infections. A total of 335 hospitalized patients aged >12 years who were DENV non-structural protein 1 (NS1) antigen-positive were enrolled in this study. Clinical and laboratory variables were compared between patients with and without obesity. Multivariate analysis showed that the following admission clinical findings and laboratory results were independently associated with obesity; chills and rigors (AOR:2.653, 95% CI: 1.286–5.474), higher temperature (AOR:1.485, 95% CI: 1.080–2.042), higher systolic BP (AOR:1.057, 95% CI:1.037–1.078), raised haematocrit (AOR: 1.953, 95% CI: 1.010–3.778), elevated creatinine (AOR:3.504, 95% CI:1.351–9.008) and elevated ALT (AOR: 4.146, 95% CI:1.878–9.154). Obesity was found to be significantly associated with hospitalization >3 days (AOR: 1.990, 95% CI: 1.134–3.494) and the presence of increasing haematocrit with decreasing platelets (AOR: 2.134, 95% CI = 1.235–3.688). Serial assessment of laboratory data revealed that peak haematocrit was significantly higher and nadir platelets levels were significantly lower in obese patients. Both peak and admission levels of leukocyte counts, AST, ALT and creatinine were significantly higher in the obese group. Conversely, both admission and nadir albumin levels were lower for the obese group, although only nadir albumin levels achieved statistical significance. These findings support closer clinical monitoring of obese patients who present with DENV infections, as this patient cohort may possess an increased tendency towards developing more severe clinical manifestations of DENV infections as compared to non-obese patients.

by Elodie Calvez, Laurence Mousson, Marie Vazeille, Olivia O’Connor, Van-Mai Cao-Lormeau, Françoise Mathieu-Daudé, Nicolas Pocquet, Anna-Bella Failloux, Myrielle Dupont-Rouzeyrol
Background In 2013, Zika virus (ZIKV) emerged in French Polynesia and spread through the Pacific region between 2013 and 2017. Several potential Aedes mosquitoes may have contributed to the ZIKV transmission including Aedes aegypti, the main arbovirus vector in the region, and Aedes polynesiensis, vector of lymphatic filariasis and secondary vector of dengue virus. The aim of this study was to analyze the ability of these two Pacific vectors to transmit ZIKV at a regional scale, through the evaluation and comparison of the vector competence of wild Ae. aegypti and Ae. polynesiensis populations from different Pacific islands for a ZIKV strain which circulated in this region during the 2013–2017 outbreak. Methodology/principal findings Field Ae. aegypti (three populations) and Ae. polynesiensis (two populations) from the Pacific region were collected for this study. Female mosquitoes were orally exposed to ZIKV (107 TCID50/mL) isolated in the region in 2014. At 6, 9, 14 and 21 days post-infection, mosquito bodies (thorax and abdomen), heads and saliva were analyzed to measure infection, dissemination, transmission rates and transmission efficiency, respectively. According to our results, ZIKV infection rates were heterogeneous between the Ae. aegypti populations, but the dissemination rates were moderate and more homogenous between these populations. For Ae. polynesiensis, infection rates were less heterogeneous between the two populations tested. The transmission rate and efficiency results revealed a low vector competence for ZIKV of the different Aedes vector populations under study. Conclusion/significance Our results indicated a low ZIKV transmission by Ae. aegypti and Ae. polynesiensis tested from the Pacific region. These results were unexpected and suggest the importance of other factors especially the vector density, the mosquito lifespan or the large immunologically naive fraction of the population that may have contributed to the rapid spread of the ZIKV in the Pacific region during the 2013–2017 outbreak.

by Parasuraman Ganeshkumar, Manoj V. Murhekar, Veeraraghavadoss Poornima, Velusamy Saravanakumar, Krishnendu Sukumaran, Anandan Anandaselvasankar, Denny John, Sanjay M. Mehendale
Introduction Dengue is the most extensively spread mosquito-borne disease; endemic in more than 100 countries. Information about dengue disease burden, its prevalence, incidence and geographic distribution is critical in planning appropriate control measures against dengue fever. We conducted a systematic review and meta-analysis of dengue fever in India Methods We searched for studies published until 2017 reporting the incidence, the prevalence or case fatality of dengue in India. Our primary outcomes were (a) prevalence of laboratory confirmed dengue infection among clinically suspected patients, (b) seroprevalence in the general population and (c) case fatality ratio among laboratory confirmed dengue patients. We used binomial–normal mixed effects regression model to estimate the pooled proportion of dengue infections. Forest plots were used to display pooled estimates. The metafor package of R software was used to conduct meta-analysis. Results Of the 2285 identified articles on dengue, we included 233 in the analysis wherein 180 reported prevalence of laboratory confirmed dengue infection, seven reported seroprevalence as evidenced by IgG or neutralizing antibodies against dengue and 77 reported case fatality. The overall estimate of the prevalence of laboratory confirmed dengue infection among clinically suspected patients was 38.3% (95% CI: 34.8%–41.8%). The pooled estimate of dengue seroprevalence in the general population and CFR among laboratory confirmed patients was 56.9% (95% CI: 37.5–74.4) and 2.6% (95% CI: 2–3.4) respectively. There was significant heterogeneity in reported outcomes (p-values

by Cristiano Fernandes da Costa, Arlesson Viana da Silva, Valdinete Alves do Nascimento, Victor Costa de Souza, Dana Cristina da Silva Monteiro, Wagner Cosme Morhy Terrazas, Ricardo Augusto dos Passos, Suzete Nascimento, José Bento Pereira Lima, Felipe Gomes Naveca
Background Arboviruses are viruses transmitted to humans and other animals by the bite of hematophagous arthropods. Infections caused by chikungunya virus (CHIKV), dengue virus (DENV), Zika virus (ZIKV), and the deadlier yellow fever virus (YFV) are current public health problems in several countries, mainly those located in tropical and subtropical regions. One of the main prevention strategies continues to be vector control, with the elimination of breeding sites and surveillance of infested areas. The use of ovitraps for Aedes mosquitos monitoring has already demonstrated promising results, and maybe be also useful for arboviral surveillance. Methods This work aimed to detect natural vertical transmission of arboviruses in Aedes aegypti and Aedes albopictus. Mosquito egg collection was carried out using ovitraps in Itacoatiara, a mid-size city in Amazonas state, Brazil. Collected eggs were allowed to hatch and larvae were tested for CHIKV, DENV, and ZIKV RNA by RT-qPCR. Results A total of 2,057 specimens (1,793 Ae. aegypti and 264 Ae. albopictus), in 154 larvae pools were processed. Results showed one positive pool for CHIKV and one positive pool for ZIKV. The active ZIKV infection was further confirmed by the detection of the negative-strand viral RNA and nucleotide sequencing which confirmed the Asian genotype. The Infection Rate per 1,000 mosquitoes tested was assessed by Maximum Likelihood Estimation (MLE) with 0.45 and 0.44 for CHIKV and ZIKV, respectively, and by Minimum Infection Rate (MIR) with 0.45 for both viruses. Conclusion To our knowledge, this is the first detection of ZIKV in natural vertical transmission in the Ae. aegypti, a fact that may contribute to ZIKV maintenance in nature during epidemics periods. Furthermore, our results highlight that the use of ovitraps and the molecular detection of arbovirus may contribute to health surveillance, directing the efforts to more efficient transmission blockade.

by Camille Fritzell, Dominique Rousset, Antoine Adde, Mirdad Kazanji, Maria D. Van Kerkhove, Claude Flamand
Background Arboviral infections are a public health concern and an escalating problem worldwide. Estimating the burden of these diseases represents a major challenge that is complicated by the large number of unapparent infections, especially those of dengue fever. Serological surveys are thus required to identify the distribution of these diseases and measure their impact. Therefore, we undertook a scoping review of the literature to describe and summarize epidemiological practices, findings and insights related to seroprevalence studies of dengue, chikungunya and Zika virus, which have rapidly expanded across the globe in recent years. Methodology/Principal findings Relevant studies were retrieved through a literature search of MEDLINE, WHOLIS, Lilacs, SciELO and Scopus (2000 to 2018). In total, 1389 publications were identified. Studies addressing the seroprevalence of dengue, chikungunya and/or Zika written in English or French and meeting the inclusion and exclusion criteria were included. In total, 147 studies were included, from which 185 data points were retrieved, as some studies used several different samples. Most of the studies were exclusively conducted on dengue (66.5%), but 16% were exclusively conducted on chikungunya, and 7 were exclusively conducted on Zika; the remainder were conducted on multiple arboviruses. A wide range of designs were applied, but most studies were conducted in the general population (39%) and in households (41%). Although several assays were used, enzyme-linked immunosorbent assays (ELISAs) were the predominant test used (77%). The temporal distribution of chikungunya studies followed the virus during its rapid expansion since 2004. The results revealed heterogeneity of arboviruses seroprevalence between continents and within a given country for dengue, chikungunya and Zika viruses, ranging from 0 to 100%, 76% and 73% respectively. Conclusions/Significance Serological surveys provide the most direct measurement for defining the immunity landscape for infectious diseases, but the methodology remains difficult to implement. Overall, dengue, chikungunya and Zika serosurveys followed the expansion of these arboviruses, but there remain gaps in their geographic distribution. This review addresses the challenges for researchers regarding study design biases. Moreover, the development of reliable, rapid and affordable diagnosis tools represents a significant issue concerning the ability of seroprevalence surveys to differentiate infections when multiple viruses co-circulate.

Title: Influência de diferentes tipos de material biológico na quantificação de anticorpos neutralizantes pelo micro PRNT de Febre Amarela e Sarampo
Authors: Simões, Marisol; Pereira, Renata Carvalho; Silva, Stephanie Almeida da; Miranda, Emily Hime; Cajaraville, Ana Carolina R. A.; Linhares, José Henrique Rezende; Santos, Vanessa de Oliveira; Lima, Sheila Maria Barbosa de

by Sakaorat Lertjuthaporn, Ladawan Khowawisetsut, Rassamon Keawvichit, Korakot Polsrila, Ampaiwan Chuansumrit, Kulkanya Chokephaibulkit, Premrutai Thitilertdecha, Nattawat Onlamoon, Aftab A. Ansari, Kovit Pattanapanyasat

Dengue virus (DENV) is the most prevalent arthropod-borne viral disease in humans. DENV causes a spectrum of illness ranging from mild to potentially severe complications. Dendritic cells (DCs) play a critical role in initiating and regulating highly effective antiviral immune response that include linking innate and adaptive immune responses. This study was conducted to comparatively characterize in detail the relative proportion, phenotypic changes, and maturation profile of subsets of both myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) in children with dengue fever (DF), dengue hemorrhagic fever (DHF) and for purposes of control healthy individuals. The mDCs (Lin-CD11c+CD123lo), the pDCs (Lin-CD11c-CD123+) and the double negative (DN) subset (Lin-/HLA-DR+/CD11c-CD123-) were analyzed by polychromatic flow cytometry. The data were first analyzed on blood samples collected from DENV-infected patients at various times post-infection. Results showed that the relative proportion of mDCs were significantly decreased which was associated with an increase in disease severity in samples from DENV-infected patients. While there was no significant difference in the relative proportion of pDCs between healthy and DENV-infected patients, there was a marked increase in the DN subset. Analysis of the kinetics of changes of pDCs showed that there was an increase but only during the early febrile phase. Additionally, samples from patients during acute disease showed marked decreases in the relative proportion of CD141+ and CD16+ mDC subsets that were the major mDC subsets in healthy individuals. In addition, there was a significant decrease in the level of CD33-expressing mDCs in DENV patients. While the pDCs showed an up-regulation of maturation profile during acute DENV infection, the mDCs showed an alteration of maturation status. This study suggests that different relative proportion and phenotypic changes as well as alteration of maturation profile of DC subsets may play a critical role in the dengue pathogenesis and disease outcome.

by Megan A. Sheridan, Velmurugan Balaraman, Danny J. Schust, Toshihiko Ezashi, R. Michael Roberts, Alexander W. E. Franz

Zika virus (ZIKV) drew worldwide attention when a recent epidemic was linked to fetal microcephaly. Here we used human embryonic stem cell derived trophoblasts as a model for primitive placental trophoblast to test the hypothesis that there are differences in how the two genetically distinct ZIKV lineages, African (AF) and Asian (AS), target the human placenta. Upon infection with three AF (ib-H30656, SEN/1984/41525-DAK, and MR-766) and three AS (FSS13025, MexI-44, and PANcdc259249) ZIKV strains, we observed that severe placental cell lysis was only induced after infection with AF strains, while viral replication rates remained similar between both lineages. Differences in cytopathic effects (CPE) were not observed in Vero cells, indicating that the AF strains were not inherently superior at cell lysis. Taken together, we propose that infection with AF strains of ZIKV early in pregnancy would likely result in pregnancy loss, rather than allow further fetal development with accompanying brain damage. Our results also suggest that the long term laboratory-adapted MR-766 strain does not behave aberrantly in cell culture relative to other AF lineage strains.

Title: Immunization with recombinant, plant-produced yellow fever virus envelope (E) protein vaccine candidates in rhesus macaques
Authors: Guimarães, Rosane Cuber; Silva, Andrea Nazare Monteiro Rangel da; Gaspar, Luciane Pinto; Simões, Marisol; Neves, Patrícia Cristina da Costa; Trindade, Gisela; Marchevsky, Renato

by Selene M. Garcia-Luna, James Weger-Lucarelli, Claudia Rückert, Reyes A. Murrieta, Michael C. Young, Alex D. Byas, Joseph R. Fauver, Rushika Perera, Adriana E. Flores-Suarez, Gustavo Ponce-Garcia, Americo D. Rodriguez, Gregory D. Ebel, William C. Black IV
Background ZIKV is a new addition to the arboviruses circulating in the New World, with more than 1 million cases since its introduction in 2015. A growing number of studies have reported vector competence (VC) of Aedes mosquitoes from several areas of the world for ZIKV transmission. Some studies have used New World mosquitoes from disparate regions and concluded that these have a variable but relatively low competence for the Asian lineage of ZIKV. Methodology/Principal findings Ten Aedes aegypti (L) and three Ae. albopictus (Skuse) collections made in 2016 from throughout Mexico were analyzed for ZIKV (PRVABC59—Asian lineage) VC. Mexican Ae. aegypti had high rates of midgut infection (MIR), dissemination (DIR) and salivary gland infection (SGIR) but low to moderate transmission rates (TR). It is unclear whether this low TR was due to heritable salivary gland escape barriers or to underestimating the amount of virus in saliva due to the loss of virus during filtering and random losses on surfaces when working with small volumes. VC varied among collections, geographic regions and whether the collection was made north or south of the Neovolcanic axis (NVA). The four rates were consistently lower in northeastern Mexico, highest in collections along the Pacific coast and intermediate in the Yucatan. All rates were lowest north of the NVA. It was difficult to assess VC in Ae. albopictus because rates varied depending upon the number of generations in the laboratory. Conclusions/Significance Mexican Ae. aegypti and Ae. albopictus are competent vectors of ZIKV. There is however large variance in vector competence among geographic sites and regions. At 14 days post infection, TR varied from 8–51% in Ae. aegypti and from 2–26% in Ae. albopictus.

Title: Avaliação da incerteza de medição como ferramenta para delineamento da zona cinza na determinação de anticorpos neutralizantes anti-Febre Amarela
Authors: Ferreira, Victor de Oliveira Silva; Simões, Marisol; Lima, Sheila Maria Barbosa de; Carvalho, Erika Martins; Borges, Maria Denise Neves; Oliveira, Rodrigo Borges de