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Title: Zika virus infection: epidemiology, clinical manifestations and diagnosis
Authors: Calvet, Guilherme Amaral; Santos, Flavia Barreto dos; Sequeira, Patricia Carvalho

by Hannah E. Clapham, Derek A. T. Cummings, Michael A. Johansson

Dengue is an important vector-borne pathogen found across much of the world. Many factors complicate our understanding of the relationship between infection with one of the four dengue virus serotypes, and the observed incidence of disease. One of the factors is a large proportion of infections appear to result in no or few symptoms, while others result in severe infections. Estimates of the proportion of infections that result in no symptoms (inapparent) vary widely from 8% to 100%, depending on study and setting. To investigate the sources of variation of these estimates, we used a flexible framework to combine data from multiple cohort studies and cluster studies (follow-up around index cases). Building on previous observations that the immune status of individuals affects their probability of apparent disease, we estimated the probability of apparent disease among individuals with different exposure histories. In cohort studies mostly assessing infection in children, we estimated the proportion of infections that are apparent as 0.18 (95% Credible Interval, CI: 0.16, 0.20) for primary infections, 0.13 (95% CI: 0.05, 0.17) for individuals infected in the year following a first infection (cross-immune period), and 0.41 (95% CI: 0.36, 0.45) for those experiencing secondary infections after this first year. Estimates of the proportion of infections that are apparent from cluster studies were slightly higher than those from cohort studies for both primary and secondary infections, 0.22 (95% CI: 0.15, 0.29) and 0.57 (95% CI: 0.49, 0.68) respectively. We attempted to estimate the apparent proportion by serotype, but current published data were too limited to distinguish the presence or absence of serotype-specific differences. These estimates are critical for understanding dengue epidemiology. Most dengue data come from passive surveillance systems which not only miss most infections because they are asymptomatic and often underreported, but will also vary in sensitivity over time due to the interaction between previous incidence and the symptomatic proportion, as shown here. Nonetheless the underlying incidence of infection is critical to understanding susceptibility of the population and estimating the true burden of disease, key factors for effectively targeting interventions. The estimates shown here help clarify the link between past infection, observed disease, and current transmission intensity.

by Amanda E. Calvert, Brad J. Biggerstaff, Nathan A. Tanner, Molly Lauterbach, Robert S. Lanciotti

Zika virus (ZIKV) has emerged as a major global public health concern in the last two years due to its link as a causative agent of human birth defects. Its rapid expansion into the Western Hemisphere as well as the ability to be transmitted from mother to fetus, through sexual transmission and possibly through blood transfusions has increased the need for a rapid and expansive public health response to this unprecedented epidemic. A non-invasive and rapid ZIKV diagnostic screening assay that can be performed in a clinical setting throughout pregnancy is vital for prenatal care of women living in areas of the world where exposure to the virus is possible. To meet this need we have developed a sensitive and specific reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) assay to detect ZIKV RNA in urine and serum with a simple visual detection. RT-LAMP results were shown to have a limit of detection 10-fold higher than qRT-PCR. As little as 1.2 RNA copies/μl was detected by RT-LAMP from a panel of 178 diagnostic specimens. The assay was shown to be highly specific for ZIKV RNA when tested with diagnostic specimens positive for dengue virus (DENV) and chikungunya virus (CHIKV). The assay described here illustrates the potential for a fast, reliable, sensitive and specific assay for the detection of ZIKV from urine or serum that can be performed in a clinical or field setting with minimal equipment and technological expertise.

by Yesim Tozan, Pitcha Ratanawong, Maquines Odhiambo Sewe, Annelies Wilder-Smith, Pattamaporn Kittayapong
Background Dengue-related illness is a leading cause of hospitalization and death in Thailand and other Southeast Asian countries, imposing a major economic burden on households, health systems, and governments. This study aims to assess the economic impact of hospitalized dengue cases on households in Chachoengsao province in eastern Thailand. Methods We conducted a prospective cost-of-illness study of hospitalized pediatric and adult dengue patients at three public hospitals. We examined all hospitalized dengue cases regardless of disease severity. Patients or their legal guardians were interviewed using a standard questionnaire to determine household-level medical and non-medical expenditures and income losses during the illness episode. Results Between March and September 2015, we recruited a total of 224 hospitalized patients (

by Yannick Simonin, Debby van Riel, Philippe Van de Perre, Barry Rockx, Sara Salinas

by Nicola Luigi Bragazzi, Cristiano Alicino, Cecilia Trucchi, Chiara Paganino, Ilaria Barberis, Mariano Martini, Laura Sticchi, Eugen Trinka, Francesco Brigo, Filippo Ansaldi, Giancarlo Icardi, Andrea Orsi
Objective The recent spreading of Zika virus represents an emerging global health threat. As such, it is attracting public interest worldwide, generating a great amount of related Internet searches and social media interactions. The aim of this research was to understand Zika-related digital behavior throughout the epidemic spreading and to assess its consistence with real-world epidemiological data, using a behavioral informatics and analytics approach. Methods In this study, the global web-interest and reaction to the recently occurred outbreaks of the Zika Virus were analyzed in terms of tweets and Google Trends (GT), Google News, YouTube, and Wikipedia search queries. These data streams were mined from 1st January 2004 to 31st October 2016, with a focus on the period November 2015—October 2016. This analysis was complemented with the use of epidemiological data. Spearman’s correlation was performed to correlate all Zika-related data. Moreover, a multivariate regression was performed using Zika-related search queries as a dependent variable, and epidemiological data, number of inhabitants in 2015 and Human Development Index as predictor variables. Results Overall 3,864,395 tweets, 284,903 accesses to Wikipedia pages dedicated to the Zika virus were analyzed during the study period. All web-data sources showed that the main spike of researches and interactions occurred in February 2016 with a second peak in August 2016. All novel data streams-related activities increased markedly during the epidemic period with respect to pre-epidemic period when no web activity was detected. Correlations between data from all these web platforms resulted very high and statistically significant. The countries in which web searches were particularly concentrated are mainly from Central and South Americas. The majority of queries concerned the symptoms of the Zika virus, its vector of transmission, and its possible effect to babies, including microcephaly. No statistically significant correlation was found between novel data streams and global real-world epidemiological data. At country level, a correlation between the digital interest towards the Zika virus and Zika incidence rate or microcephaly cases has been detected. Conclusions An increasing public interest and reaction to the current Zika virus outbreak was documented by all web-data sources and a similar pattern of web reactions has been detected. The public opinion seems to be particularly worried by the alert of teratogenicity of the Zika virus. Stakeholders and health authorities could usefully exploited these internet tools for collecting the concerns of public opinion and reply to them, disseminating key information.

by Natasha M. Agramonte, Jeffrey R. Bloomquist, Ulrich R. Bernier

Emerging insecticide resistance is a major issue for vector control. It decreases the effectiveness of insecticides, thereby requiring greater quantities for comparable control with a net increase in risk of disease resurgence, product cost, and damage risk to the ecosystem. Pyrethroid resistance has been documented in Puerto Rican populations of Aedes aegypti (L.) mosquitoes. In this study, topical toxicity of five insecticides (permethrin, etofenprox, deltamethrin, DDT, transfluthrin) was determined for susceptible (Orlando—ORL) and resistant (Puerto Rico—PR) strains of Ae. aegypti. Resistance ratios were calculated using LD50 values, and high resistance ratios for permethrin (112) and etofenprox (228) were observed for the Puerto Rico strain. Behavioral differences in blood-feeding activity for pyrethroid-resistant and pyrethroid-susceptible strains of Ae. aegypti when exposed to pyrethroid-treated cloth were also explored. Strains were exposed for 15 min to a range of concentrations of pyrethroid-treated uniform fabric in a cage that contained 60 female Ae. aegypti mosquitoes. Interestingly, the resistance ratios for blood-feeding were similar for permethrin (61) and etofenprox (70), but were lower than their respective resistance ratios for topical toxicity, suggesting that knockdown resistance was the primary mechanism of resistance in the blood feeding assays. Results showed a rightward shift in the dose-response curves for blood-feeding that indicated higher concentrations of pyrethroids were necessary to deter blood-feeding behavior in the pyrethroid-resistant Puerto Rican strain of Ae. aegypti.

by Marco Ajelli, Imelda K. Moise, Tricia Caroline S. G. Hutchings, Scott C. Brown, Naresh Kumar, Neil F. Johnson, John C. Beier
Background Zika virus transmission dynamics in urban environments follow a complex spatiotemporal pattern that appears unpredictable and barely related to high mosquito density areas. In this context, human activity patterns likely have a major role in Zika transmission dynamics. This paper examines the effect of host variability in the amount of time spent outdoors on Zika epidemiology in an urban environment. Methodology/Principal findings First, we performed a survey on time spent outdoors by residents of Miami-Dade County, Florida. Second, we analyzed both the survey and previously published national data on outdoors time in the U.S. to provide estimates of the distribution of the time spent outdoors. Third, we performed a computational modeling evaluation of Zika transmission dynamics, based on the time spent outdoors by each person. Our analysis reveals a strong heterogeneity of the host population in terms of time spent outdoors–data are well captured by skewed gamma distributions. Our model-based evaluation shows that in a heterogeneous population, Zika would cause a lower number of infections than in a more homogenous host population (up to 4-fold differences), but, at the same time, the epidemic would spread much faster. We estimated that in highly heterogeneous host populations the timing of the implementation of vector control measures is the major factor for limiting the number of Zika infections. Conclusions/Significance Our findings highlight the need of considering host variability in exposure time for managing mosquito-borne infections and call for the revision of the triggers for vector control strategies, which should integrate mosquito density data and human outdoor activity patterns in specific areas.

by Kay M. Tomashek, Olga D. Lorenzi, Doris A. Andújar-Pérez, Brenda C. Torres-Velásquez, Elizabeth A. Hunsperger, Jorge Luis Munoz-Jordan, Janice Perez-Padilla, Aidsa Rivera, Gladys E. Gonzalez-Zeno, Tyler M. Sharp, 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, Jesús Cruz-Correa, Robert Muns-Sosa, Juan D. Ortiz-Rivera, Gerson Jiménez, Ivonne E. Galarza, Kalanthe Horiuchi, Harold S. Margolis, Luisa I. Alvarado

Identifying etiologies of acute febrile illnesses (AFI) is challenging due to non-specific presentation and limited availability of diagnostics. Prospective AFI studies provide a methodology to describe the syndrome by age and etiology, findings that can be used to develop case definitions and multiplexed diagnostics to optimize management. We conducted a 3-year prospective AFI study in Puerto Rico. Patients with fever ≤7 days were offered enrollment, and clinical data and specimens were collected at enrollment and upon discharge or follow-up. Blood and oro-nasopharyngeal specimens were tested by RT-PCR and immunodiagnostic methods for infection with dengue viruses (DENV) 1–4, chikungunya virus (CHIKV), influenza A and B viruses (FLU A/B), 12 other respiratory viruses (ORV), enterovirus, Leptospira spp., and Burkholderia pseudomallei. Clinical presentation and laboratory findings of participants infected with DENV were compared to those infected with CHIKV, FLU A/B, and ORV. Clinical predictors of laboratory-positive dengue compared to all other AFI etiologies were determined by age and day post-illness onset (DPO) at presentation. Of 8,996 participants enrolled from May 7, 2012 through May 6, 2015, more than half (54.8%, 4,930) had a pathogen detected. Pathogens most frequently detected were CHIKV (1,635, 18.2%), FLU A/B (1,074, 11.9%), DENV 1–4 (970, 10.8%), and ORV (904, 10.3%). Participants with DENV infection presented later and a higher proportion were hospitalized than those with other diagnoses (46.7% versus 27.3% with ORV, 18.8% with FLU A/B, and 11.2% with CHIKV). Predictors of dengue in participants presenting

by André Barretto Bruno Wilke, Ramon Wilk-da-Silva, Mauro Toledo Marrelli

Aedes aegypti is one of the species most favored by changes in the environment caused by urbanization. Its abundance increases rapidly in the face of such changes, increasing the risk of disease transmission. Previous studies have shown that mosquito species that have adapted to anthropogenic environmental changes benefit from urbanization and undergo population expansion. In light of this, we used microsatellite markers to explore how urbanization processes may be modulating Ae. aegypti populations collected from three areas with different levels of urbanization in the city of São Paulo, Brazil. Specimens were collected at eleven sites in three areas with different degrees of urbanization in the city of São Paulo: conserved, intermediate and urbanized. Ten microsatellite loci were used to characterize the populations from these areas genetically. Our findings suggest that as urbanized areas grow and the human population density in these areas increases, Ae. aegypti populations undergo a major population expansion, which can probably be attributed to the species’ adaptability to anthropogenic environmental changes. Our findings reveal a robust association between, on the one hand, urbanization processes and densification of the human population and, on the other, Ae. aegypti population structure patterns and population expansion. This indicates that this species benefits from anthropogenic effects, which are intensified by migration of the human population from rural to urban areas, increasing the risk of epidemics and disease transmission to an ever-increasing number of people.

Title: Fitness cost in field and laboratory Aedes aegypti populations associated with resistance to the insecticide temephos
Authors: Diniz, Diego Felipe Araujo; de Melo-Santos, Maria Alice Varjal; Santos, Eloína Maria de Mendonça; Beserra, Eduardo Barbosa; Helvecio, Elisama; de Carvalho-Leandro, Danilo; dos Santos, Bianka Santana; de Menezes Lima, Vera Lúcia; Ayres, Constância Flávia Junqueira

by Debora Ferreira Barreto-Vieira, Fernanda Cunha Jácome, Marcos Alexandre Nunes da Silva, Gabriela Cardoso Caldas, Ana Maria Bispo de Filippis, Patrícia Carvalho de Sequeira, Elen Mello de Souza, Audrien Alves Andrade, Pedro Paulo de Abreu Manso, Gisela Freitas Trindade, Sheila Maria Barbosa Lima, Ortrud Monika Barth

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

by Giorgio Guzzetta, Filippo Trentini, Piero Poletti, Frederic Alexandre Baldacchino, Fabrizio Montarsi, Gioia Capelli, Annapaola Rizzoli, Roberto Rosà, Stefano Merler, Alessia Melegaro

In the last decades, several European countries where arboviral infections are not endemic have faced outbreaks of diseases such as chikungunya and dengue, initially introduced by infectious travellers from tropical endemic areas and then spread locally via mosquito bites. To keep in check the epidemiological risk, interventions targeted to control vector abundance can be implemented by local authorities. We assessed the epidemiological effectiveness and economic costs and benefits of routine larviciding in European towns with temperate climate, using a mathematical model of Aedes albopictus populations and viral transmission, calibrated on entomological surveillance data collected from ten municipalities in Northern Italy during 2014 and 2015.We found that routine larviciding of public catch basins can limit both the risk of autochthonous transmission and the size of potential epidemics. Ideal larvicide interventions should be timed in such a way to cover the month of July. Optimally timed larviciding can reduce locally transmitted cases of chikungunya by 20% - 33% for a single application (dengue: 18–22%) and up to 43% - 65% if treatment is repeated four times throughout the season (dengue: 31–51%). In larger municipalities (>35,000 inhabitants), the cost of comprehensive larviciding over the whole urban area overcomes potential health benefits related to preventing cases of disease, suggesting the adoption of more localized interventions. Small/medium sized towns with high mosquito abundance will likely have a positive cost-benefit balance. Involvement of private citizens in routine larviciding activities further reduces transmission risks but with disproportionate costs of intervention. International travels and the incidence of mosquito-borne diseases are increasing worldwide, exposing a growing number of European citizens to higher risks of potential outbreaks. Results from this study may support the planning and timing of interventions aimed to reduce the probability of autochthonous transmission as well as the nuisance for local populations living in temperate areas of Europe.

by Patricia Najera Hamrick, Sylvain Aldighieri, Gustavo Machado, Deise Galan Leonel, Luz Maria Vilca, Sonia Uriona, Maria Cristina Schneider
Background In the Americas, yellow fever virus transmission is a latent threat due to the proximity between urban and wild environments. Although yellow fever has nearly vanished from North and Central America, there are still 13 countries in the Americas considered endemic by the World Health Organization. Human cases usually occur as a result of the exposure to sylvatic yellow fever in tropical forested environments; but urban outbreaks reported during the last decade demonstrate that the risk in this environment still exists. The objective of this study was to identify spatial patterns and the relationship between key geographic and environmental factors with the distribution of yellow fever human cases in the Americas. Methodology/Principal findings An ecological study was carried out to analyze yellow fever human cases reported to the Pan American Health Organization from 2000 to 2014, aggregated by second administrative level subdivisions (counties). Presence of yellow fever by county was used as the outcome variable and eight geo-environmental factors were used as independent variables. Spatial analysis was performed to identify and examine natural settings per county. Subsequently, a multivariable logistic regression model was built. During the study period, 1,164 cases were reported in eight out of the 13 endemic countries. Nearly 83.8% of these cases were concentrated in three countries: Peru (37.4%), Brazil (28.1%) and Colombia (18.4%); and distributed in 57 states/provinces, specifically in 286 counties (3.4% of total counties). Yellow fever presence was significantly associated with altitude, rain, diversity of non-human primate hosts and temperature. A positive spatial autocorrelation revealed a clustered geographic pattern in 138/286 yellow fever positive counties (48.3%). Conclusions/Significance A clustered geographic pattern of yellow fever was identified mostly along the Andes eastern foothills. This risk map could support health policies in endemic countries. Geo-environmental factors associated with presence of yellow fever could help predict and adjust the limits of other risk areas of epidemiological concern.

by Elizabeth A. Hunsperger, Claudia N. Duarte dos Santos, Huong Thi Que Vu, Sutee Yoksan, Vincent Deubel

by Amy L. Frank, Emily R. Beales, Gilles de Wildt, Graciela Meza Sanchez, Laura L. Jones
Background Dengue Fever presents a significant and growing burden of disease to endemic countries, where children are at particular risk. Worldwide, no effective anti-viral treatment has been identified, thus vector control is key for disease prevention, particularly in Peru where no vaccine is currently available. This qualitative study aimed to explore the perceptions of dengue control in caregivers’ of children under 5 years in Peru, to help direct future mosquito control programmes and strategy. Methods Eighteen semi-structured interviews were conducted in one health centre in Iquitos, Peru. Interviews were audio-recorded, transcribed and translated by an independent translator. Data were analysed using an inductive thematic approach. Findings Three core analytic themes were interpreted: (1) awareness of dengue and its control, (2) perceived susceptibility of children, rural riverside communities and city inhabitants, and (3) perceived responsibility of vector control. Participants were aware of dengue symptoms, transmission and larvae eradication strategies. Misconceptions about the day-time biting behaviour of the Aedes aegypti mosquito and confusion with other mosquito-borne diseases influenced preventative practice. Community-wide lack of cooperation was recognised as a key barrier. This was strengthened by attitudes that the government or health centre were responsible for dengue control and a belief that the disease cannot be prevented through individual actions. Participants felt powerless to prevent dengue due to assumed inevitability of infection and lack of faith in preventative practices. However, children and rural communities were believed to be most vulnerable. Conclusions Perceptions of dengue control amongst caregivers to under 5’s were important in shaping their likelihood to participate in preventative practices. There is a need to address the perceived lack of community cooperation through strategies creating a sense of ownership of community control and enhancing social responsibility. The belief that dengue cannot be prevented by individual actions in a community also warrants attention. Specific misconceptions about dengue should be addressed through the community health worker system and further research directed to identify the needs of certain vulnerable groups.

by Moody Samuel, Dorit Maoz, Pablo Manrique, Tara Ward, Silvia Runge-Ranzinger, Joao Toledo, Ross Boyce, Olaf Horstick
Background The prevention and control of dengue rely mainly on vector control methods, including indoor residual spraying (IRS) and indoor space spraying (ISS). This study aimed to systematically review the available evidence on community effectiveness of indoor spraying. Methods A systematic review was conducted using seven databases (PubMed, EMBASE, LILACS, Web of Science, WHOLIS, Cochrane, and Google Scholar) and a manual search of the reference lists of the identified studies. Data from included studies were extracted, analysed and reported. Results The review generated seven studies only, three IRS and four ISS (two/three controlled studies respectively). Two IRS studies measuring human transmission showed a decline. One IRS and all four ISS studies measuring adult mosquitoes showed a very good effect, up to 100%, but not sustained. Two IRS studies and one ISS measuring immature mosquitoes, showed mixed results. Conclusions It is evident that IRS and also ISS are effective adulticidal interventions against Aedes mosquitoes. However, evidence to suggest effectiveness of IRS as a larvicidal intervention and to reduce human dengue cases is limited–and even more so for ISS. Overall, there is a paucity of studies available on these two interventions that may be promising for dengue vector control, particularly for IRS with its residual effect.

by Peter J. Hotez, Kristy O. Murray

Title: Dengue research networks: building evidence for policy and planning in Brazil
Authors: Fonseca, Bruna de Paula Fonseca e; Zicker, Fabio

by Sheena Francis, Karla Saavedra-Rodriguez, Rushika Perera, Mark Paine, William C. Black IV, Rupika Delgoda

by Ashley R. Styczynski, Juliane M. A. S. Malta, Elisabeth R. Krow-Lucal, Jadher Percio, Martha E. Nóbrega, Alexander Vargas, Tatiana M. Lanzieri, Priscila L. Leite, J. Erin Staples, Marc X. Fischer, Ann M. Powers, Gwong-Jen J. Chang, P. L. Burns, Erin M. Borland, Jeremy P. Ledermann, Eric C. Mossel, Lawrence B. Schonberger, Ermias B. Belay, Jorge L. Salinas, Roberto D. Badaro, James J. Sejvar, Giovanini E. Coelho

In mid-2015, Salvador, Brazil, reported an outbreak of Guillain-Barré syndrome (GBS), coinciding with the introduction and spread of Zika virus (ZIKV). We found that GBS incidence during April–July 2015 among those ≥12 years of age was 5.6 cases/100,000 population/year and increased markedly with increasing age to 14.7 among those ≥60 years of age. We conducted interviews with 41 case-patients and 85 neighborhood controls and found no differences in demographics or exposures prior to GBS-symptom onset. A higher proportion of case-patients (83%) compared to controls (21%) reported an antecedent illness (OR 18.1, CI 6.9–47.5), most commonly characterized by rash, headache, fever, and myalgias, within a median of 8 days prior to GBS onset. Our investigation confirmed an outbreak of GBS, particularly in older adults, that was strongly associated with Zika-like illness and geo-temporally associated with ZIKV transmission, suggesting that ZIKV may result in severe neurologic complications.

by Brendan J. Trewin, Jonathan M. Darbro, Cassie C. Jansen, Nancy A. Schellhorn, Myron P. Zalucki, Tim P. Hurst, Gregor J. Devine

Aedes aegypti (L.) (Diptera: Culicidae) is a highly invasive mosquito whose global distribution has fluctuated dramatically over the last 100 years. In Australia the distribution of Ae. aegypti once spanned the eastern seaboard, for 3,000 km north to south. However, during the 1900s this distribution markedly reduced and the mosquito disappeared from its southern range. Numerous hypotheses have been proffered for this retraction, however quantitative evidence of the mechanisms driving the disappearance are lacking. We examine historical records during the period when Ae. aegypti disappeared from Brisbane, the largest population centre in Queensland, Australia. In particular, we focus on the targeted management of Ae. aegypti by government authorities, that led to local elimination, something rarely observed in large cities. Numerous factors are likely to be responsible including the removal of larval habitat, especially domestic rainwater tanks, in combination with increased mosquito surveillance and regulatory enforcement. This account of historical events as they pertain to the elimination of Ae. aegypti from Brisbane, will inform assessments of the risks posed by recent human responses to climate change and the reintroduction of 300,000 rainwater tanks into the State over the past decade.

by Eliza Little, Waheed Bajwa, Jeffrey Shaman

Ae. albopictus, an invasive mosquito vector now endemic to much of the northeastern US, is a significant public health threat both as a nuisance biter and vector of disease (e.g. chikungunya virus). Here, we aim to quantify the relationships between local environmental and meteorological conditions and the abundance of Ae. albopictus mosquitoes in New York City. Using statistical modeling, we create a fine-scale spatially explicit risk map of Ae. albopictus abundance and validate the accuracy of spatiotemporal model predictions using observational data from 2016. We find that the spatial variability of annual Ae. albopictus abundance is greater than its temporal variability in New York City but that both local environmental and meteorological conditions are associated with Ae. albopictus numbers. Specifically, key land use characteristics, including open spaces, residential areas, and vacant lots, and spring and early summer meteorological conditions are associated with annual Ae. albopictus abundance. In addition, we investigate the distribution of imported chikungunya cases during 2014 and use these data to delineate areas with the highest rates of arboviral importation. We show that the spatial distribution of imported arboviral cases has been mostly discordant with mosquito production and thus, to date, has provided a check on local arboviral transmission in New York City. We do, however, find concordant areas where high Ae. albopictus abundance and chikungunya importation co-occur. Public health and vector control officials should prioritize control efforts to these areas and thus more cost effectively reduce the risk of local arboviral transmission. The methods applied here can be used to monitor and identify areas of risk for other imported vector-borne diseases.

by Sheila B. Agha, Edith Chepkorir, Francis Mulwa, Caroline Tigoi, Samwel Arum, Milehna M. Guarido, Peris Ambala, Betty Chelangat, Joel Lutomiah, David P. Tchouassi, Michael J. Turell, Rosemary Sang
Background In April, 2004, chikungunya virus (CHIKV) re-emerged in Kenya and eventually spread to the islands in the Indian Ocean basin, South-East Asia, and the Americas. The virus, which is often associated with high levels of viremia in humans, is mostly transmitted by the urban vector, Aedes aegypti. The expansion of CHIKV presents a public health challenge both locally and internationally. In this study, we investigated the ability of Ae. aegypti mosquitoes from three distinct cities in Kenya; Mombasa (outbreak prone), Kisumu, and Nairobi (no documented outbreak) to transmit CHIKV. Methodology/Principal findings Aedes aegypti mosquito populations were exposed to different doses of CHIKV (105.6–7.5 plaque-forming units[PFU]/ml) in an infectious blood meal. Transmission was ascertained by collecting and testing saliva samples from individual mosquitoes at 5, 7, 9, and 14 days post exposure. Infection and dissemination were estimated by testing body and legs, respectively, for individual mosquitoes at selected days post exposure. Tissue culture assays were used to determine the presence of infectious viral particles in the body, leg, and saliva samples. The number of days post exposure had no effect on infection, dissemination, or transmission rates, but these rates increased with an increase in exposure dose in all three populations. Although the rates were highest in Ae. aegypti from Mombasa at titers ≥106.9 PFU/ml, the differences observed were not statistically significant (χ2 ≤ 1.04, DF = 1, P ≥ 0.31). Overall, about 71% of the infected mosquitoes developed a disseminated infection, of which 21% successfully transmitted the virus into a capillary tube, giving an estimated transmission rate of about 10% for mosquitoes that ingested ≥106.9 PFU/ml of CHIKV. All three populations of Ae. aegypti were infectious as early as 5–7 days post exposure. On average, viral dissemination only occurred when body titers were ≥104 PFU/ml in all populations. Conclusions/Significance Populations of Ae. aegypti from Mombasa, Nairobi, and Kisumu were all competent laboratory vectors of CHIKV. Viremia of the infectious blood meal was an important factor in Ae. aegypti susceptibility and transmission of CHIKV. In addition to viremia levels, temperature and feeding behavior of Ae. aegypti may also contribute to the observed disease patterns.

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

Dengue (DEN) and yellow fever (YF) are re-emerging in East Africa, with contributing drivers to this trend being unplanned urbanization and increasingly adaptable anthropophilic Aedes (Stegomyia) vectors. Entomological risk assessment of these diseases remains scarce for much of East Africa and Kenya even in the dengue fever-prone urban coastal areas. Focusing on major cities of Kenya, we compared DEN and YF risk in Kilifi County (DEN-outbreak-prone), and Kisumu and Nairobi Counties (no documented DEN outbreaks). We surveyed water-holding containers for mosquito immature (larvae/pupae) indoors and outdoors from selected houses during the long rains, short rains and dry seasons (100 houses/season) in each County from October 2014-June 2016. House index (HI), Breteau index (BI) and Container index (CI) estimates based on Aedes (Stegomyia) immature infestations were compared by city and season. Aedes aegypti and Aedes bromeliae were the main Stegomyia species with significantly more positive houses outdoors (212) than indoors (88) (n = 900) (χ2 = 60.52, P 0.0001). Overall, Ae. aegypti estimates of HI (17.3 vs 11.3) and BI (81.6 vs 87.7) were higher in Kilifi and Kisumu, respectively, than in Nairobi (HI, 0.3; BI,13). However, CI was highest in Kisumu (33.1), followed by Kilifi (15.1) then Nairobi (5.1). Aedes bromeliae indices were highest in Kilifi, followed by Kisumu, then Nairobi with HI (4.3, 0.3, 0); BI (21.3, 7, 0.7) and CI (3.3, 3.3, 0.3), at the respective sites. HI and BI for both species were highest in the long rains, compared to the short rains and dry seasons. We found strong positive correlations between the BI and CI, and BI and HI for Ae. aegypti, with the most productive container types being jerricans, drums, used/discarded containers and tyres. On the basis of established vector index thresholds, our findings suggest low-to-medium risk levels for urban YF and high DEN risk for Kilifi and Kisumu, whereas for Nairobi YF risk was low while DEN risk levels were low-to-medium. The study provides a baseline for future vector studies needed to further characterise the observed differential risk patterns by vector potential evaluation. Identified productive containers should be made the focus of community-based targeted vector control programs.

by Christopher Fitzpatrick, Alexander Haines, Mathieu Bangert, Andrew Farlow, Janet Hemingway, Raman Velayudhan
Introduction Dengue is a rapidly emerging vector-borne Neglected Tropical Disease, with a 30-fold increase in the number of cases reported since 1960. The economic cost of the illness is measured in the billions of dollars annually. Environmental change and unplanned urbanization are conspiring to raise the health and economic cost even further beyond the reach of health systems and households. The health-sector response has depended in large part on control of the Aedes aegypti and Ae. albopictus (mosquito) vectors. The cost-effectiveness of the first-ever dengue vaccine remains to be evaluated in the field. In this paper, we examine how it might affect the cost-effectiveness of sustained vector control. Methods We employ a dynamic Markov model of the effects of vector control on dengue in both vectors and humans over a 15-year period, in six countries: Brazil, Columbia, Malaysia, Mexico, the Philippines, and Thailand. We evaluate the cost (direct medical costs and control programme costs) and cost-effectiveness of sustained vector control, outbreak response and/or medical case management, in the presence of a (hypothetical) highly targeted and low cost immunization strategy using a (non-hypothetical) medium-efficacy vaccine. Results Sustained vector control using existing technologies would cost little more than outbreak response, given the associated costs of medical case management. If sustained use of existing or upcoming technologies (of similar price) reduce vector populations by 70–90%, the cost per disability-adjusted life year averted is 2013 US$ 679–1331 (best estimates) relative to no intervention. Sustained vector control could be highly cost-effective even with less effective technologies (50–70% reduction in vector populations) and in the presence of a highly targeted and low cost immunization strategy using a medium-efficacy vaccine. Discussion Economic evaluation of the first-ever dengue vaccine is ongoing. However, even under very optimistic assumptions about a highly targeted and low cost immunization strategy, our results suggest that sustained vector control will continue to play an important role in mitigating the impact of environmental change and urbanization on human health. If additional benefits for the control of other Aedes borne diseases, such as Chikungunya, yellow fever and Zika fever are taken into account, the investment case is even stronger. High-burden endemic countries should proceed to map populations to be covered by sustained vector control.

Title: A epidemia de zika e os limites da saúde global
Authors: Nunes, João; Pimenta, Denise Nacif
Abstract: O vírus Zika foi isolado pela primeira vez em 1947 em Uganda. Se a doença existe desde então, por que somente agora há atenção da mídia, da ciência, das agências financiadoras e dos órgãos nacionais e internacionais? A partir de uma visão crítica da saúde global, que considera os contextos sociais, políticos e ideológicos, nos quais a Zika é enquadrada, almeja-se analisar a atual epidemia de Zika em quatro eixos: (1) investigação dos processos sociais, culturais e políticos; (2) análise das práticas de significação; (3) estudo das zonas negligenciadas/silenciadas; e (4) atenção à diversidade de experiências individuais de saúde e de doença. As tensões políticas aqui identificadas e discutidas – referentes ao controle das doenças negligenciadas, determinantes sociais, de classe e de gênero – enquadram-se em dinâmicas que ultrapassam as fronteiras nacionais. Nesse sentido, os processos de significação e as respostas dadas à epidemia mostram os atuais limites da saúde global.

by Evlyn Pless, Andrea Gloria-Soria, Benjamin R. Evans, Vicki Kramer, Bethany G. Bolling, Walter J. Tabachnick, Jeffrey R. Powell

The yellow fever mosquito Aedes aegypti inhabits much of the tropical and subtropical world and is a primary vector of dengue, Zika, and chikungunya viruses. Breeding populations of A. aegypti were first reported in California (CA) in 2013. Initial genetic analyses using 12 microsatellites on collections from Northern CA in 2013 indicated the South Central US region as the likely source of the introduction. We expanded genetic analyses of CA A. aegypti by: (a) examining additional Northern CA samples and including samples from Southern CA, (b) including more southern US populations for comparison, and (c) genotyping a subset of samples at 15,698 SNPs. Major results are: (1) Northern and Southern CA populations are distinct. (2) Northern populations are more genetically diverse than Southern CA populations. (3) Northern and Southern CA groups were likely founded by two independent introductions which came from the South Central US and Southwest US/northern Mexico regions respectively. (4) Our genetic data suggest that the founding events giving rise to the Northern CA and Southern CA populations likely occurred before the populations were first recognized in 2013 and 2014, respectively. (5) A Northern CA population analyzed at multiple time-points (two years apart) is genetically stable, consistent with permanent in situ breeding. These results expand previous work on the origin of California A. aegypti with the novel finding that this species entered California on multiple occasions, likely some years before its initial detection. This work has implications for mosquito surveillance and vector control activities not only in California but also in other regions where the distribution of this invasive mosquito is expanding.

by Jing Hua Zhang, Juan Yuan, Tao Wang
Background Zhongshan City of Guangdong Province (China) is a key provincial and national level area for dengue fever prevention and control. The aim of this study is to analyze how the direct hospitalization costs and the length of stay of dengue hospitalization cases vary according to associated factors such as the demographics, virus types and hospital accreditation. Method This study is based on retrospective census data from the Chinese National Disease Surveillance Reporting System. Totally, the hospital administrative data of 1432 confirmed dengue inpatients during 2013–2014 was obtained. A quantile regression model was applied to analyze how the direct cost of Dengue hospitalization varies with the patient demographics and hospital accreditation across the data distribution. The Length of Stay (LOS) was also examined. Main findings The average direct hospitalization cost of a dengue case in this study is US$ 499.64 during 2013, which corresponded to about 3.71% of the gross domestic product per capita in Zhongshan that year. The mean of the Length of Stay (LOS) is 7.2 days. The multivariate quantile regression results suggest that, after controlling potential compounding variables, the median hospitalization costs of male dengue patients were significantly higher than female ones by about US$ 18.23 (p

by Huaiyu Tian, Zhe Sun, Nuno Rodrigues Faria, Jing Yang, Bernard Cazelles, Shanqian Huang, Bo Xu, Qiqi Yang, Oliver G. Pybus, Bing Xu

The incidence of dengue has grown dramatically in recent decades worldwide, especially in Southeast Asia and the Americas with substantial transmission in 2014–2015. Yet the mechanisms underlying the spatio-temporal circulation of dengue virus (DENV) serotypes at large geographical scales remain elusive. Here we investigate the co-circulation in Asia of DENV serotypes 1–3 from 1956 to 2015, using a statistical framework that jointly estimates migration history and quantifies potential predictors of viral spatial diffusion, including socio-economic, air transportation and maritime mobility data. We find that the spread of DENV-1, -2 and -3 lineages in Asia is significantly associated with air traffic. Our analyses suggest the network centrality of air traffic hubs such as Thailand and India contribute to seeding dengue epidemics, whilst China, Cambodia, Indonesia, and Singapore may establish viral diffusion links with multiple countries in Asia. Phylogeographic reconstructions help to explain how growing air transportation networks could influence the dynamics of DENV circulation.