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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. [ABSTRACT FROM AUTHOR]

Background: Leprosy is a chronic infectious disease neglected, caused by Mycobacterium leprae, considered a public health problem because may cause permanent physical disabilities and deformities, leading to severe limitations. This review presents an overview of the results of epidemiological studies on leprosy occurrence in childhood in Brazil, aiming to alert health planners and managers to the actual need to institute special control strategies. Methodology/Principal findings: Data collection consisted of an electronic search for publications in eight databases: Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Scientific Electronic Library Online (SciELO), PuBMed, Biblioteca Virtual em Saúde (BVS), SciVerse Scopus (Scopus), CAPES theses database, CAPES journals database and Web of Science of papers published up to 2016. After apply selection criteria, twenty-two papers of studies conducted in four different regions of Brazil and published between 2001 and 2016 were included in the review. The leprosy detection rate ranged from 10.9 to 78.4 per 100,000 inhabitants. Despite affecting both sexes, leprosy was more common in boys and in 10-14-year-olds. Although the authors reported a high cure proportion (82–90%), between 1.7% and 5.5% of the individuals developed a disability resulting from the disease. Conclusions/Significance: The findings of this review shows that leprosy situation in Brazilian children under 15 years is extremely adverse in that the leprosy detection rate remains high in the majority of studies. The proportion of cases involving disability is also high and reflects the difficulties and the poor effectiveness of actions aimed at controlling the disease. The authors suggest the development of studies in spatial clusters of leprosy, where beyond the routine actions established, are included news strategies of active search and campaigns and actions of educations inside the clusters of this disease. The new agenda needs to involve the precepts of ethical, humane and supportive care, in order to achieve a new level of leprosy control in Brazil. [ABSTRACT FROM AUTHOR]

Background: In the Cameroon, previous efforts to identify Buruli ulcer (BU) through the mobilization of community health workers (CHWs) yielded poor results. In this paper, we describe the successful creation of a BU community of practice (BUCOP) in Bankim, Cameroon composed of hospital staff, former patients, CHWs, and traditional healers. Methods and principle findings: All seven stages of a well-defined formative research process were conducted during three phases of research carried out by a team of social scientists working closely with Bankim hospital staff. Phase one ethnographic research generated interventions tested in a phase two proof of concept study followed by a three- year pilot project. In phase three the pilot project was evaluated. An outcome evaluation documented a significant rise in BU detection, especially category I cases, and a shift in case referral. Trained CHW and traditional healers initially referred most suspected cases of BU to Bankim hospital. Over time, household members exposed to an innovative and culturally sensitive outreach education program referred the greatest number of suspected cases. Laboratory confirmation of suspected BU cases referred by community stakeholders was above 30%. An impact and process evaluation found that sustained collaboration between health staff, CHWs, and traditional healers had been achieved. CHWs came to play a more active role in organizing BU outreach activities, which increased their social status. Traditional healers found they gained more from collaboration than they lost from referral. Conclusion/ Significance: Setting up lines of communication, and promoting collaboration and trust between community stakeholders and health staff is essential to the control of neglected tropical diseases. It is also essential to health system strengthening and emerging disease preparedness. The BUCOP model described in this paper holds great promise for bringing communities together to solve pressing health problems in a culturally sensitive manner. [ABSTRACT FROM AUTHOR]

Background: The Bangladesh Lymphatic Filariasis (LF) Elimination Programme has made significant progress in interrupting transmission through mass drug administration (MDA) and has now focussed its efforts on scaling up managing morbidity and preventing disability (MMDP) activities to deliver the minimum package of care to people affected by LF clinical conditions. This paper highlights the Bangladesh LF Programme’s success in conducting a large-scale cross-sectional survey to determine the number of people affected by lymphoedema and hydrocoele, which enabled clinical risk maps to be developed for targeted interventions across the 34 endemic districts (19 high endemic; 15 low endemic). Methodology/Principal findings: In the 19 high endemic districts, 8,145 community clinic staff were trained to identify and report patients in their catchment area. In the 15 low endemic districts, a team of 10 trained field assistants conducted active case finding with cases reported via a SMS mHealth tool. Disease burden and prevalence maps were developed, with morbidity hotspots identified at sub-district level based on a combination of the highest prevalence rates per 100,000 and case-density rates per square kilometre (km2). The relationship between morbidity and baseline microfilaria (mf) prevalence was also examined. In total 43,678 cases were identified in the 19 high endemic districts; 30,616 limb lymphoedema (70.1%; female 55.3%), 12,824 hydrocoele (29.4%), and 238 breast/female genital swelling (0.5%). Rangpur Division reported the highest cases numbers and prevalence of lymphoedema (26,781 cases, 195 per 100,000) and hydrocoele (11661 cases, 169.6 per 100,000), with lymphoedema predominately affecting females (n = 21,652). Rangpur and Lalmonirhat Districts reported the highest case numbers (n = 11,199), and prevalence (569 per 100,000) respectively, with five overlapping lymphoedema and hydrocoele sub-district hotspots. In the 15 low endemic districts, 732 cases were identified; 661 lymphoedema (90.2%; female 39.6%), 56 hydrocoele (7.8%), and 15 both conditions (2.0%). Spearman’s correlation analysis found morbidity and mf prevalence significantly positively correlated (r = 0.904; p<0.01). Conclusions/Significance: The Bangladesh LF Programme has developed one of the largest, most comprehensive country databases on LF clinical conditions in the world. It provides an essential database for health workers to identify local morbidity hotspots, deliver the minimum package of care, and address the dossier elimination requirements. [ABSTRACT FROM AUTHOR]

Background: Yaws is targeted for eradication by 2020 in the WHA66.12 resolution of the World Health Assembly. The objective of this study was to describe the occurrence of yaws in the Americas and to contribute to the compilation of evidence based on published data to undertake the certification of yaws eradication. Methodology: A systematic review of the epidemiological situation of yaws in the Americas was performed by searching in MEDLINE, Embase, LILACS, SCOPUS, Web of Science, DARE and Cochrane Database of Systematic Reviews. Experts on the topic were consulted, and institutional WHO/PAHO library databases were reviewed. Principal findings: Seventy-five full-text articles published between 1839 and 2012 met the inclusion criteria. Haiti and Jamaica were the two countries with the highest number of papers (14.7% and 12.0%, respectively). Three-quarters of the studies were conducted before 1970. Thirty-three countries reported yaws case count or prevalence data. The largest foci in the history were described in Brazil and Haiti. The most recent cases reported were recorded in eight countries: Suriname, Guyana, Colombia, Haiti, Martinique, Dominica, Trinidad and Tobago, and Brazil. Gaps in information and heterogeneity were detected in the methodologies used and outcome reporting, making cross-national and chronological comparisons difficult. Conclusions: The lack of recent yaws publications may reflect, in the best-case scenario, the interruption of yaws transmission. It should be possible to reach the eradication goal in the region of the Americas, but it is necessary to collect more information. We suggest updating the epidemiological status of yaws, especially in two countries that need to assess ongoing transmission. Twenty-four countries need to demonstrate the interruption of transmission and declare its status of yaws endemicity, and sixteen countries should declare if they are yaws-free. It is necessary to formally verify the achievement of this goal in Ecuador. [ABSTRACT FROM AUTHOR]

Background: The goal of the global lymphatic filariasis (LF) program is to eliminate the disease as a public health problem by the year 2020. The WHO mapping protocol that is used to identify endemic areas in need of mass drug administration (MDA) uses convenience-based sampling. This rapid mapping has allowed the global program to dramatically scale up treatment, but as the program approaches its elimination goal, it is important to ensure that all endemic areas have been identified and have received MDA. In low transmission settings, the WHO mapping protocol for LF mapping has several limitations. To correctly identify the LF endemicity of woredas, a new confirmatory mapping tool was developed to test older school children for circulating filarial antigen (CFA) in settings where it is uncertain. Ethiopia is the first country to implement this new tool. In this paper, we present the Ethiopian experience of implementing the new confirmatory mapping tool and discuss the implications of the results for the LF program in Ethiopia and globally. Methods: Confirmatory LF mapping was conducted in 1,191 schools in 45 woredas, the implementation unit in Ethiopia, in the regions of Tigray, Amhara, Oromia, SNNP, Afar and Harari, where the results of previous mapping for LF using the current WHO protocol indicated that LF endemicity was uncertain. Within each woreda schools were selected using either cluster or systematic sampling. From selected schools, a total of 18,254 children were tested for circulating filarial antigen (CFA) using the immuno-chromatographic test (ICT). Results: Of the 18,254 children in 45 woredas who participated in the survey, 28 (0.16%) in 9 woredas tested CFA positive. According to the confirmatory mapping threshold, which is ≥2% CFA in children 9–14 years of age, only 3 woredas out of the total 45 had more CFA positive results than the threshold and thus were confirmed to be endemic; the remaining 42 woredas were declared non-endemic. These results drastically decreased the estimated total population living in LF-endemic woredas in Ethiopia and in need of MDA by 49.1%, from 11,580,010 to 5,893,309. Conclusion: This study demonstrated that the new confirmatory mapping tool for LF can benefit national LF programs by generating information that not only can confirm where LF is endemic, but also can save time and resources by preventing MDA where there is no evidence of ongoing LF transmission. [ABSTRACT FROM AUTHOR]

Background: Mycobacterium ulcerans infection, commonly known as Buruli ulcer (BU), is a debilitating neglected tropical disease. Its management remains complex and has three main components: antibiotic treatment combining rifampicin and streptomycin for 56 days, wound dressings and skin grafts for large ulcerations, and physical therapy to prevent functional limitations after care. In Benin, BU patient care is being integrated into the government health system. In this paper, we report on an innovative pilot program designed to introduce BU decentralization in Ouinhi district, one of Benin’s most endemic districts previously served by centralized hospital-based care. Methodology/Principal findings: We conducted intervention-oriented research implemented in four steps: baseline study, training of health district clinical staff, outreach education, outcome and impact assessments. Study results demonstrated that early BU lesions (71% of all detected cases) could be treated in the community following outreach education, and that most of the afflicted were willing to accept decentralized treatment. Ninety-three percent were successfully treated with antibiotics alone. The impact evaluation found that community confidence in decentralized BU care was greatly enhanced by clinic staff who came to be seen as having expertise in the care of most chronic wounds. Conclusions/Significance: This study documents a successful BU outreach and decentralized care program reaching early BU cases not previously treated by a proactive centralized BU program. The pilot program further demonstrates the added value of integrated wound management for NTD control. [ABSTRACT FROM AUTHOR]

Background: The monitoring and evaluation of lymphatic filariasis (LF) has largely relied on the detection of antigenemia and antibodies in human populations. Molecular xenomonitoring (MX), the detection of parasite DNA/RNA in mosquitoes, may be an effective complementary method, particularly for detecting signals in low-level prevalence areas where Culex is the primary mosquito vector. This paper investigated the application of a household-based sampling method for MX in Tamil Nadu, India. Methods: MX surveys were conducted in 2010 in two evaluation units (EUs): 1) a hotspot area, defined as sites with community microfilaria prevalence ≥1%, and 2) a larger area that also encompassed the hotspots. Households were systematically selected using a sampling interval proportional to the number of households in the EU. Mosquito pools were collected and analyzed by real-time polymerase chain reaction (qPCR). Two independent samples were taken in each EU to assess reproducibility of results. Follow-up surveys were conducted in 2012. Results: In 2010, the proportion of positive pools in the hotspot EU was 49.3% compared to 23.4% in the overall EU. In 2012, pool positivity was significantly reduced to 24.3% and 6.5%, respectively (p<0.0001). Pool positivity based on independent samples taken from each EU in 2010 and 2012 were not significantly different except for the hotspot EU in 2012 (p = 0.009). The estimated prevalence of infection in mosquitoes, measured by PoolScreen, declined from 2.2–2.7% in 2010 to 0.6–1.2% in 2012 in the hotspot area and from 0.9–1.1% to 0.2–0.3% in the larger area. Conclusions: The household-based sampling strategy for MX led to mostly reproducible results and supported the observed LF infection trends found in humans. MX has the potential to be a cost-effective, non-invasive monitoring and evaluation tool with sensitive detection of infection signals in low prevalence settings. Further investigation and application of this sampling strategy for MX are recommended to support its adoption as a standardized method for global LF elimination programs. [ABSTRACT FROM AUTHOR]

Background: Reducing social distance between hospital staff and patients and establishing clear lines of communication is a major challenge when providing in-patient care for people afflicted by Buruli ulcer (BU) and chronic ulcers. Research on hospitals as therapeutic communities is virtually non-existent in Africa and is currently being called for by medical anthropologists working in the field of health service and policy planning. This paper describes a pioneering attempt to establish a therapeutic community for patients suffering from BU and other chronic ulcers requiring long term hospital care in Benin. Methods: A six-month pilot project was undertaken with the objectives of establishing a therapeutic community and evaluating its impact on practitioner and patient relations. The project was designed and implemented by a team of social scientists working in concert with the current and previous director of a hospital serving patients suffering from advanced stage BU and other chronic ulcers. Qualitative research initially investigated patients’ understanding of their illness and its treatment, identified questions patients had about their hospitalization, and ascertained their level of social support. Newly designed question–answer health education sessions were developed. Following these hospital wide education sessions, open forums were held each week to provide an opportunity for patients and hospital staff to express concerns and render sources of discontent transparent. Patient group representatives then met with hospital staff to problem solve issues in a non-confrontational manner. Psychosocial support for individual patients was provided in a second intervention which took the form of drop-in counseling sessions with social scientists trained to serve as therapy facilitators and culture brokers. Results: Interviews with patients revealed that most patients had very little information about the identity of their illness and the duration of their treatment. This knowledge gap surprised clinic staff members, who assumed someone had provided this information. Individual counseling and weekly education sessions corrected this information gap and reduced patient concerns about their treatment and the status of their healing process. This led to positive changes in staff–patient interactions. There was widespread consensus among both patients and staff that the quality of communication had increased significantly. Open forums providing an opportunity for patients and staff to air grievances were likewise popular and patient representative meetings resulted in productive problem solving supported by the hospital administration. Some systemic problems, however, remained persistent challenges. Patients with ulcers unrelated to BU questioned why BU patients were receiving preferential treatment, given special medicines, and charged less for their care. The idea of subsidized treatment for one disease and not another was hard to justify, especially given that BU is not contagious. Conclusion: This pilot project illustrates the basic principles necessary for transforming long term residential hospitals into therapeutic communities. Although the focus of this case study was patients suffering from chronic ulcers, the model presented is relevant for other types of patients with cultural adaptation. [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: Arbovirus infections are a serious concern in tropical countries due to their high levels of transmission and morbidity. With the outbreaks of chikungunya (CHIKV) in surrounding regions in recent years and the fact that the environment in Vietnam is suitable for the vectors of CHIKV, the possibility of transmission of CHIKV in Vietnam is of great interest. However, information about CHIKV activity in Vietnam remains limited. Methodology: In order to address this question, we performed a systematic review of CHIKV in Vietnam and a CHIKV seroprevalence survey. The seroprevalence survey tested for CHIKV IgG in population serum samples from individuals of all ages in 2015 from four locations in Vietnam. Principal findings: The four locations were An Giang province (n = 137), Ho Chi Minh City (n = 136), Dak Lak province (n = 137), and Hue City (n = 136). The findings give us evidence of some CHIKV activity: 73/546 of overall samples were seropositive (13.4%). The age-adjusted seroprevalences were 12.30% (6.58–18.02), 13.42% (7.16–19.68), 7.97% (3.56–12.38), and 3.72% (1.75–5.69) in An Giang province, Ho Chi Minh City, Dak Lak province, and Hue City respectively. However, the age-stratified seroprevalence suggests that the last transmission ended around 30 years ago, consistent with results from the systematic review. We see no evidence for on-going transmission in three of the locations, though with some evidence of recent exposure in Dak Lak, most likely due to transmission in neighbouring countries. Before the 1980s, when transmission was occurring, we estimate on average 2–4% of the population were infected each year in HCMC and An Giang and Hue (though transmision ended earlier in Hue). We estimate lower transmission in Dak Lak, with around 1% of the population infected each year. Conclusion: In conclusion, we find evidence of past CHIKV transmission in central and southern Vietnam, but no evidence of recent sustained transmission. When transmission of CHIKV did occur, it appeared to be widespread and affect a geographically diverse population. The estimated susceptibility of the population to chikungunya is continually increasing, therefore the possibility of future CHIKV transmission in Vietnam remains. [ABSTRACT FROM AUTHOR]

Background: Trachoma is a progressive blinding disease initiated by infection of the conjunctiva with Chlamydia trachomatis. Repeated infections are thought to cause chronic inflammation, which drives scarring, leading to in-turning of the eyelids. The relationship between C. trachomatis, clinical inflammation and scarring development in children is not fully understood due to a paucity of longitudinal studies with infection data at frequent follow-up. Methods and findings: This longitudinal cohort study took place in northern Tanzania. Children aged 6–10 years at baseline were eligible for inclusion. Participants were visited every three months for four years. Clinical signs and conjunctival swabs for C. trachomatis detection by qPCR were collected at each time-point. Conjunctival photographs from baseline and final time-points were graded and compared side-by-side to determine scarring incidence and progression. Of the 666 children enrolled in the study, outcome data were obtained for 448. Scarring progression was detected in 103/448 (23%) children; 48 (11%) of which had incident scarring and 55 (12%) had progression of existing scarring. Scarring was strongly associated with increasing episodes of trachomatous papillary inflammation (TP). Weaker associations were found between episodes of C. trachomatis infection and follicular trachoma (TF) with scarring progression in unadjusted models, which were absent in multivariable analysis after adjusting for inflammation (multivariable results: C. trachomatis p = 0.44, TF p = 0.25, TP p = <0.0001, age p = 0.13, female sex p = 0.05). Individuals having TP at 30% or more of the time-points they were seen had an odds ratio of 7.5 (95%CI = 2.7–20.8) for scarring progression relative to individuals without any TP detected during the study period. Conclusions: These data suggest that the effect of infection on scarring progression is mediated through papillary inflammation, and that other factors contributing to the development of inflammation, in addition to C. trachomatis infection, may be important in driving conjunctival scarring progression in children. The addition of TP as a measure in trachoma control programs would provide an indication of the future risk of developing scarring sequelae. [ABSTRACT FROM AUTHOR]

Lymphatic filariasis (LF) elimination as a public health problem requires the interruption of transmission by administration of preventive mass drug administration (MDA) to the eligible population living in endemic districts. Suboptimal MDA coverage leads to persistent parasite transmission with consequential infection, disease and disability, and the need for continuing MDA rounds, requiring considerable investment. Routine coverage reports must be verified in each MDA implementation unit (IU) due to incorrect denominators and numerators used to calculate coverage estimates with administrative data. IU are usually the health districts. Coverage is verified so IU teams can evaluate their outreach and take appropriate action to improve performance. Mozambique and the Democratic Republic of Congo (DRC) have conducted MDA campaigns for LF since 2009 and 2014, respectively. To verify district reports and assess the declared achievement using administrative data of the minimum 80% coverage of eligible people (or 65% of the total population), both countries conducted rapid probability surveys using Lot Quality Assurance Sampling (LQAS)(n = 1102) in 2015 and 2016 in 58 IU in 49 districts. The surveys identified IU with suboptimal coverage, reasons for not residents did not take the medication, place where the medication was received, information sources, and knowledge about diseases prevented by the MDA. LQAS identified four inadequately covered IU triggering district team performance reviews with provincial and national teams and district retreatment. Provincial estimates using probability samples (weighted by populations sizes) were 10 and 17 percentage points lower than reported coverage in DRC and Mozambique. The surveys identified: absence from home during annual MDA rounds as the main reason for low performance and provided valuable information about pre-campaign and campaign activities resulting in improved strategies and continued progress towards elimination of LF and co-endemic Neglected Tropical Diseases. [ABSTRACT FROM AUTHOR]

Prevalence is a common epidemiological measure for assessing soil-transmitted helminth burden and forms the basis for much public-health decision-making. Standard diagnostic techniques are based on egg detection in stool samples through microscopy and these techniques are known to have poor sensitivity for individuals with low infection intensity, leading to poor sensitivity in low prevalence populations. PCR diagnostic techniques offer very high sensitivities even at low prevalence, but at a greater cost for each diagnostic test in terms of equipment needed and technician time and training. Pooling of samples can allow prevalence to be estimated while minimizing the number of tests performed. We develop a model of the relative cost of pooling to estimate prevalence, compared to the direct approach of testing all samples individually. Analysis shows how expected relative cost depends on both the underlying prevalence in the population and the size of the pools constructed. A critical prevalence level (approx. 31%) above which pooling is never cost effective, independent of pool size. When no prevalence information is available, there is no basis on which to choose between pooling and testing all samples individually. We recast our model of relative cost in a Bayesian framework in order to investigate how prior information about prevalence in a given population can be used to inform the decision to choose either pooling or full testing. Results suggest that if prevalence is below 10%, a relatively small exploratory prevalence survey (10–15 samples) can be sufficient to give a high degree of certainty that pooling may be relatively cost effective. [ABSTRACT FROM AUTHOR]

Background: Trachomatous trichiasis (TT) will continue to develop among those people who have had repeated infections after active trachoma is controlled. Detecting and treating affected individuals will remain necessary for years; a long “tail” of incident cases is anticipated. As the prevalence of TT declines, there will be fewer cases available for training trachoma graders (TG), necessitating alternative methods. Methodology/Principal findings: Prospective, diagnostic accuracy study assessing sensitivity and specificity of 3D and 2D photography as a tool for training TG to detect TT. Individuals with TT in Ethiopia were examined, and 2D and 3D clinical images taken. Images were independently graded by four graders for presence or absence of trichiasis and compared to field grading. We recruited 153 participants. Clinical assessments and images were available for 306 eyes. Trichiasis was identified in 204 eyes by field grading. Image grading was performed on a selection of 262 eyes (131 with trichiasis). Most eyes with trichiasis had minor trichiasis (94/131). Pooled sensitivity was 88.3% (3D) and 98.0% (2D); pooled specificity was 59.8% (3D) and 26.8% (2D). 3D photo grading was 33.0% more specific than the 2D photo grading (p = 0.0002). The overall Kappa scores were 0.48 (3D) and 0.25 (2D). We trained 26 novice TG in Ethiopia using 3D images. They were tested on a 3D images set and had 71.4% agreement (kappa 0.46), relative to an expert. They were then tested examining 50 people, and had 86.8% agreement (kappa 0.75). We also tested 27 experienced TG on the same cases (86.4% agreement, kappa 0.75). There was no difference in performance between groups (p = 0.76). All participants preferred 3D over 2D images for training. Conclusions/Significance: The slightly higher sensitivity of 2D photos comes at considerable cost in specificity. Training with 3D images enabled novice TG to identify cases as well as experienced TG. 3D were preferred to conventional 2D photos for training. Standardized 3D images of TT could be a useful tool for training TG, in settings where there are now few TT cases. [ABSTRACT FROM AUTHOR]

Background: Epilepsy and progressively worsening severe chronic headaches (WSCH) are the two most common clinical manifestations of neurocysticercosis, a form of cysticercosis. Most community-based studies in sub-Saharan Africa (SSA) use a two-step approach (questionnaire and confirmation) to estimate the prevalence of these neurological disorders and neurocysticercosis. Few validate the questionnaire in the field or account for the imperfect nature of the screening questionnaire and the fact that only those who screen positive have the opportunity to be confirmed. This study aims to obtain community-based validity estimates of a screening questionnaire, and to assess the impact of verification bias and misclassification error on prevalence estimates of epilepsy and WSCH. Methodology/Principal findings: Baseline screening questionnaire followed by neurological examination data from a cluster randomized controlled trial collected between February 2011 and January 2012 were used. Bayesian latent-class models were applied to obtain verification bias adjusted validity estimates for the screening questionnaire. These models were also used to compare the adjusted prevalence estimates of epilepsy and WSCH to those directly obtained from the data (i.e. unadjusted prevalence estimates). Different priors were used and their corresponding posterior inference was compared for both WSCH and epilepsy. Screening data were available for 4768 individuals. For epilepsy, posterior estimates for the sensitivity varied with the priors used but remained robust for the specificity, with the highest estimates at 66.1% (95%BCI: 56.4%;75.3%) for sensitivity and 88.9% (88.0%;89.8%) for specificity. For WSCH, the sensitivity and specificity estimates remained robust, with the highest at 59.6% (49.7%;69.1%) and 88.6% (87.6%;89.6%), respectively. The unadjusted prevalence estimates were consistently lower than the adjusted prevalence estimates for both epilepsy and WSCH. Conclusions/Significance: This study demonstrates that in some settings, the prevalence of epilepsy and WSCH can be considerably underestimated when using the two-step approach. We provide an analytic solution to obtain more valid prevalence estimates of these neurological disorders, although more community-based validity studies are needed to reduce the uncertainty of the estimates. Valid estimates of these two neurological disorders are essential to obtain accurate burden values for neglected tropical diseases such as neurocysticercosis that manifest as epilepsy or WSCH. Trial registration: ClinicalTrials.gov . [ABSTRACT FROM AUTHOR]

Background: Age patterns in asymptomatic and symptomatic infection with Leishmania donovani, the causative agent of visceral leishmaniasis (VL) in the Indian subcontinent (ISC), are currently poorly understood. Age-stratified serology and infection incidence have been used to assess transmission levels of other diseases, which suggests that they may also be of use for monitoring and targeting control programmes to achieve elimination of VL and should be included in VL transmission dynamic models. We therefore analysed available age-stratified data on both disease incidence and prevalence of immune markers with the aim of collating the currently available data, estimating rates of infection, and informing modelling and future data collection. Methodology/Principal findings: A systematic literature search yielded 13 infection prevalence and 7 VL incidence studies meeting the inclusion criteria. Statistical tests were performed to identify trends by age, and according to diagnostic cut-off. Simple reversible catalytic models with age-independent and age-dependent infection rates were fitted to the prevalence data to estimate infection and reversion rates, and to test different hypotheses about the origin of variation in these rates. Most of the studies showed an increase in infection prevalence with age: from ≲10% seroprevalence (<20% Leishmanin skin test (LST) positivity) for 0-10-year-olds to >10% seroprevalence (>20% LST-positivity) for 30-40-year-olds, but overall prevalence varied considerably between studies. VL incidence was lower amongst 0-5-year-olds than older age groups in most studies; most showing a peak in incidence between ages 5 and 20. The age-independent catalytic model provided the best overall fit to the infection prevalence data, but the estimated rates for the less parsimonious age-dependent model were much closer to estimates from longitudinal studies, suggesting that infection rates may increase with age. Conclusions/Significance: Age patterns in asymptomatic infection prevalence and VL incidence in the ISC vary considerably with geographical location and time period. The increase in infection prevalence with age and peaked age-VL-incidence distribution may be due to lower exposure to infectious sandfly bites in young children, but also suggest that acquired immunity to the parasite increases with age. However, poor standardisation of serological tests makes it difficult to compare data from different studies and draw firm conclusions about drivers of variation in observed age patterns. [ABSTRACT FROM AUTHOR]

The gold-standard method for quantifying neutralizing antibody responses to many viruses, including dengue virus (DENV), is the plaque reduction neutralization test (PRNT, also called the immunofocus reduction neutralization test). The PRNT conducted on 96-well plates is high-throughput and requires a smaller volume of antiserum than on 6- or 24-well plates, but manual plaque counting is challenging and existing automated plaque counters are expensive or difficult to optimize. We have developed Viridot (Viridot package), a program for R with a user interface in shiny, that counts viral plaques of a variety of phenotypes, estimates neutralizing antibody titers, and performs other calculations of use to virologists. The Viridot plaque counter includes an automatic parameter identification mode (misses <10 plaques/well for 87% of diverse DENV strains [n = 1521]) and a mode that allows the user to fine-tune the parameters used for counting plaques. We compared standardized manual and Viridot plaque counting methods applied to the same wells by two analyses and found that Viridot plaque counts were as similar to the same analyst's manual count (Lin’s concordance correlation coefficient, ρc = 0.99 [95% confidence interval: 0.99–1.00]) as manual counts between analysts (ρc = 0.99 [95% CI: 0.98–0.99]). The average ratio of neutralizing antibody titers based on manual counted plaques to Viridot counted plaques was 1.05 (95% CI: 0.98–1.14), similar to the average ratio of antibody titers based on manual plaque counts by the two analysts (1.06 [95% CI: 0.84–1.34]). Across diverse DENV and ZIKV strains (n = 14), manual and Viridot plaque counts were mostly consistent (range of ρc = 0.74 to 1.00) and the average ratio of antibody titers based on manual and Viridot counted plaques was close to 1 (0.94 [0.86–1.02]). Thus, Viridot can be used for plaque counting and neutralizing antibody titer estimation of diverse DENV strains and potentially other viruses on 96-well plates as well as for formalization of plaque-counting rules for standardization across experiments and analysts. [ABSTRACT FROM AUTHOR]

Background: The recommended strategy for control of schistosomiasis is preventive chemotherapy with praziquantel (PZQ). Pre-school children (PSC) are excluded from population treatment programs. In high endemic areas, these children are also at risk, and require treatment with PZQ. The Government of Kenya initiated the National School-Based Deworming Programme (NSBDP) where PSC in Early Childhood Development Education (ECDE) Centers are only eligible for treatment with albendazole (ABZ) but not with PZQ. Methodology/Principal findings: 400 PSC were enrolled, from 10 randomly selected ECDE Centers in Kwale County, Kenya where children were treated with crushed PZQ tablets mixed with orange juice, at a single dose of 40 mg/kg. Adverse events were assessed 24 hours post-treatment through questionnaires administered to the parents or guardians. Acceptability was determined by observing if the child spat and/ or vomited all or part of the PZQ dose immediately after treatment. Efficacy was assessed by examining urine samples for Schistosoma haematobium eggs in the 5 weeks post-treatment follow-up. Children testing negative for S. haematobium during the follow-up were considered cured. Egg reduction rate (ERR) was calculated as the decrement in the infection intensity (group’s geometric mean egg counts per 10 ml of urine) following treatment expressed as a proportion of the pre-treatment infection intensity. Before treatment, 80 out of the 400 children enrolled in the study tested positive for S. haematobium (20.0% (95% confidence interval (CI) 16.4–24.2%). Of these, 41 had infections of heavy intensity (51.3%) while the rest (48.7%) were of light intensity. Five weeks post-treatment, 10 children who had heavy intensity infection were diagnosed with S. haematobium (prevalence: 2.5% (95% CI 1.5–4.9%). Infection intensities decreased significantly from 45.9 (95% CI: 31.0–68.0) eggs/ 10 ml urine to1.4 (95% CI: 1.1–1.7) eggs/ 10 ml urine during pre-and post-treatment respectively. The ERR was 96.9%. There were no severe adverse events during follow up 24 hours post treatment. Treatment tolerability among the 400 children was high as none of the children spat and/ or vomited as observed in this study. Conclusion/Significance: The study revealed that crushed PZQ is safe and effective in the treatment of urogenital schistosomiasis in this age group. It is therefore recommended that PZQ should be administered to the PSC in Kwale County. [ABSTRACT FROM AUTHOR]

Background: In India, dengue disease is emerging as the most important vector borne public health problem due to rapid and unplanned urbanization, high human density and week management of the disease. Clinical cases are grossly underreported and not much information is available on prevalence and incidence of the disease. Methodology: A cross sectional, stratified, facility based, multistage cluster sampling was conducted between May 4 and June 27, 2017 in Pune city. A total of 1,434 participants were enrolled. The serum samples were tested for detection of historical dengue IgG antibodies by ELISA using the commercial Panbio Dengue IgG Indirect ELISA kit. Anti-dengue IgG-capture Panbio ELISA was used for detection of high titered antibodies to detect recent secondary infection. We used this data to estimate key transmission parameters like force of infection and basic reproductive number. A subset of 120 indirect ELISA positive samples was also tested for Plaque Reduction Neutralizing Antibodies for determining serotype-specific prevalence. Findings: Overall, 81% participants were infected with dengue virus (DENV) at least once if not more. The positivity was significantly different in different age groups. All the adults above 70 years were positive for DENV antibodies. Over 69% participants were positive for neutralizing antibodies against all 4 serotypes suggesting intense transmission of all DENV serotypes in Pune. Age-specific seroprevalence was consistent with long-term, endemic circulation of DENV. There was an increasing trend with age, from 21.6% among <36 months to 59.4% in age group 10–12 years. We estimate that 8.68% of the susceptible population gets infected by DENV each year resulting into more than 3,00,000 infections and about 47,000 to 59,000 cases per year. This transmission intensity is similar to that reported from other known hyper-endemic settings in Southeast Asia and the Americas but significantly lower than report from Chennai. Conclusions: Our study suggests that Pune city has high disease burden, all 4 serotypes are circulating, significant spatial heterogeneity in seroprevalence and suboptimal immunity in younger age groups. This would allow informed decisions to be made on management of dengue and introduction of upcoming dengue vaccines in the city. [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]

Background: Onchocerciasis, also known as river blindness, is a parasitic disease. More than 99 percent of all cases occur in Africa. Bioko Island (Equatorial Guinea) is the only island endemic for onchocerciasis in the world. Since 2005, when vector Simulium yahense was eliminated, there have not been any reported cases of infection. This study aimed to demonstrate that updated WHO criteria for stopping mass drug administration (MDA) have been met. Methodology/Principal findings: A cross-sectional study was conducted from September 2016 to January 2017. Participants were 5- to 9-year-old school children. Onchocerciasis/lymphatic Filariasis (LF, only in endemic districts) rapid diagnostic tests (RDTs) were performed. Blood spots were collected from RDT positive children and 10 percent of the RDT negatives to determine Ov16 and Wb123 IgG4 antibodies through enzyme-linked immunosorbent assay (ELISA). Skin snips were collected from RDT positives. Filarial detection was performed by PCR in positives and indeterminate sera. Black fly collection was carried out in traditional breeding sites. A total of 7,052 children, ranging from 5 to 9 years of age, were included in the study. Four children (0.06%) were Ov16 IgG4 RDT positives, but negative by ELISA Ov16, while 6 RDT negative children tested positive by ELISA. A total of 1,230 children from the Riaba and Baney districts were tested for LF. One child was Wb123 RDT positive (0.08%), but ELISA negative, while 3 RDT negative children were positive by Wb123 ELISA. All positive samples were negative by PCR for onchocerciasis and LF (in blood spot and skin snip). All fly collections and larval prospections in the traditional catching and prospection sites were negative. Conclusions/Significance: WHO criteria have been met, therefore MDA in Bioko Island can be stopped. Three years of post-treatment surveillance should be implemented to identify any new occurrences of exposure or infection. [ABSTRACT FROM AUTHOR]

Background: Soil-transmitted helminths (STH) infect nearly 1.5 billion individuals globally, and contribute to poor physical and cognitive development in children. STH control programs typically consist of regular delivery of anthelminthic drugs, targeting school-aged children. Expanding STH control programs community-wide may improve STH control among school-aged children, and combining deworming with improvements to water, sanitation and hygiene (WASH) may further reduce transmission. The (S)WASH-D for Worms pilot study aims to compare the differential impact of integrated WASH and deworming programs when implemented at primary schools only versus when additionally implemented community-wide. Methodology/Principal findings: A two-arm, non-randomized cluster intervention study was conducted. Six communities were identified by partner WASH agencies and enrolled in the study. All communities received a school-based WASH and deworming program, while three additionally received a community-based WASH and deworming program. STH infections were measured in school-aged children at baseline and six months after deworming. Over 90% of eligible children were recruited for the study, of whom 92.3% provided stool samples at baseline and 88.9% at follow-up. The school WASH intervention improved school sanitation, while the community WASH intervention reduced open defecation from 50.4% (95% CI 41.8–59.0) to 23.5% (95% CI 16.7–32.0). There was a trend towards reduced odds of N. americanus infection among children who received the community-wide intervention (OR 0.42, 95% CI 0.07–2.36, p = 0.32). Conclusions: This pilot study provides proof of principle for testing the hypothesis that community-wide STH control programs have a greater impact on STH infections among children than school-based programs, and supports the rationale for conducting a full-scale cluster randomized controlled trial. High recruitment and participation rates and successful implementation of school WASH programs demonstrate study feasibility and acceptability. However, eliminating open defecation remains a challenge; ongoing work is required to develop community sanitation programs that achieve high and sustainable latrine coverage. Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR) [ABSTRACT FROM AUTHOR]

Introduction: The WHO yaws eradication strategy consists of one round of total community treatment (TCT) of single-dose azithromycin with coverage of > 90%.The efficacy of the strategy to reduce the levels on infection has been demonstrated previously in isolated island communities in the Pacific region. We aimed to determine the efficacy of a single round of TCT with azithromycin to achieve a decrease in yaws prevalence in communities that are endemic for yaws and surrounded by other yaws-endemic areas. Methods: Surveys for yaws seroprevalence and prevalence of skin lesions were conducted among schoolchildren aged 5–15 years before and one year after the TCT intervention in the Abamkrom sub-district of Ghana. We used a cluster design with the schools as the primary sampling unit. Among 20 eligible primary schools in the sub district, 10 were assigned to the baseline survey and 10 to the post-TCT survey. The field teams conducted a physical examination for skin lesions and a dual point-of-care immunoassay for non-treponemal and treponemal antibodies of all children present at the time of the visit. We also undertook surveys with non-probabilistic sampling to collect lesion swabs for etiology and macrolide resistance assessment. Results: At baseline 14,548 (89%) of 16,287 population in the sub-district received treatment during TCT. Following one round of TCT, the prevalence of dual seropositivity among all children decreased from 10.9% (103/943) pre-TCT to 2.2% (27/1211) post-TCT (OR 0.19; 95%CI 0.09–0.37). The prevalence of serologically confirmed skin lesions consistent with active yaws was reduced from 5.7% (54/943) pre-TCT to 0.6% (7/1211) post-TCT (OR 0.10; 95% CI 0.25–0.35). No evidence of resistance to macrolides against Treponema pallidum subsp. pertenue was seen. Discussion: A single round of high coverage TCT with azithromycin in a yaws affected sub-district adjoining other endemic areas is effective in reducing the prevalence of seropositive children and the prevalence of early skin lesions consistent with yaws one year following the intervention. These results suggest that national yaws eradication programmes may plan the gradual expansion of mass treatment interventions without high short-term risk of reintroduction of infection from contiguous untreated endemic areas. [ABSTRACT FROM AUTHOR]

Objective: Antibiotic treatment of Group A Streptococcus (GAS) pharyngitis is important in acute rheumatic fever (ARF) prevention, however clinical guidelines for prescription vary. GAS carriers with acute viral infections may receive antibiotics unnecessarily. This review assessed the prevalence of GAS pharyngitis and carriage in different settings. Methods: A random-effects meta-analysis was performed. Prevalence estimates for GAS+ve pharyngitis, serologically-confirmed GAS pharyngitis and asymptomatic pharyngeal carriage were generated. Findings were stratified by age group, recruitment method and country income level. Medline and EMBASE databases were searched for relevant literature published between 1 January 1946 and 7 April 2017. Studies reporting prevalence data on GAS+ve or serologically-confirmed GAS pharyngitis that stated participants exhibited symptoms of pharyngitis or upper respiratory tract infection (URTI) were included. Included studies reporting the prevalence of asymptomatic GAS carriage needed to state participants were asymptomatic. Results: 285 eligible studies were identified. The prevalence of GAS+ve pharyngitis was 24.1% (95% CI: 22.6–25.6%) in clinical settings (which used ‘passive recruitment’ methods), but less in sore throat management programmes (which used ‘active recruitment’, 10.0%, 8.1–12.4%). GAS+ve pharyngitis was more prevalent in high-income countries (24.3%, 22.6–26.1%) compared with low/middle-income countries (17.6%, 14.9–20.7%). In clinical settings, approximately 10% of children swabbed with a sore throat have serologically-confirmed GAS pharyngitis, but this increases to around 50–60% when the child is GAS culture-positive. The prevalence of serologically-confirmed GAS pharyngitis was 10.3% (6.6–15.7%) in children from high-income countries and their asymptomatic GAS carriage prevalence was 10.5% (8.4–12.9%). A lower carriage prevalence was detected in children from low/middle income countries (5.9%, 4.3–8.1%). Conclusions: In active sore throat management programmes, if the prevalence of GAS detection approaches the asymptomatic carriage rate (around 6–11%), there may be little benefit from antibiotic treatment as the majority of culture-positive patients are likely carriers. [ABSTRACT FROM AUTHOR]

Background: Current WHO recommendations for lymphatic filariasis (LF) surveillance advise programs to implement activities to monitor for new foci of transmission after stopping mass drug administration (MDA). A current need in the global effort to eliminate LF is to standardize diagnostic tools and surveillance activities beyond the recommended transmission assessment survey (TAS). Methodology: TAS was first conducted in American Samoa in 2011 (TAS 1) and a repeat TAS was carried out in 2015 (TAS 2). Circulating filarial antigen (CFA) and serologic results from both surveys were analyzed to determine whether interruption of LF transmission has been achieved in American Samoa. Principal findings: A total of 1,134 and 864 children (5–10 years old) were enrolled in TAS 1 and TAS 2, respectively. Two CFA-positive children were identified in TAS 1, and one CFA-positive child was identified in TAS 2. Results of both surveys were below the threshold for which MDA was warranted. Additionally, 1,112 and 836 dried blood spots from TAS 1 and TAS 2, respectively were tested for antibodies to Wb123, Bm14 and Bm33 by luciferase immunoprecipitation system (LIPS) assay and multiplex bead assay. In 2011, overall prevalence of responses to Wb123, Bm14, and Bm33 was 1.0%, 6.8% and 12.0%, respectively. In 2015, overall prevalence of positive Bm14 and Bm33 responses declined significantly to 3.0% (p<0.001) and 7.8% (p = 0.013), respectively. Conclusions/Significance: Although passing TAS 1 and TAS 2 and an overall decline in the prevalence of antibodies to Bm14 and Bm33 between these surveys suggests decreased exposure and infection among young children, there were persistent responses in some schools. Clustering and persistence of positive antibody responses in schools may be an indication of ongoing transmission. There is a need to better understand the limitations of current antibody tests, but our results suggest that serologic tools can have a role in guiding programmatic decision making. [ABSTRACT FROM AUTHOR]

Rabies is an important neglected disease, which kills around 59,000 people a year. Over a third of these deaths are in children less than 15 years of age. Almost all human rabies deaths in Africa and Asia are due to bites from infected dogs. Despite the high efficacy of current rabies vaccines, awareness about rabies preventive healthcare is often low in endemic areas. It is therefore common for educational initiatives to be conducted in conjunction with other rabies control activities such as mass dog vaccination, however there are few examples where the efficacy of education activities has been assessed. Here, primary school children in Zomba, Malawi, were given a lesson on rabies biology and preventive healthcare. Subsequently, a mass dog vaccination programme was delivered in the same region. Knowledge and attitudes towards rabies were assessed by a questionnaire before the lesson, immediately after the lesson and 9 weeks later to assess the impact the lesson had on school children’s knowledge and attitudes. This assessment was also undertaken in children who were exposed to the mass dog vaccination programme but did not receive the lesson. Knowledge of rabies and how to be safe around dogs increased following the lesson (both p<0.001), and knowledge remained higher than baseline 9 weeks after the lesson (both p<0.001). Knowledge of rabies and how to be safe around dogs was greater amongst school children who had received the lesson compared to school children who had not received the lesson, but had been exposed to a rabies vaccination campaign in their community (both p<0.001) indicating that the lesson itself was critical in improving knowledge. In summary, we have shown that a short, focused classroom-based lesson on rabies can improve short and medium-term rabies knowledge and attitudes of Malawian schoolchildren. [ABSTRACT FROM AUTHOR]

Background: Trachoma is the leading infectious cause of blindness worldwide. In communities where the district level prevalence of trachomatous inflammation-follicular among children ages 1–9 years is ≥5%, WHO recommends annual mass drug administration (MDA) of antibiotics with the aim of at least 80% coverage. Population-based post-MDA coverage surveys are essential to understand the effectiveness of MDA programs, yet published reports from trachoma programs are rare. Methods: In the Amhara region of Ethiopia, a population-based MDA coverage survey was conducted 3 weeks following the 2016 MDA to estimate the zonal prevalence of self-reported drug coverage in all 10 administrative zones. Survey households were selected using a multi-stage cluster random sampling design and all individuals in selected households were presented with a drug sample and asked about taking the drug during the campaign. Zonal estimates were weighted and confidence intervals were calculated using survey procedures. Self-reported drug coverage was then compared with regional reported administrative coverage. Results: Region-wide, 24,248 individuals were enumerated, of which, 20,942 (86.4%) individuals were present. The regional self-reported antibiotic coverage was 76.8% (95%Confidence Interval (CI):69.3–82.9%) in the population overall and 77.4% (95%CI = 65.7–85.9%) among children ages 1–9 years old. Zonal coverage ranged from 67.8% to 90.2%. Five out of 10 zones achieved a coverage >80%. In all zones, the reported administrative coverage was greater than 90% and was considerably higher than self-reported MDA coverage. Main reasons reported for MDA campaign non-attendance included being physically unable to get to MDA site (22.5%), traveling (20.6%), and not knowing about the campaign (21.0%). MDA refusal was low (2.8%) in this population. Conclusions: Although self-reported MDA coverage in Amhara was greater than 80% in some zones, programmatic improvements are warranted throughout Amhara to achieve higher coverage. These results will be used to enhance community mobilization and improve training for MDA distributors and supervisors to improve coverage in future MDAs. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) remains one of the most threatening diseases and Nigeria has one of the world’s largest burdens. This study performed high-throughput spoligotyping directly on sputum smears to describe the Mycobacterium tuberculosis strains circulating among new TB patients in Nigeria. Methods: All State TB control programmes in Nigeria were requested to submit 25–50 smear-positive Ziehl-Neelsen (ZN) stained slides for screening during 2013–2014. DNA was extracted from 929 slides for spoligotyping and drug-resistance analysis using microbead-based flow-cytometry suspension arrays. Results: Spoligotyping results were obtained for 549 (59.1%) of 929 samples. Lineage 4 Cameroon sublineage (L4.6.2) represented half of the patterns, Mycobacterium africanum (L5 and L6) represented one fifth of the patterns, and all other lineages, including other L4 sublineages, represented one third of the patterns. Sublineage L4.6.2 was mostly identified in the north of the country whereas L5 was mostly observed in the south and L6 was scattered. The spatial distribution of genotypes had genetic geographic gradients. We did not obtain results enabling the detection of drug-resistance mutations. Conclusion/Significance: We present the first national snapshot of the M. tuberculosis spoligotypes circulating in Nigeria based on ZN slides. Spoligotyping data can be obtained in a rapid and high-throughput manner with DNA extracted from ZN-stained slides, which may potentially improve our understanding of the genetic epidemiology of TB. [ABSTRACT FROM AUTHOR]

Most part of Southeast Asia is considered endemic for human-infecting Taenia tapeworms; Taenia solium, T. saginata, and T. asiatica. However, until now there was no report of the occurrence of human cases of T. asiatica in Lao PDR. This study, conducted in Savannakhet Province, Lao PDR, microscopically examined a total of 470 fecal samples by Kato Katz method and found 86% of people harboring at least one helminth. Hookworms were detected in 56% of the samples besides Opisthorchis like eggs (42%), Trichuris trichiura (27%), Ascaris spp. (14%), and Taenia spp. (4%) eggs. Serology for cysticercosis showed 6.8% positives with results varying from 3% to 14.3% in Ethnic School students and Kalouk Kao village respectively. Species-specific PCR targeting mitochondrial DNA (mtDNA) of 28 tapeworms, recovered from 16 patients, revealed T. solium (n = 2), T. saginata (n = 21), and T. asiatica (n = 5). Two patients were confirmed to be coinfected with T. saginata and T. asiatica, indicating the endemicity of the 3 human Taenia in Lao PDR. However, nucleotide sequencing of a nuclear DNA gene, DNA polymerase delta (pold) revealed that all the tapeworms identified as T. asiatica using mtDNA had T. saginata type allele at pold locus, demonstrating that they are not “pure T. asiatica” but the hybrid descendants between the two species, confirming the wide distribution of hybrids of T. saginata/ T. asiatica in Southeast Asia. The high prevalence of several helminthic NTDs in east Savannakhet area even with conventional control measures indicates the importance to establish wide and multifaceted health programs to sustainably improve the quality of life of the populations living in these communities. [ABSTRACT FROM AUTHOR]

Mosquito-borne Zika virus (ZIKV) typically causes a mild and self-limiting illness known as Zika fever. Since its recent emergence in 2014 in the American continent, ZIKV infection during pregnancy has been closely associated with a wide range of congenital abnormalities. To date, no vaccines or antivirals are publicly available. We developed Zika virus-like particles (VLPs) and evaluated their immunogenicity and protective efficacy in mouse models. ZIKV VLPs (ZIKVLPs) formulated with alum were injected into 6-8-week-old interferon deficient AG129 mice as well as wild type BALB/c mice. Control mice received PBS/alum. Animals were challenged with 200 PFU (>1000 AG129 LD50s) of ZIKV strain H/PF/2013. All vaccinated mice survived with no morbidity or weight loss while control animals either died at 9 days post challenge (AG129) or had increased viremia (BALB/c). Neutralizing antibodies were observed in all ZIKVLP vaccinated mice. The role of neutralizing antibodies in protecting mice was demonstrated by passive transfer. Our findings demonstrate the protective efficacy of the ZIKVLP vaccine and highlight the important role that neutralizing antibodies play in protection against ZIKV infection. [ABSTRACT FROM AUTHOR]

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

Background: Although the malaria burden in the Lao PDR has gradually decreased, the elimination of malaria by 2030 presents many challenges. Microscopy and malaria rapid diagnostic tests (RDTs) are used to diagnose malaria in the Lao PDR; however, some studies have reported the prevalence of sub-microscopic Plasmodium infections or asymptomatic Plasmodium carriers in endemic areas. Thus, highly sensitive detection methods are needed to understand the precise malaria situation in these areas. Methodology/Principal findings: A cross-sectional malaria field survey was conducted in 3 highly endemic malaria districts (Xaysetha, Sanamxay, Phouvong) in Attapeu province, Lao PDR in 2015, to investigate the precise malaria endemicity in the area; 719 volunteers from these villages participated in the survey. Microscopy, RDTs and a real-time nested PCR were used to detect Plasmodium infections and their results were compared. A questionnaire survey of all participants was also conducted to estimate risk factors of Plasmodium infection. Numbers of infections detected by the three methods were microscopy: P. falciparum (n = 1), P. vivax (n = 2); RDTs: P. falciparum (n = 2), P. vivax (n = 3); PCR: Plasmodium (n = 47; P. falciparum [n = 4], P. vivax [n = 41], mixed infection [n = 2]; 6.5%, 47/719). Using PCR as a reference, the sensitivity and specificity of microscopy were 33.3% and 100.0%, respectively, for detecting P. falciparum infection, and 7.0% and 100.0%, for detecting P. vivax infection. Among the 47 participants with parasitemia, only one had a fever (≥37.5°C) and 31 (66.0%) were adult males. Risk factors of Plasmodium infection were males and soldiers, whereas a risk factor of asymptomatic Plasmodium infection was a history of ≥3 malaria episodes. Conclusions/Significance: There were many asymptomatic Plasmodium carriers in the study areas of Attapeu province in 2015. Adult males, probably soldiers, were at high risk for malaria infection. P. vivax, the dominant species, accounted for 87.2% of the Plasmodium infections among the participants. To achieve malaria elimination in the Lao PDR, highly sensitive diagnostic tests, including PCR-based diagnostic methods should be used, and plans targeting high-risk populations and elimination of P. vivax should be designed and implemented. [ABSTRACT FROM AUTHOR]

The Special Programme for Research and Training in Tropical Diseases (TDR) co-sponsored by UNICEF, UNDP, World Bank and WHO has been supporting research capacity strengthening in low- and middle-income countries for over 40 years. In order to assess and continuously optimize its capacity strengthening approaches, an evaluation of the influence of TDR training grants on research career development was undertaken. The assessment was part of a larger evaluation conducted by the European Science Foundation. A comprehensive survey questionnaire was developed and sent to a group of 117 trainees supported by TDR who had completed their degree (masters or PhD) between 2000 and 2012; of these, seventy seven (77) responded. Most of the respondents (80%) rated TDR support as a very important factor that influenced their professional career achievements. The “brain drain” phenomenon towards high-income countries was particularly low amongst TDR grantees: the rate of return to their region of origin upon completion of their degree was 96%. A vast majority of respondents are still working in research (89%), with 81% of respondents having participated in multidisciplinary research activities; women engaged in multidisciplinary collaboration to a higher extent than men. However, only a minority of all have engaged in intersectoral collaboration, an aspect that would require further study. The post-degree career choices made by the respondents were strongly influenced by academic considerations. At the time of the survey, 92% of all respondents hold full-time positions, mainly in the public sector. Almost 25% of the respondents reported that they had influenced policy and practice changes. Some of the challenges and opportunities faced by trainees at various stages of their research career have been identified. Modalities to overcome these will require further investigation. The survey evidenced how TDR’s research capacity grant programmes made a difference on researchers’ career development and on south-south collaborations, by strengthening and localizing research capacity in lower income regions, and also showed there is more that needs to be done. The factors involved, challenges and lessons learnt may help donors and policy makers improve their future interventions with regard to designing capacity strengthening programmes and setting funding priorities. [ABSTRACT FROM AUTHOR]

Human excreta is a low cost source of nutrients vital to plant growth, but also a source of pathogens transmissible to people and animals. We investigated the cost-savings and infection risk of soil transmitted helminths (STHs) in four scenarios where farmers used either inorganic fertilizer or fresh/composted human excreta supplemented by inorganic fertilizer to meet the nutrient requirements of rice paddies in the Red River Delta, Vietnam. Our study included two main components: 1) a risk estimate of STH infection for farmers who handle fresh excreta, determined by systematic review and meta-analysis; and 2) a cost estimate of fertilizing rice paddies, determined by nutrient assessment of excreta, a retailer survey of inorganic fertilizer costs, and a literature review to identify region-specific inputs. Our findings suggest that farmers who reuse fresh excreta are 1.24 (95% CI: 1.13–1.37, p-value<0.001) times more likely to be infected with any STH than those who do not handle excreta or who compost appropriately, and that risk varies by STH type (Ascaris lumbricoides RR = 1.17, 95% CI = 0.87–1.58, p-value = 0.29; Hookworm RR = 1.02, 95% CI = 0.50–2.06, p-value = 0.96; Trichuris trichiura RR = 1.38, 95% CI = 0.79–2.42, p-value = 0.26). Average cost-savings were highest for farmers using fresh excreta (847,000 VND) followed by those who composted for 6 months as recommended by the WHO (312,000 VND) and those who composted for a shorter time (5 months) with lime supplementation (37,000 VND/yr); however, this study did not assess healthcare costs of treating acute or chronic STH infections in the target group. Our study provides evidence that farmers in the Red River Delta are able to use a renewable and locally available resource to their economic advantage, while minimizing the risk of STH infection. [ABSTRACT FROM AUTHOR]

Background: The mainstay of current schistosomiasis control programs is mass preventive chemotherapy of school-aged children with praziquantel. This treatment is delivered through school-based, community-based, or combined school- and community-based systems. Attaining very high coverage rates for children is essential in mass schistosomiasis treatment programs, as is ensuring that there are no persistently untreated subpopulations, a potential challenge for school-based programs in areas with low school enrollment. This review sought to compare the different treatment delivery methods based both on their coverage of school-aged children overall and on their coverage specifically of non-enrolled children. In addition, qualitative community or programmatic factors associated with high or low coverage rates were identified, with suggestions for overall coverage improvement. Methodology/Principal findings: This review was registered prospectively with PROSPERO (CRD 42015017656). Five hundred forty-nine publication of potential relevance were identified through database searches, reference lists, and personal communications. Eligible studies included those published before October 2015, written in English or French, containing quantitative or qualitative data about coverage rates for MDA of school-aged children with praziquantel. Among the 22 selected studies, combined community- and school-based programs achieved the highest median coverage rates (89%), followed by community-based programs (72%). School-based programs had both the lowest median coverage of children overall (49%) and the lowest coverage of the non-enrolled subpopulation of children. Qualitatively, major factors affecting program success included fear of side effects, inadequate education about schistosomiasis, lack of incentives for drug distributors, and inequitable distribution to minority groups. Conclusions/Significance: This review provides an evidence-based framework for the development of future schistosomiasis control programs. Based on our results, a combined community and school-based delivery system should maximize coverage for both in- and out-of-school children, especially when combined with interventions such as snacks for treated children, educational campaigns, incentives for drug distributors, and active inclusion of marginalized groups. Trial registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Background: The Esperanza Window Trap (EWT) baited with CO2 and human sweat compounds is attractive to Simulium ochraceum s.l., the primary vector of Onchocerca volvulus in the historically largest endemic foci in México and Guatemala. Methodology/Principal findings: The ability of the EWT to locally reduce numbers of questing S. ochraceum s.l. was evaluated in two formerly onchocerciasis endemic communities in Southern México. At each community, two EWTs were placed in or near a school or household and flies were collected sequentially for a total of 10 days. Black fly collections were then carried out for an additional 10 days in the absence of the EWTs. Flies were also collected outside the dwellings to control for variations in the local fly populations. When the EWTs were present, there was a significant reduction in the human biting rate at both the household and school locations at collection sites, with a greater effect observed in the schools. Conclusions/Significance: These results indicate that the EWTs not only have potential as a black fly monitoring tool but may be used for reducing personal exposure to fly bites in Mesoamerica. [ABSTRACT FROM AUTHOR]

Background: During the past 20 years, enormous efforts have been expended globally to eliminate lymphatic filariasis (LF) through mass drug administration (MDA). However, small endemic foci (microfoci) of LF may threaten the presumed inevitable decline of infections after MDA cessation. We conducted microsimulation modeling to assess the ability of different types of surveillance to identify microfoci in these settings. Methods: Five or ten microfoci of radius 1, 2, or 3 km with infection marker prevalence (intensity) of 3, 6, or 10 times background prevalence were placed in spatial simulations, run in R Version 3.2. Diagnostic tests included microfilaremia, immunochromatographic test (ICT), and Wb123 ELISA. Population size was fixed at 360,000 in a 60 x 60 km area; demographics were based on literature for Sub-Saharan African populations. Background ICT prevalence in 6–7 year olds was anchored at 1.0%, and the prevalence in the remaining population was adjusted by age. Adults≥18 years, women aged 15–40 years (WCBA), children aged 6–7 years, or children≤5 years were sampled. Cluster (CS), simple random sampling (SRS), and TAS-like sampling were simulated, with follow-up testing of the nearest 20, 100, or 500 persons around each infection-marker-positive person. A threshold number of positive persons in follow-up testing indicated a suspected microfocus. Suspected microfoci identified during surveillance and actual microfoci in the simulation were compared to obtain a predictive value positive (PVP). Each parameter set was referred to as a protocol. Protocols were scored by efficiency, defined as the most microfoci identified, the fewest persons requiring primary and follow-up testing, and the highest PVP. Negative binomial regression was used to estimate aggregate effects of different variables on efficiency metrics. Results: All variables were significantly associated with efficiency metrics. Additional follow-up tests beyond 20 did not greatly increase the number of microfoci detected, but significantly negatively impacted efficiency. Of 3,402 protocols evaluated, 384 (11.3%) identified all five microfoci (PVP 3.4–100.0%) and required testing 0.73–35.6% of the population. All used SRS and 378 (98.4%) only identified all five microfoci if they were 2–3 km diameter or high-intensity (6x or 10x); 374 (97.4%) required ICT or Wb123 testing to identify all five microfoci, and 281 (73.0%) required sampling adults or WCBA. The most efficient CS protocols identified two (40%) microfoci. After limiting to protocols with 1-km radius microfoci of 3x intensity (n = 378), eight identified all five microfoci; all used SRS and ICT and required testing 31.2–33.3% of the population. The most efficient CS and TAS-like protocols as well as those using microfilaremia testing identified only one (20%) microfocus when they were limited to 1-km radius and 3x intensity. Conclusion: In this model, SRS, ICT, and sampling of adults maximized microfocus detection efficiency. Follow-up sampling of more persons did not necessarily increase protocol efficiency. Current approaches towards surveillance, including TAS, may not detect small, low-intensity LF microfoci that could remain after cessation of MDA. The model provides many surveillance protocols that can be selected for optimal outcomes. [ABSTRACT FROM AUTHOR]

Background: Strongyloides seroprevalence is hyper-endemic in many Australian Aboriginal and Torres Strait Islander communities, ranging from 35–60%. We report the impact on Strongyloides seroprevalence after two oral ivermectin mass drug administrations (MDAs) delivered 12 months apart in a remote Australian Aboriginal community. Methods: Utilizing a before and after study design, we measured Strongyloides seroprevalence through population census with sequential MDAs at baseline and month 12. Surveys at months 6 and 18 determined changes in serostatus. Serodiagnosis was undertaken by ELISA that used sonicated Strongyloides ratti antigen to detect anti-Strongyloides IgG. Non-pregnant participants weighing ≥15 kg were administered a single 200 μg/kg ivermectin dose, repeated after 10–42 days if Strongyloides and/or scabies was diagnosed; others followed a standard alternative algorithm. A questionnaire on clinical symptoms was administered to identify adverse events from treatment and self-reported symptoms associated with serostatus. Findings: We surveyed 1013 participants at the baseline population census and 1060 (n = 700 from baseline cohort and 360 new entrants) at month 12. Strongyloides seroprevalence fell from 21% (175/818) at baseline to 5% at month 6. For participants from the baseline cohort this reduction was sustained at month 12 (34/618, 6%), falling to 2% at month 18 after the second MDA. For new entrants to the cohort at month 12, seroprevalence reduced from 25% (75/297) to 7% at month 18. Strongyloides positive seroconversions for the baseline cohort six months after each MDA were 2.5% (4/157) at month 6 and 1% at month 18, whilst failure to serorevert remained unchanged at 18%. At 12 months, eosinophilia was identified in 59% of baseline seropositive participants and 89% of seropositive new entrants, compared with 47%baseline seronegative participants and 51% seronegative new entrants. Seropositivity was not correlated with haemoglobin or any self-reported clinical symptoms. Clinical symptoms ascertained on the day of treatment and 24–72 hrs after, did not identify any adverse events. Significance: Two community ivermectin MDAs delivered 12 months apart by trained Aboriginal researchers in collaboration with non-Indigenous researchers resulted in a sustained and significant reduction in Strongyloides seroprevalence over 18 months. Similar reductions were seen in the baseline cohort and new entrants. [ABSTRACT FROM AUTHOR]

Background: The growing burden of dengue in many countries worldwide and the difficulty of preventing outbreaks have increased the urgency to identify alternative public health management strategies and effective approaches to control and prevent dengue outbreaks. The objectives of this study were to understand the impact of dengue outbreak on different stakeholders in Brazil, to explore their perceptions of approaches used by governmental authorities to control and prevent dengue outbreaks and to define the challenges and implications of preventing future outbreaks. Methods: In 2015, a qualitative study was conducted in two urban states in Brazil: São Paulo, which was experiencing an outbreak in 2015, and Rio de Janeiro, which experienced outbreaks in 2011 and 2012. Face-to-face interviews using a semi-structured questionnaire were conducted with nine different categories of stakeholders: health workers (physicians, nurses), hospital administrators, municipal government representatives, community members and leaders, school administrators, business leaders and vector control managers. Interviews were focused on the following areas: impact of the dengue outbreak, perceptions of control measures implemented by governmental authorities during outbreaks and challenges in preventing future dengue outbreaks. Results: A total of 40 stakeholders were included in the study. Health workers and community members reported longer waiting times at hospitals due to the increased number of patients receiving care for dengue-related symptoms. Health workers and hospital administrators reported that there were no major interruptions in access to care. Overall financial impact of dengue outbreaks on households was greatest for low-income families. Despite prevention and control campaigns implemented between outbreak periods, various stakeholders reported that dengue prevention and control efforts performed by municipal authorities remained insufficient, suggesting that efforts should be reinforced and better coordinated by governmental authorities, particularly during outbreak periods. Conclusion: The study shows that a dengue outbreak has a multisectorial impact in the medical, societal, economic and political sectors. The study provides useful insights and knowledge in different stakeholder populations that could guide local authorities and government officials in planning, designing and initiating public health programs. Research focused on a better understanding of how communities and political authorities respond to dengue outbreaks is a necessary component for designing and implementing plans to decrease the incidence and impact of dengue outbreaks in Brazil. [ABSTRACT FROM AUTHOR]

Background: Since 2001, Haiti’s National Program for the Elimination of Lymphatic Filariasis (NPELF) has worked to reduce the transmission of LF through annual mass drug administration with diethylcarbamazine and albendazole. The NPELF reached full national coverage with MDA for LF in 2012, and by 2014, a total of 14 evaluation units (48 communes) had met WHO eligibility criteria to conduct LF transmission assessment surveys (TAS) to determine whether prevalence had been reduced to below a threshold, such that transmission is assumed to be no longer sustainable. Haiti is also endemic for malaria and many communities suffer a high burden of soil transmitted helminths (STH). Heeding the call from WHO for integration of neglected tropical diseases (NTD) activities, Haiti’s NPELF worked with the national malaria control program (NMCP) and with partners to develop an integrated TAS (LF-STH-malaria) to include assessments for malaria and STH. Methodology/Principle findings: The aim of this study was to evaluate the feasibility of using TAS surveys for LF as a platform to collect information about STH and malaria. Between November 2014 and June 2015, TAS were conducted in 14 evaluation units (EUs) including 1 TAS (LF-only), 1 TAS-STH-malaria, and 12 TAS-malaria, with a total of 16,655 children tested for LF, 14,795 tested for malaria, and 298 tested for STH. In all, 12 of the 14 EUs passed the LF TAS, allowing the program to stop MDA for LF in 44 communes. The EU where children were also tested for STH will require annual school-based treatment for STH to maintain reduced STH levels. Finally, only 12 of 14,795 children tested positive for malaria by RDT in 38 communes. Conclusions/Significance: Haiti’s 2014–2015 Integrated TAS surveys provide evidence of the feasibility of using the LF TAS as a platform for integration of assessments for STH and or malaria. [ABSTRACT FROM AUTHOR]

Background: Onchocerciasis is targeted for elimination in Africa through annual or biannual ivermectin mass drug administration (MDA). An immunodiagnostic test, based on the detection of human IgG4 antibodies in the blood to the Onchocerca volvulus-specific antigen Ov16, is one of the recommended tools for determining whether transmission is interrupted and mass treatment can stop. For different transmission settings, the relationship between post-MDA Ov16 antibody prevalence in children (measured 1 year after the last round of MDA) and the duration and coverage of MDA, the mf prevalence in the population, and the probability that onchocerciasis is eventually eliminated is explored through mathematical modelling. Methodology: The ONCHOSIM model was extended with new output on the Ov16 antibody serostatus of individuals. Seroconversion was assumed to be triggered by the first worm establishing in the host, with seroconversion occurring either before maturation, after maturation or only after the start of mf production. We are mainly interested in seroconversion rates in children, and for now ignore the possibility of seroreversion to simplify the model. Principal findings: Yearly repeated MDA leads to a strong reduction in the in the parasite acquisition rate in humans. This reduces the seroconversion rate in newborns and young children, while those who seroconverted before the start of control remain antibody positive. Both the microfiladermia prevalence in the population aged 5 years and above and the Ov16 antibody prevalence in children under 10 declined with increasing duration of MDA. The association between either of these indicators and the model-predicted probability of elimination was not influenced much by the assumed treatment coverage levels, but was found to depend on baseline endemicity levels, assumptions regarding the trigger of seroconversion, and diagnostic test characteristics (sensitivity and specificity). Conclusions: Better understanding of the dynamics of Ov16 antibody responses is required for accurate interpretation of seroprevalence data and more precise estimation of endpoint for MDA. Our study demonstrates that this endpoint will be dependent on baseline endemicity levels, which should be taken into account in guidelines for defining when to stop MDA. [ABSTRACT FROM AUTHOR]

The emergence of mobile technology offers new opportunities to improve clinical guideline adherence in resource-limited settings. We conducted a clinical pilot study in rural Bangladesh to evaluate the impact of a smartphone adaptation of the World Health Organization (WHO) diarrheal disease management guidelines, including a modality for age-based weight estimation. Software development was guided by end-user input and evaluated in a resource-limited district and sub-district hospital during the fall 2015 cholera season; both hospitals lacked scales which necessitated weight estimation. The study consisted of a 6 week pre-intervention and 6 week intervention period with a 10-day post-discharge follow-up. Standard of care was maintained throughout the study with the exception that admitting clinicians used the tool during the intervention. Inclusion criteria were patients two months of age and older with uncomplicated diarrheal disease. The primary outcome was adherence to guidelines for prescriptions of intravenous (IV) fluids, antibiotics and zinc. A total of 841 patients were enrolled (325 pre-intervention; 516 intervention). During the intervention, the proportion of prescriptions for IV fluids decreased at the district and sub-district hospitals (both p < 0.001) with risk ratios (RRs) of 0.5 and 0.2, respectively. However, when IV fluids were prescribed, the volume better adhered to recommendations. The proportion of prescriptions for the recommended antibiotic azithromycin increased (p < 0.001 district; p = 0.035 sub-district) with RRs of 6.9 (district) and 1.6 (sub-district) while prescriptions for other antibiotics decreased; zinc adherence increased. Limitations included an absence of a concurrent control group and no independent dehydration assessment during the pre-intervention. Despite limitations, opportunities were identified to improve clinical care, including better assessment, weight estimation, and fluid/ antibiotic selection. These findings demonstrate that a smartphone-based tool can improve guideline adherence. This study should serve as a catalyst for a randomized controlled trial to expand on the findings and address limitations. [ABSTRACT FROM AUTHOR]

Historically the western sahelian dry regions of Mali are known to be highly endemic for cutaneous leishmaniasis (CL) caused by Leishmania major, while cases are rarely reported from the Southern savanna forest of the country. Here, we report baseline prevalence of CL infection in 3 ecologically distinct districts of Mali (dry sahelian, north savanna and southern savanna forest areas). We screened 195 to 250 subjects from 50 to 60 randomly selected households in each of the 6 villages (four from the western sahelian district of Diema in Kayes region, one from the central district of Kolokani and one from the southern savanna district of Kolodieba, region of Sikasso). The screening consisted of: 1] A Leishmanin Skin Test (LST) for detection of exposure to Leishmania parasites; 2] clinical examination of suspected lesions, followed by validation with PCR and 3] finger prick blood sample to determine antibody levels to sand fly saliva. LST positivity was higher in the western district of Diema (49.9%) than in Kolokani (24.9%) and was much lower in Kolondieba (2.6%). LST positivity increased with age rising from 13.8% to 88% in Diema for age groups 2–5 years and 41–65 years, respectively. All eight PCR-confirmed L. major CL cases were diagnosed in subjects below 18 years of age and all were residents of the district of Diema. Exposure to sand fly bites, measured by anti-saliva antibody titers, was comparable in individuals living in all three districts. However, antibody titers were significantly higher in LST positive individuals (P<0.0001). In conclusion, CL transmission remains active in the western region of Mali where lesions were mainly prevalent among children under 18 years old. LST positivity correlated to higher levels of antibodies to sand fly salivary proteins, suggesting their potential as a risk marker for CL acquisition in Mali. [ABSTRACT FROM AUTHOR]

Estimating the age distribution of mosquito populations is crucial for assessing their capacity to transmit disease and for evaluating the efficacy of available vector control programs. This study reports on the capacity of the near-infrared spectroscopy (NIRS) technique to rapidly predict the ages of the principal dengue and Zika vector, Aedes aegypti. The age of wild-type males and females, and males and females infected with wMel and wMelPop strains of Wolbachia pipientis were characterized using this method. Calibrations were developed using spectra collected from their heads and thoraces using partial least squares (PLS) regression. A highly significant correlation was found between the true and predicted ages of mosquitoes. The coefficients of determination for wild-type females and males across all age groups were R2 = 0.84 and 0.78, respectively. The coefficients of determination for the age of wMel and wMelPop infected females were 0.71 and 0.80, respectively (P< 0.001 in both instances). The age of wild-type female Ae. aegypti could be identified as < or ≥ 8 days old with an accuracy of 91% (N = 501), whereas female Ae. aegypti infected with wMel and wMelPop were differentiated into the two age groups with an accuracy of 83% (N = 284) and 78% (N = 229), respectively. Our results also indicate NIRS can distinguish between young and old male wild-type, wMel and wMelPop infected Ae. aegypti with accuracies of 87% (N = 253), 83% (N = 277) and 78% (N = 234), respectively. We have demonstrated the potential of NIRS as a predictor of the age of female and male wild-type and Wolbachia infected Ae. aegypti mosquitoes under laboratory conditions. After field validation, the tool has the potential to offer a cheap and rapid alternative for surveillance of dengue and Zika vector control programs. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis affects millions of people, yet treatment options are limited. The antimalarial Synriam (piperaquine 150 mg/arterolane 750 mg) and the anthelminthic moxidectin revealed promising antischistosomal properties in preclinical or clinical studies. Methodology: We conducted two single-blind, randomized exploratory Phase 2 trials in Schistosoma mansoni and S. haematobium-infected adolescents in northern and central Côte d’Ivoire. Our primary endpoints were cure rates (CRs) and egg reduction rates (ERRs) based on geometric mean and safety. Each subject was asked to provide two stool samples (S. mansoni trial) for Kato-Katz analysis or three urine samples (S. haematobium trial) for urine filtration and one finger prick for malaria screening at baseline and follow-up. Participants were randomly assigned to either moxidectin, Synriam, Synriam plus praziquantel or praziquantel. Principal Findings: 128 adolescents (age: 12–17 years) were included in each study. Against S. haematobium moxidectin and Synriam revealed low efficacy. On the other hand, Synriam plus praziquantel and praziquantel yielded CRs of 60.0% and 38.5% and ERRs of 96.0% and 93.5%, respectively. CRs observed in the treatment of S. mansoni were 13.0%, 6.7%, 27.0%, and 27.6% for moxidectin, Synriam, Synriam plus praziquantel and praziquantel, respectively. ERRs ranged from 64.9% (Synriam) to 87.5% (praziquantel). Conclusion/Significance: Synriam and moxidectin show low efficacy against S. haematobium, hence an ancillary benefit is not expected when these drugs are used for treating onchocerciasis and malaria in co-endemic settings. Further studies are needed to corroborate our findings that moxidectin and Synriam show moderate ERRs against S. mansoni. [ABSTRACT FROM AUTHOR]

Introduction: Both yaws and trachoma are endemic in the Pacific. Mass treatment with azithromycin is the mainstay of the WHO strategy for both the eradication of yaws and the elimination of trachoma as a public health problem, but the dose recommended for trachoma is lower than that for yaws. In countries where both diseases are endemic, there is a potential for synergy between yaws and trachoma control programs if mass treatment with the lower dose of azithromycin was shown to be effective for the treatment of yaws. In an earlier study, we demonstrated a profound reduction in the clinical and serological prevalence of yaws following a single round of mass treatment with azithromycin 20 mg/kg undertaken for the purposes of trachoma elimination. Methods: This survey was conducted 18 months following a single round of azithromycin mass treatment in the same communities in which we had conducted our previous six-month follow-up survey. We examined children aged 1–14 years and took blood and lesion samples for yaws diagnosis using the Treponema pallidum particle agglutination assay (TPPA) and the non-treponemal Rapid Plasma Reagin (RPR) test. Results: A total of 1,284 children were enrolled in the study. Amongst children aged 5–14 years, 223 had a positive TPPA (27.5%, 95% CI 13.6–47.7%). The TPPA seroprevalence amongst this age group did not differ significantly from either our pre-mass treatment survey or our initial follow-up survey. Thirty-five children had positive TPPA and positive RPR (4.3%, 95% CI 2.1–8.7%), and this did not differ significantly from our initial post-mass drug administration (MDA) follow-up survey (4.3% versus 3.5%, p = 0.43) but remained significantly lower than our initial pre-MDA survey (4.3% vs 21.7%, p <0.0001). Village-level MDA coverage was strongly associated with dual-seropositivity (p = 0.005). Amongst children aged 1–4 years, 16 had a positive TPPA (3.5%, 95% CI 1.6–7.1%). This did not differ significantly from the seroprevalence in this age group that had been predicted based on our previous surveys (3.5% vs 5%, p = 0.11). Fourteen children (1.1%) were considered to have a skin lesion clinically consistent with yaws, but none of these individuals was seropositive for yaws. Of nine cases where a swab could be collected for PCR, all were negative for Treponema pallidum subsp. pertenue DNA. Discussion: In this study we have shown that the benefit of a single round of mass treatment with azithromycin 20mg/kg appears to extend to 18 months without any further intervention. The lack of a significant change in seroprevalence from 6 to 18 months after mass treatment might suggest that interventions could be spaced at yearly intervals without a significant loss of impact, and that this might facilitate integration of yaws eradication with other neglected tropical disease (NTD) control programmes. MDA coverage above 90% was associated with significantly better outcomes than coverages lower than this threshold, and strategies to improve coverage at all stages of yaws eradication efforts should be investigated. [ABSTRACT FROM AUTHOR]