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Author(s): Jacob, Christopher G; Thuy-Nhien, Nguyen; Mayxay, Mayfong; Maude, Richard J; Quang, Huynh Hong; Hongvanthong, Bouasy; Vanisaveth, Viengxay; Ngo Duc, Thang; Rekol, Huy; van der Pluijm, Rob; von Seidlein, Lorenz; Fairhurst, Rick; Nosten, Francois; Hossain, Md Amir; Park, Naomi; Goodwin, Scott; Ringwald, Pascal; Chindavongsa, Keobouphaphone; Newton, Paul; Ashley, Elizabeth; Phalivong, Sonexay; Maude, Rapeephan; Leang, Rithea; Huch, Cheah; Dong, Le Thanh; Nguyen, Kim-Tuyen; Nhat, Tran Minh; Hien, Tran Tinh; Nguyen, Hoa; Zdrojewski, Nicole; Canavati, Sara; Sayeed, Abdullah Abu; Uddin, Didar; Buckee, Caroline; Fanello, Caterina I; Onyamboko, Marie; Peto, Thomas; Tripura, Rupam; Amaratunga, Chanaki; Myint Thu, Aung; Delmas, Gilles; Landier, Jordi; Parker, Daniel M; Chau, Nguyen Hoang; Lek, Dysoley; Suon, Seila; Callery, James; Jittamala, Podjanee; Hanboonkunupakarn, Borimas; Pukrittayakamee, Sasithon; Phyo, Aung Pyae; Smithuis, Frank; Lin, Khin; Thant, Myo; Hlaing, Tin Maung; Satpathi, Parthasarathi; Satpathi, Sanghamitra; Behera, Prativa K; Tripura, Amar; Baidya, Subrata; Valecha, Neena; Anvikar, Anupkumar R; Ul Islam, Akhter; Faiz, Abul; Kunasol, Chanon; Drury, Eleanor; Kekre, Mihir; Ali, Mozam; Love, Katie; Rajatileka, Shavanthi; Jeffreys, Anna E; Rowlands, Kate; Hubbart, Christina S; Dhorda, Mehul; Vongpromek, Ranitha; Kotanan, Namfon; Wongnak, Phrutsamon; Almagro Garcia, Jacob; Pearson, Richard D; Ariani, Cristina V; Chookajorn, Thanat; Malangone, Cinzia; Nguyen, T; Stalker, Jim; Jeffery, Ben | Abstract: BackgroundNational Malaria Control Programmes (NMCPs) currently make limited use of parasite genetic data. We have developed GenRe-Mekong, a platform for genetic surveillance of malaria in the Greater Mekong Subregion (GMS) that enables NMCPs to implement large-scale surveillance projects by integrating simple sample collection procedures in routine public health procedures.MethodsSamples from symptomatic patients are processed by SpotMalaria, a high-throughput system that produces a comprehensive set of genotypes comprising several drug resistance markers, species markers and a genomic barcode. GenRe-Mekong delivers Genetic Report Cards, a compendium of genotypes and phenotype predictions used to map prevalence of resistance to multiple drugs.ResultsGenRe-Mekong has worked with NMCPs and research projects in eight countries, processing 9623 samples from clinical cases. Monitoring resistance markers has been valuable for tracking the rapid spread of parasites resistant to the dihydroartemisinin-piperaquine combination therapy. In Vietnam and Laos, GenRe-Mekong data have provided novel knowledge about the spread of these resistant strains into previously unaffected provinces, informing decision-making by NMCPs.ConclusionsGenRe-Mekong provides detailed knowledge about drug resistance at a local level, and facilitates data sharing at a regional level, enabling cross-border resistance monitoring and providing the public health community with valuable insights. The project provides a rich open data resource to benefit the entire malaria community.FundingThe GenRe-Mekong project is funded by the Bill and Melinda Gates Foundation (OPP11188166, OPP1204268). Genotyping and sequencing were funded by the Wellcome Trust (098051, 206194, 203141, 090770, 204911, 106698/B/14/Z) and Medical Research Council (G0600718). A proportion of samples were collected with the support of the UK Department for International Development (201900, M006212), and Intramural Research Program of the National Institute of Allergy and Infectious Diseases.

Global urbanization is leading to an inexorable spread of several major diseases that need to be stemmed. Dengue is one of these major diseases spreading in cities today, with its principal mosquito vector superbly adapted to the urban environment. Current mosquito control strategies are proving inadequate, especially in the face of such urbanisation and novel, evidence-based targeted approaches are needed. Through combined epidemiological and entomological approaches, we aimed to identify a novel sanitation strategy to alleviate the burden of dengue through how the dengue virus spreads through the community. We combined surveillance case mapping, prospective serological studies, year-round mosquito surveys, socio-economic and Knowledge Attitudes and Practices surveys across Delhi. We identified lack of access to tap water (≤98%) as an important risk factor for dengue virus IgG sero-positivity (adjusted Odds Ratio 4.69, 95% C.I. 2.06–10.67) and not poverty per se. Wealthier districts had a higher dengue burden despite lower mosquito densities than the Intermediary income communities (adjusted Odds Ratio 2.92, 95% C.I. 1.26–6.72). This probably reflects dengue being introduced by people travelling from poorer areas to work in wealthier houses. These poorer, high density areas, where temperatures are also warmer, also had dengue cases during the winter. Control strategies based on improved access to a reliable supply of tap water plus focal intervention in intra-urban heat islands prior to the dengue season could not only lead to a reduction in mosquito abundance but also eliminate the reservoir of dengue virus clearly circulating at low levels in winter in socio-economically disadvantaged areas., Author summary Identifying disease hotspots and individual risk factors for dengue can enable targeted intervention strategies. We conducted combined serological, entomological and socio-economic surveys across 18 areas within Delhi, taken from the total 1280 colonies (i.e. the administrative units of reference in Delhi) for which we classified their socio-economic typology. We additionally performed a Knowledge, Attitudes, Practices survey at a household level within the most socially disadvantaged sub-districts. Finally, we mapped all the winter dengue cases to 250 m x 250 m units along with their winter mean temperatures. We found that access to tap water was an important risk factor for exposure to dengue virus (DENV) and this was confirmed even within the socially disadvantaged sub-districts. The Wealthy colonies had a high burden of DENV infection despite low mosquito densities, likely linked to their connectedness through daily human mobility. The winter burden of dengue occurred majoritarily in the socio-economically disadvantaged colonies, which also have higher mean temperatures and urban heat islands. Improved access to tap water could lead to a reduction in dengue, not only for those directly affected but for the general population. Targeted intervention through mosquito control in winter in the socially disadvantaged areas could offer a rational strategy for optimising control efforts.

International audience; Delhi, the capital of India, is an important metropolitan hub for major financial and sociocultural exchanges, offering challenging threats to current public health infrastructure. In recent past, an upsurge of dengue cases in Delhi posed a significant menace to the existing dengue control policies. To reform the control strategies and take timely intervention to prevent future epidemics, an epidemiological study on the proportion of both asymptomatic and symptomatic dengue infections in selected population was conducted. The aim of the study was to investigate and assess the epidemiology of dengue infection and to estimate the proportion of asymptomatic and symptomatic dengue infections in Delhi. In this study, around 50 confirmed dengue cases, a total of 2125 individuals as household and neighbourhood contacts, with or without dengue febrile illness, were finger pricked and serologically detected as dengue positive or negative using SD Duo Bioline Rapid Diagnostic Test (SD Inc, Korea) with NS1, IgM & IgG combo test, which detected dengue virus antigen and antibodies to dengue virus in human blood. Out of 2125 individuals , 768 (36.1%) individuals showed positive dengue test with past (25.5%), primary (1.88%) or secondary (8.8%) dengue infections. Higher percentage of IgG was found in age groups 15–24 years and 25–50 years (36% each). Infants (

International audience; Background: Dengue is a major international public health concern, one of the most important arthropod-borne diseases. More than 3.5 billion people are at risk of dengue infection and there are an estimated 390 million dengue infections annually. This prolific increase has been connected to societal changes such as population growth and increasing urbanization generating intense agglomeration leading to proliferation of synanthropic mosquito species. Quantifying the spatio-temporal epidemiology of dengue in large cities within the context of a Geographic Information System is a first step in the identification of socio-economic risk factors.Methodology/Principal Findings: This Project has been approved by the ethical committee of Institut Pasteur. Data has been anonymized and de-identified prior to geolocalisation and analysis. A GIS was developed for Delhi, enabling typological characterization of the urban environment. Dengue cases identified in the Delhi surveillance system from 2008 to 2010 were collated, localised and embedded within this GIS. The spatio-temporal distribution of dengue cases and extent of clustering were analyzed. Increasing distance from the forest in Delhi reduced the risk of occurrence of a dengue case. Proximity to a hospital did not increase risk of a notified dengue case. Overall, there was high heterogeneity in incidence rate within areas with the same socio-economical profiles and substantial inter-annual variability. Dengue affected the poorest areas with high density of humans, but rich areas were also found to be infected, potentially because of their central location with respect to the daily mobility network of Delhi. Dengue cases were highly clustered in space and there was a strong relationship between the time of introduction of the virus and subsequent cluster size. At a larger scale, earlier introduction predicted the total number of cases.Conclusions/Significance: DENV epidemiology within Delhi has a forest fire signature. The stochastic nature of this invasion process likely smothers any detectable socio-economic risk factors. However, the significant finding that the size of the dengue case cluster depends on the timing of its emergence emphasizes the need for early case detection and implementation of effective mosquito control. A better understanding of the role of population mobility in contributing to dengue risk could also help focus control on areas at particular risk of dengue virus importation.