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Background: Current soil-transmitted helminth (STH) control guidelines endorse the use of albendazole or mebendazole for school-based targeted preventive chemotherapy (PC), yet their reduced efficacy against Strongyloides stercoralis and Trichuris trichiura presents significant limitations. Emerging evidence indicates that community-wide PC [or mass drug administration (MDA)] using ivermectin, commonly used in other neglected tropical disease (NTD) control programs, may play an important role in controlling these parasites. We conducted a systematic review and meta-analysis to evaluate the effectiveness of ivermectin PC in reducing STH prevalence in endemic populations., Methods: We searched Pubmed, EMBASE, and Web of Science on February 14, 2023, for studies that investigated the effectiveness of ivermectin PC, either alone or in combination with other anthelmintic drugs, on STH infections, and provided a measure of STH prevalence before and after PC. We calculated pooled prevalence reductions for each STH using random-effects meta-analyses. Our protocol is available on PROSPERO (registration number CRD42023401219)., Results: A total of 21 were eligible for the systematic review, of which 15 were eligible for meta-analysis. All studies delivered ivermectin through MDA. The pooled prevalence reduction of S. stercoralis following MDA with ivermectin alone was 84.49% (95% CI 54.96-94.66) across five studies and 81.37% (95% CI 61.62-90.96) across seven studies with or without albendazole. The prevalence reduction of T. trichiura was 49.93% (95% CI 18.23-69.34) across five studies with ivermectin alone, and 89.40% (95% CI 73.66-95.73) across three studies with the addition of albendazole. There was high heterogeneity for all syntheses (I 2  > 65%)., Conclusions: This study underscores the key role of ivermectin-based MDA in addressing limitations in current global STH guidelines in terms of limited efficacy against S. stercoralis and T. trichiura. Based on these findings, revising international STH guidelines to include ivermectin is a promising option to progress the control and eventual elimination of STHs and other NTDs., (© 2024. The Author(s).)

Background: Ivermectin mass drug administration (MDA) is effective for controlling onchocerciasis and scabies, with evidence supporting its role in some species of soil-transmitted helminth (STH) infections. In the context of RISE, a cluster-randomised trial for scabies, this study evaluated the effectiveness of ivermectin MDA in reducing STH burden in the Western Province of Solomon Islands., Methods: Twenty villages were randomised 1:1 to receive ivermectin MDA as one dose (IVM-1) or two doses (IVM-2) for scabies. The effectiveness of one and two doses in reducing STH prevalence and intensity was evaluated before (May 2019) and 21 months after (February 2021) MDA in May 2019. All residents aged 12 months or older in the study villages were eligible to participate and provide stool specimens. Species-specific STH infection and intensity were assessed using quantitative PCR. We compared prevalence and intensity of infection between baseline and 21 months in each intervention arm individually using cluster-level analysis (adjusted for clustering) and individual-level analysis (adjusted for sex, age, and clustering). The primary outcomes were the prevalence risk difference (RD) from the cluster-level analysis, and the change in adjusted odds of infection from the individual-level analysis. Secondary outcomes included change in incident rates of mean eggs per gram (epg) of stool from baseline to 21 months, relative risk difference in prevalence and relative change in odds of infection between arms at 21 months. Sex data (male/female) were self-reported., Findings: Overall, STH infection was assessed in 830 participants from 18 villages at baseline and 1172 from 20 villages at follow-up. Females represented 58% (n = 478) of the sample at baseline and 59% (n = 690) at follow-up. We observed a reduction in Strongyloides spp. prevalence following two doses of ivermectin MDA in the cluster-level analysis from 7.0% (32/458 participants) to 1.2% (8/674 participants), corresponding to a RD of -0.07 (95% CI -0.14 to -0.01, p  = 0.036), and in the individual-level analysis (OR 0.11, 95% CI 0.04-0.33, p  < 0.001). T. trichiura prevalence decreased following one dose from 19.4% (74/372 participants) to 11.7% (56/505 participants) (OR 0.44, 95% CI 0.26-0.73, p  = 0.0040), while egg count reduced in both arms (IVM-1: IRR 0.28, 95% CI 0.11-0.70, p  = 0.0070; IVM-2: IRR 0.18, 95% CI 0.08-0.40, p  < 0.001), in the individual-level analysis. We did not detect a significant difference in effect measures between the one- and two-dose arms for any species after 21 months., Interpretation: Our study highlights the long-term benefits of ivermectin MDA in reducing the burden of Strongyloides spp. and T. trichiura . STH control programs should leverage the geographical overlap of NTDs, existing drug distribution channels, and broad-spectrum agents., Funding: The National Health and Medical Research Council of Australia., Competing Interests: AS has received grants or contracts from the US National Institutes of Health and the Leducq Foundation, participated on a Data Safety Monitoring Board run by Griffith University, is Co-Director of the Australian Step A Vaccine Initiative, is Co-Chair of the Step A Vaccine Global Consortium, and is President of the Lancefield Society for Streptococci and Streptococcal Diseases. LR declares receiving a grant or contract by the Australian National Health and Medical Research Council (NHMRC) and is a member of the Executive team and Lead of Integration of the World Scabies Program. All remaining authors have no conflicts of interest to disclose., (© 2023 The Authors.)

Background: School-based targeted preventive chemotherapy (PC), the main strategy for soil-transmitted helminths (STH) control, excludes other at-risk populations including adults and preschool children. Mass drug administration (MDA), covering all age groups, would bring additional health benefits but also requires greater investment. This cost survey and cost-effectiveness analysis compared MDA with school-based targeted PC for STH control in Dak Lak, Vietnam, where STH are endemic., Methods: A cost survey was conducted in 2020 to estimate the total and per person economic and financial cost of each strategy. Monte Carlo simulation accounted for uncertainty in cost estimates. The primary effectiveness measure was hookworm-related disability-adjusted life years (DALYs) averted, and secondary measures were hookworm infection-years averted and moderate-to-heavy intensity hookworm infection-years averted. A Markov model was used to determine the incremental cost-effectiveness ratio (ICER) of MDA compared to school-based targeted PC using a government payer perspective and a ten-year time horizon. One-way and probabilistic sensitivity analyses (PSA) were performed. Costs are reported in 2020 USD ($)., Findings: The economic cost per person was $0.27 for MDA and $0.43 for school-based targeted PC. MDA in Dak Lak will cost $472,000 per year, while school-based targeted PC will cost $117,000. Over 10 years, MDA is estimated to avert an additional 121,465 DALYs; 4,019,262 hookworm infection-years, and 765,844 moderate-to-heavy intensity hookworm infection-years compared to school-based targeted PC. The ICER was $28.55 per DALY averted; $0.87 per hookworm infection-years averted, and $4.54 per moderate-to-heavy intensity hookworm infection-years averted. MDA was cost-effective in all PSA iterations., Interpretation: In areas where hookworm predominates and adults suffer a significant burden of infection, MDA is cost effective compared to school based targeted PC and is the best strategy to achieve global targets., Funding: The project was funded by the National Health and Medical Research Council (NHMRC) of Australia (Project Grant APP1139561) and JPCDT was supported by a UNSW Scientia PhD Scholarship., Competing Interests: We declare no competing interests., (© 2023 The Authors.)

Schistosomiasis and soil-transmitted helminth (STH) control programs require target population engagement, assessed through knowledge, attitudes and practices (KAP) surveys. We report the results of a KAP survey of Angolan schoolchildren supported by a school preventive chemotherapy (PC) programme, without or with a school water, sanitation and hygiene (WASH) programme (PC+/WASH- and PC+/WASH+, respectively); and schoolchildren without a school PC or WASH program (PC-/WASH-). Schoolchildren from PC+/WASH- ( N = 218), PC+/WASH+ ( N = 250) and PC-/WASH- ( N = 254) schools were interviewed. Descriptive statistics were used to report demographics and survey responses. Chi-square or Fisher's exact test was used to compare PC+/WASH- schoolchildren with (i) PC+/WASH+ and (ii) PC-/WASH- schoolchildren. A lower proportion of PC+/WASH- schoolchildren used latrines and a higher proportion practised open defecation at school compared with PC+/WASH+ schoolchildren. A lower proportion of PC+/WASH- schoolchildren always washed their hands after toileting and before meals at school compared with PC+/WASH+ schoolchildren. However, the PC+/WASH- schoolchildren reported better toileting and handwashing practices at school compared to PC-/WASH- schoolchildren. Over 90% of PC+ schoolchildren agreed with schistosomiasis and STH control and accepted schoolteacher PC delivery. Expanding the integration of both school PC and WASH programs will improve health behaviours relevant to reduce the risk of schistosomiasis and STHs in schoolchildren. This article is part of the theme issue 'Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs'.

Background: Integrated programmes that use combination mass drug administration (MDA) might improve control of multiple neglected tropical diseases simultaneously. We investigated the impact of Timor-Leste's national ivermectin, diethylcarbamazine citrate, and albendazole MDA, for lymphatic filariasis elimination and soil-transmitted helminth (STH) control, on scabies, impetigo, and STH infections., Methods: We did a before-after study in six primary schools across three municipalities in Timor-Leste (urban [Dili], semi-urban [Ermera], and rural [Manufahi]) before (April 23 to May 11, 2019) and 18 months after (Nov 9 to Nov 27, 2020) MDA delivery between May 17 and June 1, 2019. Study participants included schoolchildren, as well as infants, children, and adolescents who were incidentally present at school on study days. All schoolchildren whose parents provided consent were eligible to participate in the study. Infants, children, and adolescents younger than 19 years who were not enrolled in the school but were incidentally present at schools on study days were also eligible to participate if their parents consented. Ivermectin, diethylcarbamazine citrate, and albendazole MDA was implemented nationally, with single doses of oral ivermectin (200 μg/kg), diethylcarbamazine citrate (6 mg/kg), and albendazole (400 mg) administered by the Ministry of Health. Scabies and impetigo were assessed by clinical skin examinations, and STHs using quantitative PCR. The primary (cluster-level) analysis adjusted for clustering while the secondary (individual-level) analysis adjusted for sex, age, and clustering. The primary outcomes of the study were prevalence ratios for scabies, impetigo, and STHs (Trichuris trichiura, Ascaris lumbricoides, Necator americanus, and moderate-to-heavy A lumbricoides infections) between baseline and 18 months from the cluster-level analysis., Findings: At baseline, 1043 (87·7%) of 1190 children registered for the study underwent clinical assessment for scabies and impetigo. The mean age of those who completed skin examinations was 9·4 years (SD 2·4) and 514 (53·8%) of 956 were female (87 participants with missing sex data were excluded from this percentage calculation). Stool samples were received for 541 (45·5%) of 1190 children. The mean age of those for whom stool samples were received was 9·8 years (SD 2·2) and 300 (55·5%) were female. At baseline, 348 (33·4%) of 1043 participants had scabies, and 18 months after MDA, 133 (11·1%) of 1196 participants had scabies (prevalence ratio 0·38, 95% CI 0·18-0·88; p=0·020) in the cluster-level analysis. At baseline, 130 (12·5%) of 1043 participants had impetigo, compared with 27 (2·3%) of 1196 participants at follow-up (prevalence ratio 0·14, 95% CI 0·07-0·27; p<0·0001). There was a significant reduction in T trichiura prevalence from baseline (26 [4·8%] of 541 participants) to 18-month follow-up (four [0·6%] of 623 participants; prevalence ratio 0·16, 95% CI 0·04-0·66; p<0·0001). In the individual-level analysis, moderate-to-heavy A lumbricoides infections reduced from 54 (10·0%; 95% CI 0·7-19·6) of 541 participants to 28 (4·5%, 1·2-8·4) of 623 participants (relative reduction 53·6%; 95% CI 9·1-98·1; p=0·018)., Interpretation: Ivermectin, diethylcarbamazine citrate, and albendazole MDA was associated with substantial reductions in prevalence of scabies, impetigo, and T trichiura, and of moderate-to-heavy intensity A lumbricoides infections. Combination MDA could be used to support integrated control programmes to target multiple NTDs., Funding: National Health and Medical Research Council of Australia and the Department of Foreign Affairs and Trade Indo-Pacific Centre for Health Security., Translation: For the Tetum translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Schistosomiasis and soil-transmitted helminths (STHs) contribute high disease burdens amongst the neglected tropical diseases (NTDs) and are public health problems in Angola. This study reports the prevalence, intensity and risk factors for schistosomiasis and STH infection in Huambo, Uige and Zaire provinces, Angola, to inform a school-based preventive chemotherapy program., Methods: A two-stage cluster design was used to select schools and schoolchildren to participate in parasitological and water, sanitation and hygiene (WASH) surveys across Huambo, Uige, and Zaire provinces. Point-of-care circulating cathodic antigen and urinalysis rapid diagnostic tests (RDTs) were used to determine the prevalence of Schistosoma mansoni and S. haematobium, respectively. Kato-Katz was used to identify and quantify STH species and quantify and compare with RDTs for S. mansoni. Urine filtration was used to quantify and compare with RDTs for S. haematobium. Descriptive statistics were used for prevalence and infection intensity of schistosomiasis and STH infection. Performance of RDTs was assessed through specificity and Cohen's Kappa agreement with microscopy. A multivariate regression analysis was used to determine demographic and WASH factors associated with schistosomiasis and STH infection., Results: A total 575 schools and 17,093 schoolchildren participated in the schistosomiasis survey, of which 121 schools and 3649 schoolchildren participated in the STH survey. Overall prevalence of S. mansoni was 21.2% (municipality range 0.9-74.8%) and S. haematobium 13.6% (range 0-31.2%), with an overall prevalence of schistosomiasis of 31.4% (range 5.9-77.3%). Overall prevalence of Ascaris lumbricoides was 25.1% (range 0-89.7%), hookworm 5.2% (range 0-42.6%), and Trichuris trichiura 3.6% (range 0-24.2%), with an overall prevalence of STH infection of 29.5% (range 0.8-89.7%). Ecological zone and ethnicity were factors associated with schistosomiasis and STH infection, with older age and female sex additional risk factors for S. haematobium., Conclusions: Most municipalities met World Health Organization defined prevalence thresholds for a schistosomiasis preventive chemotherapy program. A STH preventive chemotherapy program is indicated for nearly all municipalities in Uige and select municipalities in Huambo and Zaire. The association between ecological zone and ethnicity with schistosomiasis and STH infection necessitates further evaluation of home and school environmental, sociodemographic and behavioural factors to inform targeted control strategies to complement preventive chemotherapy programs., (© 2022. The Author(s).)

Background: The Kato-Katz microscopy technique is the global standard for assessment of soil-transmitted helminth (STH) burden. However, major limitations include its poor sensitivity, requirement for rapid sample processing, and inability to differentiate hookworm species nor detect Strongyloides spp. infections. We assessed the prevalence and intensity of STH species in Solomon Islands by conducting a province-wide survey using quantitative PCR (qPCR) for diagnosis, which can provide much better characterisation of STH burden than microscopy., Methodology/principal Findings: We conducted a cross-sectional survey in 18 villages in Western Province to detect infections with six STH species and quantify intensity with three. We used linear mixed model regression to identify potential water, sanitation, and hygiene (WASH) and environmental risk factors for infection. We collected stool specimens from 830 village residents. Overall STH prevalence was 63.3% (range 27.5 to 91.5% across villages), led by Necator americanus (54.5% [range 17.5-89.4%]), followed by Ancylostoma ceylanicum (15.5% [range 2.8-45.8%]), Trichuris trichiura (9.1% [range 0-79.2%]), and Strongyloides spp. (3.2% [range 0-29.2%]). Most infections were of light intensity for N. americanus (85.7%) and T. trichiura (90.7%). Owning a household latrine was associated with a lower risk of N. americanus infection (AOR 0.41, 95% CI 0.24-0.68) while greater precipitation was linked to more common T. trichiura infection (AOR 1.14, 95% CI 1.04-1.25)., Conclusion/significance: In this first large-scale population survey of STH in the Pacific using qPCR, we found evidence that ivermectin should be incorporated into STH control programmes because of the presence of T. trichiura and Strongyloides spp., both of which are poorly responsive to albendazole. Furthermore, One Health strategies are needed for improved A. ceylanicum and Strongyloides spp. control, WASH access and use should be improved to complement deworming programmes, and control efforts should ideally be expanded to entire communities., Trial Registration: ClinicalTrials.gov Australian and New Zealand Clinical Trials Registry ACTRN12618001086257., Competing Interests: The authors have declared that no competing interests exist.

Objective: To estimate the impact of preventive chemotherapy on the prevalence and intensity of soil-transmitted helminth (STH) infections, schistosomiasis, and lymphatic filariasis in the Philippines, using systematic review and meta-analysis., Methods: We included reports reporting prevalence of STH infections, schistosomiasis, or lymphatic filariasis in the Philippines published until 31 March 2021. Peer-reviewed studies were identified in electronic databases. Grey literature reports by the University of the Philippines and the Department of Health were also included. Pooled infection prevalence, before and after the initiation of preventive chemotherapy, stratified by age group, was calculated using the inverse variance heterogeneity model., Findings: A total of 109 reports were included in the review and meta-analysis. Overall prevalence of moderate-heavy intensity Ascaris lumbricoides (6.6%) and Trichuris trichiura (2.7%) infection after initiation of preventive chemotherapy were significantly lower than the prevalence prior to initiation (23.6% for A. lumbricoides and 12.2% for T. trichiura). Prevalence reductions were also found in school and preschool-age children for A. lumbricoides and T. trichiura. Studies conducted after preventive chemotherapy initiation had significantly lower overall prevalence of moderate-heavy intensity schistosomiasis (3.1% vs 0.2%) and of schistosomiasis in school-age children (30.5% vs 1%). Pooled prevalence of lymphatic filariasis prior to preventive chemotherapy initiation was 3.2% across 12 provinces, while currently only two provinces still have prevalence of more than 1%. There were no published studies reporting prevalence of lymphatic filariasis after initiation of preventive chemotherapy. Heterogeneity was high with I2 mostly above 90%., Conclusion: The burden of STH infections and schistosomiasis in children were significantly lower in studies conducted following the initiation of preventive chemotherapy. Eliminating morbidity and interrupting transmission, however, may require expanded control initiatives including community-wide treatment, and improved water, sanitation, and hygiene. Lymphatic filariasis burden has decreased since the implementation of preventive chemotherapy, with all but two provinces having reached the elimination of lymphatic filariasis as a public health problem., Competing Interests: The authors have declared that no competing interests exist.

Background: Tuberculosis (TB) care can be costly for patients and their families. The End TB Strategy includes a target that zero TB affected households should experience catastrophic costs associated with TB care. Costs are catastrophic when a patient spends 20% or more of their annual household income on their TB diagnosis and care. In Solomon Islands the costs of TB care are unknown. The aim of this study was to determine the costs of TB diagnosis and care, the types of costs and the proportion of patients with catastrophic costs., Methods: This was a nationally representative cross-sectional survey of TB patients carried out between 2017 and 2019. Patients were recruited from health care facilities, from all ten provinces in Solomon Islands. During an interview they were asked about the costs of TB diagnosis and care. These data were analysed using descriptive statistics to describe the costs overall and the proportions of different types of costs. The proportion of patients with catastrophic costs was calculated and a multivariate logistic regression was undertaken to determine factors associated with catastrophic costs., Results: One hundred and eighty-three TB patients participated in the survey. They spent a mean of 716 USD (inter quartile range: 348-1217 USD) on their TB diagnosis and care. Overall, 62.1% of costs were attributable to non-medical costs, while income loss and medical costs comprised 28.5 and 9.4%, respectively. Overall, 19.7% (n = 36) of patients used savings, borrowed money, or sold assets as a financial coping mechanism. Three patients (1.6%) had health insurance. A total of 92.3% (95% CI: 88.5-96.2) experienced catastrophic costs, using the output approach. Being in the first, second or third poorest wealth quintile was significantly associated with catastrophic costs (adjusted odds ratio: 67.3, 95% CI: 15.86-489.74%, p <  0.001)., Conclusion: The costs of TB care are catastrophic for almost all patients in Solomon Islands. The provision of TB specific social and financial protection measures from the National TB and Leprosy Programme may be needed in the short term to ameliorate these costs. In the longer term, advancement of universal health coverage and other social and financial protection measures should be pursued., (© 2021. The Author(s).)

Background: Scabies and impetigo are endemic in many tropical, low- and middle-income countries. Mass drug administration (MDA) with ivermectin has emerged as a control strategy for these conditions. In 2019, Timor-Leste Ministry of Health planned to implement MDA including ivermectin for the control of lymphatic filariasis, so we undertook a baseline assessment of scabies and impetigo to better understand local epidemiology and contribute to future surveys assessing the impact of MDA., Methods: A cross-sectional school survey was conducted in April-May 2019 at six primary schools in a semi-urban (Dili) and two rural (Ermera and Manufahi) settings. Children under 19 years of age present at school on survey days were eligible to participate, of whom we enrolled 1183. Trained health workers interviewed and examined 1043 participants to clinically diagnose scabies using the 2020 International Alliance for the Control of Scabies (IACS) diagnostic criteria, as well as impetigo. Prevalence was adjusted for age and sex. Mixed-effects logistic regression models were used to analyse odds of scabies and impetigo infection. All models accounted for clustering at the school level through the use of random effect terms. Population attributable risk of scabies as a cause of impetigo was also estimated., Results: The overall weighted prevalence of scabies was 30.6%. Children in rural Manufahi were more likely to have scabies than those in semi-urban Dili (53.6% vs 28.2%, adjusted odds ratio [AOR] 3.5). Most cases of scabies were mild (3 to 10 lesions), and lesions were usually distributed on more than one body region. Scabies prevalence was lower among 10 to 14 year olds compared to 5 to 9 year olds. Overall weighted prevalence of impetigo was 11.3%. Relative to Dili, children in rural Ermera and Manufahi were twice as likely to have impetigo. Impetigo was twice as common in children with scabies than in those without, corresponding to an attributable risk of scabies as a cause of impetigo of 22.7%., Conclusions: Scabies and impetigo prevalence in Timor-Leste is among the highest reported globally, particularly in rural areas. Scabies infestation was strongly associated with impetigo. Comprehensive control strategies are urgently needed in Timor-Leste.

Soil-transmitted helminth (STH) infections are endemic in Indonesia. However, prevalence data for many parts of the country are incomplete. The aim of this study was to determine human STH prevalence and knowledge and practices relating to STH risk behaviour, to provide a current view of the status of STH infection in rural communities in Central Java. A cross-sectional survey of 16 villages was conducted in Semarang, Central Java in 2015. Demographic and household data together with information about knowledge and practices relating to STH and hygiene were elicited through face-to-face interviews. Stool samples were collected and examined using the flotation method. Children (aged 2-12 years) also had their haemoglobin (Hb) levels, height and weight data collected, and BMI estimated. Data were analysed using univariate logistic regression analysis. A total of 6,466 individuals with a mean age of 33.5 years (range: 2-93) from 2,195 households were interviewed. The overall prevalence of STH was 33.8% with Ascaris lumbricoides (roundworm) the predominant nematode identified (prevalence = 26.0%). Hookworm and Trichuris trichiura (whipworm) were found in 7.9% and 1.8% of participants, respectively. Females were at increased odds of infection with A. lumbricoides (adjusted OR 1.14, 95% CI [1.02-1.29], p = 0.02). Adults in age groups 51-60 and over 60 years had the highest odds of being infected with hookworm (adjusted OR 3.01, 95% CI [1.84-4.91], p<0.001 and adjusted OR 3.79, 95% CI [2.30-6.26], p<0.001, respectively) compared to 6-12 year olds. Farmers also had higher odds of being infected with hookworm (adjusted OR 2.36, 95% CI [1.17-4.76], p = 0.02) compared to other occupation categories. Poverty (OR 2.14, 95% CI [1.77-2.58], p<0.001), overcrowding (OR 1.35, 95% CI [1.27-1.44], p<0.001), goat ownership (OR 1.61, 95% CI [1.10-2.41], p = 0.02) and the presence of dry floor space in the home (OR 0.73, 95% CI [0.58-0.91], p = 0.01) were all household factors significantly associated with an increased odds of infection. Infection with STH was not significantly associated with the gastrointestinal illness (p>0.05), BMI or Hb levels; however, one third of all 2-12 year olds surveyed were found to be anaemic (i.e. Hb concentrations below 110g/l or 115g/l for children under 5 and 5 years or older, respectively), with a greater proportion of school-age children at risk. Knowledge and behaviour related to hygiene and gastrointestinal diseases varied widely and were generally not associated with STH infection. The study revealed that STH infection remains endemic in Central Java despite ongoing deworming programs. Current control efforts would benefit from being re-evaluated to determine a more effective way forward., Competing Interests: The authors have declared that no competing interests exist. Authors Budi Laksono and Suharyo Hadisaputro were unable to confirm their authorship contributions. On their behalf, the corresponding author has reported their contributions to the best of their knowledge.

Preventive chemotherapy campaigns with praziquantel and albendazole are being implemented in Angola, as a high priority public health intervention. However, there are no published data regarding adverse events associated with these medications. In this context, we analysed adverse events due to co-administration of praziquantel and albendazole in endemic areas of schistosomiasis and soil-transmitted helminths in Bengo, Angola. In the context of a targeted drug administration, between December 2012 and September 2013, we conducted two surveys after co-administrating single oral doses of praziquantel and albendazole tablets to children 2 to 15 years of age. About 24 hours after each treatment, participants answered a questionnaire about adverse events. At baseline, 605 children (55.0% male; mean age: 9.7 years) were treated; 460 were interviewed and 257 (55.9%) reported at least one adverse event, 62.3% (160/257) of children being infected with schistosoma haematobium. After six months of treatment, among 339 children surveyed, 184 (54.3%) reported adverse events, with 49.5% (91/184) of infected children. Adverse events were most common in preschool-aged children, with no significant difference between genders. The most frequent adverse events in the two surveys were abdominal pain (18.5%, 25.7%), headache (20.9%, 23.0%) and dizziness (15.7%, 19.8%). Children aged 12 to 15 years (adjusted OR = 0.40, p = 0.040) and those with mixed infection (adjusted OR = 0.04, p = 0.011) had lower odds of adverse events. After the second treatment, those with heavy infection (adjusted OR = 2.72, p = 0.018) and aged 9-11 years (adjusted OR = 2.01, p = 0.049) had significantly fewer adverse events. About 2.0% of children experienced severe adverse events. This study adds evidence that preventive chemotherapy for schistosomiasis and soil-transmitted helminths control is safe, but cases of adverse events are expected. Standardized methodologies to discriminate drug-related adverse events from the clinical manifestations of the infections are needed., Competing Interests: The authors declare no competing interests financial or nonfinancial with regards to this study. The interpretation of data and presentation of information is not influenced by any personal or financial relationship with any individual or organization.

SETTING: Seventeen health care facilities that report to the national tuberculosis (TB) programme in Timor-Leste. Participants were TB patients. OBJECTIVE: To determine the proportion of TB patients who experienced catastrophic costs due to their TB diagnosis and care, and the magnitude and composition of these costs. DESIGN: This was a cross-sectional health facility-based survey, conducted in 17 DOTS centres between October 2016 and March 2017. TB patients were interviewed by trained nurses using a standardised questionnaire. RESULTS: Among the 457 TB patients who participated (response rate 96.6%), the median age was 32 years; 39.2% were from the capital, Dili. The patient was the main income earner in 26.3% of households. Annual individual and household incomes before and after TB diagnosis decreased by respectively 30.4% and 31.1%. Using a cut-off of 20% of annual household income, 83.0% of patients experienced catastrophic costs related to their TB diagnosis and care. Income loss and nutritional supplementation accounted for respectively 40.7% and 37.9% of these costs. CONCLUSION: Four of five TB patients in Timor-Leste experienced catastrophic costs related to TB diagnosis and care. Financial and social protection to mitigate against these costs are urgently needed, in addition to universal health coverage.

Background: Acute undifferentiated febrile illness (AUFI) is caused by a multitude of diverse pathogens, with significant morbidity and mortality in the developing world. The objective of this review was to characterise the diversity and relative importance of common infectious aetiologies of AUFI in South and Southeast Asia., Methods: We conducted a comprehensive literature review to identify common aetiologies of AUFI in Asian countries. Four medical and life sciences databases including PubMed, Medline, Embase and Cochrane Central, and Google Scholar were searched for articles published from January 1998 to March 2019., Results: Forty-three studies met the inclusion criteria. Among AUFI cases, viral aetiologies at 18.5% (14888) were more common than bacterial aetiologies (12.9% [10384]). From 80,554 cases, dengue fever was the most common aetiology (11.8%, 9511), followed by leptospirosis (4.4%, 3549), typhoid (4.0%, 3258), scrub typhus (4.0%, 3243) and influenza other than H1N1 (3.1%, 2514). In both adults and children: dengue fever was the leading cause of AUFI with 16.6% (1928) and 18.7% (1281) of the total cases. In admitted patients, dengue fever was the main cause of AUFI at 16.4% (2377), however leptospirosis at 13.9% (2090) was the main cause of AUFI for outpatients. In South Asia, dengue fever was the main cause of AUFI, causing 12.0% (6821) of cases, whereas in Southeast Asia, leptospirosis was the main diagnosis, causing 12.1% (2861) of cases., Conclusions: In this study the most common causes of AUFI were viral, followed by bacterial and protozoal (malaria) infections. Dengue was the commonest virus that caused AUFI while leptospirosis and typhoid were important bacterial infectious causes. Therefore, it is imperative to maintain a sound epidemiological knowledge of AUFI so that evidence-based diagnostic criteria and treatment guidelines can be developed.

Background: Periodic mass distribution of benzimidazole anthelminthic drugs is the key strategy to control soil-transmitted helminths (STHs) globally. However, benzimidazoles have low efficacy against Trichuris trichiura, and there are concerns about benzimidazole resistance potentially emerging in humans. Therefore, identifying alternative drug regimens is a pressing priority. We present a systematic review and network meta-analysis comparing the efficacy of 21 different anthelminthic drug regimens, including standard, novel, and combination treatments., Methods: We searched PubMed, Medline, Embase, Web of Science, and Cochrane databases and identified studies comparing anthelminthic treatments to each other or placebo. The outcomes calculated were relative risk (RR) of cure and difference in egg reduction rates (dERR). We used an automated generalized pairwise modeling framework to generate mixed treatment effects against a common comparator, the current standard treatment (single-dose albendazole)., Results: Our search identified 4876 studies, of which 114 were included in the meta-analysis. Results identified several drug combinations with higher efficacy than single-dose albendazole for T. trichiura, including albendazole-ivermectin (RR of cure, 3.22 [95% confidence interval {CI}, 1.84-5.63]; dERR, 0.97 [95% CI, .21-1.74]), albendazole-oxantel pamoate (RR, 5.07 [95% CI, 1.65-15.59]; dERR, 0.51 [95% CI, .50-.52]), mebendazole-ivermectin (RR, 3.37 [95% CI, 2.20-5.16]), and tribendimidine-oxantel pamoate (RR, 4.06 [95% CI, 1.30-12.64])., Conclusions: There are several promising drug combinations that may enhance the impact of STH control programs on T. trichiura, without compromising efficacy against Ascaris lumbricoides and hookworm. We suggest further, large-scale trials of these drug combinations and consideration of their use in STH control programs where T. trichiura is present., International Prospective Register of Systematic Reviews Registration: CRD42016050739.

Appropriate diagnostic techniques are crucial to global soil-transmitted helminth (STH) control efforts. The recommended Kato-Katz method has low sensitivity in low-transmission settings. Quantitative polymerase chain reaction (qPCR) is a highly sensitive alternative diagnostic option. However, little is known about the variability in qPCR results, and there are few published comparisons between qPCR and other microscopy-based techniques such as sodium nitrate flotation (SNF). Using 865 stool samples collected from 571 individuals, we compared SNF and qPCR in terms of diagnostic sensitivity and infection intensity measurements. In addition, we conducted repeated examinations on a single Necator americanus -positive stool sample over a 6-month period. Results showed good diagnostic agreement between SNF and qPCR for Ascaris spp. (κ = 0.69, P < 0.001), and moderate agreement for hookworm (κ = 0.55, P < 0.001) and Trichuris spp. (κ = 0.50, P < 0.001). Quantitative polymerase chain reaction demonstrated higher sensitivity than SNF for Ascaris spp. (94.1% versus 68.1%) and hookworm (75.7% versus 66.9%) but not for Trichuris spp. (53.1% versus 81.3%), which had very low prevalence. Sodium nitrate flotation and qPCR infection intensity measurements were strongly correlated for Ascaris spp. (ρ = 0.82, P < 0.001) and moderately correlated for hookworm (ρ = 0.58, P < 0.001). Repeated examinations using qPCR showed that N. americanus cycle threshold values decreased significantly at 1 month and remained stable thereafter. Results confirm the high diagnostic sensitivity of qPCR for Ascaris spp. and hookworm, particularly for light-intensity infections, which is ideal for settings approaching transmission elimination. Results support the potential for qPCR to be used as a quantitative assay for STH. Further research is needed in settings where Trichuris trichiura is endemic.

Background: Soil-transmitted helminths (STH) infect nearly 1.5 billion individuals globally, and contribute to poor physical and cognitive development in children. STH control programs typically consist of regular delivery of anthelminthic drugs, targeting school-aged children. Expanding STH control programs community-wide may improve STH control among school-aged children, and combining deworming with improvements to water, sanitation and hygiene (WASH) may further reduce transmission. The (S)WASH-D for Worms pilot study aims to compare the differential impact of integrated WASH and deworming programs when implemented at primary schools only versus when additionally implemented community-wide., Methodology/principal Findings: A two-arm, non-randomized cluster intervention study was conducted. Six communities were identified by partner WASH agencies and enrolled in the study. All communities received a school-based WASH and deworming program, while three additionally received a community-based WASH and deworming program. STH infections were measured in school-aged children at baseline and six months after deworming. Over 90% of eligible children were recruited for the study, of whom 92.3% provided stool samples at baseline and 88.9% at follow-up. The school WASH intervention improved school sanitation, while the community WASH intervention reduced open defecation from 50.4% (95% CI 41.8-59.0) to 23.5% (95% CI 16.7-32.0). There was a trend towards reduced odds of N. americanus infection among children who received the community-wide intervention (OR 0.42, 95% CI 0.07-2.36, p = 0.32)., Conclusions: This pilot study provides proof of principle for testing the hypothesis that community-wide STH control programs have a greater impact on STH infections among children than school-based programs, and supports the rationale for conducting a full-scale cluster randomized controlled trial. High recruitment and participation rates and successful implementation of school WASH programs demonstrate study feasibility and acceptability. However, eliminating open defecation remains a challenge; ongoing work is required to develop community sanitation programs that achieve high and sustainable latrine coverage., Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12615001012561.

Background: Dengue remains an important public health problem in Timor-Leste, with several major epidemics occurring over the last 10 years. The aim of this study was to identify dengue clusters at high geographical resolution and to determine the association between local environmental characteristics and the distribution and transmission of the disease., Methods: Notifications of dengue cases that occurred from January 2005 to December 2013 were obtained from the Ministry of Health, Timor-Leste. The population of each suco (the third-level administrative subdivision) was obtained from the Population and Housing Census 2010. Spatial autocorrelation in dengue incidence was explored using Moran's I statistic, Local Indicators of Spatial Association (LISA), and the Getis-Ord statistics. A multivariate, Zero-Inflated, Poisson (ZIP) regression model was developed with a conditional autoregressive (CAR) prior structure, and with posterior parameters estimated using Bayesian Markov chain Monte Carlo (MCMC) simulation with Gibbs sampling., Results: The analysis used data from 3206 cases. Dengue incidence was highly seasonal with a large peak in January. Patients ≥ 14 years were found to be 74% [95% credible interval (CrI): 72-76%] less likely to be infected than those < 14 years, and females were 12% (95% CrI: 4-21%) more likely to suffer from dengue as compared to males. Dengue incidence increased by 0.7% (95% CrI: 0.6-0.8%) for a 1 °C increase in mean temperature; and 47% (95% CrI: 29-59%) for a 1 mm increase in precipitation. There was no significant residual spatial clustering after accounting for climate and demographic variables., Conclusions: Dengue incidence was highly seasonal and spatially clustered, with positive associations with temperature, precipitation and demographic factors. These factors explained the observed spatial heterogeneity of infection.

Background: Timor-Leste has a high prevalence of soil-transmitted helminth (STH) infections. High proportions of the population have been reported as being anaemic, and extremely high proportions of children as stunted or wasted. There have been no published analyses of the contributions of STH to these morbidity outcomes in Timor-Leste., Methods: Using baseline cross-sectional data from 24 communities (18 communities enrolled in a cluster randomised controlled trial, and identically-collected data from six additional communities), analyses of the association between STH infections and community haemoglobin and child development indices were undertaken. Stool samples were assessed for STH using qPCR and participant haemoglobin, heights and weights were measured. Questionnaires were administered to collect demographic and socioeconomic data. Intensity of infection was categorised using correlational analysis between qPCR quantification cycle values and eggs per gram of faeces equivalents, with algorithms generated from seeding experiments. Mixed-effects logistic and multinomial regression were used to assess the association between STH infection intensity classes and anaemia, and child stunting, wasting and underweight., Results: Very high stunting (60%), underweight (60%), and wasting (20%) in children, but low anaemia prevalence (15%), were found in the study communities. STH were not significantly associated with morbidity outcomes. Male children and those in the poorest socioeconomic quintile were significantly more likely to be moderately and severely stunted. Male children were significantly more likely than female children to be severely underweight. Increasing age was also a risk factor for being underweight. Few risk factors emerged for wasting in these analyses., Conclusions: According to World Health Organization international reference standards, levels of child morbidity in this population constitute a public health emergency, although the international reference standards need to be critically evaluated for their applicability in Timor-Leste. Strategies to improve child development and morbidity outcomes, for example via nutrition and iron supplementation programmes, are recommended for these communities. Despite the apparent lack of an association from STH in driving anaemia, stunting, wasting and underweight, high endemicity suggests a need for STH control strategies., Trial Registration: Australian and New Zealand Clinical Trials Registry ACTRN12614000680662 ; retrospectively registered.

Background: No investigations have been undertaken of risk factors for intensity of soil-transmitted helminth (STH) infection in Timor-Leste. This study provides the first analysis of risk factors for intensity of STH infection, as determined by quantitative PCR (qPCR), examining a broad range of water, sanitation and hygiene (WASH) and environmental factors, among communities in Manufahi District, Timor-Leste., Methods: A baseline cross-sectional survey of 18 communities was undertaken as part of a cluster randomised controlled trial, with additional identically-collected data from six other communities. qPCR was used to assess STH infection from stool samples, and questionnaires administered to collect WASH, demographic, and socioeconomic data. Environmental information was obtained from open-access sources and linked to infection outcomes. Mixed-effects multinomial logistic regression was undertaken to assess risk factors for intensity of Necator americanus and Ascaris infection., Results: 2152 participants provided stool and questionnaire information for this analysis. In adjusted models incorporating WASH, demographic and environmental variables, environmental variables were generally associated with infection intensity for both N. americanus and Ascaris spp. Precipitation (in centimetres) was associated with increased risk of moderate-intensity (adjusted relative risk [ARR] 6.1; 95% confidence interval [CI] 1.9-19.3) and heavy-intensity (ARR 6.6; 95% CI 3.1-14.1) N. americanus infection, as was sandy-loam soil around households (moderate-intensity ARR 2.1; 95% CI 1.0-4.3; heavy-intensity ARR 2.7; 95% CI 1.6-4.5; compared to no infection). For Ascaris, alkaline soil around the household was associated with reduced risk of moderate-intensity infection (ARR 0.21; 95% CI 0.09-0.51), and heavy-intensity infection (ARR 0.04; 95% CI 0.01-0.25). Few WASH risk factors were significant., Conclusion: In this high-prevalence setting, strong risk associations with environmental factors indicate that anthelmintic treatment alone will be insufficient to interrupt STH transmission, as conditions are favourable for ongoing environmental transmission. Integrated STH control strategies should be explored as a priority.

Background: Soil-transmitted helminth infections are a major global health issue, causing substantial morbidity in the world's poorest populations. Regular delivery of anthelmintic drugs is the mainstay for global soil-transmitted helminth control. Deworming campaigns are often targeted to school-aged children, who are at high risk of soil-transmitted-helminth-associated morbidity. However, findings from modelling studies suggest that deworming campaigns should be expanded community-wide for effective control of soil-transmitted helminth transmission. We aimed to do a systematic review and meta-analysis to compare the effect of mass (community-wide) and targeted (children only) anthelmintic delivery strategies on soil-transmitted helminth prevalence in school-aged children., Methods: In this systematic review and meta-analysis, we searched MEDLINE, Embase, and Web of Science for articles published on or before Nov 5, 2015, reporting soil-transmitted helminth prevalence before and after distribution of albendazole or mebendazole, either targeted to children or delivered to the whole community. We excluded studies in which drug delivery was restricted to infected individuals or to a subset of the community or school, or if follow-up time was less than 3 months or greater than 18 months after drug delivery. We extracted data on study year, country, drug administration strategy, drug dose, number of deworming rounds, treatment coverage, diagnostic method, follow-up interval, and soil-transmitted helminth prevalence before and after treatment. We used inverse variance weighted generalised linear models, with prevalence reduction as the outcome variable, to examine the effect of mass versus targeted drug administration, as well as baseline prevalence, number of drug doses, and follow-up time. This study is registered with PROSPERO, number CRD42016026929., Findings: Of 10 538 studies identified, 56 studies were eligible for the systematic review and 38 of these were included in meta-analysis. Results of the regression models showed that mass deworming led to a significantly greater reduction in prevalence in children than targeted deworming, for both hookworm (odds ratio 4·6, 95% CI 1·8-11·6; p=0·0020) and Ascaris lumbricoides (16·4, 2·1-125·8; p=0·0092), with no effect seen for Trichuris trichiura. There was significant heterogeneity across studies; for targeted studies I 2 was 97% for A lumbricoides and hookworm, and 96% for T trichiura, and for mass studies, I 2 was 89% for A lumbricoides, 49% for hookworm, and 66% for T trichiura., Interpretation: The results of this meta-analysis suggest that expanding deworming programmes community-wide is likely to reduce the prevalence of soil-transmitted helminths in the high-risk group of school-aged children, which could lead to improved morbidity outcomes. These findings are in support of recent calls for re-evaluation of global soil-transmitted helminth control guidelines., Funding: None., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Water, sanitation and hygiene (WASH) interventions represent an important component of soil-transmitted helminth (STH) infection control, alongside the administration of anthelmintic drugs, which are generally targeted to school-aged children. Recent modelling studies have suggested that STH control programmes should be broadened to include all age groups across the community. We describe the protocol for a pilot study investigating the impact of school-versus-community-based delivery of integrated WASH and deworming programmes on STH infections in school-aged children in Timor-Leste., Methods: The (S)WASH-D for Worms pilot is a two-arm, non-randomised cluster intervention study. The aims are to determine feasibility and acceptability of the intervention and study procedures and to establish proof of principle for the hypothesis that STH control programmes directed to the entire community will lead to greater reductions in STH infections in children than programmes directed only to school-aged children. Of the six participating communities, three receive a school-based integrated WASH and deworming programme and three additionally receive a community-based integrated WASH and deworming programme. The primary outcomes are the proportions of eligible children who enrol in the study and participate in the data collection, and outcomes relating to WASH and deworming programme completion, coverage, and use. Secondary outcomes are the cumulative incidence and mean intensity of STH infection in school-aged children at 6-month follow-up, mean haemoglobin concentration and several anthropometric indices. Results will inform the design of a cluster-randomised controlled trial (RCT)., Discussion: This pilot study is being conducted in preparation for a cluster-RCT investigating the differential impact of school- and community-based integrated STH control programmes on STH infections in school-aged children. It aims to establish feasibility and proof of principle, while results of the subsequent RCT could have significant implications for global STH control policy., Trial Registration: Australian New Zealand Clinical Trials Registry, ACTRN12615001012561.

There is little evidence on prevalence or risk factors for soil transmitted helminth infections in Timor-Leste. This study describes the epidemiology, water, sanitation and hygiene, and socioeconomic risk factors of STH and intestinal protozoa amongst communities in Manufahi District, Timor-Leste. As part of a cluster randomised controlled trial, a baseline cross-sectional survey was conducted across 18 villages, with data from six additional villages. Stool samples were assessed for soil transmitted helminth and protozoal infections using quantitative PCR (qPCR) and questionnaires administered to collect water, sanitation and hygiene and socioeconomic data. Risk factors for infection were assessed using multivariable mixed-effects logistic regression, stratified by age group (preschool, school-aged and adult). Overall, soil transmitted helminth prevalence was 69% (95% Confidence Interval 67-71%), with Necator americanus being most common (60%; 95% Confidence Interval 58-62%) followed by Ascaris spp. (24%; 95% Confidence Interval 23-26%). Ascaris-N. americanus co-infection was common (17%; 95% Confidence Interval 15%-18%). Giardia duodenalis was the main protozoan identified (13%; 95% Confidence Interval 11-14%). Baseline water, sanitation and hygiene infrastructure and behaviours were poor. Although risk factors varied by age of participants and parasite species, risk factors for N. americanus infection included, generally, age in years, male sex, and socioeconomic quintile. Risk factors for Ascaris included age in years for children, and piped water to the yard for adults. In this first known assessment of community-based prevalence and associated risk factors in Timor-Leste, soil transmitted helminth infections were highly prevalent, indicating a need for soil transmitted helminth control. Few associations with water, sanitation and hygiene were evident, despite water, sanitation and hygiene being generally poor. In our water, sanitation and hygiene we will investigate implications of improving WASH on soil transmitted helminth infection in impoverished communities., (Copyright © 2016 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.)

In this study, we have evaluated the efficacy of propidium monoazide quantitative polymerase chain reaction (PMA-qPCR) to differentiate between viable and non-viable Ancylostoma caninum ova. The newly developed method was validated using raw wastewater seeded with known numbers of A. caninum ova. Results of this study confirmed that PMA-qPCR has resulted in average of 88 % reduction (P < 0.05) in gene copy numbers for 50 % viable +50 % non-viable when compared with 100 % viable ova. A reduction of 100 % in gene copies was observed for 100 % non-viable ova when compared with 100 % viable ova. Similar reductions (79-80 %) in gene copies were observed for A. caninum ova-seeded raw wastewater samples (n = 18) collected from wastewater treatment plants (WWTPs) A and B. The newly developed PMA-qPCR method was applied to determine the viable ova of different helminths (A. caninum, A. duodenale, Necator americanus and Ascaris lumbricoides) in raw wastewater, human fecal and soil samples. None of the unseeded wastewater samples were positive for the above-mentioned helminths. N. americanus and A. lumbricoides ova were found in unseeded human fecal and soil samples. For the unseeded human fecal samples (1 g), an average gene copy concentration obtained from qPCR and PMA-qPCR was found to be similar (6.8 × 10(5) ± 6.4 × 10(5) and 6.3 × 10(5) ± 4.7 × 10(5)) indicating the presence of viable N. americanus ova. Among the 24 unseeded soil samples tested, only one was positive for A. lumbricoides. The mean gene copy concentration in the positively identified soil sample was 1.0 × 10(5) ± 1.5 × 10(4) (determined by qPCR) compared to 4.9 × 10(4) ± 3.7 × 10(3) (determined by PMA-qPCR). The newly developed PMA-qPCR methods were able to detect viable helminth ova from wastewater and soil samples and could be adapted for health risk assessment.

Background: The Dande Health and Demographic Surveillance System (HDSS) located in Bengo Province, Angola, covers nearly 65,500 residents living in approximately 19,800 households. This study aims to describe the main causes of deaths (CoD) occurred within the HDSS, from 2009 to 2012, and to explore associations between demographic or socioeconomic factors and broad mortality groups (Group I-Communicable diseases, maternal, perinatal and nutritional conditions; Group II-Non-communicable diseases; Group III-Injuries; IND-Indeterminate)., Methods: Verbal Autopsies (VA) were performed after death identification during routine HDSS visits. Associations between broad groups of CoD and sex, age, education, socioeconomic position, place of residence and place of death, were explored using chi-square tests and fitting logistic regression models., Results: From a total of 1488 deaths registered, 1009 verbal autopsies were performed and 798 of these were assigned a CoD based on the 10(th) revision of the International Classification of Diseases (ICD-10). Mortality was led by CD (61.0 %), followed by IND (18.3 %), NCD (11.6 %) and INJ (9.1 %). Intestinal infectious diseases, malnutrition and acute respiratory infections were the main contributors to under-five mortality (44.2 %). Malaria was the most common CoD among children under 15 years old (38.6 %). Tuberculosis, traffic accidents and malaria led the CoD among adults aged 15-49 (13.5 %, 10.5 % and 8.0 % respectively). Among adults aged 50 or more, diseases of the circulatory system (23.2 %) were the major CoD, followed by tuberculosis (8.2 %) and malaria (7.7 %). CD were more frequent CoD among less educated people (adjusted odds ratio, 95 % confidence interval for none vs. 5 or more years of school: 1.68, 1.04-2.72)., Conclusion: Infectious diseases were the leading CoD in this region. Verbal autopsies proved useful to identify the main CoD, being an important tool in settings where vital statistics are scarce and death registration systems have limitations.

Background: Soil-transmitted helminths (STH) have acute and chronic manifestations, and can result in lifetime morbidity. Disease burden is difficult to quantify, yet quantitative evidence is required to justify large-scale deworming programmes. A recent Cochrane systematic review, which influences Global Burden of Disease (GBD) estimates for STH, has again called into question the evidence for deworming benefit on morbidity due to STH. In this narrative review, we investigate in detail what the shortfalls in evidence are., Methodology/principal Findings: We systematically reviewed recent literature that used direct measures to investigate morbidity from STH and we critically appraised systematic reviews, particularly the most recent Cochrane systematic review investigating deworming impact on morbidity. We included six systematic reviews and meta-analyses, 36 literature reviews, 44 experimental or observational studies, and five case series. We highlight where evidence is insufficient and where research needs to be directed to strengthen morbidity evidence, ideally to prove benefits of deworming., Conclusions/significance: Overall, the Cochrane systematic review and recent studies indicate major shortfalls in evidence for direct morbidity. However, it is questionable whether the systematic review methodology should be applied to STH due to heterogeneity of the prevalence of different species in each setting. Urgent investment in studies powered to detect direct morbidity effects due to STH is required.