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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: Scientific literature on cystic echinococcosis (CE) reporting data on risk factors is limited and to the best of our knowledge, no global evaluation of human CE risk factors has to date been performed. This systematic review (SR) summarizes available data on statistically relevant potential risk factors (PRFs) associated with human CE. Methodology/Principal Findings: Database searches identified 1,367 papers, of which thirty-seven were eligible for inclusion. Of these, eight and twenty-nine were case-control and cross-sectional studies, respectively. Among the eligible papers, twenty-one were included in the meta-analyses. Pooled odds ratio (OR) were used as a measure of effect and separately analysed for the two study designs. PRFs derived from case-control studies that were significantly associated with higher odds of outcome were “dog free to roam” (OR 5.23; 95% CI 2.45–11.14), “feeding dogs with viscera” (OR 4.69; 95% CI 3.02–7.29), “slaughter at home” (OR 4.67; 95% CI 2.02–10.78) or at “slaughterhouses” (OR 2.7; 95% CI 1.15–6.3), “dog ownership” (OR 3.54; 95% CI 1.27–9.85), “living in rural areas” (OR 1.83; 95% CI 1.16–2.9) and “low income” (OR 1.68; 95% CI 1.02–2.76). Statistically significant PRFs from cross-sectional studies with higher odds of outcome were “age >16 years” (OR 6.08; 95% CI 4.05–9.13), “living in rural areas” (OR 2.26; 95% CI 1.41–3.61), “being female” (OR 1.38; 95% CI 1.06–1.8) and “dog ownership” (OR 1.37; 95% CI 1.01–1.86). Conclusions/Significance: Living in endemic rural areas, in which free roaming dogs have access to offal and being a dog-owner, seem to be among the most significant PRFs for acquiring this parasitic infection. Results of data analysed here may contribute to our understanding of the PRFs for CE and may potentially be useful in planning community interventions aimed at controlling CE in endemic areas. [ABSTRACT FROM AUTHOR]

Background: Human alveolar echinococcosis (AE) is a severe zoonotic disease caused by the metacestode stage of Echinococcus multilocularis. AE is commonly associated with a long incubation period that may last for more than ten years. The objective of this systematic literature review was to identify and summarize the current knowledge on statistically relevant potential risk factors (PRFs) associated with AE in humans. Methodology/Principal findings: Six bibliographic databases were searched, generating a total of 1,009 publications. Following the removal of duplicate records and the exclusion of papers that failed to meet the criteria of a previously agreed a priori protocol, 23 publications were retained; however, 6 of these did not contain data in a format that allowed their inclusion in the meta-analysis. The remaining 17 publications (6 case-control and 11 cross-sectional studies) were meta-analysed to investigate associations between AE and PRFs. Pooled odds ratio (OR) were used as a measure of effect and separately analysed for case-control and cross-sectional studies. In the case-control studies, the following PRFs for human AE showed higher odds of outcome: “dog ownership”, “cat ownership”, “have a kitchen garden”, “occupation: farmer”, “haymaking in meadows not adjacent to water”, “went to forests for vocational reasons”, “chewed grass” and “hunting / handling foxes”. In the cross-sectional studies, the following PRFs showed higher odds of outcome: “dog ownership”, “play with dogs”, “gender: female”, “age over 20 years”, “ethnic group: Tibetan”, “low income”, “source of drinking water other than well or tap”, “occupation: herding” and “low education”. Our meta-analysis confirmed that the chance of AE transmission through ingestion of food and water contaminated with E. multilocularis eggs exists, but showed also that food- and water-borne PRFs do not significantly increase the risk of infection. Conclusions/significance: This systematic review analysed international peer-reviewed articles that have over the years contributed to our current understanding of the epidemiology of human AE. The identification of potential risk factors may help researchers and decision makers improve surveillance and/or preventive measures that aim at decreasing human infection with E. multilocularis. More primary studies are needed to confirm potential risk factors and their role in the epidemiology of human AE. [ABSTRACT FROM AUTHOR]

Background: Up to 1.45 billion people currently suffer from soil transmitted helminth infection, with the largest burden occurring in Africa and Asia. Safe and cost effective deworming treatment exists, but there is a debate about mass distribution of this treatment in high prevalence settings. While the World Health Organization recommends mass administration of anthelmintic drugs for preschool and school-aged children in high (>20%) prevalence settings, and several long run follow up studies of an influential trial have suggested large benefits that persist over time, recent systematic reviews have called this recommendation into question., Methods and Findings: This paper analyzes the long-term impact of a cluster-randomized trial in eastern Uganda that provided mass deworming treatment to preschool aged children from 2000 to 2003 on the numeracy and literacy skills of children and young adults living in those villages in 2010-2015. This study uses numeracy and literacy data collected seven to twelve years after the end of the deworming trial in a randomly selected subset of communities from the original trial, by an education-focused survey that had no relationship to the deworming study. Building on an earlier working paper which used data from 2010 and 2011 survey rounds, this paper uses an additional four years of numeracy and literacy data (2012, 2013, 2014, and 2015). Aggregating data from all survey rounds, the difference between numeracy scores in treatment versus control communities is 0.07 standard deviations (SD) (95% CI -0.10, 0.24, p = 0.40), the difference in literacy scores is 0.05 SD (95% CI -0.16, 0.27, p = 0.62), and the difference in total scores is 0.07 SD (95% CI -0.11, 0.25, p = 0.44). There are significant differences in program impact by gender, with numeracy and literacy differentially positively affected for girls, and by age, with treatment effects larger for the primary school aged subsample. There are also significant treatment interactions for those living in households with more treatment-eligible children. There is no evidence of differential treatment effects on age at program eligibility or number of years of program eligibility., Conclusions: Mass deworming of preschool aged children in high prevalence communities in Uganda resulted in no statistically significant gains in numeracy or literacy 7-12 years after program completion. Point estimates were positive but imprecise; the study lacked sufficient power to rule out substantial positive effects or more modest negative effects. However, there is suggestive evidence that deworming was relatively more beneficial for girls, primary school aged children, and children living in households with other treated children., Research Approval: As this analysis was conducted on secondary data which is publicly available, no research approval was sought or received. All individual records were anonymized by the data provider prior to public release., Competing Interests: The authors have declared that no competing interests exist.

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: 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]

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]

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. [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]

Riverine tsetse transmit the parasites that cause the most prevalent form of human African trypanosomiasis, Gambian HAT. In response to the imperative for cheap and efficient tsetse control, insecticide-treated ‘tiny targets’ have been developed through refinement of tsetse attractants based on blue fabric panels. However, modern blue polyesters used for this purpose attract many less tsetse than traditional phthalogen blue cottons. Therefore, colour engineering polyesters for improved attractiveness has great potential for tiny target development. Because flies have markedly different photoreceptor spectral sensitivities from humans, and the responses of these photoreceptors provide the inputs to their visually guided behaviours, it is essential that polyester colour engineering be guided by fly photoreceptor-based explanations of tsetse attraction. To this end, tsetse attraction to differently coloured fabrics was recently modelled using the calculated excitations elicited in a generic set of fly photoreceptors as predictors. However, electrophysiological data from tsetse indicate the potential for modified spectral sensitivities versus the generic pattern, and processing of fly photoreceptor responses within segregated achromatic and chromatic channels has long been hypothesised. Thus, I constructed photoreceptor-based models explaining the attraction of G. f. fuscipes to differently coloured tiny targets recorded in a previously published investigation, under differing assumptions about tsetse spectral sensitivities and organisation of visual processing. Models separating photoreceptor responses into achromatic and chromatic channels explained attraction better than earlier models combining weighted photoreceptor responses in a single mechanism, regardless of the spectral sensitivities assumed. However, common principles for fabric colour engineering were evident across the complete set of models examined, and were consistent with earlier work. Tools for the calculation of fly photoreceptor excitations are available with this paper, and the ways in which these and photoreceptor-based models of attraction can provide colorimetric values for the engineering of more-attractively coloured polyester fabrics are discussed. [ABSTRACT FROM AUTHOR]

Background: Conducting clinical trials to assess experimental treatments for potentially pandemic infectious diseases is challenging. Since many outbreaks of infectious diseases last only six to eight weeks, there is a need for trial designs that can be implemented rapidly in the face of uncertainty. Outbreaks are sudden and unpredictable and so it is essential that as much planning as possible takes place in advance. Statistical aspects of such trial designs should be evaluated and discussed in readiness for implementation. Methodology/Principal findings: This paper proposes a generic ordinal sequential trial design (GOST) for a randomised clinical trial comparing an experimental treatment for an emerging infectious disease with standard care. The design is intended as an off-the-shelf, ready-to-use robust and flexible option. The primary endpoint is a categorisation of patient outcome according to an ordinal scale. A sequential approach is adopted, stopping as soon as it is clear that the experimental treatment has an advantage or that sufficient advantage is unlikely to be detected. The properties of the design are evaluated using large-sample theory and verified for moderate sized samples using simulation. The trial is powered to detect a generic clinically relevant difference: namely an odds ratio of 2 for better rather than worse outcomes. Total sample sizes (across both treatments) of between 150 and 300 patients prove to be adequate in many cases, but the precise value depends on both the magnitude of the treatment advantage and the nature of the ordinal scale. An advantage of the approach is that any erroneous assumptions made at the design stage about the proportion of patients falling into each outcome category have little effect on the error probabilities of the study, although they can lead to inaccurate forecasts of sample size. Conclusions/Significance: It is important and feasible to pre-determine many of the statistical aspects of an efficient trial design in advance of a disease outbreak. The design can then be tailored to the specific disease under study once its nature is better understood. [ABSTRACT FROM AUTHOR]

Background: This paper presents a new agent-based model (ABM) for investigating T. b. rhodesiense human African trypanosomiasis (rHAT) disease dynamics, produced to aid a greater understanding of disease transmission, and essential for development of appropriate mitigation strategies. Methods: The ABM was developed to model rHAT incidence at a fine spatial scale along a 75 km transect in the Luangwa Valley, Zambia. The method offers a complementary approach to traditional compartmentalised modelling techniques, permitting incorporation of fine scale demographic data such as ethnicity, age and gender into the simulation. Results: Through identification of possible spatial, demographic and behavioural characteristics which may have differing implications for rHAT risk in the region, the ABM produced output that could not be readily generated by other techniques. On average there were 1.99 (S.E. 0.245) human infections and 1.83 (S.E. 0.183) cattle infections per 6 month period. The model output identified that the approximate incidence rate (per 1000 person-years) was lower amongst cattle owning households (0.079, S.E. 0.017), than those without cattle (0.134, S.E. 0.017). Immigrant tribes (e.g. Bemba I.R. = 0.353, S.E.0.155) and school-age children (e.g. 5–10 year old I.R. = 0.239, S.E. 0.041) were the most at-risk for acquiring infection. These findings have the potential to aid the targeting of future mitigation strategies. Conclusion: ABMs provide an alternative way of thinking about HAT and NTDs more generally, offering a solution to the investigation of local-scale questions, and which generate results that can be easily disseminated to those affected. The ABM can be used as a tool for scenario testing at an appropriate spatial scale to allow the design of logistically feasible mitigation strategies suggested by model output. This is of particular importance where resources are limited and management strategies are often pushed to the local scale. [ABSTRACT FROM AUTHOR]

In this paper we report a quantitative laser Biospeckle method using VDRL plates to monitor the activity of Trypanosoma cruzi and the calibration conditions including three image processing algorithms and three programs (ImageJ and two programs designed in this work). Benznidazole was used as a test drug. Variable volume (constant density) and variable density (constant volume) were used for the quantitative evaluation of parasite activity in calibrated wells of the VDRL plate. The desiccation process within the well was monitored as a function of volume and of the activity of the Biospeckle pattern of the parasites as well as the quantitative effect of the surface parasite quantity (proportion of the object’s plane). A statistical analysis was performed with ANOVA, Tukey post hoc and Descriptive Statistics using R and R Commander. Conditions of volume (100μl) and parasite density (2-4x104 parasites/well, in exponential growth phase), assay time (up to 204min), frame number (11 frames), algorithm and program (RCommander/SAGA) for image processing were selected to test the effect of variable concentrations of benznidazole (0.0195 to 20μg/mL / 0.075 to 76.8μM) at various times (1, 61, 128 and 204min) on the activity of the Biospeckle pattern. The flat wells of the VDRL plate were found to be suitable for the quantitative calibration of the activity of Trypanosoma cruzi using the appropriate algorithm and program. Under these conditions, benznidazole produces at 1min an instantaneous effect on the activity of the Biospeckle pattern of T. cruzi, which remains with a similar profile up to 1 hour. A second effect which is dependent on concentrations above 1.25μg/mL and is statistically different from the effect at lower concentrations causes a decrease in the activity of the Biospeckle pattern. This effect is better detected after 1 hour of drug action. This behavior may be explained by an instantaneous effect on a membrane protein of Trypanosoma cruzi that could mediate the translocation of benznidazole. At longer times the effect may possibly be explained by the required transformation of the pro-drug into the active drug. [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: Although trachoma causes more cases of preventable blindness than any other infectious disease, a combination of strategies is reducing its global prevalence. As a district moves toward eliminating trachoma as a public health problem, national programs conduct trachoma impact surveys (TIS) to assess whether to stop preventative interventions and trachoma surveillance surveys (TSS) to determine whether the prevalence of active trachoma has rebounded after interventions have halted. In some contexts, programs also conduct trachomatous trichiasis (TT)-only surveys. A few costing studies of trachoma prevalence surveys exist, but none examine TIS, TSS, or TT-only surveys. Methodology/Principal findings: We assessed the incremental financial cost to the national program of TIS, TSS, and TT-only surveys, which are standardized cluster-sampled prevalence surveys. We conducted a retrospective review of expenditures and grant disbursements for TIS and TSS in 322 evaluation units in 11 countries between 2011 and 2018. We also assessed the costs of three pilot and five standard TT-only surveys in four countries between 2017 and 2018. The median cost of TIS and TSS was $8,298 per evaluation unit [interquartile range (IQR): $6,532–$10,111, 2017 USD]. Based on a linear regression with bootstrapped confidence intervals, after controlling for country, costs per survey did not change significantly over time but did decline by $83 per survey implemented in a single round (95% CI: -$108 –-$63). Of total costs, 80% went to survey fieldwork; of that, 58% went towards per diems and 38% towards travel. TT-only surveys cost a median of $9,707 (IQR: $8,537–$11,635); within a given country, they cost slightly more (106% [IQR: 94%–136%]) than TIS and TSS. Conclusions/Significance: The World Health Organization requires trachoma prevalence estimates for validating the elimination of trachoma as a public health problem. This study will help programs improve their planning as they assemble resources for that effort. [ABSTRACT FROM AUTHOR]

Background: Cryptosporidium infection causes gastrointestinal disease and has a worldwide distribution. The highest burden is in developing countries. Objectives: We sought to conduct a systematic review and meta-analysis to identify Cryptosporidium risk factors in Low and Middle Income countries (LMICs). Methods: Medline Ovid and Scopus databases were searched with no restriction on year or language of publication. All references were screened independently in duplicate and were included if they presented data on at least 3 risk factors. Meta-analyses using random effects models were used to calculate overall estimates for each exposure. Results: The most frequently reported risk factors in the 15 included studies were overcrowding, household diarrhoea, poor quality drinking water, animal contact, open defecation/ lack of toilet and breastfeeding. The combined odds ratio for animal contact was 1.98 (95%CI: 1.11–3.54) based on 11 studies and for diarrhoea in the household 1.98 (95%CI: 1.13–3.49) based on 4 studies. Open defecation was associated with a pooled odds ratio of 1.82 (95%CI: 1.19–2.8) based on 5 studies. Poor drinking water quality was not associated with a significant Cryptosporidium risk, odds ratio 1.06 (95%CI: 0.77–1.47). Breastfeeding was protective with pooled odds ratio 0.4 (95%CI: 0.13–1.22), which was not statistically significant. Conclusions: Based on the included studies, crowded living conditions, animal contact and open defecation are responsible for the majority of Cryptosporidium cases in LMICs. Future studies investigating Cryptosporidium risk factors should have a good study design and duration, include appropriate number of cases, select suitable controls, investigate multiple relevant risk factors, fully report data and perform multivariate analysis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Epidemic forecasting and prediction tools have the potential to provide actionable information in the midst of emerging epidemics. While numerous predictive studies were published during the 2016–2017 Zika Virus (ZIKV) pandemic, it remains unknown how timely, reproducible, and actionable the information produced by these studies was. Methods: To improve the functional use of mathematical modeling in support of future infectious disease outbreaks, we conducted a systematic review of all ZIKV prediction studies published during the recent ZIKV pandemic using the PRISMA guidelines. Using MEDLINE, EMBASE, and grey literature review, we identified studies that forecasted, predicted, or simulated ecological or epidemiological phenomena related to the Zika pandemic that were published as of March 01, 2017. Eligible studies underwent evaluation of objectives, data sources, methods, timeliness, reproducibility, accessibility, and clarity by independent reviewers. Results: 2034 studies were identified, of which n = 73 met the eligibility criteria. Spatial spread, R0 (basic reproductive number), and epidemic dynamics were most commonly predicted, with few studies predicting Guillain-Barré Syndrome burden (4%), sexual transmission risk (4%), and intervention impact (4%). Most studies specifically examined populations in the Americas (52%), with few African-specific studies (4%). Case count (67%), vector (41%), and demographic data (37%) were the most common data sources. Real-time internet data and pathogen genomic information were used in 7% and 0% of studies, respectively, and social science and behavioral data were typically absent in modeling efforts. Deterministic models were favored over stochastic approaches. Forty percent of studies made model data entirely available, 29% provided all relevant model code, 43% presented uncertainty in all predictions, and 54% provided sufficient methodological detail to allow complete reproducibility. Fifty-one percent of predictions were published after the epidemic peak in the Americas. While the use of preprints improved the accessibility of ZIKV predictions by a median of 119 days sooner than journal publication dates, they were used in only 30% of studies. Conclusions: Many ZIKV predictions were published during the 2016–2017 pandemic. The accessibility, reproducibility, timeliness, and incorporation of uncertainty in these published predictions varied and indicates there is substantial room for improvement. To enhance the utility of analytical tools for outbreak response it is essential to improve the sharing of model data, code, and preprints for future outbreaks, epidemics, and pandemics. [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]

As emerging and re-emerging infectious arboviruses like dengue, chikungunya, and Zika threaten new populations worldwide, officials scramble to assess local severity and transmissibility, with little to no epidemiological history to draw upon. Indirect estimates of risk from vector habitat suitability maps are prone to great uncertainty, while direct estimates from epidemiological data are only possible after cases accumulate and, given environmental constraints on arbovirus transmission, cannot be widely generalized beyond the focal region. Combining these complementary methods, we use disease importation and transmission data to improve the accuracy and precision of a priori ecological risk estimates. We demonstrate this approach by estimating the spatiotemporal risks of Zika virus transmission throughout Texas, a high-risk region in the southern United States. Our estimates are, on average, 80% lower than published ecological estimates—with only six of 254 Texas counties deemed capable of sustaining a Zika epidemic—and they are consistent with the number of autochthonous cases detected in 2017. Importantly our method provides a framework for model comparison, as our mechanistic understanding of arbovirus transmission continues to improve. Real-time updating of prior risk estimates as importations and outbreaks arise can thereby provide critical, early insight into local transmission risks as emerging arboviruses expand their global reach. [ABSTRACT FROM AUTHOR]

The preparedness of health systems to detect, treat, and prevent onward transmission of Ebola virus disease (EVD) is central to mitigating future outbreaks. Early detection of outbreaks is critical to timely response, but estimating detection rates is difficult because unreported spillover events and outbreaks do not generate data. Using three independent datasets available on the distributions of secondary infections during EVD outbreaks across West Africa, in a single district (Western Area) of Sierra Leone, and in the city of Conakry, Guinea, we simulated realistic outbreak size distributions and compared them to reported outbreak sizes. These three empirical distributions lead to estimates for the proportion of detected spillover events and small outbreaks of 26% (range 8–40%, based on the full outbreak data), 48% (range 39–62%, based on the Sierra Leone data), and 17% (range 11–24%, based on the Guinea data). We conclude that at least half of all spillover events have failed to be reported since EVD was first recognized. We also estimate the probability of detecting outbreaks of different sizes, which is likely less than 10% for single-case spillover events. Comparing models of the observation process also suggests the probability of detecting an outbreak is not simply the cumulative probability of independently detecting any one individual. Rather, we find that any individual’s probability of detection is highly dependent upon the size of the cluster of cases. These findings highlight the importance of primary health care and local case management to detect and contain undetected early stage outbreaks at source. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis japonica is a zoonotic parasitic disease. After nearly 70 years of control efforts in China, Schistosomiasis transmission has been reduced to a much lower level. The absence or near absence of infections in humans or livestock, based on traditional fecal and serological tests, has made the targets and priorities of future control efforts difficult to determine. However, detection of schistosome cercariae in waters using sentinel mice could be an alternative way of identifying remaining foci of infection, or even serve as a tool for evaluation of control efficacy. This method has been employed in China over last forty years. We therefore performed a meta-analysis of the relevant research to investigate if infections in sentinel mice mirror the ongoing trend of schistosomiasis transmission in China. Methods: We conducted a meta-analysis of studies reporting infection rates of S. japonicum in sentinel mice in China before Sep 1, 2018 in accordance with the PRISMA guidelines. We retrieved all relative studies based on five databases (CNKI, WanFang, VIP, PubMed and Web of Science) and the reference lists of resulting articles. For each individual study, the infection rate in sentinel mice is presented together with its 95% confidence interval (CI). Point estimates of the overall infection rates and their 95% CIs were calculated. Subgroup analyses were performed according to study periods, seasons or regions. Results: We identified 90 articles, including 290 studies covering eight endemic provinces. The overall rate in sentinel mice was 12.31% (95% CI: 10.14–14.65%) from 1980 to 2018. The value of 3.66% (95% CI: 2.62–4.85%) estimated in 2004 to 2018 was significantly lower than in 1980 to 2003 (22.96%, 95% CI: 19.25–26.89%). The estimate was significantly higher in the middle and lower reaches than in the upper reaches of the Yangtze River. The highest estimates were obtained in Hunan (30.11%, 95% CI: 25.64–34.77%) followed by Anhui (26.34%, 95% CI: 12.88–42.44%) and then Jiangxi (13.73%, 95% CI: 6.71–22.56%). Unlike the other provinces in the middle and lower reaches, no significant reduction was seen in Hubei after 2003. Even in Hubei two studies carried out after 2014 reported infections in sentinel mice, although no infected snails were reported across the province. Infections were most found in April (17.40%, 95% CI: 1.13–45.49%), July (24.98%, 95% CI: 15.64–35.62%) and October (17.08%, 95% CI 5.94–32.05%). High degrees of heterogeneity were observed. Conclusion: This meta-analysis provides a comprehensive analysis of schistosome infection in sentinel mice across China. The estimates largely mirror the ongoing trends of transmission in terms of periods and regions. Infections were most likely to occur in April, July and October. In areas where no infected snails were reported infections in sentinel mice were still observed. Due to the presence of snails and infected wildlife, detection of schistosomes in waters using such a highly sensitive method as the deployment of sentinel mice, remains of importance in schistosomiasis monitoring. We would suggest the current criteria for transmission interruption or elimination of schistosomiasis in China be adjusted by integrating the results of sentinel mice based surveys. [ABSTRACT FROM AUTHOR]

The ability to appropriately mimic human disease is critical for using animal models as a tool for understanding virus pathogenesis. In the case of Nipah virus (NiV), infection of humans appears to occur either through inhalation, contact with or consumption of infected material. In two of these circumstances, respiratory or sinusoidal exposure represents a likely route of infection. In this study, intermediate-size aerosol particles (~7 μm) of NiV-Malaysia were used to mimic potential routes of exposure by focusing viral deposition in the upper respiratory tract. Our previous report showed this route of exposure extended the disease course and a single animal survived the infection. Here, analysis of the peripheral immune response found minimal evidence of systemic inflammation and depletion of B cells during acute disease. However, the animal that survived infection developed an early IgM response with rapid development of neutralizing antibodies that likely afforded protection. The increase in NiV-specific antibodies correlated with an expansion of the B cell population in the survivor. Cell-mediated immunity was not clearly apparent in animals that succumbed during the acute phase of disease. However, CD4+ and CD8+ effector memory cells increased in the survivor with correlating increases in cytokines and chemokines associated with cell-mediated immunity. Interestingly, kinetic changes of the CD4+ and CD8bright T cell populations over the course of acute disease were opposite from animals that succumbed to infection. In addition, increases in NK cells and basophils during convalescence of the surviving animal were also evident, with viral antigen found in NK cells. These data suggest that a systemic inflammatory response and “cytokine storm” are not major contributors to NiV-Malaysia pathogenesis in the AGM model using this exposure route. Further, these data demonstrate that regulation of cell-mediated immunity, in addition to rapid production of NiV specific antibodies, may be critical for surviving NiV infection. [ABSTRACT FROM AUTHOR]

Triatomine vectors transmit Trypanosoma cruzi, the etiological agent of Chagas disease in humans. Transmission to humans typically occurs when contaminated triatomine feces come in contact with the bite site or mucosal membranes. In the Southern Cone of South America, where the highest burden of disease exists, Triatoma infestans is the principal vector for T. cruzi. Recent studies of other vector-borne illnesses have shown that arthropod microbiota influences the ability of infectious agents to colonize the insect vector and transmit to the human host. This has garnered attention as a potential control strategy against T. cruzi, as vector control is the main tool of Chagas disease prevention. Here we characterized the microbiota in T. infestans feces of both wild-caught and laboratory-reared insects and examined the relationship between microbial composition and T. cruzi infection using highly sensitive high-throughput sequencing technology to sequence the V3-V4 region of the 16S ribosomal RNA gene on the MiSeq Illumina platform. We collected 59 wild (9 with T. cruzi infection) and 10 lab-reared T. infestans (4 with T. cruzi infection) from the endemic area of Arequipa, Perú. Wild T. infestans had greater hindgut bacterial diversity than laboratory-reared bugs. Microbiota of lab insects comprised a subset of those identified in their wild counterparts, with 96 of the total 124 genera also observed in laboratory-reared insects. Among wild insects, variation in bacterial composition was observed, but time and location of collection and development stage did not explain this variation. T. cruzi infection in lab insects did not affect α- or β-diversity; however, we did find that the β-diversity of wild insects differed if they were infected with T. cruzi and identified 10 specific taxa that had significantly different relative abundances in infected vs. uninfected wild T. infestans (Bosea, Mesorhizobium, Dietzia, and Cupriavidus were underrepresented in infected bugs; Sporosarcina, an unclassified genus of Porphyromonadaceae, Nestenrenkonia, Alkalibacterium, Peptoniphilus, Marinilactibacillus were overrepresented in infected bugs). Our findings suggest that T. cruzi infection is associated with the microbiota of T. infestans and that inferring the microbiota of wild T. infestans may not be possible through sampling of T. infestans reared in the insectary. [ABSTRACT FROM AUTHOR]

Objectives: We contribute a new methodological approach to the ongoing efforts towards evaluating public health surveillance. Specifically, we apply a descriptive framework, grounded in prospect theory (PT), for the evaluation of decisions on disease surveillance deployment. We focus on two attributes of any surveillance system: timeliness, and false positive rate (FPR). Methods: In a sample of 69 health professionals from a number of health related networks polled online, we elicited PT preferences, specifically respondents’ attitudes towards gains, losses and probabilities (i.e., if they overweight or underweight extreme probabilities) by means of a series of lotteries for either timeliness or FPR. Moreover, we estimated willingness to pay (WTP) for improvements in the two surveillance attributes. For contextualization, we apply our framework to rabies surveillance. Results: Our data reveal considerable probability weighting, both for gains and losses. In other words, respondents underestimate their chances of getting a good outcome in uncertain situations, and they overestimate their chances of bad outcomes. Moreover, there is convex utility for losses and loss aversion, that is, losses loom larger than gains of the same absolute magnitude to the respondents. We find no differences between the estimated parameters for timeliness and FPR. The median WTP is $7,250 per day gained in detection time and $30 per 1/10,000 reduction in FPR. Conclusion: Our results indicate that the biases described by PT are present among public health professionals, which highlights the need to incorporate a PT framework when eliciting their preferences for surveillance systems. [ABSTRACT FROM AUTHOR]

Background: A few studies investigated the relationship between toxoplasmosis and mental disorders, such as obsessive compulsive disorder (OCD). However, the specific nature of the association between Toxoplasma gondii (T. gondii) infection and OCD is not yet clear. The aim of this study was to collect information on the relationship between OCD and toxoplasmosis and assess whether patients with toxoplasmosis are prone to OCD. Methods: For the purpose of this study, 6 major electronic databases and the Internet search engine Google Scholar were searched for the published articles up to July 30th, 2018 with no restriction of language. The inverse variance method and the random effect model were used to combine the data. The values of odds ratio (OR) were estimated at 95% confidence interval (CI). Results: A total of 9 case-control and 3 cross-sectional studies were included in our systematic review. However, 11 of these 12 articles were entered into the meta-analysis containing 9873 participants, out of whom 389 were with OCD (25.96% positive for toxoplasmosis) and 9484 were without OCD (17.12% positive for toxoplasmosis). The estimation of the random effect model indicated a significant common OR of 1.96 [95% CI: 1.32–2.90]. Conclusion: This systematic review and meta-analysis revealed that toxoplasmosis could be as an associated factor for OCD (OR = 1.96). However, further prospective investigations are highly recommended to illuminate the underlying pathophysiological mechanisms of T. gondii infection in OCD and to better investigate the relationship between OCD and T. gondii infection. [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]

Endemic to the Democratic Republic of the Congo (DRC), monkeypox is a zoonotic disease that causes smallpox-like illness in humans. Observed fluctuations in reported cases over time raises questions about when it is appropriate to mount a public health response, and what specific actions should be taken. We evaluated three different thresholds to differentiate between baseline and heightened disease incidence, and propose a novel, tiered algorithm for public health action. Monkeypox surveillance data from Tshuapa Province, 2011–2013, were used to calculate three different statistical thresholds: Cullen, c-sum, and a World Health Organization (WHO) method based on monthly incidence. When the observed cases exceeded the threshold for a given month, that month was considered to be ‘aberrant’. For each approach, the number of aberrant months detected was summed by year—each method produced vastly different results. The Cullen approach generated a number of aberrant signals over the period of consideration (9/36 months). The c-sum method was the most sensitive (30/36 months), followed by the WHO method (12/24 months). We conclude that triggering public health action based on signals detected by a single method may be inefficient and overly simplistic for monkeypox. We propose instead a response algorithm that integrates an objective threshold (WHO method) with contextual information about epidemiological and spatiotemporal links between suspected cases to determine whether a response should be operating under i) routine surveillance ii) alert status, or iii) outbreak status. This framework could be modified and adopted by national and zone level health workers in monkeypox-endemic countries. Lastly, we discuss considerations for selecting thresholds for monkeypox outbreaks across gradients of endemicity and public health resources. [ABSTRACT FROM AUTHOR]

Background: To work towards reaching the WHO goal of eliminating soil-transmitted helminth (STH) infections as a public health problem, the total number of children receiving anthelmintic drugs has strongly increased over the past few years. However, as drug pressure levels rise, the development of anthelmintic drug resistance (AR) is more and more likely to appear. Currently, any global surveillance system to monitor drug efficacy and the emergence of possible AR is lacking. Consequently, it remains unclear to what extent the efficacy of drugs may have dropped and whether AR is already present. The overall aim of this study is to recommend the best diagnostic methods to monitor drug efficacy and molecular markers to assess the emergence of AR in STH control programs. Methods: A series of drug efficacy trials will be performed in four STH endemic countries with varying drug pressure (Ethiopia and Brazil: low drug pressure, Lao PDR: moderate drug pressure and Tanzania: high drug pressure). These trials are designed to assess the efficacy of a single oral dose of 400 mg albendazole (ALB) against STH infections in school-aged children (SAC) by microscopic (duplicate Kato-Katz thick smear, Mini-FLOTAC and FECPAKG2) and molecular stool-based diagnostic methods (quantitative PCR (qPCR)). Data will be collected on the cost of the materials used, as well as the time required to prepare and examine stool samples for the different diagnostic methods. Following qPCR, DNA samples will also be submitted for pyrosequencing to assess the presence and prevalence of single nucleotide polymorphisms (SNPs) in the β-tubulin gene. These SNPs are known to be linked to AR in animal STHs. Discussion: The results obtained by these trials will provide robust evidence regarding the cost-efficiency and diagnostic performance of the different stool-based diagnostic methods for the assessment of drug efficacy in control programs. The assessment of associations between the frequency of SNPs in the β-tubulin gene and the history of drug pressure and drug efficacy will allow the validation of these SNPs as a marker for AR in human STHs. Trial registration: The trial was retrospectively registered the 7th of March 2018 on Clinicaltrials.gov (ID: ). [ABSTRACT FROM AUTHOR]

Mobile applications (apps) can bring health research and its potential downstream benefits closer to underserved populations. Drawing on experience developing an app for detecting and referring cases of cutaneous leishmaniasis in Colombia, called Guaral/app, we review key steps in creating such mobile health (mHealth) tools. These require consideration of the sociotechnical context using methods such as systems analysis and human-centered design (HCD), predicated on engagement and iteration with all stakeholders. We emphasize usability and technical concerns and describe the interdependency of technical and human considerations for mHealth systems in rural communities. [ABSTRACT FROM AUTHOR]

Objective: To gain further insight on the association between human toxocariasis and epilepsy in light of the new evidence in the last years. Methods: A systematic review was conducted without date and language restriction in the following electronic databases: MEDLINE (PubMed), Ingenta Connect, Science Direct (Elsevier), RefDoc, Scopus, HighWire, Scielo and the database of the Institute of Neuroepidemiology and Tropical Neurology of the Limoges University (IENT). Two investigators independently conducted the search up to November 2017. A pooled odds ratio (OR) was estimated using a random effects model. Meta-regression was conducted to investigate potential sources of heterogeneity. Results: Database search produced 204 publications. Eleven case-control studies were included that were carried out in 13 countries worldwide. A total number of 4740 subjects were considered (2159 people with epilepsy and 2581 people without epilepsy). The overall pooled OR was 1.69 (95% CI 1.42–2.01) for the association between epilepsy and Toxocara spp. seropositivity. A positive association was constantly reported in the restricted analysis (WB as confirmatory or diagnostic test, younger population, and population–based studies). Meta-regression showed no statistically significant association between covariates and outcome. Conclusion: The updated meta-analysis provides epidemiological evidence of a positive association between Toxocara seropositivity and epilepsy. New surveys supported the association, mainly population-based studies. On this basis, health strategies to reduce the impact of Toxocara spp are strongly advised. Further research should be performed to understand the physiopathological mechanisms of toxocara-associated epileptogenesis. [ABSTRACT FROM AUTHOR]

Over 200,000 new cases of leprosy are detected each year, of which approximately 7% are associated with grade-2 disabilities (G2Ds). For achieving leprosy elimination, one of the main challenges will be targeting higher risk groups within endemic communities. Nevertheless, the socioeconomic risk markers of leprosy remain poorly understood. To address this gap we systematically reviewed MEDLINE/PubMed, Embase, LILACS and Web of Science for original articles investigating the social determinants of leprosy in countries with > 1000 cases/year in at least five years between 2006 and 2016. Cohort, case-control, cross-sectional, and ecological studies were eligible for inclusion; qualitative studies, case reports, and reviews were excluded. Out of 1,534 non-duplicate records, 96 full-text articles were reviewed, and 39 met inclusion criteria. 17 were included in random-effects meta-analyses for sex, occupation, food shortage, household contact, crowding, and lack of clean (i.e., treated) water. The majority of studies were conducted in Brazil, India, or Bangladesh while none were undertaken in low-income countries. Descriptive synthesis indicated that increased age, poor sanitary and socioeconomic conditions, lower level of education, and food-insecurity are risk markers for leprosy. Additionally, in pooled estimates, leprosy was associated with being male (RR = 1.33, 95% CI = 1.06–1.67), performing manual labor (RR = 2.15, 95% CI = 0.97–4.74), suffering from food shortage in the past (RR = 1.39, 95% CI = 1.05–1.85), being a household contact of a leprosy patient (RR = 3.40, 95% CI = 2.24–5.18), and living in a crowded household (≥5 per household) (RR = 1.38, 95% CI = 1.14–1.67). Lack of clean water did not appear to be a risk marker of leprosy (RR = 0.94, 95% CI = 0.65–1.35). Additionally, ecological studies provided evidence that lower inequality, better human development, increased healthcare coverage, and cash transfer programs are linked with lower leprosy risks. These findings point to a consistent relationship between leprosy and unfavorable economic circumstances and, thereby, underscore the pressing need of leprosy control policies to target socially vulnerable groups in high-burden countries. [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]

Background: Chagas disease (CD) is a major public health concern in Latin America and a potentially serious emerging threat in non-endemic countries. Although the association between CD and cardiac abnormalities is widely reported, study design diversity, sample size and quality challenge the information, calling for its update and synthesis, which would be very useful and relevant for physicians in non-endemic countries where health care implications of CD are real and neglected. We performed to systematically review and meta-analyze population-based studies that compared prevalence of overall and specific ECG abnormalities between CD and non-CD participants in the general population. Methods: Six databases (EMBASE, Ovid Medline, Web of Science, Cochrane Central, Google Scholar and Lilacs) were searched systematically. Observational studies were included. Odds ratios (OR) were computed using random-effects model. Results: Forty-nine studies were selected, including 34,023(12,276 CD and 21,747 non-CD). Prevalence of overall ECG abnormalities was higher in participants with CD (40.1%; 95%CIs=39.2-41.0) compared to non-CD (24.1%; 95%CIs=23.5-24.7) (OR=2.78; 95%CIs=2.37-3.26). Among specific ECG abnormalities, prevalence of complete right bundle branch block (RBBB) (OR=4.60; 95%CIs=2.97-7.11), left anterior fascicular block (LAFB) (OR=1.60; 95%CIs=1.21-2.13), combination of complete RBBB/LAFB (OR=3.34; 95%CIs=1.76-6.35), first-degree atrioventricular block (A-V B) (OR=1.71; 95%CIs=1.25-2.33), atrial fibrillation (AF) or flutter (OR=2.11; 95%CIs=1.40-3.19) and ventricular extrasystoles (VE) (OR=1.62; 95%CIs=1.14-2.30) was higher in CD compared to non-CD participants. Conclusions: This systematic review and meta-analysis provides an update and synthesis in this field. This research of observational studies indicates a significant excess in prevalence of ECG abnormalities (40.1%) related to T. cruzi infection in the general population from Chagas endemic regions, being the most common ventricular (RBBB and LAFB), and A-V B (first-degree) node conduction abnormalities as well as arrhythmias (AF or flutter and VE). Also, prevalence of ECG alterations in children was similar to that in adults and suggests earlier onset of cardiac disease. [ABSTRACT FROM AUTHOR]

Background: Toxoplasmosis is a cosmopolitan infection caused by an intracellular obligatory protozoan, Toxoplasma gondii. Infection to this parasite in immunocompetent patients is usually asymptomatic, but today it is believed that the infection can be a risk factor for a variety of diseases, including rheumatoid arthritis (RA). RA is an autoimmune disease and the most common type of inflammatory arthritis that is a major cause of disability. The aim of this systematic review and meta-analysis was to address the association between RA and toxoplasmosis in light of the available research. Methods: Based on the keywords, a systematic search of eight databases was conducted to retrieve the relevant English-language articles. Then, the studies were screened based on the inclusion and exclusion criteria. The random effect model was used to calculate the odds ratio (OR) using forest plot with 95% confidence interval (CI). Results: Overall, 4168 Individual, extracted from 9 articles were included for systematic review evaluation, with 1369 RA patients (46% positive toxoplasmosis) and 2799 individuals as controls (21% positive toxoplasmosis). Then, eight articles (10 datasets) were used for meta-analysis (1244 rheumatoid arthritis patients and 2799 controls). By random effect model, the combined OR was 3.30 (95% CI: 2.05 to 5.30) with P < 0.0001. Conclusion: Although toxoplasmosis could be considered as a potential risk factor for rheumatoid arthritis, more and better quality studies are needed to determine the effect of T. gondii infection on induction or exacerbation of RA. Our study was registered at the International Prospective Register of Systematic Reviews (PROSPERO; code: CRD42017069384). [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: There is debate over the effectiveness of deworming children against soil-transmitted helminthiasis (STH) to improve health outcomes, and current evidence may be limited in study design and generalizability. However, programmatic deworming continues throughout low and middle-income countries. Methodology and principal findings: We performed an empirical evaluation of the relationship between deworming in pre-school age children (ages 1–4 years) within the previous 6 months, as proxy-reported by the mother, and health outcomes of weight, height, and hemoglobin. We used nationally representative cross-sectional data from 45 countries using the Demographic and Health Surveys (DHS) during the period 2005–2016. We used logistic regression with coarsened exact matching, fixed effects for survey and year, and person-level covariates. We included data on 325,115 children in 45 STH-endemic countries from 66 DHS surveys. Globally in STH-endemic countries, children who received deworming treatment were less likely to be stunted (1.2 percentage point decline from mean of 36%; 95% CI [-1.9, -0.5%]; p<0.001), but we did not detect consistent associations between deworming and anemia or weight. In sub-Saharan Africa, we found that children who received deworming treatment were less likely to be stunted (1.1 percentage point decline from mean of 36%; 95% CI [-2.1, -0.2%]; p = 0.01) and less likely to have anemia (1.8 percentage point decline from mean of 58%; 95% CI [-2.8, -0.7%]; p<0.001), but we did not detect consistent associations between deworming and weight. These findings were robust across multiple statistical models, and we did not find consistently measurable associations with data from non-endemic settings. Conclusions and significance: Among pre-school age children, we detected a robust and consistent association between deworming and reduced stunting, with additional evidence for reduced anemia in sub-Saharan Africa. We did not find a consistent relationship between deworming and improved weight. This global empirical analysis provides evidence to support the deworming of pre-school age children. [ABSTRACT FROM AUTHOR]

Introduction: Schistosomiasis is a chronic parasitic trematode disease that affects over 240 million people worldwide. The Schistosoma lifecycle is complex, involving transmission via specific intermediate-host freshwater snails. Predictive mathematical models of Schistosoma transmission have often chosen to simplify or ignore the details of environmental human-snail interaction in their analyses. Schistosome transmission models now aim to provide better precision for policy planning of elimination of transmission. This heightens the importance of including the environmental complexity of vector-pathogen interaction in order to make more accurate projections. Methodology and principal findings: We propose a nonlinear snail force of infection (FOI) that takes into account an intermediate larval stage (miracidium) and snail biology. We focused, in particular, on the effects of snail force of infection (FOI) on the impact of mass drug administration (MDA) in human communities. The proposed (modified) model was compared to a conventional model in terms of their predictions. A longitudinal dataset generated in Kenya field studies was used for model calibration and validation. For each sample community, we calibrated modified and conventional model systems, then used them to model outcomes for a range of MDA regimens. In most cases, the modified model predicted more vigorous post-MDA rebound, with faster relapse to baseline levels of infection. The effect was pronounced in higher risk communities. When compared to observed data, only the modified system was able to successfully predict persistent rebound of Schistosoma infection. Conclusion and significance: The observed impact of varying location-specific snail inputs sheds light on the diverse MDA response patterns noted in operational research on schistosomiasis control, such as the recent SCORE project. Efficiency of human-to-snail transmission is likely to be much higher than predicted by standard models, which, in practice, will make local elimination by implementation of MDA alone highly unlikely, even over a multi-decade period. [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]

Background: This study aimed to investigate the spatiotemporal clustering and socio-environmental factors associated with dengue fever (DF) incidence rates at street level in Guangzhou City, China. Methods: Spatiotemporal scan technique was applied to identify the high risk region of DF. Multiple regression model was used to identify the socio-environmental factors associated with DF infection. A Poisson regression model was employed to examine the spatiotemporal patterns in the spread of DF. Results: Spatial clusters of DF were primarily concentrated at the southwest part of Guangzhou City. Age group (65+ years) (Odd Ratio (OR) = 1.49, 95% Confidence Interval = 1.13 to 2.03), floating population (OR = 1.09, 95% CI = 1.05 to 1.15), low-education (OR = 1.08, 95% CI = 1.01 to 1.16) and non-agriculture (OR = 1.07, 95% CI = 1.03 to 1.11) were associated with DF transmission. Poisson regression results indicated that changes in DF incidence rates were significantly associated with longitude (β = -5.08, P<0.01) and latitude (β = -1.99, P<0.01). Conclusions: The study demonstrated that social-environmental factors may play an important role in DF transmission in Guangzhou. As geographic range of notified DF has significantly expanded over recent years, an early warning systems based on spatiotemporal model with socio-environmental is urgently needed to improve the effectiveness and efficiency of dengue control and prevention. [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]

Background: Diarrhoea is a leading cause of death in Nigerian children under 5 years. Implementing the most cost-effective approach to diarrhoea management in Nigeria will help optimize health care resources allocation. This study evaluated the cost-effectiveness of various approaches to diarrhoea management namely: the ‘no treatment’ approach (NT); the preventive approach with rotavirus vaccine; the integrated management of childhood illness for diarrhoea approach (IMCI); and rotavirus vaccine plus integrated management of childhood illness for diarrhoea approach (rotavirus vaccine + IMCI). Methods: Markov cohort model conducted from the payer’s perspective was used to calculate the cost-effectiveness of the four interventions. The markov model simulated a life cycle of 260 weeks for 33 million children under five years at risk of having diarrhoea (well state). Disability adjusted life years (DALYs) averted was used to quantify clinical outcome. Incremental cost-effectiveness ratio (ICER) served as measure of cost-effectiveness. Results: Based on cost-effectiveness threshold of $2,177.99 (i.e. representing Nigerian GDP/capita), all the approaches were very cost-effective but rotavirus vaccine approach was dominated. While IMCI has the lowest ICER of $4.6/DALY averted, the addition of rotavirus vaccine was cost-effective with an ICER of $80.1/DALY averted. Rotavirus vaccine alone was less efficient in optimizing health care resource allocation. Conclusion: Rotavirus vaccine + IMCI approach was the most cost-effective approach to childhood diarrhoea management. Its awareness and practice should be promoted in Nigeria. Addition of rotavirus vaccine should be considered for inclusion in the national programme of immunization. Although our findings suggest that addition of rotavirus vaccine to IMCI for diarrhoea is cost-effective, there may be need for further vaccine demonstration studies or real life studies to establish the cost-effectiveness of the vaccine in Nigeria. [ABSTRACT FROM AUTHOR]