Monitoramento das Produções

by Josée Castonguay-Vanier, Raphaëlle Klitting, Onanong Sengvilaipaseuth, Géraldine Piorkowski, Cécile Baronti, Bountoy Sibounheuang, Manivanh Vongsouvath, Anisone Chanthongthip, Soulignasack Thongpaseuth, Mayfong Mayxay, Koukeo Phommasone, Phouvieng Douangdala, Saythong Inthalath, Phouthalavanh Souvannasing, Paul N. Newton, Xavier de Lamballerie, Audrey Dubot-Pérès

Few data on dengue epidemiology are available for Lao PDR. Here, we provide information on the complexity of dengue epidemiology in the country, demonstrating dynamic circulation that varies over space and time, according to serotype. We recruited 1,912 consenting patients presenting with WHO dengue criteria at Mahosot Hospital, Vientiane (central Laos), between 2006 and 2010. Between 2008 and 2010, 1,413 patients with undifferentiated fever were also recruited at Luang Namtha (LNT) Provincial Hospital (northern Laos) and 555 at Salavan (SV) Provincial Hospital (southern Laos). We report significant variations in Dengue virus (DENV) circulation between the three sites. Peaks of DENV infection were observed in the rainy seasons, although 11% of confirmed cases in the provinces and 4.6% in the capital were detected during the dry and cool seasons (between December and February). Four DENV serotypes were detected among the 867 RT-PCR positive patients: 76.9% DENV-1, 9.6% DENV-2, 7.7% DENV-4 and 5.3% DENV-3. DENV-1 was the predominant serotype throughout the study except in LNT in 2008 and 2009 when it was DENV-2. Before July 2009, DENV-2 was not detected in SV and only rarely detected in Vientiane. DENV-3 and DENV-4 were commonly detected in Vientiane, before 2008 for DENV-4 and after 2009 for DENV-3. The phylogenetic analyses of DENV envelope sequences suggest concurrent multiple introductions of new strains as well as active DENV circulation throughout Laos and with neighboring countries. It is therefore of great importance to develop and strengthen a year-round nation-wide surveillance network in order to collect data that would allow anticipation of public health issues caused by the occurrence of large dengue outbreaks.

by Camille Fritzell, Jocelyn Raude, Mirdad Kazanji, Claude Flamand
Background French Guiana is a territory that has a decades-long history of dengue outbreaks and more recently, in 2014, a chikungunya outbreak. Zika virus (ZIKV) emerged in late 2015 and subsequently led to an important outbreak. Methodology/Principal findings A cross-sectional phone survey was conducted among the general population during the outbreak in June 2016 with a total of 1,129 individuals interviewed to assess perceptions, knowledge and behaviors regarding zika infection. The population seemed aware of zika, and perceived the infection as a more serious health threat than other common mosquito-borne diseases. Furthermore, both the perceptions and behaviors related to zika and its prevention were found to vary considerably among different social groups, geographic areas and gender; less educated female participants were found to perceive the disease as more worrisome and were less likely to adopt protective behaviors. Moreover, female population has been particularly responsive to awareness campaigns and rapidly understood the extent of risks associated with ZIKV infection. Conclusions/Significance These results revealed that ZIKV appeared at the time of the survey as a new health threat that concerns the public more than chikungunya and dengue fever with differences observed among subgroups of population. These results have implications for the development of multifaceted infection control programs, including strategies for prevention and awareness, helping the population to develop an accurate perception of the threat they are facing and encouraging behavior changes.

by Liang Cui, Junxiong Pang, Yie Hou Lee, Eng Eong Ooi, Choon Nam Ong, Yee Sin Leo, Steven R. Tannenbaum

Dengue virus (DENV) is the most prevalent arbovirus leading to an estimated 100 million symptomatic dengue infections every year. DENV can cause a spectrum of clinical manifestations, ranging from mild dengue fever (DF) to more life threatening forms such as dengue hemorrhagic fever (DHF). The clinical symptoms of DHF become evident typically at the critical phase of infection (5–7 days after onset of fever), yet the mechanisms that trigger transition from DF to DHF are not well understood. We performed a mass spectrometry-based metabolomic profiling of sera from adult DF and DHF patients at the critical and recovery phases of infection. There were 29 differentially expressed metabolites identified between DF and DHF at the critical phase. These include bile acids, purines, acylcarnitines, phospholipids, and amino acids. Bile acids were observed up to 5 fold higher levels among DHF compared to DF patients and were significantly correlated to the higher levels of aspartate transaminase (AST) and alanine transaminase (ALT), suggestive of liver injury among DHF. Uric acid, the most abundant antioxidant in the blood, was observed to be 1.5 fold lower among DHF compared to DF patients. This could result in decreased capacity of endogenous antioxidant defense and elevated oxidative stress among DHF patients. In the recovery phase, the levels of eight metabolites were still significantly higher or lower among DHF patients, including chenodeoxyglycocholic acid, one of the bile acids observed at the critical phase. This indicates potential prolonged adverse impact on the liver due to DENV infection in DHF patients. Our study identified altered metabolic pathways linked to DHF in the critical and recovery phases of dengue infection and provided insights into the different host and DENV interactions between DF and DHF. The results advance our understanding on the mechanisms of DHF pathogenesis, alluding to possible novel therapeutic targets to dengue management.

by Matthew W. Eng, Anthony Clemons, Casey Hill, Roberta Engel, David W. Severson, Susanta K. Behura

The mosquito Aedes aegypti is the primary vector of human arboviral diseases caused by dengue, chikungunya and Zika viruses. Many studies have shown the potential roles of small RNA molecules such as microRNA, small interfering RNA and PIWI-interacting RNA in vector mosquitoes. The function of tRNA fragments (tRF), the newly discovered class of small RNAs, in mosquitoes is not known. In this study, we show that specific tRFs are expressed in significantly differential manner between males and females of Ae. aegypti strains. Specific tRFs also show differential response during developmental transition from larvae to adults, as well as after blood feeding of adult females. The expression pattern of tRFs upon blood feeding varied depending upon if the blood contained dengue virus, and also if the females were treated with antibiotic prior to feeding to cleanse of the gut bacteria. Our findings show that a single tRF derived from the precursor sequences of a tRNA-Gly was differentially expressed between males and females, developmental transitions and also upon blood feeding by females of two laboratory strains that vary in midgut susceptibility to dengue virus infection. The multifaceted functional implications of this specific tRF suggest that biogenesis of small regulatory molecules from a tRNA can have wide ranging effects on key aspects of Ae. aegypti vector biology.

by Dominic Paquin-Proulx, Vivian Lida Avelino-Silva, Bianca A. N. Santos, Nathália Silveira Barsotti, Fabiana Siroma, Jessica Fernandes Ramos, Adriana Coracini Tonacio, Alice Song, Alvino Maestri, Natalia Barros Cerqueira, Alvina Clara Felix, José Eduardo Levi, Benjamin C. Greenspun, Miguel de Mulder Rougvie, Michael G. Rosenberg, Douglas F. Nixon, Esper G. Kallas

Dengue virus (DENV) and Zika virus (ZIKV) are members of the Flaviviridae and are predominantly transmitted via mosquito bites. Both viruses are responsible for a growing number of infections in tropical and subtropical regions. DENV infection can cause lethargy with severe morbidity and dengue shock syndrome leading to death in some cases. ZIKV is now linked with Guillain-Barré syndrome and fetal malformations including microcephaly and developmental disorders (congenital Zika syndrome). The protective and pathogenic roles played by the immune response in these infections is unknown. Mucosal-associated invariant T (MAIT) cells are a population of innate T cells with potent anti-bacterial activity. MAIT cells have also been postulated to play a role in the immune response to viral infections. In this study, we evaluated MAIT cell frequency, phenotype, and function in samples from subjects with acute and convalescent DENV infection. We found that in acute DENV infection, MAIT cells had elevated co-expression of the activation markers CD38 and HLA-DR and had a poor IFNγ response following bacterial stimulation. Furthermore, we found that MAIT cells can produce IFNγ in response to in vitro infection with ZIKV. This MAIT cell response was independent of MR1, but dependent on IL-12 and IL-18. Our results suggest that MAIT cells may play an important role in the immune response to Flavivirus infections.

by Seth C. Britch, Kenneth J. Linthicum, Robert L. Aldridge, Mark S. Breidenbaugh, Mark D. Latham, Peter H. Connelly, Mattie J. E. Rush, Jennifer L. Remmers, Jerry D. Kerce, Charles A. Silcox, US Navy Entomology Center of Excellence Team

We conducted aerial fixed wing ultra low volume (ULV) spray trials with naled to investigate penetration of exposed and simulated cryptic habitat within opened buildings, partially sealed buildings, and outdoor locations targeting sentinel adult Aedes aegypti mosquitoes in north central Florida. Mortality was observed in open and closed buildings and outdoors, even in mosquitoes placed in cryptic habitats. Observations on the impact of building type, mosquito exposure method such as placement in cryptic habitat, and spray nozzle size on mosquito mortality are described and analyzed.

by Lauren M. Gardner, András Bóta, Karthik Gangavarapu, Moritz U. G. Kraemer, Nathan D. Grubaugh
Background An unprecedented Zika virus epidemic occurred in the Americas during 2015-2016. The size of the epidemic in conjunction with newly recognized health risks associated with the virus attracted significant attention across the research community. Our study complements several recent studies which have mapped epidemiological elements of Zika, by introducing a newly proposed methodology to simultaneously estimate the contribution of various risk factors for geographic spread resulting in local transmission and to compute the risk of spread (or re-introductions) between each pair of regions. The focus of our analysis is on the Americas, where the set of regions includes all countries, overseas territories, and the states of the US. Methodology/Principal findings We present a novel application of the Generalized Inverse Infection Model (GIIM). The GIIM model uses real observations from the outbreak and seeks to estimate the risk factors driving transmission. The observations are derived from the dates of reported local transmission of Zika virus in each region, the network structure is defined by the passenger air travel movements between all pairs of regions, and the risk factors considered include regional socioeconomic factors, vector habitat suitability, travel volumes, and epidemiological data. The GIIM relies on a multi-agent based optimization method to estimate the parameters, and utilizes a data driven stochastic-dynamic epidemic model for evaluation. As expected, we found that mosquito abundance, incidence rate at the origin region, and human population density are risk factors for Zika virus transmission and spread. Surprisingly, air passenger volume was less impactful, and the most significant factor was (a negative relationship with) the regional gross domestic product (GDP) per capita. Conclusions/Significance Our model generates country level exportation and importation risk profiles over the course of the epidemic and provides quantitative estimates for the likelihood of introduced Zika virus resulting in local transmission, between all origin-destination travel pairs in the Americas. Our findings indicate that local vector control, rather than travel restrictions, will be more effective at reducing the risks of Zika virus transmission and establishment. Moreover, the inverse relationship between Zika virus transmission and GDP suggests that Zika cases are more likely to occur in regions where people cannot afford to protect themselves from mosquitoes. The modeling framework is not specific for Zika virus, and could easily be employed for other vector-borne pathogens with sufficient epidemiological and entomological data.

by Shi Zhao, Lewi Stone, Daozhou Gao, Daihai He
Background Yellow fever (YF), transmitted via bites of infected mosquitoes, is a life-threatening viral disease endemic to tropical and subtropical regions of Africa and South America. YF has largely been controlled by widespread national vaccination campaigns. Nevertheless, between December 2015 and August 2016, YF resurged in Angola, quickly spread and becoming the largest YF outbreak for the last 30 years. Recently, YF resurged again in Brazil (December 2016). Thus, there is an urgent need to gain better understanding of the transmission pattern of YF. Model The present study provides a refined mathematical model, combined with modern likelihood-based statistical inference techniques, to assess and reconstruct important epidemiological processes underlying Angola’s YF outbreak. This includes the outbreak’s attack rate, the reproduction number (R 0), the role of the mosquito vector, the influence of climatic factors and the unusual but noticeable appearance of two-waves in the YF outbreak. The model explores actual and hypothetical vaccination strategies, and the impacts of possible human reactive behaviors (e.g., response to media precautions). Findings While there were 73 deaths reported over the study period, the model indicates that the vaccination campaign saved 5.1-fold more people from death and saved from illness 5.6-fold of the observed 941 cases. Delaying the availability of the vaccines further would have greatly worsened the epidemic in terms of increased case numbers and mortality. The analysis estimated a mean R 0 ≈ 2 . 6 - 3 . 4 and an estimated YF attack rate of 0.09-0.15% (proportion of population infected by YFV) over the whole period from December 2015 to August 2016. Our estimated lower and upper bounds of R 0 are in line with previous studies. Unusually, R 0 oscillated in a manner that was “delayed” with the reported deaths. High recent number of deaths were associated (followed) with periods of relatively low disease transmission and low R 0, and vice-versa. The time-series of Luanda’s YF cases suggest the outbreak occurred in two waves, a feature that would have become far more prominent had there been no mass vaccination. The waves could possibly be due to protective reactive behavioral changes of the population affecting the mosquito population. The second wave could well be an outcome of the March-April rainfall patterns in the 2016 El Niño year by creating ideal conditions for the breeding of the mosquito vectors. The modelling framework is a powerful tool for studying future YF epidemic outbreaks, and provides a basis for future vaccination campaign evaluations.

by Rama Dhenni, Mulya Rahma Karyanti, Nina Dwi Putri, Benediktus Yohan, Frilasita A. Yudhaputri, Chairin Nisa Ma'roef, Araniy Fadhilah, Aditya Perkasa, Restuadi Restuadi, Hidayat Trimarsanto, Irawan Mangunatmadja, Jeremy P. Ledermann, Ronald Rosenberg, Ann M. Powers, Khin Saw Aye Myint, R. Tedjo Sasmono

Although neurological manifestations associated with dengue viruses (DENV) infection have been reported, there is very limited information on the genetic characteristics of neurotropic DENV. Here we describe the isolation and complete genome analysis of DENV serotype 3 (DENV-3) from cerebrospinal fluid of an encephalitis paediatric patient in Jakarta, Indonesia. Next-generation sequencing was employed to deduce the complete genome of the neurotropic DENV-3 isolate. Based on complete genome analysis, two unique and nine uncommon amino acid changes in the protein coding region were observed in the virus. A phylogenetic tree and molecular clock analysis revealed that the neurotropic virus was a member of Sumatran-Javan clade of DENV-3 genotype I and shared a common ancestor with other isolates from Jakarta around 1998. This is the first report of neurotropic DENV-3 complete genome analysis, providing detailed information on the genetic characteristics of this virus.

by Viswanathan Ramasamy, Upasana Arora, Rahul Shukla, Ankur Poddar, Rajgokul K. Shanmugam, Laura J. White, Melissa M. Mattocks, Rajendra Raut, Ashiya Perween, Poornima Tyagi, Aravinda M. de Silva, Siddhartha K. Bhaumik, Murali Krishna Kaja, François Villinger, Rafi Ahmed, Robert E. Johnston, Sathyamangalam Swaminathan, Navin Khanna
Background Dengue is one of the fastest spreading vector-borne diseases, caused by four antigenically distinct dengue viruses (DENVs). Antibodies against DENVs are responsible for both protection as well as pathogenesis. A vaccine that is safe for and efficacious in all people irrespective of their age and domicile is still an unmet need. It is becoming increasingly apparent that vaccine design must eliminate epitopes implicated in the induction of infection-enhancing antibodies. Methodology/principal findings We report a Pichia pastoris-expressed dengue immunogen, DSV4, based on DENV envelope protein domain III (EDIII), which contains well-characterized serotype-specific and cross-reactive epitopes. In natural infection,

by Dennis Pérez, Patrick Van der Stuyft, María Eugenia Toledo, Enrique Ceballos, Francisco Fabré, Pierre Lefèvre
Background Within the context of a field trial conducted by the Cuban vector control program (AaCP), we assessed acceptability of insecticide-treated curtains (ITCs) and residual insecticide treatment (RIT) with deltamethrin by the community. We also assessed the potential influence of interviewees’ risk perceptions for getting dengue and disease severity. Methodology/principal findings We embedded a qualitative study using in-depth interviews in a cluster randomized trial (CRT) testing the effectiveness of ITCs and RIT in Santiago de Cuba. In-depth interviews (N = 38) were conducted four and twelve months after deployment of the tools with people who accepted the tools, who stopped using them and who did not accept the tools. Data analysis was deductive. Main reasons for accepting ITCs at the start of the trial were perceived efficacy and not being harmful to health. Constraints linked to manufacturer instructions were the main reason for not using ITCs. People stopped using the ITCs due to perceived allergy, toxicity and low efficacy. Few heads of households refused RIT despite the noting reasons for rejection, such as allergy, health hazard and toxicity. Positive opinions of the vector control program influenced acceptability of both tools. However, frequent insecticide fogging as part of routine AaCP vector control actions diminished perceived efficacy of both tools and, therefore, acceptability. Fifty percent of interviewees did feel at risk for getting dengue and considered dengue a severe disease. However, this did not appear to influence acceptability of ITCs or RIT. Conclusion/significance Acceptability of ITCs and RIT was linked to acceptability of AaCP routine vector control activities. However, uptake and use were not always an indication of acceptability. Factors leading to acceptability may be best identified using qualitative methods, but more research is needed on the concept of acceptability and its measurement.

by Li Wei Ang, Yiu Wing Kam, Cui Lin, Prabha Unny Krishnan, Joanne Tay, Lee Ching Ng, Lyn James, Vernon J. M. Lee, Kee Tai Goh, Lisa F. P. Ng, Raymond T. P. Lin
Objectives We determined the seroprevalence of chikungunya virus (CHIKV) infection in the adult resident population in Singapore following local outbreaks of chikungunya fever (CHIKF) in 2008–2009. Methods Our cross-sectional study involved residual sera from 3,293 adults aged 18–79 years who had participated in the National Health Survey in 2010. Sera were tested for IgG antibodies against CHIKV and dengue virus (DENV) and neutralizing antibodies against CHIKV. Results The prevalence of CHIKV-neutralizing antibodies among Singapore residents aged 18–79 years was 1.9% (95% confidence interval: 1.4%– 2.3%). The CHIKV seroprevalence was highest in the elderly aged 70–79 years at 11.5%, followed by those aged 30–39 years at 3.1%. Men had significantly higher CHIKV seroprevalence than women (2.5% versus 1.3%, p = 0.01). Among the three main ethnic groups, Indians had the highest seroprevalence (3.5%) compared to Chinese (1.6%) and Malays (0.7%) (p = 0.02 and p = 0.01, respectively). Multivariable logistic regression identified adults aged 30–39 years and 70–79 years, men, those of Indian ethnicity and ethnic minority groups, and residence on ground floor of public and private housing apartments as factors that were significantly associated with a higher likelihood of exposure to CHIKV. The overall prevalence of anti-DENV IgG antibodies was 56.8% (95% CI: 55.1%– 58.5%), while 1.5% (95% CI: 1.1%– 2.0%) of adults possessed both neutralizing antibodies against CHIKV and IgG antibodies against DENV. Conclusions Singapore remains highly susceptible to CHIKV infection. There is a need to maintain a high degree of vigilance through disease surveillance and vector control. Findings from such serological study, when conducted on a regular periodic basis, could supplement surveillance to provide insights on CHIKV circulation in at-risk population.

by Michael J. Ricciardi, Diogo M. Magnani, Alba Grifoni, Young-Chan Kwon, Martin J. Gutman, Nathan D. Grubaugh, Karthik Gangavarapu, Mark Sharkey, Cassia G. T. Silveira, Varian K. Bailey, Núria Pedreño-Lopez, Lucas Gonzalez-Nieto, Helen S. Maxwell, Aline Domingues, Mauricio A. Martins, John Pham, Daniela Weiskopf, John Altman, Esper G. Kallas, Kristian G. Andersen, Mario Stevenson, Paola Lichtenberger, Hyeryun Choe, Stephen S. Whitehead, Alessandro Sette, David I. Watkins

Zika virus (ZIKV) is a mosquito-borne flavivirus of significant public health concern. In the summer of 2016, ZIKV was first detected in the contiguous United States. Here we present one of the first cases of a locally acquired ZIKV infection in a dengue-naïve individual. We collected blood from a female with a maculopapular rash at day (D) 5 and D7 post onset of symptoms (POS) and we continued weekly blood draws out to D148 POS. To establish the ontogeny of the immune response against ZIKV, lymphocytes and plasma were analyzed in a longitudinal fashion. The plasmablast response peaked at D7 POS (19.6% of CD19+ B-cells) and was undetectable by D15 POS. ZIKV-specific IgM was present at D5 POS, peaked between D15 and D21 POS, and subsequently decreased. The ZIKV-specific IgG response, however, was not detected until D15 POS and continued to increase after that. Interestingly, even though the patient had never been infected with dengue virus (DENV), cross-reactive IgM and IgG binding against each of the four DENV serotypes could be detected. The highest plasma neutralization activity against ZIKV peaked between D15 and D21 POS, and even though DENV binding antibodies were present in the plasma of the patient, there was neither neutralization nor antibody dependent enhancement (ADE) of DENV. Interestingly, ADE against ZIKV arose at D48 POS and continued until the end of the study. CD4+ and CD8+ T-cells recognized ZIKV-NS2A and ZIKV-E, respectively. The tetramer positive CD8+ T-cell response peaked at D21 POS with elevated levels persisting for months. In summary, this is the first study to establish the timing of the ontogeny of the immune response against ZIKV.

by Djamel Tahir, Lionel Almeras, Marie Varloud, Didier Raoult, Bernard Davoust, Philippe Parola

Matrix Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) is an emerging tool for routine identification of bacteria, archaea and fungi. It has also been recently applied as an accurate approach for arthropod identification. Preliminary studies have shown that the MALDI-TOF MS was able to differentiate whether ticks and mosquitoes were infected or not with some bacteria and Plasmodium parasites, respectively. The aim of the present study was to test the efficiency of MALDI-TOF MS tool in distinguishing protein profiles between uninfected mosquitoes from specimens infected by filarioid helminths. Aedes aegypti mosquitoes were engorged on microfilaremic blood infected with Dirofilaria immitis, Brugia malayi or Brugia pahangi. Fifteen days post-infective blood feeding, a total of 534 mosquitoes were killed by freezing. To assess mass spectra (MS) profile changes following filariae infections, one compartment (legs, thorax, head or thorax and head) per mosquito was submitted for MALDI-TOF MS analysis; the remaining body parts were used to establish filariae infectious status by real-time qPCR. A database of reference MS, based on the mass profiles of at least two individual mosquitoes per compartment, was created. Subsequently, the remaining compartment spectra (N = 350) from Ae. aegypti infected or not infected by filariae were blind tested against the spectral database. In total, 37 discriminating peak masses ranging from 2062 to 14869 daltons were identified, of which 17, 11, 12 and 7 peak masses were for legs, thorax, thorax-head and head respectively. Two peak masses (4073 and 8847 Da) were specific to spectra from Ae. aegypti infected with filariae, regardless of nematode species or mosquito compartment. The thorax-head part provided better classification with a specificity of 94.1% and sensitivity of 86.6, 71.4 and 68.7% of D. immitis, B. malayi and B. pahangi respectively. This study presents the potential of MALDI-TOF MS as a reliable tool for differentiating non-infected and filariae-infected Ae. aegypti mosquitoes. Considering that the results might vary in other mosquito species, further studies are needed to consolidate the obtained preliminary results before applying this tool in entomological surveillance as a fast mass screening method of filariosis vectors in endemic areas.

by Vincent Raquin, Sarah Hélène Merkling, Valérie Gausson, Isabelle Moltini-Conclois, Lionel Frangeul, Hugo Varet, Marie-Agnès Dillies, Maria-Carla Saleh, Louis Lambrechts

Dengue virus (DENV) causes more human infections than any other mosquito-borne virus. The current lack of antiviral strategies has prompted genome-wide screens for host genes that are required for DENV infectivity. Earlier transcriptomic studies that identified DENV host factors in the primary vector Aedes aegypti used inbred laboratory colonies and/or pools of mosquitoes that erase individual variation. Here, we performed transcriptome sequencing on individual midguts in a field-derived Ae. aegypti population to identify new candidate host factors modulating DENV replication. We analyzed the transcriptomic data using an approach that accounts for individual co-variation between viral RNA load and gene expression. This approach generates a prediction about the agonist or antagonist effect of candidate genes on DENV replication based on the sign of the correlation between gene expression and viral RNA load. Using this method, we identified 39 candidate genes that went undetected by conventional pairwise comparison of gene expression levels between DENV-infected midguts and uninfected controls. Only four candidate genes were detected by both methods, emphasizing their complementarity. We demonstrated the value of our approach by functional validation of a candidate agonist gene encoding a sterol regulatory element-binding protein (SREBP), which was identified by correlation analysis but not by pairwise comparison. We confirmed that SREBP promotes DENV infection in the midgut by RNAi-mediated gene knockdown in vivo. We suggest that our approach for transcriptomic analysis can empower genome-wide screens for potential agonist or antagonist factors by leveraging inter-individual variation in gene expression. More generally, this method is applicable to a wide range of phenotypic traits displaying inter-individual variation.

by Aileen Kenneson, Efraín Beltrán-Ayala, Mercy J. Borbor-Cordova, Mark E. Polhemus, Sadie J. Ryan, Timothy P. Endy, Anna M. Stewart-Ibarra
Background In Ecuador, dengue virus (DENV) infections transmitted by the Aedes aegypti mosquito are among the greatest public health concerns in urban coastal communities. Community- and household-level vector control is the principal means of controlling disease outbreaks. This study aimed to assess the impact of knowledge, attitudes, and practices (KAPs) and social-ecological factors on the presence or absence of DENV infections in the household. Methods In 2014 and 2015, individuals with DENV infections from sentinel clinics in Machala, Ecuador, were invited to participate in the study, as well as members of their household and members of four neighboring households located within 200 meters. We conducted diagnostic testing for DENV on all study participants; we surveyed heads of households (HOHs) regarding demographics, housing conditions and KAPs. We compared KAPs and social-ecological factors between households with (n = 139) versus without (n = 80) DENV infections, using bivariate analyses and multivariate logistic regression models with and without interactions. Results Significant risk factors in multivariate models included proximity to abandoned properties, interruptions in piped water, and shaded patios (p

Title: T-cell memory responses elicited by yellow fever vaccine are targeted to overlapping epitopes containing multiple HLA-I and -II binding motifs
Authors: Melo, Andréa Barbosa de; Nascimento, Eduardo J. M.; Braga-Neto, Ulisses; Dhalia, Rafael; Silva, Ana Maria; Oelke, Mathias; Schneck, Jonathan P.; Sidney, John; Sette, Alessandro; Montenegro, Silvia M. L.; Marques, Ernesto T. A.

Title: Duração da Imunidade Pós-Vacinação Contra Febre Amarela em Adultos.
Authors: Pereira, Christiane Costa
Abstract: No Brasil, a Febre Amarela está presente principalmente na região Norte, Centro
Oeste, parte do Maranhão, Bahia e Região Sudeste. Estudos recentes do Ministério
da Saúde do Brasil (MS) têm demonstrado uma expansão considerável da área de
risco de infecção
pelo vírus da febre amarela, com consequente ampliação
mandatória da área territorial de cobertura vacinal antiamarílica. A suscetibilidade à
doença é geral e irrestrita. Não há tratamento específico para a doença e a vacina é
a forma mais segura de preven
ção. Diante disso,
foi realizado um estudo descritivo
-
analítico de aspectos fenotípicos e funcionais da memória imunológica no contexto
da duração da imunidade pós
-
vacinação contra Febre Amarela em adultos
primovacinados. E para tal,
foram aplicadas técnic
as para identificar um conjunto
mínimo de biomarcadores
como correlatos de proteção. O
Estado de memória das
células T circulantes (Naive
-
N /
early efector
-
eEf / Memória Central
-
CM / Memória
efetora
-
EM) e células B (Naive
-
N / Memória
-
não
-
clássica
-
nCM / Mem
ória
-
Clássica
-
CM) juntamente com o perfil de citocinas intracitoplasmáticas (TNF/IFN/IL
-
10/ IL
-
5)
e com
o perfil de expressão gênica de citocinas e quimiocinas (CCL2, CXL10,
CCL5
, CXCL8,
IL
-
6
, INFb1,
TNF,IL
-
12 , IFN g, IL
-
5
e IL
-
10)
foram monitorados ante
s
de vacinação NV(day0) e em pontos de tempo distintos após a vacinação primária
com a vacina 17DD (PV(day30
-
45); PV(year1
-
9) e PV(year10
-
11)
)
.
A vacinação primária desencadeou no dia 30
-
45 um aumento de vários
biomarcadores relacionados com a memória fen
otípica e funcional em comparação
com o dia 0 (eEfCD4; EMCD4; CMCD19; EMCD8; IFNCD4; IL
-
5CD8; TNFCD4;
IFNCD8; TNFCD8; IL
-
5CD19; IL
-
5CD4)
com a maioria deles persistindo em
PV(year1
-
9) e diminuindo consideravelmente 10 anos após a vacinação PV(year10
-
11), i
ndependentemente da idade do indivíduo.
A expressão gênica de CCL5,
CXCL8, TNF, IL
-
12, INF e IL
-
10 apresentou um diferença significativa nos indivíduos
vacinados
PV(day30
-
45) e PV(year1
-
9
)
em relação ao indivíduos não vacinados
NV(day0) e diminuiu consider
avelmente no grupo PV(year10
-
11).
O tratamento de dados de alta dimensionalidade, a partir de algoritmos abrangentes
de biologia de sistemas, d
efiniram EMCD8 e IL
-
5CD4 como os dois melhores
preditores fenotípicos e funcionais de memória, e IFN e IL
-
10 como
os melhores
biomar
cadores de expressão gênica pós
-
vacinação com a vacina17DD. Estes 4
biomarcadores associados ao
PRNT foram considerados uma ferramenta útil para
monitorar as respostas da vacina antiamarílica e a persistência da memória em
populações dis
tintas.
Essas descobertas podem, em última análise, contribuir para rever ou manter as
atuais diretrizes nacionais de políticas de imunização que recomendam uma dose de
reforço 10 anos após a vacinação primária com a vacina 17DD

Title: Controvérsias sobre a ampliação das áreas com vacinação de rotina contra a febre amarela no Brasil
Authors: Noronha, Tatiana Guimarães de; Camacho, Luiz Antonio Bastos
Abstract: Febre amarela é uma doença viral potencialmente grave, transmitida por mosquitos Haemagogus, Aedes e Sabethes. A vacinação é a medida mais importante para a sua prevenção e controle. Neste artigo, analisamos as recomendações de vacinação no Brasil, segundo a epidemiologia da doença nas últimas décadas. Considerando a facilidade de deslocamentos de suscetíveis para áreas de risco, e sua tendência de expansão, é provável que eventualmente todo o país tenha de adotar a vacinação rotineira. Porém, no processo decisório de ampliação da população candidata à vacinação, questões relacionadas à segurança vacinal têm sido destacadas. Apresentamos uma análise dos riscos e benefícios da vacinação e das estratégias para o controle da doença e prevenção da sua urbanização nas regiões onde a vacina ainda não é recomendada. Concluímos que a introdução da vacina contra a febre amarela no calendário de vacinação das crianças é uma estratégia proativa, de mais fácil operacionalização, como resposta ao aumento do número de casos de febre amarela silvestre no Brasil e tentativa de prevenção da reurbanização da doença.

by Chun-Yin Yeh, Po-Lin Chen, Kun-Ta Chuang, Yu-Chen Shu, Yu-Wen Chien, Guey Chuen Perng, Wen-Chien Ko, Nai-Ying Ko
Background Tainan experienced the most severe dengue epidemic in Taiwan in 2015. This study investigates the association between the signs and symptoms at the time of reporting with the adverse dengue prognoses. Methods A descriptive study was conducted using secondary data from the Dengue Disease Reporting System in Tainan, Taiwan, between January 1 and December 31, 2015. A multivariate stepwise logistic regression was used to identify the risk factors for the adverse prognoses: ICU admissions and mortality. Results There were 22,777 laboratory-confirmed reported cases (mean age 45.6 ± 21.2 years), of which 3.7% were admitted to intensive care units (ICU), and 0.8% were fatal. The most common symptoms were fever (92.8%), myalgia (26.6%), and headache (22.4%). The prevalence of respiratory distress, altered consciousness, shock, bleeding, and thrombocytopenia increased with age. The multivariate analysis indicated that being in 65–89 years old age group [Adjusted Odds Ratio (aOR):4.95], or the 90 years old and above age group (aOR: 9.06), and presenting with shock (aOR: 8.90) and respiratory distress (aOR: 5.31) were significantly associated with the risk of ICU admission. While old age (aOR: 1.11), respiratory distress (aOR: 9.66), altered consciousness (aOR: 7.06), and thrombocytopenia (aOR: 2.55) were significantly associated with the risk of mortality. Conclusions Dengue patients older than 65 and those with severe and non-specific signs and symptoms at the time of reporting were at a higher risk of ICU admission and mortality. First-line healthcare providers need to be aware of the varied presentations between the different age groups to allow early diagnosis and in-time management, which would prevent ICU admissions and fatalities in dengue patients.

Title: Prevalence and clinical profile of microcephaly in South America pre-Zika, 2005-14: prevalence and case-control study
Authors: Orioli, Iêda M.; Dolk, Helen; Lopez-Camelo, Jorge S.; Mattos, Daniel; Poletta, Fernando A.; Dutra, Maria G.; Carvalho, Flavia M.; Castilla, Eduardo E.

Title: Tracing the origin of the NS1 A188V substitution responsible for recent enhancement of Zika virus Asian genotype infectivity
Authors: Delatorre, Edson; Mir, Daiana; Bello, Gonzalo

by Xiujuan Tang, Shi Zhao, Alice P. Y. Chiu, Xin Wang, Lin Yang, Daihai He
Background Guillain-Barré Syndrome (GBS) is a severe paralytic neuropathy associated with virus infections such as Zika virus and Chikungunya virus. There were also case reports of dengue fever preceding GBS. With the aim to understand the mechanisms of GBS and dengue outbreaks, this ecological study investigates the relationships between GBS, dengue, meteorological factors in Hong Kong and global climatic factors from January 2000 to June 2016. Methods The correlations between GBS, dengue, Multivariate El Niño Southern Oscillation Index (MEI) and local meteorological data were explored by Spearman’s Rank correlations and cross-correlations. Three Poisson regression models were fitted to identify non-linear associations among GBS, dengue and MEI. Cross wavelet analyses were applied to infer potential non-stationary oscillating associations among GBS, dengue and MEI. Findings and conclusion We report a substantial increasing of local GBS and dengue cases (mainly imported) in recent year in Hong Kong. The seasonalities of GBS and dengue are different, in particular, GBS is low while dengue is high in the summer. We found weak but significant correlations between GBS and local meteorological factors. MEI could explain over 17% of dengue’s variations based on Poisson regression analyses. We report a possible non-stationary oscillating association between dengue fever and GBS cases in Hong Kong. This study has led to an improved understanding about the timing and ecological relationships between MEI, GBS and dengue.

Title: Incidence of dengue fever in an urban slum community in Salvador, Brazil
Authors: Queiroz, T. L; Kasper, A. M; Gonçalves, A. H; Silva, M. M; Lima, H. C. A. V; Calcagno, J; Cruz, J. S; Takahashi, D; Reis, Mitermayer Galvão dos; Ko, Albert Icksang; Ribeiro, Guilherme de Sousa
Abstract: Introduction: Symptoms of dengue infection are nonspecific, complicating diagnosis and case reporting.
Active surveillance is needed to better characterize disease burden. The objectives of this study were to
estimate the incidence and identify risk factors for dengue fever (DF) in an urban slum community in
Salvador, Brazil.

by Ludovic Reveiz, Michelle M. Haby, Ruth Martínez-Vega, Carlos E. Pinzón-Flores, Vanessa Elias, Emma Smith, Mariona Pinart, Nathalie Broutet, Francisco Becerra-Posada, Sylvain Aldighieri, Maria D. Van Kerkhove

Title: Development and physiological effects of an artificial diet for Wolbachia-infected Aedes aegypti
Authors: Dutra, Heverton Leandro Carneiro; Rodrigues, Silvia Lomeu; Mansur, Simone Brutman; Oliveira, Sofia Pimenta de; Caragata, Eric Pearce; Moreira, Luciano Andrade

by Peter Christ, Anna Reifenrath, Jörg Kahnt, Frank Hauser, Sharon Rose Hill, Joachim Schachtner, Rickard Ignell

Aedes aegypti is a model species in which the endogenous regulation of odor-mediated host seeking behavior has received some attention. Sugar feeding and host seeking in female A. aegypti are transiently inhibited following a blood meal. This inhibition is partially mediated by short neuropeptide F (sNPF). The paired antennal lobes (ALs), as the first processing centers for olfactory information, has been shown to play a significant role in the neuropeptidergic regulation of odor-mediated behaviors in insects. The expression of sNPF, along with other peptides in the ALs of A. aegypti, indicate parallel neuromodulatory systems that may affect olfactory processing. To identify neuropeptides involved in regulating the odor-mediated host seeking behavior in A. aegypti, we use a semi-quantitative neuropeptidomic analysis of single ALs to analyze changes in the levels of five individual neuropeptides in response to different feeding regimes. Our results show that the level of sNPF-2, allatostatin-A-5 (AstA-5) and neuropeptide-like precursor-1-5 (NPLP-1-5), but not of tachykinin-related-peptides and SIFamide (SIFa), in the AL of female mosquitoes, changes 24 h and 48 h post-blood meal, and are dependent on prior access to sugar. To assess the role of these neuropeptides in modulating host seeking behavior, when systemically injected individually, sNPF-2 and AstA-5 significantly reduced host seeking behavior. However, only the injection of the binary mixture of the two neuropeptides lead to a host seeking inhibition similar to that observed in blood fed females. We conclude that modulation of the odor mediated host seeking behavior of A. aegypti is likely regulated by a dual neuropeptidergic pathway acting in concert in the ALs.

by Raquel Martins Lana, Marcelo Ferreira da Costa Gomes, Tiago França Melo de Lima, Nildimar Alves Honório, Cláudia Torres Codeço

Human mobility, presence and passive transportation of Aedes aegypti mosquito, and environmental characteristics are a group of factors which contribute to the success of dengue spread and establishment. To understand this process, we assess data from dengue national and municipal basins regarding population and demographics, transportation network, human mobility, and Ae. aegypti monitoring for the Brazilian state of Acre since the first recorded dengue case in the year 2000 to the year 2015. During this period, several changes in Acre’s transport infrastructure and urbanization have been started. To reconstruct the process of dengue introduction in Acre, we propose an analytic framework based on concepts used in malaria literature, namely vulnerability and receptivity, to inform risk assessments in dengue-free regions as well as network theory concepts for disease invasion and propagation. We calculate the probability of dengue importation to Acre from other Brazilian states, the evolution of dengue spread between Acrean municipalities and dengue establishment in the state. Our findings suggest that the landscape changes associated with human mobility have created favorable conditions for the establishment of dengue virus transmission in Acre. The revitalization of its major roads, as well as the increased accessibility by air to and within the state, have increased dengue vulnerability. Unplanned urbanization and population growth, as observed in Acre during the period of study, contribute to ideal conditions for Ae. aegypti mosquito establishment, increase the difficulty in mosquito control and consequently its local receptivity.

by Yanouk Epelboin, Stanislas Talaga, Loïc Epelboin, Isabelle Dusfour

Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) that recently caused outbreaks in the Americas. Over the past 60 years, this virus has been observed circulating among African, Asian, and Pacific Island populations, but little attention has been paid by the scientific community until the discovery that large-scale urban ZIKV outbreaks were associated with neurological complications such as microcephaly and several other neurological malformations in fetuses and newborns. This paper is a systematic review intended to list all mosquito species studied for ZIKV infection or for their vector competence. We discuss whether studies on ZIKV vectors have brought enough evidence to formally exclude other mosquitoes than Aedes species (and particularly Aedes aegypti) to be ZIKV vectors. From 1952 to August 15, 2017, ZIKV has been studied in 53 mosquito species, including 6 Anopheles, 26 Aedes, 11 Culex, 2 Lutzia, 3 Coquillettidia, 2 Mansonia, 2 Eretmapodites, and 1 Uranotaenia. Among those, ZIKV was isolated from 16 different Aedes species. The only species other than Aedes genus for which ZIKV was isolated were Anopheles coustani, Anopheles gambiae, Culex perfuscus, and Mansonia uniformis. Vector competence assays were performed on 22 different mosquito species, including 13 Aedes, 7 Culex, and 2 Anopheles species with, as a result, the discovery that A. aegypti and Aedes albopictus were competent for ZIKV, as well as some other Aedes species, and that there was a controversy surrounding Culex quinquefasciatus competence. Although Culex, Anopheles, and most of Aedes species were generally observed to be refractory to ZIKV infection, other potential vectors transmitting ZIKV should be explored.

Title: Chikungunya virus: clinical aspects and treatment - A Review
Authors: Cunha, Rivaldo V. da; Trinta, Karen S.