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Background: Spatial modelling of STH and schistosomiasis epidemiology is now commonplace. Spatial epidemiological studies help inform decisions regarding the number of people at risk as well as the geographic areas that need to be targeted with mass drug administration; however, limited attention has been given to propagated uncertainties, their interpretation, and consequences for the mapped values. Using currently published literature on the spatial epidemiology of helminth infections we identified: (1) the main uncertainty sources, their definition and quantification and (2) how uncertainty is informative for STH programme managers and scientists working in this domain. Methodology/Principal Findings: We performed a systematic literature search using the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) protocol. We searched Web of Knowledge and PubMed using a combination of uncertainty, geographic and disease terms. A total of 73 papers fulfilled the inclusion criteria for the systematic review. Only 9% of the studies did not address any element of uncertainty, while 91% of studies quantified uncertainty in the predicted morbidity indicators and 23% of studies mapped it. In addition, 57% of the studies quantified uncertainty in the regression coefficients but only 7% incorporated it in the regression response variable (morbidity indicator). Fifty percent of the studies discussed uncertainty in the covariates but did not quantify it. Uncertainty was mostly defined as precision, and quantified using credible intervals by means of Bayesian approaches. Conclusion/Significance: None of the studies considered adequately all sources of uncertainties. We highlighted the need for uncertainty in the morbidity indicator and predictor variable to be incorporated into the modelling framework. Study design and spatial support require further attention and uncertainty associated with Earth observation data should be quantified. Finally, more attention should be given to mapping and interpreting uncertainty, since they are relevant to inform decisions regarding the number of people at risk as well as the geographic areas that need to be targeted with mass drug administration. [ABSTRACT FROM AUTHOR]

Background: There is no point of care diagnostic test for infection with M. Leprae or for leprosy, although ELISA anti PGL-1 has been considered and sometimes used as a means to identify infection. Methods: A systematic review of all cohort studies, which classified healthy leprosy contacts, at entry, according to anti-PGL1 positivity, and had at least one year follow up. The outcome was clinical diagnosis of leprosy by an experienced physician. The meta-analysis used a fixed model to estimated OR for the association of PGL-1 positivity and clinical leprosy. A fixed model also estimated the sensibility of PGL-1 positivity and positive predictive value. Results: Contacts who were anti PGL-1 positive at baseline were 3 times as likely to develop leprosy; the proportion of cases of leprosy that were PGL-1 positive at baseline varied but was always under 50%. Conclusions: Although there is a clear and consistent association between positivity to anti PGL-1 and development of leprosy in healthy contacts, selection of contacts for prophylaxis based on anti PGL1 response would miss more than half future leprosy cases. Should chemoprophylaxis of controls be incorporated into leprosy control programmes, PGL1 appears not to be a useful test in the decision of which contacts should receive chemoprophylaxis. [ABSTRACT FROM AUTHOR]

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

Background: Taenia solium, a pork-borne parasitic zoonosis, is the cause of taeniasis and cysticercosis in humans. In Vietnam, poor sanitation, the practice of outdoor defecation and consumption of raw/undercooked pork have been associated with infection/exposure to T. solium in both humans and pigs. The broad-scale geographic distribution of the prevalence of T. solium varies throughout the country with infection restricted to isolated foci in the north and a more sporadic geographic distribution in the Central Highlands and the south. While cross-sectional studies have allowed the broad-scale geographic distribution of T. solium to be described, details of the geographic distribution of T. solium at finer spatial scales have not been described in detail. This study provides a descriptive spatial analysis of T. solium exposure in humans and pigs and T. solium taeniasis in humans within individual households in village communities of Dak Lak in the Central Highlands of Vietnam. Methodology/Principal findings: We used Ripley’s K-function to describe spatial dependence in T. solium exposure positive and negative human and pig households and T. solium taeniasis exposure positive and negative households in villages within the districts of Buon Don, Krong Nang and M’Drak of Dak Lak province in the Central Highlands of Vietnam. The prevalence of exposure to T. solium in pigs in Dak Lak province was 9 (95% CI 5 to 17) cases per 1000 pigs at risk. The prevalence of exposure to the parasite in humans was somewhat higher at 5 (95% CI 3 to 8) cases per 100 individuals at risk. Spatial aggregations of T. solium exposure-positive pig and human households occurred in some, but not all of the villages in the three study districts. Human exposure-positive households were found to be aggregated within a distance of 200 to 300 m in villages in Krong Nang district compared with distances of up to 1200 m in villages in M’Drak district. Although this study demonstrated the aggregation of households in which either T. solium exposure- or taeniasis-positive individuals were present, we were unable to identify an association between the two due to the very low number of T. solium taeniasis-positive households. Conclusions: Spatial aggregations of T. solium exposure-positive pig and human households occurred in some, but not all of the villages in the three study districts. We were unable to definitively identify reasons for these findings but speculate that they were due to a combination of demographic, anthropological and micro-environmental factors. To more definitively identify characteristics that increase cysticercosis risk we propose that cross-sectional studies similar in design to that described in this paper should be applied in other provinces of Vietnam. [ABSTRACT FROM AUTHOR]

Transmission of zoonotic cutaneous leishmaniasis (ZCL) depends on the presence, density and distribution of Leishmania major rodent reservoir and the development of these rodents is known to have a significant dependence onenvironmental and climate factors. ZCL in Tunisia is one of the most common forms of leishmaniasis. The aim of this paper was to build a regression model of ZCL cases to identify the relationship between ZCL occurrence and possible risk factors, and to develop a predicting model for ZCL's control and prevention purposes. Monthly reported ZCL cases, environmental and bioclimatic data were collected over 6 years (2009–2015). Three rural areas in the governorate of Sidi Bouzid were selected as the study area. Cross-correlation analysis was used to identify the relevant lagged effects of possible risk factors, associated with ZCL cases. Non-parametric modeling techniques known as generalized additive model (GAM) and generalized additive mixed models (GAMM) were applied in this work. These techniques have the ability to approximate the relationship between the predictors (inputs) and the response variable (output), and express the relationship mathematically. The goodness-of-fit of the constructed model was determined by Generalized cross-validation (GCV) score and residual test. There were a total of 1019 notified ZCL cases from July 2009 to June 2015. The results showed seasonal distribution of reported ZCL cases from August to January. The model highlighted that rodent density, average temperature, cumulative rainfall and average relative humidity, with different time lags, all play role in sustaining and increasing the ZCL incidence. The GAMM model could be applied to predict the occurrence of ZCL in central Tunisia and could help for the establishment of an early warning system to control and prevent ZCL in central Tunisia. [ABSTRACT FROM AUTHOR]

Epidemics of communicable diseases place a huge burden on public health infrastructures across the world. Producing accurate and actionable forecasts of infectious disease incidence at short and long time scales will improve public health response to outbreaks. However, scientists and public health officials face many obstacles in trying to create such real-time forecasts of infectious disease incidence. Dengue is a mosquito-borne virus that annually infects over 400 million people worldwide. We developed a real-time forecasting model for dengue hemorrhagic fever in the 77 provinces of Thailand. We created a practical computational infrastructure that generated multi-step predictions of dengue incidence in Thai provinces every two weeks throughout 2014. These predictions show mixed performance across provinces, out-performing seasonal baseline models in over half of provinces at a 1.5 month horizon. Additionally, to assess the degree to which delays in case reporting make long-range prediction a challenging task, we compared the performance of our real-time predictions with predictions made with fully reported data. This paper provides valuable lessons for the implementation of real-time predictions in the context of public health decision making. [ABSTRACT FROM AUTHOR]

Background: The Philippines is one of the developing countries highly affected by rabies. Dog vaccination campaigns implemented through collaborative effort between the government and NGOs have played an important role in successfully reducing the burden of disease within the country. Nevertheless, rabies vaccination of the domestic animal population requires continuous commitment not only from governments and NGOs, but also from local communities that are directly affected by such efforts. To create such long-term sustained programs, the introduction of affordable dog vaccination and registration fees is essential and has been shown to be an important strategy in Bohol, Philippines. The aim of this study, therefore, was to estimate the average amount of money that individuals were willing to pay for dog vaccination and registration in Ilocos Norte, Philippines. This study also investigated some of the determinants of individuals’ willingness to pay (WTP). Methods: A cross-sectional questionnaire was administered to 300 households in 17 municipalities (out of a total of 21) selected through a multi-stage cluster survey technique. At the time of the survey, Ilocos Norte had a population of approximately 568,017 and was predominantly rural. The Contingent Valuation Method was used to elicit WTP for dog rabies vaccination and registration. A ‘bidding game’ elicitation strategy that aims to find the maximum amount of money individuals were willing to pay was also employed. Data were collected using paper-based questionnaires. Linear regression was used to examine factors influencing participants’ WTP for dog rabies vaccination and registration. Key Results: On average, Ilocos Norte residents were willing to pay 69.65 Philippine Pesos (PHP) (equivalent to 1.67 USD in 2012) for dog vaccination and 29.13PHP (0.70 USD) for dog registration. Eighty-six per cent of respondents were willing to pay the stated amount to vaccinate each of their dogs, annually. This study also found that WTP was influenced by demographic and knowledge factors. Among these, we found that age, income, participants’ willingness to commit to pay each year, municipality of residency, knowledge of the signs of rabies in dogs, and number of dogs owed significantly predicted WTP. [ABSTRACT FROM AUTHOR]

Background: As of February 25, 2019, 875 cases of Ebola virus disease (EVD) were reported in North Kivu and Ituri Provinces, Democratic Republic of Congo. Since the beginning of October 2018, the outbreak has largely shifted into regions in which active armed conflict has occurred, and in which EVD cases and their contacts have been difficult for health workers to reach. We used available data on the current outbreak, with case-count time series from prior outbreaks, to project the short-term and long-term course of the outbreak. Methods: For short- and long-term projections, we modeled Ebola virus transmission using a stochastic branching process that assumes gradually quenching transmission rates estimated from past EVD outbreaks, with outbreak trajectories conditioned on agreement with the course of the current outbreak, and with multiple levels of vaccination coverage. We used two regression models to estimate similar projection periods. Short- and long-term projections were estimated using negative binomial autoregression and Theil-Sen regression, respectively. We also used Gott’s rule to estimate a baseline minimum-information projection. We then constructed an ensemble of forecasts to be compared and recorded for future evaluation against final outcomes. From August 20, 2018 to February 25, 2019, short-term model projections were validated against known case counts. Results: During validation of short-term projections, from one week to four weeks, we found models consistently scored higher on shorter-term forecasts. Based on case counts as of February 25, the stochastic model projected a median case count of 933 cases by February 18 (95% prediction interval: 872–1054) and 955 cases by March 4 (95% prediction interval: 874–1105), while the auto-regression model projects median case counts of 889 (95% prediction interval: 876–933) and 898 (95% prediction interval: 877–983) cases for those dates, respectively. Projected median final counts range from 953 to 1,749. Although the outbreak is already larger than all past Ebola outbreaks other than the 2013–2016 outbreak of over 26,000 cases, our models do not project that it is likely to grow to that scale. The stochastic model estimates that vaccination coverage in this outbreak is lower than reported in its trial setting in Sierra Leone. Conclusions: Our projections are concentrated in a range up to about 300 cases beyond those already reported. While a catastrophic outbreak is not projected, it is not ruled out, and prevention and vigilance are warranted. Prospective validation of our models in real time allowed us to generate more accurate short-term forecasts, and this process may prove useful for future real-time short-term forecasting. We estimate that transmission rates are higher than would be seen under target levels of 62% coverage due to contact tracing and vaccination, and this model estimate may offer a surrogate indicator for the outbreak response challenges. [ABSTRACT FROM AUTHOR]

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

Background: Individual helminth infections are ubiquitous in the tropics; geographical overlaps in endemicity and epidemiological reports suggest areas endemic for multiple helminthiases are also burdened with high prevalences of intestinal protozoan infections, malaria, tuberculosis (TB), and human immunodeficiency virus (HIV). Despite this, pathogens tend to be studied in isolation, and there remains a need for a better understanding of the community ecology and health consequences of helminth polyparasitism to inform the design of effective parasite control programs. Methodology: We performed meta-analyses to (i) evaluate the commonality of polyparasitism for helminth-helminth, helminth-intestinal protozoa, helminth-malaria, helminth-TB, and helminth-HIV co-infections, (ii) assess the potential for interspecies interactions among helminth-helminth and helminth-intestinal protozoan infections, and (iii) determine the presence and magnitude of association between specific parasite pairs. Additionally, we conducted a review of reported health consequences of multiply-infected individuals compared to singly- or not multiply-infected individuals. Principal findings: We found that helminth-helminth and helminth-intestinal protozoan multiple infections were significantly more common than single infections, while individuals with malaria, TB, and HIV were more likely to be singly-infected with these infections than co-infected with at least one helminth. Most observed species density distributions significantly differed from the expected distributions, suggesting the potential presence of interspecies interactions. All significant associations between parasite pairs were positive in direction, irrespective of the combination of pathogens. Polyparasitized individuals largely exhibited lower hemoglobin levels and higher anemia prevalence, while the differences in growth-related variables were mostly statistically insignificant. Conclusions: Our findings confirm that helminth polyparasitism and co-infection with major diseases is common in the tropics. A multitude of factors acting at various hierarchical levels, such as interspecies interactions at the within-host infra-parasite community level and environmental variables at the higher host community level, could explain the observed positive associations between pathogens; there remains a need to develop new frameworks which can consider these multilevel factors to better understand the processes structuring parasite communities to accomplish their control. [ABSTRACT FROM AUTHOR]

Rabies remains a disease of significant zoonotic and economic concern in rabies endemic areas of Bhutan. Rabies outbreaks in livestock threaten the livelihoods of subsistent farming communities and pose a potential public health threat. As a part of identifying approaches to prevent rabies in cattle, a Knowledge, Attitude, and Practice (KAP) survey was conducted among cattle owners in selected rural areas of the southern rabies high-risk zone and low-risk zone in eastern Bhutan. Between March and April 2017, 562 cattle owners (281 in the east and 281 in the south) were interviewed using a questionnaire. Eighty-eight percent of the participants had heard of rabies but only 39% of the participants who had heard of rabies had adequate knowledge about rabies. Multivariable logistic regression analysis showed that residing in the south [OR = 9.25 (95% CI: 6.01–14.53)] and having seen a rabies case [OR = 2.46 (95% CI: 1.6–3.82)] were significantly associated with having adequate knowledge about rabies. Based on our scoring criteria, 65% of the total participants who had heard of rabies had a favorable attitude towards rabies control and prevention programs. The participants residing in the east were two times more likely to have a favourable attitude than their counterparts in the south [OR = 2.08 (95% CI: 1.43–3.05)]. More than 70% of the participants reported engaging in farm activities such as examining the oral cavity of sick cattle and assisting cattle during parturition. Only 25% of the participants reported using personal protective equipment while undertaking these activities. Despite a high level of rabies awareness, we observed that there is a lack of comprehensive knowledge about rabies regarding susceptible hosts, transmission routes, the health outcome of rabies infection in humans, and appropriate health-seeking behaviours. This study highlights the need to strengthen rabies education programs in rural communities to address the knowledge gaps that have been identified. [ABSTRACT FROM AUTHOR]

Introduction: Brucellosis and leptospirosis are among neglected tropical zoonotic diseases particularly in the resource limited countries. Despite being endemic in these countries, there is paucity of information on its magnitude. This study investigated seropositivity of Brucella spp. and Leptospira spp., and associated factors among abattoir workers and meat vendors in the city of Mwanza, Tanzania. Methodology: A community based cross-sectional study was conducted in Mwanza city from May to July 2017. Socio-demographic and other relevant information were collected. Detection of Brucella spp. and Leptospira spp. antibodies were done using slide agglutination test and microscopic agglutination test, respectively. Data were analyzed using STATA version 13 Software. Findings: A total of 250 participants (146 abattoir workers and 104 meat vendors) were enrolled with median age of 31 (IQR: 25–38) years. The overall, seropositivity of Brucella spp. antibodies was 48.4% (95% Cl: 42–54). Seropositivity of B. abortus was significantly higher than that of B. melitensis (46.0%, 95%Cl: 39–52 vs. 23.6%, 95% Cl: 18–28, P<0.001) while seropositivity of both species was 21.2% (95%Cl: 16–26). The seropositivity of Leptospira spp. was 10.0% (95% CI: 6–13) with predominance of Leptospira kirschneri serovar Sokoine which was detected in 7.2% of the participants. Being abattoir worker (OR: 2.19, 95% CI 1.06–4.54, p = 0.035) and long work duration (OR: 1.06, 95%CI: 1.01–1.11, p = 0.014) predicted presence of both B.abortus and B. melitensis antibodies. Only being married (p = 0.041) was significantly associated with seropositivity of Leptospira spp. Primary education was the only factor independently predicted presence of Brucella spp. antibodies among abattoir workers on sub-analysis of occupational exposure. None of factors were found to be associated with presence of Brucella spp. antibodies among meat vendors on sub-analysis. Conclusion: Seropositivity of B.abortus antibodies among abattoir workers and meat vendors is high and seem to be a function of being abattoir worker, having worked for long duration in the abattoir and having primary education. In addition, a significant proportion of abattoir workers and meat vendors in the city was seropositive for Leptospira kirschneri serovar Sokoine. There is a need to consider ‘one health approach’ in devising appropriate strategies to control these diseases in the developing countries. [ABSTRACT FROM AUTHOR]

Model-based epidemiological assessment is useful to support decision-making at the beginning of an emerging Aedes-transmitted outbreak. However, early forecasts are generally unreliable as little information is available in the first few incidence data points. Here, we show how past Aedes-transmitted epidemics help improve these predictions. The approach was applied to the 2015–2017 Zika virus epidemics in three islands of the French West Indies, with historical data including other Aedes-transmitted diseases (Chikungunya and Zika) in the same and other locations. Hierarchical models were used to build informative a priori distributions on the reproduction ratio and the reporting rates. The accuracy and sharpness of forecasts improved substantially when these a priori distributions were used in models for prediction. For example, early forecasts of final epidemic size obtained without historical information were 3.3 times too high on average (range: 0.2 to 5.8) with respect to the eventual size, but were far closer (1.1 times the real value on average, range: 0.4 to 1.5) using information on past CHIKV epidemics in the same places. Likewise, the 97.5% upper bound for maximal incidence was 15.3 times (range: 2.0 to 63.1) the actual peak incidence, and became much sharper at 2.4 times (range: 1.3 to 3.9) the actual peak incidence with informative a priori distributions. Improvements were more limited for the date of peak incidence and the total duration of the epidemic. The framework can adapt to all forecasting models at the early stages of emerging Aedes-transmitted outbreaks. [ABSTRACT FROM AUTHOR]

Background: Evidence from recent studies assessing the impact of school water, sanitation and hygiene (WASH) interventions on child health has been mixed. Self-reports of disease are subject to bias, and few WASH impact evaluations employ objective health measures to assess reductions in disease and exposure to pathogens. We utilized antibody responses from dried blood spots (DBS) to measure the impact of a school WASH intervention on infectious disease among pupils in Mali. Methodology/Principal findings: We randomly selected 21 beneficiary primary schools and their 21 matched comparison schools participating in a matched-control trial of a comprehensive school-based WASH intervention in Mali. DBS were collected from 20 randomly selected pupils in each school (n = 807). We analyzed eluted IgG from the DBS using a Luminex multiplex bead assay to 28 antigens from 17 different pathogens. Factor analysis identified three distinct latent variables representing vector-transmitted disease (driven primarily by dengue), food/water-transmitted enteric disease (driven primarily by Escherichia coli and Vibrio cholerae), and person-to-person transmitted enteric disease (driven primarily by norovirus). Data were analyzed using a linear latent variable model. Antibody evidence of food/water-transmitted enteric disease (change in latent variable mean (β) = -0.24; 95% CI: -0.53, -0.13) and person-to-person transmitted enteric disease (β = -0.17; 95% CI: -0.42, -0.04) was lower among pupils attending beneficiary schools. There was no difference in antibody evidence of vector-transmitted disease (β = 0.11; 95% CI: -0.05, 0.33). Conclusions/Significance: Evidence of enteric disease was lower among pupils attending schools benefitting from school WASH improvements than students attending comparison schools. These findings support results from the parent study, which also found reduced incidence of self-reported diarrhea among pupils of beneficiary schools. DBS collection was feasible in this resource-poor field setting and provided objective evidence of disease at a low cost per antigen analyzed, making it an effective measurement tool for the WASH field. Trial registration: The trial was registered at ClinicalTrials.gov () [ABSTRACT FROM AUTHOR]

Background: Diagnosing scrub typhus clinically is difficult, hence laboratory tests play a very important role in diagnosis. As performing sophisticated laboratory tests in resource-limited settings is not feasible, accurate point-of-care testing (POCT) for scrub typhus diagnosis would be invaluable for patient diagnosis and management. Here we summarise the existing evidence on the accuracy of scrub typhus POCTs to inform clinical practitioners in resource-limited settings of their diagnostic value. Methodology/principal findings: Studies on POCTs which can be feasibly deployed in primary health care or outpatient settings were included. Thirty-one studies were identified through PubMed and manual searches of reference lists. The quality of the studies was assessed with the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). About half (n = 14/31) of the included studies were of moderate quality. Meta-analysis showed the pooled sensitivity and specificity of commercially available immunochromatographic tests (ICTs) were 66.0% (95% CI 0.37–0.86) and 92.0% (95% CI 0.83–0.97), respectively. There was a significant and high degree of heterogeneity between the studies (I2 value = 97.48%, 95% CI 96.71–98.24 for sensitivity and I2 value = 98.17%, 95% CI 97.67–98.67 for specificity). Significant heterogeneity was observed for total number of samples between studies (p = 0.01), study design (whether using case-control design or not, p = 0.01), blinding during index test interpretation (p = 0.02), and QUADAS-2 score (p = 0.01). Conclusions/significance: There was significant heterogeneity between the scrub typhus POCT diagnostic accuracy studies examined. Overall, the commercially available scrub typhus ICTs demonstrated better performance when ‘ruling in’ the diagnosis. There is a need for standardised methods and reporting of diagnostic accuracy to decrease between-study heterogeneity and increase comparability among study results, as well as development of an affordable and accurate antigen-based POCT to tackle the inherent weaknesses associated with serological testing. [ABSTRACT FROM AUTHOR]

Few animal models of Zika virus (ZIKV) infection have incorporated arthropod-borne transmission. Here, we establish an Aedes aegypti mosquito model of ZIKV infection of mice, and demonstrate altered vector competency among three strains, (Orlando, ORL, Ho Chi Minh, HCM, and Patilas, PAT). All strains acquired ZIKV in their midguts after a blood meal from infected mice, but ZIKV transmission only occurred in mice fed upon by HCM, and to a lesser extent PAT, but not ORL, mosquitoes. This defect in transmission from ORL or PAT mosquitoes was overcome by intrathoracic injection of ZIKV into mosquito. Genetic analysis revealed significant diversity among these strains, suggesting a genetic basis for differences in ability for mosquito strains to transmit ZIKV. The intrathoracic injection mosquito-mouse transmission model is critical to understanding the influence of mosquitoes on ZIKV transmission, infectivity and pathogenesis in the vertebrate host, and represents a natural transmission route for testing vaccines and therapeutics. (152 words) [ABSTRACT FROM AUTHOR]

The increasing spread of the Asian tiger mosquito, Aedes albopictus, in Europe and US raises public health concern due to the species competence to transmit several exotic human arboviruses, among which dengue, chikungunya and Zika, and urges the development of suitable modeling approach to forecast the spatial and temporal distribution of the mosquito. Here we developed a dynamical species distribution modeling approach forecasting Ae. albopictus eggs abundance at high spatial (0.01 degree WGS84) and temporal (weekly) resolution over 10 Balkan countries, using temperature times series of Modis data products and altitude as input predictors. The model was satisfactorily calibrated and validated over Albania based observed eggs abundance data weekly monitored during three years. For a given week of the year, eggs abundance was mainly predicted by the number of eggs and the mean temperature recorded in the preceding weeks. That is, results are in agreement with the biological cycle of the mosquito, reflecting the effect temperature on eggs spawning, maturation and hatching. The model, seeded by initial egg values derived from a second model, was then used to forecast the spatial and temporal distribution of eggs abundance over the selected Balkan countries, weekly in 2011, 2012 and 2013. The present study is a baseline to develop an easy-handling forecasting model able to provide information useful for promoting active surveillance and possibly prevention of Ae. albopictus colonization in presently non-infested areas in the Balkans as well as in other temperate regions. [ABSTRACT FROM AUTHOR]

Background: Severe dengue infection often has unpredictable clinical progressions and outcomes. Obesity may play a role in the deterioration of dengue infection due to stronger body immune responses. Several studies found that obese dengue patients have a more severe presentation with a poorer prognosis. However, the association was inconclusive due to the variation in the results of earlier studies. Therefore, we conducted a systematic review and meta-analysis to explore the relationship between obesity and dengue severity. Methods: We performed a systematic search of relevant studies on Ovid (MEDLINE), EMBASE, the Cochrane Library, Web of Science, Scopus and grey literature databases. At least two authors independently conducted the literature search, selecting eligible studies, and extracting data. Meta-analysis using random-effects model was conducted to compute the pooled odds ratio with 95% confidence intervals (CI). Findings: We obtained a total of 13,333 articles from the searches. For the final analysis, we included a total of fifteen studies among pediatric patients. Three cohort studies, two case-control studies, and one cross-sectional study found an association between obesity and dengue severity. In contrast, six cohort studies and three case-control studies found no significant relationship between obesity and dengue severity. Our meta-analysis revealed that there was 38 percent higher odds (Odds Ratio = 1.38; 95% CI:1.10, 1.73) of developing severe dengue infection among obese children compared to non-obese children. We found no heterogeneity found between studies. The differences in obesity classification, study quality, and study design do not modify the association between obesity and dengue severity. Conclusion: This review found that obesity is a risk factor for dengue severity among children. The result highlights and improves our understanding that obesity might influence the severity of dengue infection. [ABSTRACT FROM AUTHOR]

Background: Salmonella Typhi and Salmonella Paratyphi A are the agents of enteric (typhoid) fever; both can establish chronic carriage in the gallbladder. Chronic Salmonella carriers are typically asymptomatic, intermittently shedding bacteria in the feces, and contributing to disease transmission. Detecting chronic carriers is of public health relevance in areas where enteric fever is endemic, but there are no routinely used methods for prospectively identifying those carrying Salmonella in their gallbladder. Methodology/Principal findings: Here we aimed to identify biomarkers of Salmonella carriage using metabolite profiling. We performed metabolite profiling on plasma from Nepali patients undergoing cholecystectomy with confirmed S. Typhi or S. Paratyphi A gallbladder carriage (and non-carriage controls) using two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GCxGC-TOFMS) and supervised pattern recognition modeling. We were able to significantly discriminate Salmonella carriage samples from non-carriage control samples. We were also able to detect differential signatures between S. Typhi and S. Paratyphi A carriers. We additionally compared carriage metabolite profiles with profiles generated during acute infection; these data revealed substantial heterogeneity between metabolites associated with acute enteric fever and chronic carriage. Lastly, we found that Salmonella carriers could be significantly distinguished from non-carriage controls using only five metabolites, indicating the potential of these metabolites as diagnostic markers for detecting chronic Salmonella carriers. Conclusions/Significance: Our novel approach has highlighted the potential of using metabolomics to search for diagnostic markers of chronic Salmonella carriage. We suggest further epidemiological investigations of these potential biomarkers in alternative endemic enteric fever settings. [ABSTRACT FROM AUTHOR]

Internet-based surveillance methods for vector-borne diseases (VBDs) using “big data” sources such as Google, Twitter, and internet newswire scraping have recently been developed, yet reviews on such “digital disease detection” methods have focused on respiratory pathogens, particularly in high-income regions. Here, we present a narrative review of the literature that has examined the performance of internet-based biosurveillance for diseases caused by vector-borne viruses, parasites, and other pathogens, including Zika, dengue, other arthropod-borne viruses, malaria, leishmaniasis, and Lyme disease across a range of settings, including low- and middle-income countries. The fundamental features, advantages, and drawbacks of each internet big data source are presented for those with varying familiarity of “digital epidemiology.” We conclude with some of the challenges and future directions in using internet-based biosurveillance for the surveillance and control of VBD. [ABSTRACT FROM AUTHOR]

Host and parasite gene expression in skin biopsies from Leishmania braziliensis-infected patients were simultaneously analyzed using high throughput RNA-sequencing. Biopsies were taken from 8 patients with early cutaneous leishmaniasis and 17 patients with late cutaneous leishmaniasis. Although parasite DNA was found in all patient lesions at the time of biopsy, the patients could be stratified into two groups: one lacking detectable parasite transcripts (PTNeg) in lesions, and another in which parasite transcripts were readily detected (PTPos). These groups exhibited substantial differences in host responses to infection. PTPos biopsies contained an unexpected increase in B lymphocyte-specific and immunoglobulin transcripts in the lesions, and an upregulation of immune inhibitory molecules. Biopsies without detectable parasite transcripts showed decreased evidence for B cell activation, but increased expression of antimicrobial genes and genes encoding skin barrier functions. The composition and abundance of L. braziliensis transcripts in PTPos lesions were surprisingly conserved among all six patients, with minimal meaningful differences between lesions from patients with early and late cutaneous leishmaniasis. The most abundant parasite transcripts expressed in lesions were distinct from transcripts expressed in vitro in human macrophage cultures infected with L. amazonensis or L. major. Therefore in vitro gene expression in macrophage monolayers may not be a strong predictor of gene expression in lesions. Some of the most highly expressed in vivo transcripts encoded amastin-like proteins, hypothetical genes, putative parasite virulence factors, as well as histones and tubulin. In summary, RNA sequencing allowed us to simultaneously analyze human and L. braziliensis transcriptomes in lesions of infected patients, and identify unexpected differences in host immune responses which correlated with active transcription of parasite genes. [ABSTRACT FROM AUTHOR]

Background: Scrub typhus is endemic in the Asia-Pacific region including China, and the number of reported cases has increased dramatically in the past decade. However, the spatial-temporal dynamics and the potential risk factors in transmission of scrub typhus in mainland China have yet to be characterized. Objective: This study aims to explore the spatiotemporal dynamics of reported scrub typhus cases in mainland China between January 2006 and December 2014, to detect the location of high risk spatiotemporal clusters of scrub typhus cases, and identify the potential risk factors affecting the re-emergence of the disease. Method: Monthly cases of scrub typhus reported at the county level between 2006 and 2014 were obtained from the Chinese Center for Diseases Control and Prevention. Time-series analyses, spatiotemporal cluster analyses, and spatial scan statistics were used to explore the characteristics of the scrub typhus incidence. To explore the association between scrub typhus incidence and environmental variables panel Poisson regression analysis was conducted. Results: During the time period between 2006 and 2014 a total of 54,558 scrub typhus cases were reported in mainland China, which grew exponentially. The majority of cases were reported each year between July and November, with peak incidence during October every year. The spatiotemporal dynamics of scrub typhus varied over the study period with high-risk clusters identified in southwest, southern, and middle-eastern part of China. Scrub typhus incidence was positively correlated with the percentage of shrub and meteorological variables including temperature and precipitation. Conclusions: The results of this study demonstrate areas in China that could be targeted with public health interventions to mitigate the growing threat of scrub typhus in the country. [ABSTRACT FROM AUTHOR]

The epidemiology of dengue fever is characterized by highly seasonal, multi-annual fluctuations, and the irregular circulation of its four serotypes. It is believed that this behaviour arises from the interplay between environmental drivers and serotype interactions. The exact mechanism, however, is uncertain. Constraining mathematical models to patterns characteristic to dengue epidemiology offers a means for detecting such mechanisms. Here, we used a pattern-oriented modelling (POM) strategy to fit and assess a range of dengue models, driven by combinations of temporary cross protective-immunity, cross-enhancement, and seasonal forcing, on their ability to capture the main characteristics of dengue dynamics. We show that all proposed models reproduce the observed dengue patterns across some part of the parameter space. Which model best supports the dengue dynamics is determined by the level of seasonal forcing. Further, when tertiary and quaternary infections are allowed, the inclusion of temporary cross-immunity alone is strongly supported, but the addition of cross-enhancement markedly reduces the parameter range at which dengue dynamics are produced, irrespective of the strength of seasonal forcing. The implication of these structural uncertainties on predicted vulnerability to control is also discussed. With ever expanding spread of dengue, greater understanding of dengue dynamics and control efforts (e.g. a near-future vaccine introduction) has become critically important. This study highlights the capacity of multi-level pattern-matching modelling approaches to offer an analytic tool for deeper insights into dengue epidemiology and control. [ABSTRACT FROM AUTHOR]

Background: Sexual transmission of Ebola virus disease (EVD) 6 months after onset of symptoms has been recently documented, and Ebola virus RNA has been detected in semen of survivors up to 9 months after onset of symptoms. As countries affected by the 2013–2015 epidemic in West Africa, by far the largest to date, are declared free of Ebola virus disease (EVD), it remains unclear what threat is posed by rare sexual transmission events that could arise from survivors. Methodology/Principal Findings: We devised a compartmental mathematical model that includes sexual transmission from convalescent survivors: a SEICR (susceptible-exposed-infectious-convalescent-recovered) transmission model. We fitted the model to weekly incidence of EVD cases from the 2014–2015 epidemic in Sierra Leone. Sensitivity analyses and Monte Carlo simulations showed that a 0.1% per sex act transmission probability and a 3-month convalescent period (the two key unknown parameters of sexual transmission) create very few additional cases, but would extend the epidemic by 83 days [95% CI: 68–98 days] (p < 0.0001) on average. Strikingly, a 6-month convalescent period extended the average epidemic by 540 days (95% CI: 508–572 days), doubling the current length, despite an insignificant rise in the number of new cases generated. Conclusions/Significance: Our results show that reductions in the per sex act transmission probability via abstinence and condom use should reduce the number of sporadic sexual transmission events, but will not significantly reduce the epidemic size and may only minimally shorten the length of time the public health community must maintain response preparedness. While the number of infectious survivors is expected to greatly decline over the coming months, our results show that transmission events may still be expected for quite some time as each event results in a new potential cluster of non-sexual transmission. Precise measurement of the convalescent period is thus important for planning ongoing surveillance efforts. [ABSTRACT FROM AUTHOR]

Background: Dermatophytosis, and particularly the subtype tinea capitis, is common among African children; however, the risk factors associated with this condition are poorly understood. To describe the epidemiology of dermatophytosis in distinct eco-climatic zones, three cross-sectional surveys were conducted in public primary schools located in the Sahelian, Sudanian and Sudano-Guinean eco-climatic zones in Mali. Principal Findings: Among 590 children (average age 9.7 years) the overall clinical prevalence of tinea capitis was 39.3%. Tinea capitis prevalence was 59.5% in the Sudano-Guinean zone, 41.6% in the Sudanian zone and 17% in the Sahelian eco-climatic zone. Microsporum audouinii was isolated primarily from large and/or microsporic lesions. Trichophyton soudanense was primarily isolated from trichophytic lesions. Based on the multivariate analysis, tinea capitis was independently associated with male gender (OR = 2.51, 95%CI [1.74–3.61], P<10−4) and residing in the Sudano-Guinean eco-climatic zone (OR = 7.45, 95%CI [4.63–11.99], P<10−4). Two anthropophilic dermatophytes species, Trichophyton soudanense and Microsporum audouinii, were the most frequent species associated with tinea capitis among primary schoolchildren in Mali. Conclusions: Tinea capitis risk increased with increasing climate humidity in this relatively homogenous schoolchild population in Mali, which suggests a significant role of climatic factors in the epidemiology of dermatophytosis. [ABSTRACT FROM AUTHOR]

Background: Access to laboratory diagnosis can be a challenge for individuals suspected of Buruli Ulcer (BU). Our objective was to develop a clinical score to assist clinicians working in resource-limited settings for BU diagnosis. Methododology/Principal Findings: Between 2011 and 2013, individuals presenting at Akonolinga District Hospital, Cameroon, were enrolled consecutively. Clinical data were collected prospectively. Based on a latent class model using laboratory test results (ZN, PCR, culture), patients were categorized into high, or low BU likelihood. Variables associated with a high BU likelihood in a multivariate logistic model were included in the Buruli score. Score cut-offs were chosen based on calculated predictive values. Of 325 patients with an ulcerative lesion, 51 (15.7%) had a high BU likelihood. The variables identified for the Buruli score were: characteristic smell (+3 points), yellow color (+2), female gender (+2), undermining (+1), green color (+1), lesion hyposensitivity (+1), pain at rest (-1), size >5cm (-1), locoregional adenopathy (-2), age above 20 up to 40 years (-3), or above 40 (-5). This score had AUC of 0.86 (95%CI 0.82–0.89), indicating good discrimination between infected and non-infected individuals. The cut-off to reasonably exclude BU was set at scores <0 (NPV 96.5%; 95%CI 93.0–98.6). The treatment threshold was set at a cut-off ≥4 (PPV 69.0%; 95%CI 49.2–84.7). Patients with intermediate BU probability needed to be tested by PCR. Conclusions/Significance: We developed a decisional algorithm based on a clinical score assessing BU probability. The Buruli score still requires further validation before it can be recommended for wide use. [ABSTRACT FROM AUTHOR]

Background: Although a vaccine could be available as early as 2016, vector control remains the primary approach used to prevent dengue, the most common and widespread arbovirus of humans worldwide. We reviewed the evidence for effectiveness of vector control methods in reducing its transmission. Methodology/Principal Findings: Studies of any design published since 1980 were included if they evaluated method(s) targeting Aedes aegypti or Ae. albopictus for at least 3 months. Primary outcome was dengue incidence. Following Cochrane and PRISMA Group guidelines, database searches yielded 960 reports, and 41 were eligible for inclusion, with 19 providing data for meta-analysis. Study duration ranged from 5 months to 10 years. Studies evaluating multiple tools/approaches (23 records) were more common than single methods, while environmental management was the most common method (19 studies). Only 9/41 reports were randomized controlled trials (RCTs). Two out of 19 studies evaluating dengue incidence were RCTs, and neither reported any statistically significant impact. No RCTs evaluated effectiveness of insecticide space-spraying (fogging) against dengue. Based on meta-analyses, house screening significantly reduced dengue risk, OR 0.22 (95% CI 0.05–0.93, p = 0.04), as did combining community-based environmental management and water container covers, OR 0.22 (95% CI 0.15–0.32, p<0.0001). Indoor residual spraying (IRS) did not impact significantly on infection risk (OR 0.67; 95% CI 0.22–2.11; p = 0.50). Skin repellents, insecticide-treated bed nets or traps had no effect (p>0.5), but insecticide aerosols (OR 2.03; 95% CI 1.44–2.86) and mosquito coils (OR 1.44; 95% CI 1.09–1.91) were associated with higher dengue risk (p = 0.01). Although 23/41 studies examined the impact of insecticide-based tools, only 9 evaluated the insecticide susceptibility status of the target vector population during the study. Conclusions/Significance: This review and meta-analysis demonstrate the remarkable paucity of reliable evidence for the effectiveness of any dengue vector control method. Standardised studies of higher quality to evaluate and compare methods must be prioritised to optimise cost-effective dengue prevention. [ABSTRACT FROM AUTHOR]

Background: Dengue virus (DENV) is the most prominent arbovirus worldwide, causing major epidemics in South-East Asia, South America and Africa. In 2010, a major DENV-2 outbreak occurred in Gabon with cases of patients co-infected with chikungunya virus (CHIKV). Although the innate immune response is thought to be of primordial importance in the development and outcome of arbovirus-associated pathologies, our knowledge of the role of natural killer (NK) cells during DENV-2 infection is in its infancy. Methodology: We performed the first extensive comparative longitudinal characterization of NK cells in patients infected by DENV-2, CHIKV or both viruses. Hierarchical clustering and principal component analyses were performed to discriminate between CHIKV and DENV-2 infected patients. Principal Findings: We observed that both activation and differentiation of NK cells are induced during the acute phase of infection by DENV-2 and CHIKV. Combinatorial analysis however, revealed that both arboviruses induced two different signatures of NK-cell responses, with CHIKV more associated with terminal differentiation, and DENV-2 with inhibitory KIRs. We show also that intracellular production of interferon-γ (IFN-γ) by NK cells is strongly stimulated in acute DENV-2 infection, compared to CHIKV. Conclusions/Significance: Although specific differences were observed between CHIKV and DENV-2 infections, the significant remodeling of NK cell populations observed here suggests their potential roles in the control of both infections. [ABSTRACT FROM AUTHOR]

Background: Dengue is a re-emerging infectious disease of humans, rapidly growing from endemic areas to dengue-free regions due to favorable conditions. In recent decades, Guangzhou has again suffered from several big outbreaks of dengue; as have its neighboring cities. This study aims to examine the impact of dengue epidemics in Guangzhou, China, and to develop a predictive model for Zhongshan based on local weather conditions and Guangzhou dengue surveillance information. Methods: We obtained weekly dengue case data from 1st January, 2005 to 31st December, 2014 for Guangzhou and Zhongshan city from the Chinese National Disease Surveillance Reporting System. Meteorological data was collected from the Zhongshan Weather Bureau and demographic data was collected from the Zhongshan Statistical Bureau. A negative binomial regression model with a log link function was used to analyze the relationship between weekly dengue cases in Guangzhou and Zhongshan, controlling for meteorological factors. Cross-correlation functions were applied to identify the time lags of the effect of each weather factor on weekly dengue cases. Models were validated using receiver operating characteristic (ROC) curves and k-fold cross-validation. Results: Our results showed that weekly dengue cases in Zhongshan were significantly associated with dengue cases in Guangzhou after the treatment of a 5 weeks prior moving average (Relative Risk (RR) = 2.016, 95% Confidence Interval (CI): 1.845–2.203), controlling for weather factors including minimum temperature, relative humidity, and rainfall. ROC curve analysis indicated our forecasting model performed well at different prediction thresholds, with 0.969 area under the receiver operating characteristic curve (AUC) for a threshold of 3 cases per week, 0.957 AUC for a threshold of 2 cases per week, and 0.938 AUC for a threshold of 1 case per week. Models established during k-fold cross-validation also had considerable AUC (average 0.938–0.967). The sensitivity and specificity obtained from k-fold cross-validation was 78.83% and 92.48% respectively, with a forecasting threshold of 3 cases per week; 91.17% and 91.39%, with a threshold of 2 cases; and 85.16% and 87.25% with a threshold of 1 case. The out-of-sample prediction for the epidemics in 2014 also showed satisfactory performance. Conclusion: Our study findings suggest that the occurrence of dengue outbreaks in Guangzhou could impact dengue outbreaks in Zhongshan under suitable weather conditions. Future studies should focus on developing integrated early warning systems for dengue transmission including local weather and human movement. [ABSTRACT FROM AUTHOR]

Background: Depending on the epidemiological setting, a variable proportion of leprosy patients will suffer from excessive pro-inflammatory responses, termed type-1 reactions (T1R). The LRRK2 gene encodes a multi-functional protein that has been shown to modulate pro-inflammatory responses. Variants near the LRRK2 gene have been associated with leprosy in some but not in other studies. We hypothesized that LRRK2 was a T1R susceptibility gene and that inconsistent association results might reflect different proportions of patients with T1R in the different sample settings. Hence, we evaluated the association of LRRK2 variants with T1R susceptibility. Methodology: An association scan of the LRRK2 locus was performed using 156 single-nucleotide polymorphisms (SNPs). Evidence of association was evaluated in two family-based samples: A set of T1R-affected and a second set of T1R-free families. Only SNPs significant for T1R-affected families with significant evidence of heterogeneity relative to T1R-free families were considered T1R-specific. An expression quantitative trait locus (eQTL) analysis was applied to evaluate the impact of T1R-specific SNPs on LRRK2 gene transcriptional levels. Principal Findings: A total of 18 T1R-specific variants organized in four bins were detected. The core SNP capturing the T1R association was the LRRK2 missense variant M2397T (rs3761863) that affects LRRK2 protein turnover. Additionally, a bin of nine SNPs associated with T1R were eQTLs for LRRK2 in unstimulated whole blood cells but not after exposure to Mycobacterium leprae antigen. Significance: The results support a preferential association of LRRK2 variants with T1R. LRRK2 involvement in T1R is likely due to a pathological pro-inflammatory loop modulated by LRRK2 availability. Interestingly, the M2397T variant was reported in association with Crohn’s disease with the same risk allele as in T1R suggesting common inflammatory mechanism in these two distinct diseases. [ABSTRACT FROM AUTHOR]

Background: Vibrio cholerae infections cluster in households. This study's objective was to quantify the relative contribution of direct, within-household exposure (for example, via contamination of household food, water, or surfaces) to endemic cholera transmission. Quantifying the relative contribution of direct exposure is important for planning effective prevention and control measures. Methodology/Principal Findings: Symptom histories and multiple blood and fecal specimens were prospectively collected from household members of hospital-ascertained cholera cases in Bangladesh from 2001–2006. We estimated the probabilities of cholera transmission through 1) direct exposure within the household and 2) contact with community-based sources of infection. The natural history of cholera infection and covariate effects on transmission were considered. Significant direct transmission (p-value<0.0001) occurred among 1414 members of 364 households. Fecal shedding of O1 El Tor Ogawa was associated with a 4.9% (95% confidence interval: 0.9%–22.8%) risk of infection among household contacts through direct exposure during an 11-day infectious period (mean length). The estimated 11-day risk of O1 El Tor Ogawa infection through exposure to community-based sources was 2.5% (0.8%–8.0%). The corresponding estimated risks for O1 El Tor Inaba and O139 infection were 3.7% (0.7%–16.6%) and 8.2% (2.1%–27.1%) through direct exposure, and 3.4% (1.7%–6.7%) and 2.0% (0.5%–7.3%) through community-based exposure. Children under 5 years-old were at elevated risk of infection. Limitations of the study may have led to an underestimation of the true risk of cholera infection. For instance, available covariate data may have incompletely characterized levels of pre-existing immunity to cholera infection. Transmission via direct exposure occurring outside of the household was not considered. Conclusions: Direct exposure contributes substantially to endemic transmission of symptomatic cholera in an urban setting. We provide the first estimate of the transmissibility of endemic cholera within prospectively-followed members of households. The role of direct transmission must be considered when planning cholera control activities. [ABSTRACT FROM AUTHOR]

Introduction: Insecticide-treated nets (ITNs) are one of the main interventions used for malaria control. However, these nets may also be effective against other vector borne diseases (VBDs). We conducted a systematic review and meta-analysis to estimate the efficacy of ITNs, insecticide-treated curtains (ITCs) and insecticide-treated house screening (ITS) against Chagas disease, cutaneous and visceral leishmaniasis, dengue, human African trypanosomiasis, Japanese encephalitis, lymphatic filariasis and onchocerciasis. Methods: MEDLINE, EMBASE, LILACS and Tropical Disease Bulletin databases were searched using intervention, vector- and disease-specific search terms. Cluster or individually randomised controlled trials, non-randomised trials with pre- and post-intervention data and rotational design studies were included. Analysis assessed the efficacy of ITNs, ITCs or ITS versus no intervention. Meta-analysis of clinical data was performed and percentage reduction in vector density calculated. Results: Twenty-one studies were identified which met the inclusion criteria. Meta-analysis of clinical data could only be performed for four cutaneous leishmaniasis studies which together showed a protective efficacy of ITNs of 77% (95%CI: 39%–91%). Studies of ITC and ITS against cutaneous leishmaniasis also reported significant reductions in disease incidence. Single studies reported a high protective efficacy of ITS against dengue and ITNs against Japanese encephalitis. No studies of Chagas disease, human African trypanosomiasis or onchocerciasis were identified. Conclusion: There are likely to be considerable collateral benefits of ITN roll out on cutaneous leishmaniasis where this disease is co-endemic with malaria. Due to the low number of studies identified, issues with reporting of entomological outcomes, and few studies reporting clinical outcomes, it is difficult to make strong conclusions on the effect of ITNs, ITCs or ITS on other VBDs and therefore further studies be conducted. Nonetheless, it is clear that insecticide-treated materials such as ITNs have the potential to reduce pathogen transmission and morbidity from VBDs where vectors enter houses. [ABSTRACT FROM AUTHOR]