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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: Neglected tropical diseases (NTDs) are generally assumed to be concentrated in poor populations, but evidence on this remains scattered. We describe within-country socioeconomic inequalities in nine NTDs listed in the London Declaration for intensified control and/or elimination: lymphatic filariasis (LF), onchocerciasis, schistosomiasis, soil-transmitted helminthiasis (STH), trachoma, Chagas’ disease, human African trypanosomiasis (HAT), leprosy, and visceral leishmaniasis (VL). Methodology: We conducted a systematic literature review, including publications between 2004–2013 found in Embase, Medline (OvidSP), Cochrane Central, Web of Science, Popline, Lilacs, and Scielo. We included publications in international peer-reviewed journals on studies concerning the top 20 countries in terms of the burden of the NTD under study. Principal findings: We identified 5,516 publications, of which 93 met the inclusion criteria. Of these, 59 papers reported substantial and statistically significant socioeconomic inequalities in NTD distribution, with higher odds of infection or disease among poor and less-educated people compared with better-off groups. The findings were mixed in 23 studies, and 11 studies showed no substantial or statistically significant inequality. Most information was available for STH, VL, schistosomiasis, and, to a lesser extent, for trachoma. For the other NTDs, evidence on their socioeconomic distribution was scarce. The magnitude of inequality varied, but often, the odds of infection or disease were twice as high among socioeconomically disadvantaged groups compared with better-off strata. Inequalities often took the form of a gradient, with higher odds of infection or disease each step down the socioeconomic hierarchy. Notwithstanding these inequalities, the prevalence of some NTDs was sometimes also high among better-off groups in some highly endemic areas. Conclusions: While recent evidence on socioeconomic inequalities is scarce for most individual NTDs, for some, there is considerable evidence of substantially higher odds of infection or disease among socioeconomically disadvantaged groups. NTD control activities as proposed in the London Declaration, when set up in a way that they reach the most in need, will benefit the poorest populations in poor countries. [ABSTRACT FROM AUTHOR]

Background: The province of Formosa, Argentina, is endemic for leprosy. In the present paper, we assessed the trend (T, 2002–2016 time series) and the forecast for 2022 of new case detection rate (NCDR) and determined the spatial distribution of new cases detected (NCD) of leprosy. Methodology/Principal findings: This is a descriptive observational study of 713 NCD of leprosy from provincial medical records between January 2002 and December 2016. The whole dataset from the provincial medical record was used to independently estimate the NCDR trends of the general population, age groups, sexes and Departments. This same database was used to estimate the NCDR forecast of the general population for 2022, applying a dynamic linear model with a local linear trend, using the MCMC algorithm. The NCDR was higher in men (p<0.05), increased with age (0.20, 8.17, 21.04, and 29.49 for the 0–14, 15–44, 45–64 and over 65-year-old age groups, respectively; p<0.05) and showed a downward trend (negative values) of estimated slopes for the whole province and each Department. Bermejo Department showed the highest (T:-1.02, 95%CI: [-1.42, -0.66]) and Patiño the lowest decreasing trend (T:-0.45, 95%CI: [-0.74, -0.11]). The NCDR trend for both sexes was similar (T:-0.55, 95%CI: [-0.64, -0.46]), and age groups showed a decreasing trend (S15-44:-103, S45-64:-81, S>65:-61, p<0.05), except for the 0–14 age group (S:-3, p>0.05), which showed no trend. Forecasts predicted that leprosy will not be eliminated by 2022 (3.64, 95%CI: [1.22, 10.25]). Conclusions/Significance: Our results highlight the status of leprosy in Formosa and provide information to the provincial public health authorities on high-risk populations, stressing the importance of timely detection of new cases for further elimination of the disease in the province. Author summary: Leprosy, a neglected tropical disease, is a public health problem in northern Argentina, causing permanent damage, stigmatization and discrimination. The Program for the Control of Leishmaniasis and Leprosy in Formosa province (PCLyLF) is responsible for the diagnosis and treatment of the disease and the active search for household contacts. The present study aimed to determine the spatial distribution of new cases of leprosy and the status of the disease using new case detection rate (NCDR) as the main epidemiological indicator. We determined the NCDR trends (2002–2016 time series) of the general population, age groups, sexes and Departments, and the NCDR forecast for the province by 2022. Our results indicated that leprosy was spread throughout Formosa, with higher rates in men and in patients over 65 years old. The NCDR showed a downward trend in the whole province and in each Department. The Departments of Bermejo and Matacos had the highest decreasing trend and the Department of Patiño the lowest one. Future projections show that leprosy will not be eliminated by 2022. [ABSTRACT FROM AUTHOR]

Background: Samoa conducted eight nationwide rounds of mass drug administration (MDA) for lymphatic filariasis (LF) between 1999 and 2011, and two targeted rounds in 2015 and 2017 in North West Upolu (NWU), one of three evaluation units (EUs). Transmission Assessment Surveys (TAS) were conducted in 2013 (failed in NWU) and 2017 (all three EUs failed). In 2018, Samoa was the first in the world to distribute nationwide triple-drug MDA using ivermectin, diethylcarbamazine, and albendazole. Surveillance and Monitoring to Eliminate LF and Scabies from Samoa (SaMELFS Samoa) is an operational research program designed to evaluate the effectiveness of triple-drug MDA on LF transmission and scabies prevalence in Samoa, and to compare the usefulness of different indicators of LF transmission. This paper reports results from the 2018 baseline survey and aims to i) investigate antigen (Ag) prevalence and spatial epidemiology, including geographic clustering; ii) compare Ag prevalence between two different age groups (5–9 years versus ≥10 years) as indicators of areas of ongoing transmission; and iii) assess the prevalence of limb lymphedema in those aged ≥15 years. Methods: A community-based cluster survey was conducted in 30 randomly selected and five purposively selected clusters (primary sampling units, PSUs), each comprising one or two villages. Participants were recruited through household surveys (age ≥5 years) and convenience surveys (age 5–9 years). Alere Filariasis Test Strips (FTS) were used to detect Ag, and prevalence was adjusted for survey design and standardized for age and gender. Adjusted Ag prevalence was estimated for each age group (5–9, ≥10, and all ages ≥5 years) for random and purposive PSUs, and by region. Intraclass correlation (ICC) was used to quantify clustering at regions, PSUs, and households. Results: A total of 3940 persons were included (1942 children aged 5–9 years, 1998 persons aged ≥10 years). Adjusted Ag prevalence in all ages ≥5 years in randomly and purposively selected PSUs were 4.0% (95% CI 2.8–5.6%) and 10.0% (95% CI 7.4–13.4%), respectively. In random PSUs, Ag prevalence was lower in those aged 5–9 years (1.3%, 95% CI 0.8–2.1%) than ≥10 years (4.7%, 95% CI 3.1–7.0%), and poorly correlated at the PSU level (R2 = 0.1459). Adjusted Ag prevalence at PSUs ranged from 0% to 10.3% (95% CI 5.9–17.6%) in randomly selected and 3.8% (95% CI 1.3–10.8%) to 20.0% (95% CI 15.3–25.8%) in purposively selected PSUs. ICC for Ag-positive individuals was higher at households (0.46) compared to PSUs (0.18) and regions (0.01). Conclusions: Our study confirmed ongoing transmission of LF in Samoa, in accordance with the 2017 TAS results. Ag prevalence varied significantly between PSUs, and there was poor correlation between prevalence in 5–9 year-olds and older ages, who had threefold higher prevalence. Sampling older age groups would provide more accurate estimates of overall prevalence, and be more sensitive for identifying residual hotspots. Higher prevalence in purposively selected PSUs shows local knowledge can help identify at least some hotspots. Author summary: Lymphatic filariasis (LF), a disease caused by infection with worms transmitted by mosquitoes, has long been present in Samoa. Since the 1960s, Samoa has attempted to control the disease through many rounds of annual administration of two deworming drugs to the whole population. However, Samoa recently observed that LF transmission was still occurring, prompting mass drug administration (MDA) with three drugs in 2018. Here, we report the baseline survey of an operational research program to evaluate the triple drug MDA. The survey assessed prevalence and geographical distribution of LF in the population, compared prevalence by age groups, and investigated the burden of elephantiasis (swollen limbs caused by long-term LF infection). The study confirmed ongoing transmission, with 4% of those aged ≥5 years showing antigen in their blood as evidence of infection. Antigen prevalence was more than three times higher in those aged ≥10 years (4.7%) than in 5–9 year-old children (1.3%). Infection was highly clustered within households and villages, with up to 20% of residents infected in known hotspot villages. Future surveillance strategies should consider that i) testing older age groups would provide more accurate indication of LF transmission, and ii) local knowledge can help identify transmission hotspots. [ABSTRACT FROM AUTHOR]

Background: This paper reports on the baseline prevalence and associated risk factor findings of a pilot, longitudinal study exploring community-wide treatment of schistosomiasis and soil-transmitted helminthiasis, using albendazole plus praziquantel in the Greater Accra region of Ghana. Method: From three communities, at least, 658 individuals were enrolled into the study via random household selection. Prevalence and intensity of schistosomiasis and STH infection were determined from stool and urine samples with a questionnaire being administered in order to explore other morbidities and risk factors. Factor analysis of household demographic variables was undertaken to generate a socioeconomic score; this was then further categorised into tertiles. Proportional-odds cumulative logit generalised estimating equation (GEE) models were used to investigate categorical ordinal intensity of infection associations with morbidity. Separately, logistic GEE models were used to investigate risk factor associations with infection prevalence. Results: Both Schistosoma haematobium and S. mansoni were prevalent in the three communities, with the prevalence of S. haematobium ranging from 3.3% (24/679; 95% CI = 1.9–4.7) to 19% (114/632; 95% CI = 15.8–22.2) and S. mansoni ranging from 30% (202/679; 95% CI = 26.5–33.5) to 78.3% (409/536; 95% CI = 74.7–81.9). The total prevalence of STH across all three sites was negligible at 1.3% (24/1847; 95% CI = 0.8–1.9) comprising mainly hookworm (10/1847). Multivariable statistical models indicated males to be 2.3 (95% CI = 1.7–3.3) times more likely to have a high intensity S. mansoni infection and 1.5 (95% CI = 1.1–2) times more likely to have a high intensity of S. haematobium infection compared to females. There was no significant difference in the likelihood of infection with S. mansoni between adults and school age children (SAC), however S. haematobium infections were found to be 2.5 (95% CI = 1.8–3.5) times more likely to occur in school age children than in adults. Multivariable statistical models (adjusted for age and sex) indicated an association between schistosomiasis and a number of self-reported morbidity indicators (notably diarrhoea and blood in stool and urine). Low socio-economic status was also associated with SCH infection (OR: 2; 95% CI = 1.3–3.2). Conclusion: The communities targeted by this study showed a range of Schistosoma prevalence's of infection, from hypo-endemic through to meso-endemic and hyper-endemic. The prevalence of SCH across the different age groups in the study locations highlights the large number of individuals currently being left out of the standard morbidity control method of annual treatment of the SAC. Author summary: In this manuscript we detail the baseline results of a broader study investigating the feasibility of expanding access of albendazole and praziquantel to additional at-risk groups in three communities (Tomefa, Maheam and Torgahkope-Adakope) located around the Weija reservoir in the Greater Accra district of Ghana. Our results show that intestinal schistosomiasis was the most common form of disease across all three sites (44.2%) with Tomefa possessing the highest prevalence at 78.3%. The prevalence of urinary schistosomiasis was found to be 11.9% with the highest prevalence found in Torgahkope-Adakope (19%). STH was found to have a very low prevalence across the three communities with only 1.3% of participants found to be positive. No significant difference in STH prevalence was observed between males (0.92%; 95% CI = 0.4–1.81) and females (1.07%; 95% CI = 0.51–1.95). Statistical analysis revealed that males were more likely to be infected and to have high intensity infections of both forms of schistosomiasis. Pre-school age children (PSAC) were found to be less likely to be infected for either form of schistosomiasis in communities with low to medium prevalence of disease, however in Tomefa, where prevalence of intestinal schistosomiasis is high, there was little difference in the prevalence of disease between PSAC, school-age children (SAC) and adults. Our study shows that there is a need to treat the wider community outside of the current morbidity control strategy of mass-drug administration to SAC. [ABSTRACT FROM AUTHOR]

Background: Despite being the most widely distributed mosquito-borne viral infection, estimates of dengue transmission intensity and associated burden remain ambiguous. With advances in the development of novel control measures, obtaining robust estimates of average dengue transmission intensity is key for assessing the burden of disease and the likely impact of interventions. Methodology/Principle Findings: We estimated the force of infection (λ) and corresponding basic reproduction numbers (R0) by fitting catalytic models to age-stratified incidence data identified from the literature. We compared estimates derived from incidence and seroprevalence data and assessed the level of under-reporting of dengue disease. In addition, we estimated the relative contribution of primary to quaternary infections to the observed burden of dengue disease incidence. The majority of R0 estimates ranged from one to five and the force of infection estimates from incidence data were consistent with those previously estimated from seroprevalence data. The baseline reporting rate (or the probability of detecting a secondary infection) was generally low (<25%) and varied within and between countries. Conclusions/Significance: As expected, estimates varied widely across and within countries, highlighting the spatio-temporally heterogeneous nature of dengue transmission. Although seroprevalence data provide the maximum information, the incidence models presented in this paper provide a method for estimating dengue transmission intensity from age-stratified incidence data, which will be an important consideration in areas where seroprevalence data are not available. [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]

Mass drug administration (MDA) is, and has been, the principal method for the control of the schistosome helminths. Using MDA only is unlikely to eliminate the infection in areas of high transmission and the implementation of other measures such as reduced water contact improved hygiene and sanitation are required. Ideally a vaccine is needed to ensure long term benefits and eliminate the need for repeated drug treatment since infection does not seem to induce lasting protective immunity. Currently, a candidate vaccine is under trial in a baboon animal model, and very encouraging results have been reported. In this paper, we develop an individual-based stochastic model to evaluate the effect of a vaccine with similar properties in humans to those recorded in baboons in achieving the World Health Organization (WHO) goals of morbidity control and elimination as a public health problem in populations living in a variety of transmission settings. MDA and vaccination assuming different durations of protection and coverage levels, alone or in combination, are examined as treatment strategies to reach the WHO goals of the elimination of morbidity and mortality in the coming decade. We find that the efficacy of a vaccine as an adjunct or main control tool will depend critically on a number of factors including the average duration of protection it provides, vaccine efficacy and the baseline prevalence prior to immunization. In low prevalence settings, simulations suggest that the WHO goals can be achieved for all treatment strategies. In moderate prevalence settings, a vaccine that provides 5 years of protection, can achieve both goals within 15 years of treatment. In high prevalence settings, by vaccinating at age 1, 6 and 11 we can achieve the morbidity control with a probability of nearly 0.89 but we cannot achieve elimination as a public health problem goal. A combined vaccination and MDA treatment plan has the greatest chance of achieving the WHO goals in the shorter term. [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: Mass drug administration (MDA), targeted at school-aged children (SAC) is the method recommended by the World Health Organization for the control of morbidity induced by soil-transmitted helminth (STH) infection in endemic countries. However, MDA does not prevent reinfection between treatment rounds and research suggests that only treating SAC will not be sufficient to bring prevalence to low levels and possibly interrupt transmission of STH. In countries with endemic infection, such as Myanmar, the coverage, who is targeted, and rates of reinfection will determine how effective MDA is in suppressing transmission in the long-term. Methods/principal findings: In this paper, data from an epidemiological study on STH, comprising three surveys conducted between June 2015 and June 2016 in the delta region of Myanmar, are analysed to determine how STH prevalence and intensity in the study community changes over the course of a year, including reinfection after two MDA rounds in which the whole study sample (all age groups, n = 523) were treated with albendazole. Prevalence in the first survey (August 2015) was 27.92% for any STH, 5.54% for Ascaris lumbricoides, 17.02% for Trichuris trichiura and 9.75% for hookworm. Over the year (survey one to survey three), prevalence of any STH decreased by 8.99% (P < 0.001) and mean EPG significantly decreased for T. trichiura (P < 0.01) and hookworm (P < 0.001). Risk ratios (RRs) for a four-month reinfection period (August to December) were statistically significant and were below one, indicating that STH prevalence had not bounced back to the prevalence levels recorded immediately prior to the last round of treatment (any STH RR = 0.67, 95% CI 0.56–0.81; A. lumbricoides RR = 0.31, 95% CI 0.16–0.59; T. trichiura RR = 0.70, 95% CI 0.55–0.88; hookworm RR = 0.69, 95% CI 0.50–0.95). The only statistically significant RR for the six-month reinfection period (December to June) was for A. lumbricoides infection in SAC (RR = 2.67, 95% CI 1.37–5.21). All six-month RRs were significantly higher than four-month RRs (P < 0.05). Evidence of predisposition to infection (low and high), as measured by the Kendall Tau-b statistic, was found for all species overall and within most age groups stratifications, except for hookworm infection in preschool-aged children. Conclusions/significance: This study demonstrates that, for certain demographic groups, a six-month gap between MDA in these communities is enough time for STH infection to return to STH prevalence levels recorded immediately before the previous MDA round, and that on average the same individuals are being consistently infected between MDA rounds. [ABSTRACT FROM AUTHOR]

School health and nutrition (SHN) programmes are recognized as a significant contributor to both health and education sector goals. The school system offers an ideal platform from which to deliver basic health interventions that target the most common health conditions affecting school-age children (SAC) in low-income countries, leading to improved participation and learning outcomes. However, governments require evidence to cost, design, and implement these programmes. In Ethiopia, prevalent health conditions affecting SAC's education participation and learning outcomes include infection with soil-transmitted helminths (STHs), hunger, and malnutrition. In recognition of the multiple issues affecting the health and education of SAC, the government has taken a proactive approach, coordinating an integrated SHN programme designed to be implemented in partnership and monitored and financed through a single, integrated mechanism. The programme, known as the Enhanced School Health Initiative (ESHI), integrates three complimentary health interventions: deworming; school feeding; and provision of a water, sanitation, and hygiene (WASH) package in schools, which in delivery aim to maximize the benefits of each of the individual components. Operational research surrounding the ESHI programme includes both qualitative and quantitative analyses. Here, we present an overview of the ESHI programme and its genesis. We also introduce three additional supporting papers that provide in-depth analyses of key findings, including the baseline situational analysis, the costs, and community perceptions of the programme. The findings from ESHI provide initial evidence to develop an understanding of the related costs and synergies of integrating multiple health interventions onto a single platform. The work has translated into strengthened institutional capacity and improved cross-sectoral coordination. The government is now committed to supporting 25 million school children in Ethiopia through SHN. The ESHI model serves as a reference point for other countries looking to scale up targeted SHN interventions. [ABSTRACT FROM AUTHOR]

Dengue viruses (DENV) are endemic in the US territories of Puerto Rico, American Samoa, and the US Virgin Islands, with focal outbreaks also reported in the states of Florida and Hawaii. However, little is known about the intensity of dengue virus transmission over time and how dengue viruses have shaped the level of immunity in these populations, despite the importance of understanding how and why levels of immunity against dengue may change over time. These changes need to be considered when responding to future outbreaks and enacting dengue management strategies, such as guiding vaccine deployment. We used catalytic models fitted to case surveillance data stratified by age from the ArboNET national arboviral surveillance system to reconstruct the history of recent dengue virus transmission in Puerto Rico, American Samoa, US Virgin Islands, Florida, Hawaii, and Guam. We estimated average annual transmission intensity (i.e., force of infection) of DENV between 2010 and 2019 and the level of seroprevalence by age group in each population. We compared models and found that assuming all reported cases are secondary infections generally fit the surveillance data better than assuming all cases are primary infections. Using the secondary case model, we found that force of infection was highly heterogeneous between jurisdictions and over time within jurisdictions, ranging from 0.00003 (95% CrI: 0.00002–0.0004) in Florida to 0.08 (95% CrI: 0.044–0.14) in American Samoa during the 2010–2019 period. For early 2020, we estimated that seropositivity in 10 year-olds ranged from 0.09% (0.02%–0.54%) in Florida to 56.3% (43.7%–69.3%) in American Samoa. In the absence of serological data, age-specific case notification data collected through routine surveillance combined with mathematical modeling are powerful tools to monitor arbovirus circulation, estimate the level of population immunity, and design dengue management strategies. Author summary: Viruses transmitted by Aedes mosquitoes are a substantial public health burden globally. In the US, the increasing number of outbreaks in recent decades and the co-circulation of the four dengue viruses present a risk of experiencing sequential infections, which can result in more severe disease. However, reported cases only represent a proportion of all infections, so the intensity of dengue circulation in US jurisdictions and the level of population immunity are largely unknown. Combining dengue surveillance data stratified by age with mathematical models enables direct estimation of transmission intensity and previous exposure. We found that dengue virus transmission intensity was highest in American Samoa and Puerto Rico. The US Virgin Islands also showed patterns of endemic transmission, while Hawaii and Guam present more sporadic outbreak profiles. These estimates can help improve risk assessment in these locations and guide interventions to the populations who most need them. [ABSTRACT FROM AUTHOR]

Background: Socioeconomically deprived children are at increased risk of ill-health associated with sedentary behavior, malnutrition, and helminth infection. The resulting reduced physical fitness, growth retardation, and impaired cognitive abilities may impede children’s capacity to pay attention. The present study examines how socioeconomic status (SES), parasitic worm infections, stunting, food insecurity, and physical fitness are associated with selective attention and academic achievement in school-aged children. Methodology: The study cohort included 835 children, aged 8–12 years, from eight primary schools in socioeconomically disadvantaged neighborhoods of Port Elizabeth, South Africa. The d2-test was utilized to assess selective attention. This is a paper and pencil letter-cancellation test consisting of randomly mixed letters d and p with one to four single and/or double quotation marks either over and/or under each letter. Children were invited to mark only the letters d that have double quotation marks. Cardiorespiratory fitness was assessed via the 20 m shuttle run test and muscle strength using the grip strength test. The Kato-Katz thick smear technique was employed to detect helminth eggs in stool samples. SES and food insecurity were determined with a pre-tested questionnaire, while end of year school results were used as an indicator of academic achievement. Principal findings: Children infected with soil-transmitted helminths had lower selective attention, lower school grades (academic achievement scores), and lower grip strength (all p<0.05). In a multiple regression model, low selective attention was associated with soil-transmitted helminth infection (p<0.05) and low shuttle run performance (p<0.001), whereas higher academic achievement was observed in children without soil-transmitted helminth infection (p<0.001) and with higher shuttle run performance (p<0.05). Conclusions/Significance: Soil-transmitted helminth infections and low physical fitness appear to hamper children’s capacity to pay attention and thereby impede their academic performance. Poor academic achievement will make it difficult for children to realize their full potential, perpetuating a vicious cycle of poverty and poor health. Trial registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Background: Proper evaluation of therapeutic responses in Chagas disease is hampered by the prolonged persistence of antibodies to Trypanosoma cruzi measured by conventional serological tests and by the lack of sensitivity of parasitological tests. Previous studies indicated that tGPI-mucins, an α-Gal (α-d-Galp(1→3)-β-d-Galp(1→4)-d-GlcNAc)-rich fraction obtained from T. cruzi trypomastigotes surface coat, elicit a strong and protective antibody response in infected individuals, which disappears soon after successful treatment. The cost and technical difficulties associated with tGPI-mucins preparation, however, preclude its routine implementation in clinical settings. Methods/principle findings: We herein developed a neoglycoprotein consisting of a BSA scaffold decorated with several units of a synthetic α-Gal antigenic surrogate (α-d-Galp(1→3)-β-d-Galp(1→4)-β-d-Glcp). Serological responses to this reagent, termed NGP-Tri, were monitored by means of an in-house enzyme-linked immunosorbent assay (α-Gal-ELISA) in a cohort of 82 T. cruzi-infected and Benznidazole- or Nifurtimox-treated children (3 days to 16 years-old). This cohort was split into 3 groups based on the age of patients at the time of treatment initiation: Group 1 comprised 24 babies (3 days to 5 months-old; median = 26 days-old), Group 2 comprised 31 children (7 months to 3 years-old; median = 1.0-year-old) and Group 3 comprised 26 patients (3 to 16 years-old; median = 8.4 years-old). A second, control cohort (Group 4) included 39 non-infected infants (3 days to 5 months-old; median = 31 days-old) born to T. cruzi-infected mothers. Despite its suboptimal seroprevalence (58.4%), α-Gal-ELISA yielded shorter median time values of negativization (23 months [IC 95% 7 to 36 months] vs 60 months [IC 95% 15 to 83 months]; p = 0.0016) and higher rate of patient negative seroconversion (89.2% vs 43.2%, p < 0.005) as compared to conventional serological methods. The same effect was verified for every Group, when analyzed separately. Most remarkably, 14 out of 24 (58.3%) patients from Group 3 achieved negative seroconversion for α-Gal-ELISA while none of them were able to negativize for conventional serology. Detailed analysis of patients showing unconventional serological responses suggested that, in addition to providing a novel tool to shorten follow-up periods after chemotherapy, the α-Gal-ELISA may assist in other diagnostic needs in pediatric Chagas disease. Conclusions/significance: The tools evaluated here provide the cornerstone for the development of an efficacious, reliable, and straightforward post-therapeutic marker for pediatric Chagas disease. Author summary: The limits of the current criterion for cure, i.e., negative seroconversion determined by conventional serology, and the lack of validated and sensitive markers for early assessment of response to trypanocidal drugs in Chagas disease stress the necessity of novel therapeutic response markers. Towards this goal, we herein developed by synthetic chemistry a neoglycoprotein bearing an α-Gal antigenic surrogate, termed NGP-Tri, and evaluated its performance in a large cohort of T. cruzi-infected and treated children. An α-Gal-ELISA built upon NGP-Tri showed a very good performance on the assessment of therapy efficacy, as it displayed significantly shorter median time value of negativization and higher rate of patient negative seroconversion as compared to conventional serology methods. These findings indicate that the tools developed here, as well as optimized versions derived from them, should have a positive impact on the clinical management of Chagas disease and the identification and/or clinical validation of novel drug candidates for the treatment of T. cruzi infections. [ABSTRACT FROM AUTHOR]

Typhoid fever is a major cause of death worldwide with a major part of the disease burden in developing regions such as the Indian sub-continent. Bangladesh is part of this highly endemic region, yet little is known about the spatial and temporal distribution of the disease at a regional scale. This research used a Geographic Information System to explore, spatially and temporally, the prevalence of typhoid in Dhaka Metropolitan Area (DMA) of Bangladesh over the period 2005–9. This paper provides the first study of the spatio-temporal epidemiology of typhoid for this region. The aims of the study were: (i) to analyse the epidemiology of cases from 2005 to 2009; (ii) to identify spatial patterns of infection based on two spatial hypotheses; and (iii) to determine the hydro-climatological factors associated with typhoid prevalence. Case occurrences data were collected from 11 major hospitals in DMA, geocoded to census tract level, and used in a spatio-temporal analysis with a range of demographic, environmental and meteorological variables. Analyses revealed distinct seasonality as well as age and gender differences, with males and very young children being disproportionately infected. The male-female ratio of typhoid cases was found to be 1.36, and the median age of the cases was 14 years. Typhoid incidence was higher in male population than female (χ2 = 5.88, p<0.05). The age-specific incidence rate was highest for the 0–4 years age group (277 cases), followed by the 60+ years age group (51 cases), then there were 45 cases for 15–17 years, 37 cases for 18–34 years, 34 cases for 35–39 years and 11 cases for 10–14 years per 100,000 people. Monsoon months had the highest disease occurrences (44.62%) followed by the pre-monsoon (30.54%) and post-monsoon (24.85%) season. The Student's t test revealed that there is no significant difference on the occurrence of typhoid between urban and rural environments (p>0.05). A statistically significant inverse association was found between typhoid incidence and distance to major waterbodies. Spatial pattern analysis showed that there was a significant clustering of typhoid distribution in the study area. Moran's I was highest (0.879; p<0.01) in 2008 and lowest (0.075; p<0.05) in 2009. Incidence rates were found to form three large, multi-centred, spatial clusters with no significant difference between urban and rural rates. Temporally, typhoid incidence was seen to increase with temperature, rainfall and river level at time lags ranging from three to five weeks. For example, for a 0.1 metre rise in river levels, the number of typhoid cases increased by 4.6% (95% CI: 2.4–2.8) above the threshold of 4.0 metres (95% CI: 2.4–4.3). On the other hand, with a 1°C rise in temperature, the number of typhoid cases could increase by 14.2% (95% CI: 4.4–25.0). Author Summary: This research studies the spatial and temporal distribution of typhoid infections in the Dhaka metropolitan area of Bangladesh in the period 2005 to 2009. Data from hospital admission records was analysed together with a range of demographic, environmental and climatic data, in what is believed to be the first study of this nature; clear periodicity was found in the timing of case occurrences, with most cases occurring in the monsoon season. Men and very young children appear to be at greatest risk of contracting the disease. Closeness to rivers was also found to be a contributor to increased typhoid risk. While a difference in rates between urban and rural locations suggested by other studies was not found, distinct clustering of the disease was uncovered. Two of these clusters are located in central Dhaka with a third in the north of the metropolitan area. [ABSTRACT FROM AUTHOR]

Objectives: A national survey in 1997 demonstrated that trachoma was endemic in Mali. Interventions to control trachoma including mass drug administration (MDA) with azithromycin were launched in the regions of Kayes and Koulikoro in 2003. MDA was discontinued after three annual rounds in 2006, and an impact survey conducted. We resurveyed all districts in Kayes and Koulikoro in 2009 to reassess trachoma prevalence and determine intervention objectives for the future. In this paper we present findings from both the 2006 and 2009 surveys. Methods: Population-based cluster surveys were conducted in each of the nine districts in Koulikoro in 2006 and 2009, whilst in Kayes, four of seven districts in 2006 and all seven districts in 2009 were surveyed. Household members present were examined for clinical signs of trachoma. Results: Overall, 29,179 persons from 2,528 compounds, in 260 clusters were examined in 2006 and 32,918 from 7,533 households in 320 clusters in 2009. The prevalence of TF in children aged 1–9 years in Kayes and Koulikoro was 3.9% (95%CI 2.9–5.0%, range by district 1.2–5.4%) and 2.7% (95%CI 2.3–3.1%, range by district 0.1–5.0%) respectively in 2006. In 2009 TF prevalence was 7.26% (95%CI 6.2–8.2%, range by district 2.5–15.4%) in Kayes and 8.19% (95%CI 7.3–9.1%, range by district 1.7–17.2%) in Koulikoro among children of the same age group. TT in adults 15 years of age and older was 2.37% (95%CI 1.66–3.07%, range by district 0.30–3.54%) in 2006 and 1.37% (95%CI 1.02–1.72%, range by district 0.37–1.87%) in 2009 in Kayes and 1.75% (95%CI 1.31–2.23%, range by district 1.06–2.49%) in 2006 and 1.08% (95%CI 0.86–1.30%, range by district 0.34–1.78%) in 2009 in Koulikoro. Conclusions: Using WHO guidelines for decision making, four districts, Bafoulabe in Kayes Region; and Banamba, Kolokani and Koulikoro in Koulikoro Region, still meet criteria for district-wide implementation of the full SAFE strategy as TF in children exceeds 10%. A community-by-community approach to trachoma control may now be required in the other twelve districts. Trichiasis surgery provision remains a need in all districts and should be enhanced in six districts in Kayes and five in Koulikoro where the prevalence exceeded 1.0% in adults. Since 1997 great progress has been observed in the fight against blinding trachoma; however, greater effort is required to meet the elimination target of 2015. Author Summary: Trachoma, a blinding bacterial disease, is targeted for elimination by 2020. To achieve the elimination target, the World Health Organization (WHO) recommends member states implement the SAFE strategy; surgery, mass administration of antibiotics, promotion of hygiene and facial cleanliness and water and sanitation as environmental improvements. We present results from evaluation surveys conducted in 2006 and 2009 from the regions of Kayes and Koulikoro, Mali. Prevalence of active trachoma in 2006 was below baseline intervention thresholds in all surveyed districts and the national program stopped antibiotic distribution. The prevalence of trachoma in 2009 remained well below levels in 1998. However, in 8 of 13 districts compared, the prevalence of active trachoma was higher in 2009 than 2006. Three years of antibiotic intervention did not equate in all districts to a sustained reduction of active trachoma. No surveillance activities were implemented after stopping interventions. Surgical interventions may have reduced the burden of blinding trachoma but there is an ongoing need for surgeries specifically targeting affected women. Four districts meet the WHO criteria for resuming district-wide mass antibiotic distribution. A community-by-community approach to elimination may be needed in other districts. The promotion of facial cleanliness and good hygiene behavior should be reintroduced. [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: The prevalence of Strongyloides stercoralis infection is estimated to be 30–100 million worldwide, although this an underestimate. Most cases remain undiagnosed due to the asymptomatic nature of the infection. We wanted to estimate the seroprevalence of S. stercoralis infection in a South Indian adult population. Methods: To this end, we performed community-based screening of 2351 individuals (aged 18–65) in Kanchipuram District of Tamil Nadu between 2013 and 2020. Serological testing for S. stercoralis was performed using the NIE ELISA. Results: Our data shows a seroprevalence of 33% (768/2351) for S. stercoralis infection which had a higher prevalence among males 36% (386/1069) than among females 29.8% (382/1282). Adults aged ≥55 (aOR = 1.65, 95% CI: 1.25–2.18) showed higher adjusted odds of association compared with other age groups. Eosinophil levels (39%) (aOR = 1.43, 95% CI: 1.19–1.74) and hemoglobin levels (24%) (aOR = 1.25, 95% CI: 1.11–1.53) were significantly associated with S. stercoralis infection. In contrast, low BMI (aOR = 1.15, 95% CI: 0.82–1.61) or the presence of diabetes mellitus (OR = 1.18, 95% CI: 0.83–1.69) was not associated with S. stercoralis seropositivity. Conclusions: Our study provides evidence for a very high baseline prevalence of S. stercoralis infection in South Indian communities and this information could provide realistic and concrete planning of control measures. Author summary: Strongyloidiasis is a neglected tropical disease caused by a parasite which is endemic to parts of Latin America, Asia and Africa. Due to its characteristic life cycle, individuals can carry the infection lifelong with few or no symptoms. With the aim of knowing the prevalence of S. stercoralis at the community level, a population in the rural area of South India was studied using serologic assessments. There was a seroprevalence of S. stercoralis infection in this study of 33%. This suggests a need to revise control programs in order to avoid continued transmission. [ABSTRACT FROM AUTHOR]

Background: A global stockpile of oral cholera vaccine (OCV) was established in 2013 for use in outbreak response and are licensed as two-dose regimens. Vaccine availability, however, remains limited. Previous studies have found that a single dose of OCV may provide substantial protection against cholera. Methods: Using a mathematical model with two age groups paired with optimization algorithms, we determine the optimal vaccination strategy with one and two doses of vaccine to minimize cumulative overall infections, symptomatic infections, and deaths. We explore counterfactual vaccination scenarios in three distinct settings: Maela, the largest refugee camp in Thailand, with high in- and out-migration; N'Djamena, Chad, a densely populated region; and Haiti, where departments are connected by rivers and roads. Results: Over the short term under limited vaccine supply, the optimal strategies for all objectives prioritize one dose to the older age group (over five years old), irrespective of setting and level of vaccination coverage. As more vaccine becomes available, it is optimal to administer a second dose for long-term protection. With enough vaccine to cover the whole population with one dose, the optimal strategies can avert up to 30% to 90% of deaths and 36% to 92% of symptomatic infections across the three settings over one year. The one-dose optimal strategies can avert 1.2 to 1.8 times as many cases and deaths compared to the standard two-dose strategy. Conclusions: In an outbreak setting, speedy vaccination campaigns with a single dose of OCV is likely to avert more cases and deaths than a two-dose pro-rata campaign under a limited vaccine supply. Author summary: Cholera is a major global burden, with 21,000–143,000 deaths annually. The oral cholera vaccine (OCV) is given as two doses and is less effective in children under five years old than in those aged five years and older. However, supply is limited. In this study, we used mathematical models paired with optimization algorithms to find the optimal strategies to allocate vaccines in order to minimize the number of cases and deaths for three distinct settings in Chad, Thailand, and Haiti. We found that in the short term (1 year) when there is limited vaccine supply, it is optimal to vaccinate individuals over five years old with one dose and young children under five years old with two doses. Across the three settings, these optimal strategies prevent the most cases, save the most lives, and avert 1.2 to 1.8 times as many cases and deaths as the standard two-dose untargeted strategy. Our results support that if vaccine supply is limited, under an outbreak setting, mass vaccination campaigns with a single dose of OCV may prevent more cases and save more lives than would a standard two-dose untargeted campaign. [ABSTRACT FROM AUTHOR]

Introduction: While Shigellae and strains of enterotoxigenic Escherichia coli (ETEC) are important causes of diarrhea-associated morbidity and mortality among infants and young children (<5 years of age), their health impact in older age groups is unclear. We sought to quantify the overall burden of shigellosis and ETEC diarrhea among older children, adolescents, and adults in Africa and South Asia, the two regions with the highest levels of diarrhea-related morbidity and mortality worldwide. Methods: We employed two distinct methodological approaches to estimate the burden of diarrhea due to Shigellae and ETEC among persons ≥5 years of age in the WHO regions of South Asia (SEAR) and Africa (AFR). Under method 1, we conducted a systematic review to identify the median proportion of total deaths due to diarrhea and then applied this figure to the number of all-cause deaths that occurred in 2010 among this age group. To estimate the total number of diarrhea deaths attributable to Shigellae and ETEC, we subsequently applied previously published estimates of the median percentage of diarrhea hospitalizations due to Shigellae and ETEC to the estimated number of diarrhea deaths. For method 2, we applied previously published incidence rates to 2010 population figures and estimated the total number of episodes due to Shigellae and ETEC using published estimates of the average proportion of pathogen-positive outpatients from studies of >4 pathogens. We then estimated the number of pathogen-specific deaths by determining the number of hospitalized patients and applying the case-fatality rate. Results: By method 1, there were 19,451 deaths due to Shigellae and 42,973 due to ETEC in AFR, and 20,691 due to Shigellae and 45,713 due to ETEC in SEAR in 2010. By method 2, there were 15.0 million ETEC episodes and 30.4 million episodes due to Shigellae in AFR, and 28.7 million episodes due to ETEC and 58.1 million episodes due to Shigellae in SEAR in 2010. We were unable to identify published case-fatality rates for ETEC and thus could only estimate Shigellae-related deaths using method 2, by which there were 5,308 and 10,158 Shigellae-related deaths in AFR and SEAR in 2010, respectively. Discussion: Methods 1 and 2 underscore the importance of Shigellae and ETEC as major causes of morbidity and mortality among older children, adolescents, and adults in AFR and SEAR. Understanding the epidemiology of these pathogens is imperative for the development and use of future vaccines and other preventative interventions. Author Summary: We aimed to estimate the burden of diarrhea due to Shigellae and ETEC among persons ≥5 years of age in Africa and South Asia using two methodological approaches. Method 1 employed diarrhea proportionate mortality and published estimates of pathogen-specific hospitalization. Method 2 utilized published incidence rates and case-fatality rates. Method 1 resulted in 19,451 deaths due to Shigellae and 42,973 deaths due to ETEC in AFR, and 20,691 deaths due to Shigellae and 45,713 deaths due to ETEC in SEAR in 2010. Method 2 resulted in 15.0 million episodes due to ETEC and 30.4 million episodes due to Shigellae in AFR, and 28.7 million episodes due to ETEC and 58.1 million episodes due to Shigellae in SEAR in 2010. These figures highlight the importance of Shigellae and ETEC as major causes of morbidity and mortality among older children, adolescents and adults in Africa and South Asia. [ABSTRACT FROM AUTHOR]

Background: Childhood diarrhoea, a major cause of morbidity and mortality in low-income regions, remains scarcely studied in many countries, such as Guinea-Bissau. Stool sample drying enables later qPCR analyses of pathogens without concern about electricity shortages. Methods: Dried stool samples of children under five years treated at the Bandim Health Centre in Bissau, Guinea-Bissau were screened by qPCR for nine enteric bacteria, five viruses, and four parasites. The findings of children having and not having diarrhoea were compared in age groups 0–11 and 12–59 months. Results: Of the 429 children– 228 with and 201 without diarrhoea– 96.9% and 93.5% had bacterial, 62.7% and 44.3% viral, and 52.6% and 48.3% parasitic pathogen findings, respectively. Enteroaggregarive Escherichia coli (EAEC; 60.5% versus 66.7%), enteropathogenic E. coli (EPEC; 61.4% versus 62.7%), Campylobacter (53.2% versus 51.8%), and enterotoxigenic E. coli (ETEC; 54.4% versus 44.3%) were the most common bacterial pathogens. Diarrhoea was associated with enteroinvasive E. coli (EIEC)/Shigella (63.3%), astrovirus (75.0%), norovirus GII (72.6%) and Cryptosporidium (71.2%). The only pathogen associated with severe diarrhoea was EIEC/Shigella (p<0.001). EAEC was found more frequent among the infants, and EIEC/Shigella, Giardia duodenalis and Dientamoeba fragilis among the older children. Conclusions: Stool pathogens proved common among all the children regardless of them having diarrhoea or not. Author summary: Diarrhoeal diseases rank second as cause of childhood mortality and morbidity in low-income countries, yet prospective cohort studies in children with and without diarrhea covering the large variety of diarrhoeal pathogens are limited. While some studies have been conducted among Guinea-Bissauan children, many of them were from the 1990s, when the coverage of the various pathogens was less extensive and the diagnostic methods less sensitive than the modern qPCR methods. We conducted an observational study with a large cohort and covered concomitantly the various bacterial, viral and parasitic agents, and analyzed their associations with the presence/absence of diarrhoeal symptoms and age groups. Importantly, the assay performed well with dried stool samples and, therefore, appears applicable for epidemiological studies in resource-poor regions. A pathogen finding was recorded for almost all (98%) children: bacteria in 97%, viruses in 59% and parasites in 51%. Ongoing diarrhoea was associated with findings of enteroninvasive Escherichia coli/Shigella, astrovirus, norovirus GII and Cryptosporidium. Differences were seen between age groups, infants and young children. The only pathogen associated with severe diarrhoea was enteroninvasive Escherichia coli/Shigella. [ABSTRACT FROM AUTHOR]

Malawi has successfully leveraged multiple delivery platforms to scale-up and sustain the implementation of preventive chemotherapy (PCT) for the control of morbidity caused by soil-transmitted helminths (STH). Sentinel monitoring demonstrates this strategy has been successful in reducing STH infection in school-age children, although our understanding of the contemporary epidemiological profile of STH across the broader community remains limited. As part of a multi-site trial evaluating the feasibility of interrupting STH transmission across three countries, this study aimed to describe the baseline demographics and the prevalence, intensity and associated risk factors of STH infection in Mangochi district, southern Malawi. Between October-December 2017, a community census was conducted across the catchment area of seven primary healthcare facilities, enumerating 131,074 individuals across 124 villages. A cross-sectional parasitological survey was then conducted between March-May 2018 in the censused area as a baseline for a cluster randomised trial. An age-stratified random sample of 6,102 individuals were assessed for helminthiasis by Kato-Katz and completed a detailed risk-factor questionnaire. The age-cluster weighted prevalence of any STH infection was 7.8% (95% C.I. 7.0%-8.6%) comprised predominantly of hookworm species and of entirely low-intensity infections. The presence and intensity of infection was significantly higher in men and in adults. Infection was negatively associated with risk factors that included increasing levels of relative household wealth, higher education levels of any adult household member, current school attendance, or recent deworming. In this setting of relatively high coverage of sanitation facilities, there was no association between hookworm and reported access to sanitation, handwashing facilities, or water facilities. These results describe a setting that has reduced the prevalence of STH to a very low level and confirms many previously recognised risk-factors for infection. Expanding the delivery of anthelmintics to groups where STH infection persist could enable Malawi to move past the objective of elimination of morbidity, and towards the elimination of STH. Trial registration:NCT03014167. Author summary: The major public health strategy to control soil-transmitted helminths (STH) is preventive chemotherapy, whereby those at greatest risk of morbidity–including children and women of childbearing age–are presumptively treated with a safe, effective and inexpensive anthelminthic drug. In Malawi, this has been successfully sustained for nearly a decade through annual school-based deworming, in addition to integration within child health campaigns and antenatal care. Routine surveillance of schoolchildren demonstrates that STH has been reduced to very low levels in this age group, but few community-based epidemiological surveys have been conducted to investigate STH in the broader population. In this study, we observed that while infection with STH has been reduced to low levels overall, it is much higher in adults and particularly in males, with the odds of being infected greater in those from less wealthy households or from households with lower levels of adult education. These results underline that while preventive chemotherapy has likely been key to reductions in STH; sub-populations not routinely targeted by preventive chemotherapy, and the most disadvantaged members of society, continue to be disproportionately affected. We propose that evaluation of more comprehensive control strategies–such as entire-community deworming–could overcome these limitations, and present a route to STH elimination. [ABSTRACT FROM AUTHOR]

Under the Global Programme to Eliminate Lymphatic Filariasis (LF), American Samoa conducted mass drug administration (MDA) from 2000–2006. Despite passing Transmission Assessment Surveys (TAS) in 2011/2012 and 2015, American Samoa failed TAS-3 in 2016, with antigen (Ag) prevalence of 0.7% (95%CI 0.3–1.8%) in 6–7 year-olds. A 2016 community survey (Ag prevalence 6.2% (95%CI 4.4–8.5%) in age ≥8 years) confirmed resurgence. Using data from the 2016 survey, this study aims to i) investigate antibody prevalence in TAS-3 and the community survey, ii) identify risk factors associated with being seropositive for Ag and anti-filarial antibodies, and iii) compare the efficiency of different sampling strategies for identifying seropositive persons in the post-MDA setting. Antibody prevalence in TAS-3 (n = 1143) were 1.6% for Bm14 (95%CI 0.9–2.9%), 7.9% for Wb123 (95%CI 6.4–9.6%), and 20.2% for Bm33 (95%CI 16.7–24.3%); and in the community survey (n = 2507), 13.9% for Bm14 (95%CI 11.2–17.2%), 27.9% for Wb123 (95%CI 24.6–31.4%), and 47.3% for Bm33 (95%CI 42.1–52.6%). Multivariable logistic regression was used to identify risk factors for being seropositive for Ag and antibodies. Higher Ag prevalence was found in males (adjusted odds ratio [aOR] 3.01), age ≥18 years (aOR 2.18), residents of Fagali'i (aOR 15.81), and outdoor workers (aOR 2.61). Ag prevalence was 20.7% (95%CI 9.7–53.5%) in households of Ag-positive children identified in TAS-3. We used NNTestav (average number needed to test to identify one positive) to compare the efficiency of the following strategies for identifying persons who were seropositive for Ag and each antibody: i) TAS of 6–7 year-old children, ii) population representative surveys of older age groups, and iii) targeted surveillance of subpopulations at higher risk of being seropositive (older ages, householders of Ag-positive TAS children, and known hotspots). For Ag, NNTestav ranged from 142.5 for TAS, to <5 for households of index children. NNTestav was lower in older ages, and highest for Ag, followed by Bm14, Wb123 and Bm33 antibodies. We propose a multi-stage surveillance strategy, starting with population-representative sampling (e.g. TAS or population representative survey of older ages), followed by strategies that target subpopulations and/or locations with low NNTestav. This approach could potentially improve the efficiency of identifying remaining infected persons and residual hotspots. Surveillance programs should also explore the utility of antibodies as indicators of transmission. Author summary: Lymphatic filariasis (LF) is a parasitic infection transmitted by mosquito bites. Globally, tens of millions are infected, with many disfigured and disabled by severe damage to their lymphatic systems, such as severe swelling of the legs (elephantiasis) or scrotum (hydrocele). The Global Programme to Eliminate LF (GPELF) aims to interrupt disease transmission through mass drug administration (MDA), and to control illness and suffering in affected persons. The World Health Organization recommends conducting Transmission Assessment Surveys (TAS) in school children aged 6 to 7 years, to determine if infection rates have dropped to levels where disease transmission is no longer sustainable. From 2000–2006, American Samoa conducted MDA and made significant progress towards eliminating LF. However, despite passing TAS in 2011/2012 and 2015, surveys in 2016 showed evidence of resurgence. This study aimed to investigate the prevalence of anti-filarial antibodies in American Samoa in 2016; identify risk factors for testing positive for antigen, microfilaria and antibodies; and compare the efficiency of different sampling strategies for identifying persons who test positive. The sampling strategies that we compared included testing of 6–7 year-old children, population representative surveys of older age groups, and targeted surveys of high-risk groups such as older people, household members of infected children identified through TAS, and known hotspots. Based on our findings, we recommended that in addition to TAS, strategies that target high-risk populations and hotspots would strengthen surveillance and help countries achieve their goals of LF elimination. [ABSTRACT FROM AUTHOR]

Global efforts to control morbidity associated with soil-transmitted helminth infections (STH) have focused largely on the targeted treatment of high-risk groups, including children and pregnant women. However, it is not clear when such programs can be discontinued and there are concerns about the sustainability of current STH control programs. The DeWorm3 project is a large multi-country community cluster randomized trial in Benin, India and Malawi designed to determine the feasibility of interrupting the transmission of STH using community-wide delivery of mass drug administration (MDA) with anthelmintics over multiple rounds. Here, we present baseline data and estimate key epidemiological parameters important in determining the likelihood of transmission interruption in the DeWorm3 trial. A baseline census was conducted in October-December 2017 in India, November-December 2017 in Malawi and in January-February 2018 in Benin. The baseline census enumerated all members of each household and collected demographic data and information on occupation, assets, and access to water, sanitation and hygiene (WASH). Each study site was divided into 40 clusters of at least 1,650 individuals per cluster. Clusters were randomized to receive twice yearly community-wide MDA with albendazole (GSK) targeting eligible individuals of all ages (20 clusters), or to receive the standard-of-care deworming program targeting children provided in each country. In each site, a randomly selected group of 150 individuals per cluster (6,000 total per site) was selected from the baseline census using stratified random sampling, and each individual provided a single stool sample for analysis of STH infection using the Kato-Katz technique. Study site, household and individual characteristics were summarized as appropriate. We estimated key epidemiological parameters including the force of infection and the degree of parasite aggregation within the population. The DeWorm3 sites range in population from 94,969 to 140,932. The population age distribution varied significantly by site, with the highest proportion of infants and young children in Malawi and the highest proportion of adults in India. The baseline age- and cluster-weighted prevalence, as measured by Kato-Katz, varied across sites and by species, Baseline hookworm prevalence in India was 21.4% (95% CI: 20.4–22.4%), while prevalence of Ascaris and Trichuris by Kato-Katz was low (0.1% and 0.3% overall). In Malawi, the overall age- and cluster-weighted STH prevalence was 7.7% (95% CI: 7.1–8.4%) predominantly driven by hookworm infections (7.4%) while Ascaris (0.1%) and Trichuris (0.3%) infections were rare. In Benin, the overall age- and cluster-weighted prevalence was significantly lower (5.6%, 95% CI: 5.1–6.2%) and Ascaris (2.0%, 95% CI: 1.6–2.3%) was more common than in other sites. Ascaris infections were more likely to be moderate- or heavy-intensity (43.7%, unweighted) compared to hookworm (5.0%). The force of infection for hookworm was highest in adults in India and Malawi but appeared relatively stable across age groups in Benin. These data demonstrate the significant variability between the sites in terms of demography, socio-economic status and environmental characteristics. In addition, the baseline prevalence and intensity data from DeWorm3 suggest that each site has unique epidemiologic characteristics that will be critical in determining correlates of achieving STH transmission interruption in the DeWorm3 trial. Trial registration: The trial was registered at ClinicalTrials.gov (NCT03014167). Author summary: Intestinal parasitic worms, soil-transmitted helminths, are among the most common infectious organisms of humans. In many low-resource settings, these infections result in considerable morbidity, including reductions in childhood growth and development, increased risk of anemia and reductions in future educational achievement and income earning potential. The current global strategy for controlling these infections is through routine deworming of school and pre-school aged children as well as pregnant women. Since many adults and non-school going children are infected with these parasites, the current strategy does not prevent the rapid reinfection of individuals despite repeated treatment. The DeWorm3 trial is a large multi-country trial being conducted in Benin, India and Malawi to test the feasibility of using mass drug administration of deworming medications to all individuals in a community to interrupt these infections in some geographic areas. Here we present baseline data from these communities and estimate the transmission potential of these infections at each of the sites. [ABSTRACT FROM AUTHOR]

Background: Recent Zika virus (ZIKV) outbreaks in the Pacific and the Americas have highlighted clinically significant congenital neurological abnormalities resulting from ZIKV infection in pregnancy. However, little is known about ZIKV infections in children and adolescents, a group that is potentially vulnerable to ZIKV neurovirulence. Methods: We conducted a systematic review on the clinical presentation and complications of children and adolescents aged 0 to 18 years with a robust diagnosis of ZIKV infection. We searched PubMed, Web of Science, LILACs, and EMBASE until 13 February 2020 and screened reference lists of eligible articles. We assessed the studies' risk of bias using pre-specified criteria. Findings: Our review collated the evidence from 2543 pediatric ZIKV cases representing 17 countries and territories, identified in 1 cohort study, 9 case series and 22 case reports. The most commonly observed signs and symptoms of ZIKV infection in children and adolescents were mild and included fever, rash, conjunctivitis and arthralgia. The frequency of neurological complications was reported only in the largest case series (identified in 1.0% of cases) and in an additional 14 children identified from hospital-based surveillance studies and case reports. ZIKV-related mortality was primarily accompanied by co-morbidity and was reported in one case series (<0.5% of cases) and three case reports. One death was attributed to complications of Guillain-Barré Syndrome secondary to ZIKV infection. Conclusions and relevance: Based on the current evidence, the clinical presentation of ZIKV infection in children and adolescents appears to be primarily mild and similar to the presentation in adults, with rare instances of severe complications and/or mortality. However, reliable estimation of the risks of ZIKV complications in these age groups is limited by the scarcity and quality of published data. Additional prospective studies are needed to improve understanding of the relative frequency of the signs, symptoms, and complications associated with pediatric ZIKV infections and to investigate any potential effects of early life ZIKV exposure on neurodevelopment. Author summary: Although the number of Zika virus (ZIKV) cases has declined following the 2015–2016 outbreak in the Americas, ZIKV remains a public health concern due to the potentially severe consequences of in utero exposure to the virus. While there is an increasing understanding of the effects of prenatal congenital ZIKV infection, less is known regarding the potential consequences of postnatal non-congenital ZIKV infection in children and adolescents. As this age group may also be vulnerable to the adverse effects of ZIKV on the nervous system, a better understanding of ZIKV infection in this population is needed. This knowledge may help to inform the case definition for ZIKV disease in children and elucidate whether children and adolescents should be included in strategies and measures for prevention of ZIKV infection, which are currently aimed primarily at pregnant women. After a review of the existing literature, the authors found that ZIKV infection in children and adolescents appears to be similar to adults and primarily mild, with little evidence of severe neurological consequences. Further research using prospective methods and neurodevelopmental assessments is warranted. [ABSTRACT FROM AUTHOR]

Background: Shifts have occurred in the epidemiological characteristics of Japanese encephalitis (JE), extending from the molecular level to the population level. The aim of this study was to investigate the seroprevalence of JE neutralizing antibodies in healthy populations from different age groups in Zhejiang Province, and to conduct mosquito monitoring to evaluate the infection rate of Japanese encephalitis virus (JEV) among vectors, as well as the molecular characteristics of the E gene of isolated JEV strains. Methodology/Principal findings: A total of 1190 sera samples were screened by a microseroneutralization test, including 429 infants (28d-11m) and 761 participants (2y-82y). For those under 1 year old, the geometric mean titers (GMTs) of the JE neutralizing antibody was 9.49 at birth and significantly declined as the age of month increased (r = -0.225, P<0.001). For those above 1-year old, seropositive proportions were higher in subjects aged 1–3 years old as well as ≥25 years old (65%-75%), and relatively lower in subjects aged between 4–25 years old (22%-55%). Four or more years after the 2nd dose of JEV-L (first dose administered at 8 months and the second at 2 years of age), the seropositive proportion decreased to 32.5%-37.5%, and GMTs decreased to 8.08–9.11. A total of 87,201 mosquitoes were collected from livestock sheds in 6 surveillance sites during 2015–2018, from which 139 E gene sequences were successfully amplified. The annual infection rate according to bias-corrected maximum likelihood estimation of JEV in Culex tritaeniorhynchus was 1.56, 2.36, 5.65 and 1.77 per 1000, respectively. JEV strains isolated during 2015–2018 all belonged to Genotype I. The E gene of amplified 139 samples differed from the JEV-L vaccine strain at fourteen amino acid residues, including the eight key residues related to virulence and virus attenuation. No divergence was observed at the sites related to antigenicity. Conclusions/Significance: Zhejiang Province was at a high risk of JE exposure due to relatively lower neutralizing antibody levels among the younger-aged population and higher infection rates of JEV in mosquitoes. Continuous, timely and full coverage of JE vaccination are essential, as well as the separation of human living areas and livestock shed areas. In addition, annual mosquito surveillance and periodic antibody level monitoring are important for providing evidence for improvement in JE vaccines and immunization schedules. Author summary: Although Japanese encephalitis (JE) has been well-controlled in Zhejiang Province, it remains a hot public health issue due to heavy disease burden. The epidemiological characteristics of JE have changed recently in Zhejiang Province. Increasing proportion of adult cases (>40 years old) have been reported. Genotype I (GI) of JEV has displaced genotype III (GIII) as the dominant genotype. The population immunity against JE was notably low among participants aged 4–25 years old, with the lowest GMT being in the 7-14-year-old group. Two doses of JEV-L did not provide effective protection after 4 or more years past the 2nd dose. Therefore, issues about duration of protection and necessity of a booster dose at 6 years of age need further research. JEV strains isolated from mosquitoes during 2015–2018 in Zhejiang Province all belonged to GI. Compared with the JE vaccine strain, mutations at the eight amino acid residues on E gene related to virulence in Zhejiang strains were detected, while the antigenic sites remained the same. JE serological survey in healthy populations with different sequential immunization schedule should be conducted to provide evidence for reformation on JE immunization strategy, including type, dose and interval. [ABSTRACT FROM AUTHOR]

Background: Cutaneous leishmaniasis is one of the most neglected tropical diseases increasing in its public health importance. In Ethiopia over 28 million people are living at risk of infection. Method: Institution based cross-sectional study was conducted at Borumeda Hospital from February to May 2019. A total 205 leishmaniasis suspected patients were included by systematic random sampling technique. Socio demographic characteristics were collected using pre-tested questionnaires. Parasitological investigation was done from skin slit sample by using Geimsa staining method. Species identification was done by PCR-RFLP. Data were entered in to EpiData version 3.1 and analyzed using SPSS version 20 software. P-value of ≤ 0.05 was considered as statistically significant. Result: A total of 205 participants consisting 59% male and 41% female included in this study. The mean age (±SD) of the study participants was 31.9 (±14.29). The overall prevalence of cutaneous leishmaniasis was 22.4% (46/205). The prevalence in males (13.7%) was higher than in females (8.8%). It was more prevalent in the age group 16-45years old (15.6%). Clinically, 60% of patients' hade single lesion with 1.55 average number of lesions. About 30.7% of patients' had indurated plaque type of lesion. Most of the lesions were found on head and face (59%). House near to farmland, presence of hyrax in the village and presence of other cutaneous leishmaniasis cases in the neighborhood were independent predicator of cutaneous leishmaniasis prevalence. L.aethopica was found to be the etiologic agent of cutaneous leishmaniasis in the study participants. Conclusion: The prevalence of cutaneous leishmaniasis was 22.4%, this alerts the need of intervention. It is statistically associated with house near to farm land, presence of other cutaneous leishmaniasis cases in the neighborhood and presence of hyrax in village. Head and face were the most common sites of lesion. Author summary: Cutaneous leishmaniasis (CL) is vector-born intracellular protozoan infection of human. It is the most common form of leishmaniasis. Cutaneous leishmaniasis imposes a major public health problem to human being. Cutaneous leishmaniasis is associated with a wide spectrum of clinical presentation like nodular, Papular, nodulo-Papular, diffuse induration, nodulo-ulcerative and indurated plaque. Its clinical manifestation usually begins with an erythematous papule seen at the site of inoculation, then papule enlarges and breaks, forming a painless ulcer with a well-demarcated raised border with different centimeters in diameter, finally this will end up with depressed scar after healing. The lesions usually occur in the face and exposed extremities. Even though CL is not fatal, it can lead to disfigurement and lifelong scar leading to social exclusion and stigmatization. The number of cases and epidemiological foci of CL in Ethiopia is increasing. Here we confirm endemicity of CL in Kutaber district. We also showed as CL is associated with the presence of hyrax, working in and near to farm land and the existence of CL lesion in the neighbor. [ABSTRACT FROM AUTHOR]

Background: Soil transmitted helminths are highly prevalent worldwide. Globally, approximately 1.5 billion people are infected with Ascaris lumbricoides, Trichuris trichiura or hookworm. Endemic countries carry out periodic mass treatment of at-risk populations with albendazole or mebendazole as a control measure. Most prevalence studies have focused on school aged children and therefore control programs are implemented at school level, not at community level. In this study, the prevalence of intestinal helminths, including Strongyloides stercoralis, was examined using a comprehensive laboratory approach in a community in north-western Ethiopia. Methods: A cross-sectional survey was conducted on 792 individuals ≥5 years old in randomly selected houses in a rural district. Stools were examined using three techniques: a formol-ether concentration, the Baermann technique and a real time polymerase chain reaction test (these last two specific for S. stercoralis). Statistical analyses were performed between two large age groups, children (≤14 years old) and adults (≥15 years old). Results: The prevalence of helminths was 91.3%; (95% CI: 89.3–93.3%). Hookworm was the most prevalent, 78.7% (95% CI 75.6–81.4%), followed by S. stercoralis 55.7% (95% CI 52.2–59.1%). Co-infection with both was detected in 45.4% (95% CI 42.0–49.0%) of the participants. The mean age of hookworm-infected individuals was significantly higher than non-infected ones (p = 0.003). Also, S. stercoralis infection was significantly associated with age, being more prevalent in adults (p = 0.002). Conclusions: This is the highest prevalence of S. stercoralis detected in Ethiopia so far. Our results highlight the need of searching specifically for infection by this parasite since it usually goes unnoticed if helminth studies rely only on conventional diagnostic techniques, i.e. Kato-Katz. Moreover, the focus of these programs on children undermines the actual prevalence of hookworm. The adult population acts as a reservoir for both hookworm and S. stercoralis and this fact may negatively impact the current control programs in Ethiopia which only target treatment of school aged children. This reservoir, together with a lack of adequate water, sanitation and hygiene, increases the probability of re-infection in children. Finally, the high prevalence of S. stercoralis found calls for a comprehensive diagnostic approach in endemic areas in addition to a revision of control measures that is, adding ivermectin to current albendazole/mebendazole, since it is the drug of choice for S. stercoralis. Author summary: Soil-transmitted-helminthiases and schistosomiasis have major programs for control within the neglected tropical diseases agenda. Deworming programs, that is, periodic mass drug administration, with albendazole or mebendazole and praziquantel, for at-risk populations, are the main strategy for control and success in interrupting the transmission of these diseases. But despite huge efforts made, programs are still unsuccessful in controlling STH in endemic areas in Africa. In Ethiopia most parts of the country are suitable for helminth transmission. Mapping for identification of risk areas for hookworm, A. lumbricoides, T. trichiura and Schistosoma spp., has been conducted by the government, in order to prioritize the health agenda. The focus of the interventions are school- aged children. Another species of soil-transmitted helminth, Strongyloides stercoralis, of high morbidity, which requires special laboratory methods for diagnosis and a different treatment drug, is highly underestimated and not included in control programs. With the aim of knowing the prevalence of S. stercoralis and other intestinal helminths at the community level, a population in the rural area of north-western Ethiopia was studied using parasitological and molecular techniques. A high prevalence of helminths at the community level and specifically a high prevalence of S. stercoralis were detected. These results suggest there is a need to revise control programs in order to be able to cut transmission and to ensure universal health coverage that "leaves no one behind". [ABSTRACT FROM AUTHOR]

In South East Asia, dengue epidemics have increased in size and geographical distribution in recent years. We examined the spatiotemporal distribution and epidemiological characteristics of reported dengue cases in the predominantly rural state of Sabah, in Malaysian Borneo–an area where sylvatic and urban circulation of pathogens are known to intersect. Using a public health data set of routinely notified dengue cases in Sabah between 2010 and 2016, we described demographic and entomological risk factors, both before and after a 2014 change in the clinical case definition for the disease. Annual dengue incidence rates were spatially variable over the 7-year study period from 2010–2016 (state-wide mean annual incidence of 21 cases/100,000 people; range 5-42/100,000), but were highest in rural localities in the western districts of the state (Kuala Penyu, Nabawan, Tenom and Kota Marudu). Eastern districts exhibited lower overall dengue rates, although a high proportion of severe (haemorrhagic) dengue cases (44%) were focused in Sandakan and Tawau. Dengue incidence was highest for those aged between 10 and 29 years (24/100,000), and was slightly higher for males compared to females. Available vector surveillance data indicated that during large outbreaks in 2015 and 2016 the mosquito Aedes albopictus was more prevalent in both urban and rural households (House Index of 64%) than Ae. aegypti (15%). Demographic patterns remained unchanged both before and after the dengue case definition was changed; however, in the years following the change, reported case numbers increased substantially. Overall, these findings suggest that dengue outbreaks in Sabah are increasing in both urban and rural settings. Future studies to better understand the drivers of risk in specific age groups, genders and geographic locations, and to test the potential role of Ae. albopictus in transmission, may help target dengue prevention and control efforts. Author summary: In order to combat the rising regional incidence of dengue in South East Asia, incidence patterns must be better characterised within different ecological settings. We conducted the first retrospective analysis of dengue epidemiology in the predominantly rural state of Sabah, Malaysia, where both urban and sylvatic transmission cycles exist. Human notification data over a 7-year period were reviewed and spatiotemporal and demographic risk factors identified. We found that: 1. While urban habitats do play a role in mediating the spread of dengue in Sabah, cases from both urban and rural localities contributed equally to dengue outbreaks; 2. Human demographic risk factors included being aged between 10 and 29 years, and being male; 3. Cases of severe dengue were more common in the eastern districts of the state–almost half of severe dengue cases were reported from Sandakan and Tawau; and 4. The presence of Aedes albopictus in and around the majority of urban and rural case households, often in the apparent absence of Ae. aegypti, suggests that its role in transmission requires further investigation. This study emphasises that increasing incidence of dengue in urban South East Asia is also mirrored in more rural areas, and suggests a need for control strategies that address both urban and rural dengue risk. [ABSTRACT FROM AUTHOR]

After the large influx of Rohingya nationals (termed Forcibly Displaced Myanmar National; FDMN) from Rakhine State of Myanmar to Cox's Bazar in Bangladesh, it was apparent that outbreaks of cholera was very likely in this setting where people were living under adverse water and sanitation conditions. Large campaigns of oral cholera vaccine (OCV) were carried out as a preemptive measure to control cholera epidemics. The aim of the study was to evaluate the immune responses of healthy adults and children after administration of two doses of OCV at 14 days interval in FDMN population and compare with the response observed in Bangladeshi's vaccinated earlier. A cross-sectional immunogenicity study was conducted among FDMNs of three age cohort; in adults (18+years; n = 83), in older children (6–17 years; n = 63) and in younger children (1–5 years; n = 80). Capillary blood was collected at three time points to measure vibriocidal antibodies using either plasma or dried blood spot (DBS) specimens. There was a significant increase of responder frequency of vibriocidal antibody titer at day 14 in all groups for Vibrio cholerae O1 (Ogawa/Inaba: adults-64%/64%, older children-70%/89% and younger children-51%/75%). There was no overall difference of vibriocidal antibody titer between FDMN and Bangladeshi population at baseline (p = 0.07–0.08) and at day 14, day 28 in all age groups for both serotypes. The seroconversion rate and geometric mean titer (GMT) of either serotype were comparable using both plasma and DBS specimens. These results showed that OCV is capable of inducing robust immune responses in adults and children among the FDMN population which is comparable to that seen in Bangladeshi participants in different age groups or that reported from other cholera endemic countries. Our results also suggest that the displaced population were exposed to V. cholerae prior to seeking shelter in Bangladesh. Author summary: Oral cholera vaccines (OCV) are now on the WHO stockpile and targeted for use for countries with outbreaks and epidemics but also for control of endemic cholera. In Bangladesh many studies have been carried out to assess the safety, immunogenicity as well as feasibility of vaccination in the endemic settings of the country. However, with the large recent influx of displaced Rohingya nationals from Myanmar (termed Forcibly Displace Myanmar National; FDMN), mass campaigns with OCV were conducted between October 2017-December 2018. However, no data is available of the previous exposure to cholera of this population, prior to their arrival in Bangladesh. An assessment of immunogenicity status of FDMN is needed to find out if OCV is able to elicit comparable immune response and whether the same dose regimen of OCV was immunogenic among the FDMNs. In this study, we have measured the immune responses to the OCV, Shanchol, in adults (18 years and above), older children (6–17 years), and younger children (1–5 years). The results of this study shows that the oral cholera vaccine capable of inducing an immune response in adults and children among this FDMN population and the responses were comparable to that seen in Bangladeshi participants in earlier studies. [ABSTRACT FROM AUTHOR]

Background: Trachoma is the leading infectious cause of blindness. However, little is known about the behavioural and environmental determinants of transmission of the causative organism, Chlamydia trachomatis. We conducted formative research in a trachoma hyper-endemic area of Ethiopia to explore the behaviours which are likely to contribute to trachoma transmission and map their determinants. Methodology/Principal findings: Data on water use, hygiene, defecation, and sleeping arrangements were collected from five communities during the dry and rainy seasons in 2016. Data collection involved direct observation in households (n = 20), interviews with caregivers (n = 20) and focus group discussions (n = 11). Although several behaviours that likely contribute to trachoma transmission were identified, no single behaviour stood out as the dominant contributor. Hygiene practices reflected high levels of poverty and water scarcity. Face washing and soap use varied within and between households, and were associated with other factors such as school attendance. Children’s faces were rarely wiped to remove nasal or ocular discharge, which was not perceived to be socially undesirable. Bathing and laundry were performed infrequently due to the amount of time and water required. Open defecation was a normative practice, particularly for young children. Latrines, when present, were poorly constructed, maintained and used. Young children and parents slept closely together and shared bedding that was infrequently washed. Conclusions/Significance: Existing norms and enabling factors in this context favour the development of interventions to improve facial cleanliness as more feasible than those that reduce unsafe faeces disposal. Interventions to increase the frequency of bathing and laundry may also be infeasible unless water availability within the home is improved. [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]

Background: Worldwide, snakebite envenomations total ~2.7 million reported cases annually with ~100,000 fatalities. Since 2009, snakebite envenomation has intermittently been classified as a very important ‘neglected tropical disease’ by the World Health Organisation. Despite this emerging awareness, limited efforts have been geared towards addressing the serious public health implications of snakebites, particularly in sub-Saharan Africa, where baseline epidemiological and ecological data remain incomplete. Due to poverty as well as limited infrastructure and public health facilities, people in rural Africa, including Ghana, often have no other choice than to seek treatment from traditional medical practitioners (TMPs). The African ‘snakebite crisis’ is highlighted here using regionally representative complementary data from a community-based epidemiological and ecological study in the savanna zone of northern Ghana. Methodology and findings: Our baseline study involved two data collection methods in the Savelugu-Nanton District (in 2019 the district was separated into Savelugu and Nanton districts) in northern Ghana, comprising a cross-sectional study of 1,000 residents and 24 TMPs between December 2008 and May 2009. Semi-structured interviews, as well as collection of retrospective snakebite and concurrent rainfall records from the Savelugu-Nanton District Hospital and Ghana Meteorological Authority respectively over 10-years (1999–2008) were used in the study. Variables tested included demography, human activity patterns, seasonality, snake ecology and clinical reports. Complementary data showed higher snakebite prevalence during the rainy season, and a hump-shaped correlation between rainfall intensity and snakebite incidences. Almost 6% of respondents had experienced a personal snakebite, whereas ~60% of respondents had witnessed a total of 799 snakebite cases. Out of a total of 857 reported snakebite cases, 24 (~2.8%) died. The highest snakebite prevalence was recorded for males in the age group 15–44 years during farming activities, with most bites occurring in the leg/foot region. The highest snakebite rate was within farmlands, most severe bites frequently caused by the Carpet viper (Echis ocellatus). Conclusion: The relatively high community-based prevalence of ~6%, and case fatality ratio of ~3%, indicate that snakebites represent an important public health risk in northern Ghana. Based on the high number of respondents and long recording period, we believe these data truly reflect the general situation in the rural northern savanna zone of Ghana and West Africa at large. We recommend increased efforts from both local and international health authorities to address the current snakebite health crisis generally compromising livelihoods and productivity of rural farming communities in West Africa. [ABSTRACT FROM AUTHOR]

Background: Trachoma, caused by Chlamydia trachomatis, remains the leading infectious cause of blindness worldwide. Persistence and progression of the resulting clinical disease appears to be an immunologically mediated process. Azithromycin, which is distributed at the community level for trachoma control, has immunomodulatory properties. We investigated the impact of one round of oral azithromycin on conjunctival immune responses, C. trachomatis infection and clinical signs three- and six- months post treatment relative to three pre-treatment time-points. Methodology: A cohort of children aged 6 to 10 years were recruited from a trachoma endemic region of northern Tanzania and were visited five times in a 12-month period. They were examined for clinical signs of trachoma and conjunctival swabs were collected for laboratory analysis. C. trachomatis infection was detected and the expression of 46 host genes was quantified using quantitative PCR. All community members were offered azithromycin treatment immediately after the six-month timepoint according to international guidelines. Findings: The prevalence of C. trachomatis infection and inflammatory disease signs were significantly reduced three- and six- months post-mass drug administration (MDA). C. trachomatis infection was strongly associated with clinical signs at all five time-points. A profound anti-inflammatory effect on conjunctival gene expression was observed 3 months post-MDA, however, gene expression had largely returned to pre-treatment levels of variation by 6 months. This effect was less marked, but still observed, after adjusting for C. trachomatis infection and when the analysis was restricted to individuals who were free from both infection and clinical disease at all five time-points. Interestingly, a modest effect was also observed in individuals who did not receive treatment. Conclusion: Conjunctival inflammation is the major clinical risk factor for progressive scarring trachoma, therefore, the reduction in inflammation associated with azithromycin treatment may be beneficial in limiting the development of potentially blinding disease sequelae. Future work should seek to determine whether this effect is mediated directly through inhibition of pro-inflammatory intracellular signalling molecules, through reductions in concurrent, sub-clinical infections, and/or through reduction of infection exposure. [ABSTRACT FROM AUTHOR]

Background: Podoconiosis, also known as mossy foot or endemic non-filarial elephantiasis, is a preventable form of lower-leg lymphoedema caused by prolonged (typically barefoot) exposure to soil derived from volcanic rocks. Acute adenolymphangitis (also called ‘acute attack’) is a serious complication of podoconiosis resulting in significant symptoms and worsening disability. Despite the well-known morbidity associated with podoconiosis, to date there have been no studies looking at the impact, or burden, of podoconiosis on caregivers. This study explored the experiences and impact of acute attacks on the caregivers of those with podoconiosis in one endemic district of Ethiopia. Methods/Principal findings: This qualitative study was based in Wayu Tuka woreda (district), Oromia, Western Ethiopia. 27 semi-structured interviews of those with podoconiosis and their caregivers were conducted in June 2018. Here we report the findings from the caregiver’s interviews. Data were analysed using NVivo 12. Directed content analysis, a qualitative approach related to thematic analysis, was used to analyse the results. This study highlights a previously unreported impact of acute attacks on the caregivers of those affected by podoconiosis. The findings demonstrate the significant social and financial pressures placed on podoconiosis-affected families which are exacerbated during acute attacks. This study also highlighted the emotional burden experienced by caregivers, the range of care activities placed on them and the limited support available. Conclusions: This study found a significant impact on the caregivers of those with podoconiosis, especially during acute attacks, in in Wayu Tuka woreda. It also highlighted the limited support available to caregivers. Further research is needed to understand whether this impact applies to podoconiosis caregivers across Ethiopia, and beyond, and to establish if there are wider implications of this important consequence of podoconiosis, for example on the economy and caregivers’ mental and physical health. [ABSTRACT FROM AUTHOR]

Background: Soil-transmitted helminth (STH) infections remain highly endemic across the Philippines, and are believed to be important contributors to delayed cognitive development of school-aged children. Identification of communities where children are at risk of functional illiteracy is important for the attainment of Sustainable Development Goals target for literacy. We aimed to quantify the associations between the spatial variation of STH infections and functional literacy indicators adjusting for other important contributors, and identify priority areas in the Philippines in need of interventions. Methodology/Principal findings: We used data from 11,313 school-aged children on functional literacy indicators collected in 2008. Nested fixed-effects multinomial regression models were built to determine associations between STH endemicity and geographical distribution of functional literacy, adjusting for demographics, household level variables, and the prevalence of malaria. Bayesian multinomial geostatistical models were built to geographically predict the prevalence of each level of functional literacy. The number of school-aged children belonging to each of the functional literacy indicator classes was forecast for 2017. We estimated 4.20% of functional illiteracy burden among school-aged children in Mindanao might be averted by preventing T. trichiura infections. Areas predicted with the highest prevalence of functional illiteracy were observed in localised areas of the eastern region of the Visayas, and the south-eastern portion of Mindanao. Conclusions/Significance: The study demonstrates significant geographical variation in burden of functional illiteracy in school-aged children associated with STH infections suggesting that targeted helminth control could potentially promote the development of cognitive function of school-aged children in the Philippines. The benefits of a spatially targeted strategy should be tested by future studies. [ABSTRACT FROM AUTHOR]

Background: Nodding Syndrome was first reported from Tanzania in the 1960s but appeared as an epidemic in Northern Uganda in the 1990s during the LRA civil war. It is characterized by repetitive head nodding, often followed by other types of seizures, developmental retardation and growth faltering with onset occurring in children aged 5–15 years. More than 50 years after the first reports, the aetiology remains unknown and there is still no cure. The recent hypothesis that Nodding Syndrome is caused by onchocerciasis also increases the relevance of onchocerciasis control. Northern Uganda, with its unique socio-political history, adds challenges to the prevention and treatment for Nodding Syndrome. This article aims to show how and why Nodding Syndrome has been politicised in Uganda; how this politicisation has affected health interventions including research and dissemination; and, the possible implications this can have for disease prevention and treatment. Methodology: Ethnographic research methods were used triangulating in-depth interviews, focus group discussions, informal conversations and participant observation, for an understanding of the various stakeholders’ perceptions of Nodding Syndrome and how these perceptions impact future interventions for prevention, treatment and disease control. Principal findings: Distrust towards the government was a sentiment that had developed in Northern Uganda over several decades of war and was particularly linked to the political control and ethnic divisions between the north and south. This coincided with the sudden appearance of Nodding Syndrome, an unknown epidemic disease of which the cause could not be clearly identified and optimal treatment had not clearly been established. Additionally, the dissemination of the inconclusive results of research conducted in the area lacked sufficient community involvement which further fueled this political distrust. Disease perceptions revolved around rumours that the entire Acholi ethnic group of the north would be annihilated, or that international researchers were making money by stealing study samples. This discouraged some community members from participating in research or from accepting the mass drug administration of ivermectin for prevention and treatment of onchocerciasis. Such rumour and distrust led to suspicions concerning the integrity of the disseminated results, which may negatively impact future disease management and control interventions. Conclusions and recommendations: Trust must be built up gradually through transparency and by de-politicising interventions. This can be done by engaging the community at regular intervals during research and data collection and the dissemination of results in addition to involvement during service delivery for prevention and treatment. Maintaining a regular feedback loop with the community will help control rumours, build trust, and improve the preparations for adequate dissemination. [ABSTRACT FROM AUTHOR]

Background: Rift Valley fever (RVF) is a mosquito-borne zoonotic disease characterized in South Africa by large epidemics amongst ruminant livestock at very long, irregular intervals, mainly in the central interior. However, the presence and patterns of occurrence of the virus in the eastern parts of the country are poorly known. This study aimed to detect the presence of RVF virus (RVFV) in cattle and goats in far northern KwaZulu-Natal province and to estimate the prevalence of antibodies to the virus and the incidence rate of seroconversion. Methodology: Cross-sectional studies were performed in communally farmed cattle (n = 423) and goats (n = 104), followed by longitudinal follow-up of seronegative livestock (n = 253) 14 times over 24 months, representing 160.3 animal-years at risk. Exposure to RVFV was assessed using an IgG sandwich ELISA and a serum neutralization test (SNT) and seroconversion was assessed using SNT. Incidence density was estimated and compared using multivariable Poisson models and hazard of seroconversion was estimated over time. Principal findings: Initial overall seroprevalence was 34.0% (95%CI: 29.5–38.8%) in cattle and 31.7% (95%CI: 22.9–41.6%) in goats, varying by locality from 18–54%. Seroconversions to RVFV based on SNT were detected throughout the year, with the incidence rate peaking during the high rainfall months of January to March, and differed considerably between years. Overall seroconversion rate in cattle was 0.59 per animal-year (95% CI: 0.46–0.75) and in goats it was 0.41 per animal-year (95% CI: 0.25–0.64), varying significantly over short distances. Conclusions/Significance: The high seroprevalence in all age groups and evidence of year-round viral circulation provide evidence for a hyperendemic situation in the study area. This is the first study to directly estimate infection rate of RVFV in livestock in an endemic area in the absence of reported outbreaks and provides the basis for further investigation of factors affecting viral circulation and mechanisms for virus survival during interepidemic periods. [ABSTRACT FROM AUTHOR]

Mycetoma is a neglected tropical disease, endemic in many tropical and subtropical regions, characterised by massive deformity and disability and can be fatal if untreated early and appropriately. Interleukins (IL) -35 and IL-37 are newly discovered cytokines that play an important role in suppressing the immune system. However, the expression of these interleukins in patients with Madurella mycetomatis (M. mycetomatis) induced eumycetoma has not yet been explored. The aim of this study is to determine the levels of IL-1 family (IL-1β, IL-37) and IL-12 family (IL-12, IL-35) in a group of these patients and the association between these cytokines levels and the patients’ demographic characteristics. The present, case-control study was conducted at the Mycetoma Research Centre, Soba University Hospital, University of Khartoum, Sudan and it included 140 individuals. They were divided into two groups; group I: healthy controls [n = 70; median age 25 years (range 12 to 70 years)]. Group II: mycetoma patients [n = 70 patients; median age 25 (range 13 to 70 years)]. Cytokines levels were measured in sera using enzyme linked immunosorbent assay (ELISA). There was a significant negative correlation between IL-1β and IL-12 levels and lesion size and disease duration, while IL-37 and IL-35 levels were significantly positively correlated with both lesion size and disease duration. The analysis of the risk factors of higher circulatory levels of IL-37 in patients of mycetoma showed a negative significant association with IL-1β cytokine, where a unit increment in IL-1β will decrease the levels of IL-37 by 35.28 pg/ml. The levels of IL-37 among the patients with a duration of mycetoma infection ≤ 1 year were significantly low by an average of 18.45 pg/ml compared to patients with a mycetoma infection’s duration of ≥ 5years (reference group). Furthermore, the risk factors of higher levels of IL-35 in mycetoma patients revealed a negative significant association with IL-12, as a unit increment in IL-12 decreases the levels of IL-35 by 8.99 pg/ml (p < 0.001). Levels of IL-35 among the patients with duration of mycetoma infection ≤ one year were significantly low on average by 41.82 pg/ml (p value = 0.002) compared to patients with a duration of mycetoma infection ≥ 5 years (reference group). In conclusion, this study indicates that both IL-35 and IL-37 are negatively associated with the levels of IL-1β and IL-12 in eumycetoma mycetoma infection; and high levels of IL-37 and IL-35 may have a negative impact on disease progression. [ABSTRACT FROM AUTHOR]

Background: Urogenital schistosomiasis is endemic throughout Ghana with elevated infection levels in certain areas e.g. Lake Volta Region. While the primary focus of the national control program is on mass drug administration of praziquantel to school-aged children, Female Genital Schistosomiasis (FGS), a disease-specific affliction of girls and women, has been largely overlooked. To better focus future actions, our study investigated the perceptions, knowledge and understanding of FGS amongst community members and health providers. Method/Principal findings: We used qualitative methods including 12 focus group discussions and 34 in-depth interviews. We purposively selected 16 communities along the Lake Volta in the Shai-Osudoku District. Participant selection was based on gender, age and occupation; providing an opportunity to explore community understanding of FGS through participants own words and perceptions. Awareness of schistosomiasis was reported and is commonly experienced among children (12–17 years) and younger adults (18–25 years) in the study communities but is typically considered a boy's disease. Knowledge of FGS was lacking in women, girls and front-line health workers. There was a general misconception that FGS may be the result of sexual promiscuity. Adolescent girls reporting vaginal discharge and itching were often stigmatized by health workers and treated for sexually transmitted infections. Limited alternatives to the river as key source of water meant that all members of the community faced the regular risk of schistosomiasis. Conclusion/Significance: There is a clear imperative for the national control program to better engage on FGS and implement interventions to meet girls and women's needs. The key consideration is to integrate more adequately preventive services with sexual and reproductive primary health care with future training of health workers for improved management of FGS cases. More broadly, harmonizing the portfolio of all actions on FGS is needed, especially with a call for improved access to safe water and sanitation for all those at current or future risk. [ABSTRACT FROM AUTHOR]

The article evaluate the "worm wars" literature and highlighting gaps in the current discourse on deworming, which have been ignored by both economists and epidemiologists. It mentions that six different helminths resulting in high prevalence human infections are currently targeted by deworming; and mentions the major deworming drugs have differential effects on these helminths, especially when used in a single dose.

Madariaga virus (MADV), also known as South American eastern equine encephalitis virus, has been identified in animals and humans in South and Central America, but not previously in Hispaniola or the northern Caribbean. MADV was isolated from virus cultures of plasma from an 8-year-old child in a school cohort in the Gressier/Leogane region of Haiti, who was seen in April, 2015, with acute febrile illness (AFI). The virus was subsequently cultured from an additional seven AFI case patients from this same cohort in February, April, and May 2016. Symptoms most closely resembled those seen with confirmed dengue virus infection. Sequence data were available for four isolates: all were within the same clade, with phylogenetic and molecular clock data suggesting recent introduction of the virus into Haiti from Panama sometime in the period from October 2012-January 2015. Our data document the movement of MADV into Haiti, and raise questions about the potential for further spread in the Caribbean or North America. [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]

Background: A pioneering strategy developed by the World Health Organization (WHO) for the control of schistosomiasis was the concept of a height-based dose pole to determine praziquantel (PZQ) dosing in large-scale treatment campaigns. However, some recent studies have shown variable accuracy for the dose pole in terms of predicting correct mg/Kg dosing, particularly for treatment of adults. According to the WHO, 91 million adults in 52 countries are targeted to be treated by 2020. Methods/Principal findings: The present study aimed to test the accuracy of the dose pole in determining PZQ dosage by comparing the number of tablets determined by the dose pole with the number of tablets determined according to total body weight. The analysis included height-for-weight data from 9,827 school-aged children (SAC) and adults from 42 villages in the province of Cabo Delgado in Mozambique. The results revealed that of the 7,596 SAC, 91.8% has received an appropriate dose (30-60mg/Kg), 6% received an insufficient dose (<30mg/Kg) and 2% an excessive dose (> 60mg/Kg). On the other hand, 13.7% out of 2,231 adults were treated inaccurately with 13.5% receiving an insufficient dose. When the percentage of insufficient dosing was disaggregated by gender, the frequency of adult females who were underdosed reached 18.3% versus 10.8% of adult males. Adult females aged 21–55 years were found to have an underdose frequency of 21.3%, compared to 11.8% of adult males in the same age range. The performance of a proposed modified dose pole was compared using the same dataset of adult Mozambicans. The results showed that the modified dose pole reduced the underdose frequency among adults from 13.5% to 10.4%, and subsequently increasing the percentage of optimal dosing from 33.7% to 45.3%. Conclusions: Our findings highlight the need to update the WHO-dose pole to avoid administration of insufficient PZQ doses to adults and therefore minimize the potential emergence of PZQ-resistant strains. Trial registration: International Standard Randomized Controlled Trial registry under ISRTC number [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]

It is estimated that 190 million individuals are at risk of blindness from trachoma, and that control by mass drug administration (MDA) is reducing this risk in many populations. Programs are monitored using prevalence of follicular trachoma disease (TF) in children. However, as programs progress to low prevalence there are challenges interpreting this indirect measure of infection. PCR and sero-surveillance are being considered as complementary tools to monitor low-level transmission, but there are questions on how they can be most effectively used. We use a previously-published, mathematical model to explore the dynamic relationship between TF and PCR throughout a control program and a sero-catalytic model to evaluate the utility of two cross-sectional sero-surveys for estimating sero-conversion rates. The simulations show that whilst PCR is more sensitive than TF at detecting infection, the probability of detecting at least one positive individual declines during an MDA program more quickly for PCR than for TF (for the same sample size). Towards the end of a program there is a moderate chance of a random sample showing both low PCR prevalence and higher TF prevalence, which may contribute to the lack of correlation observed in epidemiological studies. We also show that conducting two cross-sectional sero-surveys 10 years apart can provide more precise and accurate estimation of epidemiological parameters than a single survey, supporting previous findings that whilst serology holds great promise, multiple cross-sections from the same community are needed to generate the most valuable information about transmission. These results highlight that the quantitative dynamics of infection and disease should be included alongside the many logistical and practical factors to be considered in designing a monitoring and evaluation strategy at the operational research level, in order to help subsequently inform data collection for individual country programs. Whilst our simulations provide some insight, they also highlight that some level of longitudinal, individual-level data on reinfection and disease may be needed to monitor elimination progress. [ABSTRACT FROM AUTHOR]

Background: Cholera remains an important public health problem in major cities in Bangladesh, especially in slum areas. In response to growing interest among local policymakers to control this disease, this study estimated the impact and cost-effectiveness of preventive cholera vaccination over a ten-year period in a high-risk slum population in Dhaka to inform decisions about the use of oral cholera vaccines as a key tool in reducing cholera risk in such populations. Methodology/Principal findings: Assuming use of a two-dose killed whole-cell oral cholera vaccine to be produced locally, the number of cholera cases and deaths averted was estimated for three target group options (1–4 year olds, 1–14 year olds, and all persons 1+), using cholera incidence data from Dhaka, estimates of vaccination coverage rates from the literature, and a dynamic model of cholera transmission based on data from Matlab, which incorporates herd effects. Local estimates of vaccination costs minus savings in treatment costs, were used to obtain incremental cost-effectiveness ratios for one- and ten-dose vial sizes. Vaccinating 1–14 year olds every three years, combined with annual routine vaccination of children, would be the most cost-effective strategy, reducing incidence in this population by 45% (assuming 10% annual migration), and costing was $823 (2015 USD) for single dose vials and $591 (2015 USD) for ten-dose vials per disability-adjusted life year (DALY) averted. Vaccinating all ages one year and above would reduce incidence by >90%, but would be 50% less cost-effective ($894–1,234/DALY averted). Limiting vaccination to 1–4 year olds would be the least cost-effective strategy (preventing only 7% of cases and costing $1,276-$1,731/DALY averted), due to the limited herd effects of vaccinating this small population and the lower vaccine efficacy in this age group. Conclusions/Significance: Providing cholera vaccine to slum populations in Dhaka through periodic vaccination campaigns would significantly reduce cholera incidence and inequities, and be especially cost-effective if all 1–14 year olds are targeted. [ABSTRACT FROM AUTHOR]

Introduction: A global strategy of mass drug administration (MDA) has greatly reduced the burden of lymphatic filariasis (LF) in endemic countries. In Madagascar, the National Programme to eliminate LF has scaled-up annual MDA of albendazole and diethylcarbamazine across the country in the last decade, but its impact on LF transmission has never been reported. The objective of this study was to evaluate progress towards LF elimination in southeastern Madagascar. Methods: Three different surveys were carried out in parallel in four health districts of the Vatovavy Fitovinany region in 2016: i) a school-based transmission assessment survey (TAS) in the districts of Manakara Atsimo, Mananjary, and Vohipeno (following a successful pre-TAS in 2013); ii) a district-representative community prevalence survey in Ifanadiana district; and iii) a community prevalence survey in sentinel and spot-check sites of these four districts. LF infection was assessed using the Alere Filariasis Test Strips, which detect circulating filarial antigens (CFA) of adult worms. A brief knowledge, attitudes and practices questionnaire was included in the community surveys. Principal findings: None of the 1,825 children sampled in the TAS, and only one in 1,306 children from sentinel and spot-check sites, tested positive to CFA. However, CFA prevalence rate in individuals older than 15 years was still high in two of these three districts, at 3.5 and 9.7% in Mananjary and Vohipeno, respectively. Overall CFA prevalence in sentinel and spot-check sites of these three districts was 2.80% (N = 2,707), but only two individuals had detectable levels of microfilaraemia (0.06%). Prevalence rate estimates for Ifanadiana were substantially higher in the district-representative survey (15.8%; N = 545) than in sentinel and spot-check sites (0.8%; N = 618). Only 51.2% of individuals surveyed in these four districts reported taking MDA in the last year, and 42.2% reported knowing about LF. Conclusions: Although TAS results suggest that MDA can be stopped in three districts of southeastern Madagascar, the adult population still presents high CFA prevalence levels. This discordance raises important questions about the TAS procedures and the interpretation of their results. [ABSTRACT FROM AUTHOR]