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As part of its diverse portfolio, the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) included two cluster-randomized trials evaluating interventions that could potentially lead to interruption of schistosomiasis transmission (elimination) in areas of Africa with low prevalence and intensity of infection. These studies, conducted in Zanzibar and Côte d’Ivoire, demonstrated that multiyear mass drug administration (MDA) with praziquantel failed to interrupt the transmission of urogenital schistosomiasis, even when provided biannually and/or supplemented by small-scale implementation of additional interventions. Other SCORE activities related to elimination included a feasibility and acceptability assessment of test–treat–track–test–treat (T5) strategies and mathematical modeling. Future evaluations of interventions to eliminate schistosomiasis should recognize the difficulties inherent in conducting randomized controlled trials on elimination and in measuring small changes where baseline prevalence is low. Highly sensitive and specific diagnostic tests for use in very low–prevalence areas for schistosomiasis are not routinely available, which complicates accurate measurement of infection rates and assessment of changes resulting from interventions in these settings. Although not encountered in these two studies, as prevalence and intensity decrease, political and community commitment to population-wide MDA may decrease. Because of this potential problem, SCORE developed and funded the T5 strategy implemented in Egypt, Kenya, and Tanzania. It is likely that focal MDA campaigns, along with more targeted approaches, including a T5 strategy and snail control, will need to be supplemented with the provision of clean water and sanitation and behavior change communications to achieve interruption of schistosome transmission.

The neglected tropical disease trichuriasis is caused by the whipwormTrichuris trichiura, a soil-transmitted helminth that has infected humans for millennia. Today,T. trichiurainfects as many as 500 million people, predominantly in communities with poor sanitary infrastructure enabling sustained faecal-oral transmission. Using whole-genome sequencing of geographically distributed worms collected from human and other primate hosts, together with ancient samples preserved in archaeologically-defined latrines and deposits dated up to one thousand years old, we present the first population genomics study ofT. trichiura. We describe the continent-scale genetic structure between whipworms infecting humans and baboons relative to those infecting other primates. Admixture and population demographic analyses support a stepwise distribution of genetic variation that is highest in Uganda, consistent with an African origin and subsequent translocation with human migration. Finally, genome-wide analyses between human samples and between human and non-human primate samples reveal local regions of genetic differentiation between geographically distinct populations. These data provide insight into zoonotic reservoirs of human-infectiveT. trichiuraand will support future efforts toward the implementation of genomic epidemiology of this globally important helminth.

Background Albendazole (ALB) is administered annually to millions of children through global deworming programs targeting soil-transmitted helminths (STHs: Ascaris lumbricoides, Trichuris trichiura and hookworms, Necator americanus and Ancylostoma duodenale). However, due to the lack of large individual patient datasets collected using standardized protocols and the application of population-based statistical methods, little is known about factors that may affect individual responses to treatment. Methodology/Principal findings We re-analyzed 645 individual patient data from three standardized clinical trials designed to assess the efficacy of a single 400 mg oral dose of ALB against STHs in schoolchildren from different study sites, each with varying history of drug pressure based on duration of mass drug administration programs: Ethiopia, low; Lao People’s Democratic Republic (PDR), moderate; Pemba Island (Tanzania), high. Using a Bayesian statistical modelling approach to estimate individual responses (individual egg reduction rates, ERRi), we found that efficacy was lower in Pemba Island, particularly for T. trichiura. For this STH, the proportion of participants with a satisfactory response (ERRi ≥50%), was 65% in Ethiopia, 61% in Lao PDR but only 29% in Pemba Island. There was a significant correlation between ERRi and infection intensity prior to drug administration (ERRi decreasing as a function of increasing infection intensity). Individual age and sex also affected the drug response, but these were of negligible clinical significance and not consistent across STHs and study sites. Conclusions/Significance We found decreased efficacy of ALB against all the STHs analyzed in Pemba Island (Tanzania), an area with high drug pressure. This does not indicate causality, as this association may also be partially explained by differences in infection intensity prior to drug administration. Notwithstanding, our results indicate that without alternative treatment regimens, program targets will not be achievable on Pemba Island because of inadequate efficacy of ALB. Trial registration The study was registered on Clinicaltrials.gov (ID: NCT03465488) on March 7, 2018., Author summary More than 500 million children worldwide receive a single oral dose of albendazole or mebendazole annually to reduce disease caused by intestinal worms (roundworm, whipworm and hookworm). However, it is unclear whether individuals respond differently to treatment. We re-analyzed 645 individual patient data from three standardized clinical trials with albendazole using a statistical method and explored how drug responses among individuals from study sites with different prior rounds of drug distribution. We found that individuals’ responses were worse when drug pressure and infection intensity were greater. Individual age and sex also affected the response, but these were often of negligible clinical significance and not consistent across worm species and study sites. We confirmed that albendazole is ineffective against whipworm on Pemba Island, but given the high intensity of infection at this study side, it remains unclear whether this treatment failure is explained by high drug pressure (and emerging anthelmintic resistance) or high infection intensity. Nevertheless, our results indicate that alternative treatment regimens are required to control intestinal worms in Pemba Island.

Background Soil-transmitted helminthiasis affects almost 2 billion people worldwide in tropical climates. Preventive chemotherapy, using the benzimidazoles (albendazole and mebendazole) is the current main recommended control strategy. Nevertheless, there is limited efficacy of these drugs against hookworm infection and, to a greater extent, against trichuriasis. We describe a protocol for a trial investigating the efficacy and safety of the co-administration of ivermectin and albendazole against trichuriasis. Methods A double-blind, placebo-controlled randomized controlled trial will be conducted in three countries (Côte d’Ivoire, Tanzania and Lao PDR) with the aim to determine the efficacy, safety and extended effects of co-administered ivermectin and albendazole compared to standard albendazole monotherapy. We will enroll 600 participants aged 6–60 years in each setting. The primary outcome is cure rate (CR) against Trichuris trichiura infection as assessed by Kato-Katz 14–21 days after treatment. Secondary outcomes include CRs against concomitant soil-transmitted helminth (STH) infections (Ascaris lumbricoides, hookworm and Strongyloides stercoralis) and egg reduction rates (ERRs) against STH at 14–21 days, 180 days and 360 days. Tolerability of treatment, infection status assessed by polymerase chain reaction (PCR), and potential benefits of deworming on nutritional and morbidity indicators will be assessed. The primary analysis will include an available-case set and use logistic regression models adjusted for age, sex and weight. Discussion This trial will provide robust results on the efficacy and safety of co-administration of ivermectin and albendazole with the aim to better inform WHO recommendations on control of STHs. Furthermore, secondary and explanatory outcomes will provide direct evidence on the extended effects of combination therapy and insight on the relationship between nutrition and morbidity parameters and infection status and intensity. Trial registration NCT03527732 (date assigned: 17 May 2018). Electronic supplementary material The online version of this article (10.1186/s12879-019-3882-x) contains supplementary material, which is available to authorized users.

Background Preventive chemotherapy is the cornerstone of soil-transmitted helminth (STH) control. Long-term outcomes and adequate treatment frequency of the recently recommended albendazole-ivermectin have not been studied to date. Methodology/principal findings Double-blind randomized controlled trials were conducted in Lao PDR, Pemba Island, Tanzania and Côte d’Ivoire between 2018 and 2020 to evaluate the efficacy and safety of ivermectin-albendazole versus albendazole-placebo in Trichuris trichiura-infected individuals aged 6 to 60. In the framework of this study, in Lao PDR 466 and 413 participants and on Pemba Island, 558 and 515 participants were followed-up six and 12 months post-treatment, respectively. From each participant at least one stool sample was processed for Kato-Katz diagnosis and cure rates (CRs), egg reduction rates (ERRs) and apparent reinfection rates were calculated. If found helminth-positive at six months, participants were re-treated according to their allocated treatment. Long-term outcomes against T. trichiura based on CRs and ERRs of ivermectin-albendazole compared to albendazole were significantly higher at six months in Lao PDR (CR, 65.8 vs 13.4%, difference; 52.4; 95% CI 45.0–60.0; ERRs, 99.0 vs 79.6, difference 19.4; 95% CI 14.4–24.4) and Pemba Island (CR, 17.8 vs 1.4%, difference; 16.4; 95% CI 11.6–21.0; ERRs, 84.9 vs 21.2, difference 63.8; 95% CI 50.6–76.9) and also at 12 months in Lao PDR (CR, 74.0 vs 23.4%, difference; 50.6; 95% CI 42.6–61.0; ERRs, 99.6 vs 91.3, difference 8.3; 95% CI 5.7–10.8) and Pemba Island (CR, 19.5 vs 3.4%, difference; 16.1; 95% CI 10.7–21.5; ERRs, 92.9 vs 53.6, difference 39.3; 95% CI 31.2–47.4) respectively. Apparent reinfection rates with T. trichiura were considerably higher on Pemba Island (100.0%, 95% CI, 29.2–100.0) than in Lao PDR (10.0%, 95% CI, 0.2–44.5) at 12 months post-treatment for participants treated with albendazole alone. Conclusions/significance The long-term outcomes against T. trichiura of ivermectin-albendazole are superior to albendazole in terms of CRs and ERRs and in reducing infection intensities. Our results will help to guide decisions on how to best use ivermectin-albendazole in the context of large-scale PC programs tailored to the local context to sustainably control STH infections. Trial registration ClinicalTrials.gov registered with clinicaltrials.gov, reference: NCT03527732, date assigned: 17 May 2018., Author summary Around 1.5 billion people are infected with the gastrointestinal dwelling nematodes, the so-called soil-transmitted helminths (STHs). Especially chronic high-intensity infections with these parasites can cause substantial morbidity in endemic regions. Preventive chemotherapy, which is the regular administration of a single dose of an anthelmintic drug to at-risk populations, aims to reduce morbidity by lowering the prevalence and intensity of STH infections. Due to the suboptimal efficacy of these recommended single dose monotherapies, particularly against Trichuris trichiura, the use of drug combinations with dissimilar modes of action may enhance treatment efficacy. In double-blind randomized controlled trials in Lao PDR and on Pemba Island, Tanzania, we examined the long-term outcomes of ivermectin-albendazole versus albendazole alone, against T. trichiura. We assessed the infection status, apparent reinfections, new infections and the change of infection intensity for the three major STH species six and 12 months post-treatment. The long-term outcomes (in terms of cure and egg-reduction rates) of the ivermectin-albendazole combination therapy against T. trichiura were significantly higher than that of albendazole alone at all-time points and in both countries. Bi-annual treatment intervals using the ivermectin-albendazole combination might be necessary to sustainably decrease transmission of STH infections.

BACKGROUND: Preventive chemotherapy with albendazole or mebendazole remains one of the cornerstones of soil-transmitted helminth control. However, these drugs are less effective against Trichuris trichiura. Combined ivermectin-albendazole is a promising treatment alternative, yet robust evidence is lacking. We aimed to demonstrate superiority of co-administered ivermectin-albendazole over albendazole monotherapy in three distinct epidemiological settings. METHODS: We conducted a double-blind, parallel-group, phase 3, randomised controlled trial in community members aged 6-60 years infected with T trichiura in Cote d'Ivoire, Laos, and Pemba Island, Tanzania, between Sept 26, 2018, and June 29, 2020. Participants with at least 100 T trichiura eggs per g of stool at baseline were randomly assigned (1:1) using computer-generated randomisation sequences in varying blocks of four, six, and eight, stratified by baseline T trichiura infection intensity, to orally receive either a single dose of ivermectin (200 mug/kg) plus albendazole (400 mg) or albendazole (400 mg) plus placebo. Patients, field staff, and outcome assessors were masked to treatment assignment. The primary outcome was cure rate against T trichiura, defined as the proportion of participants with no eggs in their faeces 14-21 days after treatment, assessed by Kato-Katz thick smears, and analysed in the available-case population according to intention-to-treat principles. Safety was a secondary outcome and was assessed 3 h and 24 h after drug administration. The trial is registered at ClinicalTrials.gov, NCT03527732. FINDINGS: Between Sept 13 and Dec 18, 2019, Jan 12 and April 5, 2019, and Sept 26 and Nov 5, 2018, 3737, 3694, and 1435 community members were screened for trial eligibility in Cote d'Ivoire, Laos, and Pemba Island, respectively. In Cote d'Ivoire, Laos, and Pemba Island, 256, 274, and 305 participants, respectively, were randomly assigned to the albendazole group, and 255, 275, and 308, respectively, to the ivermectin-albendazole group. Primary outcome data were available for 722 participants treated with albendazole and 733 treated with ivermectin-albendazole. Ivermectin-albendazole showed significantly higher cure rates against T trichiura than albendazole in Laos (66% [140 of 213]vs 8% [16 of 194]; difference 58 percentage points, 95% CI 50 to 65, p

Background Soil-transmitted helminthiases are important neglected tropical diseases that result in a notably high number of disability-adjusted life years worldwide. Characterizing the interactions between the human intestinal microbiome and helminths is of interest in the development of alternative treatments that do not rely on chemotherapeutics and do not lead to drug resistance. Methods We recruited and obtained fecal samples from 32 pairs of mothers and children on Pemba Island and monitored their intestinal microbiota using 16S rRNA gene sequencing. Results We observed that microbial changes occur in the gut microbiota of infected mothers and children. Some short-chain fatty acid (SCFA)-producing bacteria and carbohydrate-degrading bacteria exhibited lower abundance in the infected individuals. Potentially pathogenic Campylobacter and proinflammatory Methanobrevibacter in infected mothers and opportunistic Enterococcus in infected children exhibited greater abundance. Conclusions Our findings could reveal the microbiota profiling in T. trichiura-infected individuals, indicate the potential roles of key microbiota in the host and aid to the development of novel strategies to control T. trichiura infection. Graphical Abstract

Background Considerable progress towards the elimination of urogenital schistosomiasis was made by the Zanzibar Elimination of Schistosomiasis Transmission project from 2012 till 2016, when biannual praziquantel mass drug administration (MDA) alone or with additional snail control or behaviour change interventions were implemented. Annual MDA was continued in 2017 and 2018, but not in 2019, imposing a 16-month treatment gap. We monitored the Schistosoma haematobium prevalence from 2012 till 2020 and assessed recrudescence patterns with focus on 2020. Methodology Repeated cross-sectional surveys were conducted from 2011/12 till 2020 in 90 communities and 90 schools in Zanzibar. Annually, around 4,500 adults and up to 20,000 schoolchildren were surveyed. The S. haematobium prevalence was detected by urine filtration and reagent strips. In 2020, risk factors for infection were investigated using generalized estimated equation models. Principal findings In adults, the apparent S. haematobium prevalence was 3.9% in 2011 and 0.4% in 2020. In schoolchildren, the prevalence decreased from 6.6% in 2012 to 1.2% in 2019 with vicissitudes over the years. Prominent recrudescence of infection from 2.8% in 2019 to 9.1% (+225%) in 2020 was observed in 29 schools with historically moderate prevalences (≥10%). Compared with 2019, reinfection in 2020 was particularly striking in boys aged 9–16 years. Being male was a risk factor for infection in 2020 (adults: odds ratio (OR): 6.24, 95% confidence interval (95% CI): 1.96–19.60; schoolchildren: OR: 2.06, 95% CI: 1.52–2.78). Living near to a natural freshwater body significantly increased the odds of infection in adults (OR: 2.90, CI: 1.12–7.54). Conclusions/Significance After 11 rounds of MDA over 7 years and a 16-month treatment gap, the urogenital schistosomiasis prevalence considerably rebounded in hotspot areas. Future elimination efforts in Zanzibar should focus on re-intensifying MDA plus additional interventions in hotspot areas. In low-prevalence areas, the strategy might be adapted from MDA to targeted surveillance-response., Author summary Schistosomiasis is a neglected tropical disease caused by parasitic blood flukes of the genus Schistosoma. On the Zanzibar islands, United Republic of Tanzania, interventions to eliminate urogenital schistosomiasis commenced in 2012. From 2012 to 2016, the population was treated biannually with praziquantel and, additionally, some areas received mollusciciding against the intermediate host snail, or educational measures for behavior change. Mass drug administration (MDA) with praziquantel was continued annually in 2017 and 2018, but not in 2019. As a result of the interventions, the overall S. haematobium prevalence was reduced to 0.4% in adults and 3.4% in schoolchildren in 2020. However, in some areas, the MDA gap in 2019 resulted in a considerable rebound of infections. The recrudescence in 2020 was particularly striking for boys aged 9–16 years. In general, in 2020, male participants had higher odds of infection than females. Adults living near to a natural freshwater body also showed an increased risk of S. haematobium infection. Future elimination efforts in Zanzibar should focus on re-intensifying elimination interventions, including MDA, snail control and behavior change in hotspot areas. In low-prevalence areas, the strategy might be adapted from MDA to targeted interventions, such as surveillance-response.

Background Clinical trial participants are required to sign an informed consent form (ICF). However, information is lacking on the most effective methods to convey trial relevant information prior to inviting participants to sign the ICF, being particularly pertinent in low-income countries. A previous study on Pemba Island, Tanzania, found that a verbal information session (IS) was significantly better than providing an ICF alone. However, knowledge gaps remained. Building on these findings, we investigated the effect of adding a slideshow or a theater to the IS in the informed consent procedure of an anthelminthic clinical trial. Methodology/principal findings A total of 604 caregivers were randomized into the control group that only received an ICF (n = 150) or an ICF plus one of three intervention strategies: (i) verbal IS (n = 135), (ii) verbal IS with a slideshow (n = 174) or (iii) verbal IS followed by a theater (n = 145). All modes of information covered the same key messages. Participants’ understanding was assessed using a semi-structured questionnaire. The mean score of caregivers in the control group (ICF only) was 4.41 (standard deviation = 1.47). Caregivers attending the IS alone were more knowledgeable than those in the control group (estimated difference in mean scores: 2.40, 95% confidence interval (CI) 1.95 to 2.86, p < 0.01). However, there was no evidence of an improvement compared to the IS only when participants attended a slideshow (0.09, 95% CI -0.53 to 0.35, p = 0.68) or a theater (0.28, 95% CI -0.27 to 0.82, p = 0.32). Three out of 10 key messages remained largely misunderstood, regardless of the mode of information group. Conclusions/significance Our study confirmed that, in this setting, an ICF alone was not sufficient to convey clinical trial-related information. An IS was beneficial, however, additional theater and slideshows did not further improve understanding. Future research should explore methods to improve communication between study teams and participants for different key messages, study types and settings., Author summary Legally, participants of clinical trials must sign an informed consent form prior to the start of a trial. To be truly informed, participants (or their caregivers, if underaged) need to understand the trial objectives, procedures, benefits, potential risks and their rights throughout the study. However, in regions where literacy and health literacy are still quite low, delivering information exclusively in written format using an informed consent form is not the best way to convey information. A previous study on Pemba Island, Tanzania, found that a spoken information session in addition to the informed consent form alone, significantly improved the clinical trial-related knowledge of the caregivers of participants. However, not all questions could be answered correctly. In the current study, we explored the addition of two further modes of information to the information session: a slideshow or a theater show. Caregivers’ understanding was measured using a questionnaire. We confirmed that having an oral information session is significantly better than only receiving the informed consent form. However, adding a slideshow and theater did not further improve caregivers’ knowledge. We conclude that future studies should work on improving these modes of information or explore new ones.

This diagnostic/prognostic study describes the use of cell-free transcriptomics, urine metabolomics, and plasma proteomics for identifying the biological measurements associated with preterm birth., Key Points Question What maternal biological modalities are associated with preterm birth (PTB)? Findings In this diagnostic/prognostic study of 81 pregnant women from 5 birth cohorts in low- and middle-income countries, several correlates of preterm birth in urine and blood were found to be associated with PTB. Although cohort-specific signatures were present, a machine learning algorithm was able to generate a model that was capable of predicting PTB across the cohorts. Meaning Results of this study suggest that most PTBs can be predicted using blood and urine samples collected early in the pregnancy, providing opportunities for interventions., Importance Worldwide, preterm birth (PTB) is the single largest cause of deaths in the perinatal and neonatal period and is associated with increased morbidity in young children. The cause of PTB is multifactorial, and the development of generalizable biological models may enable early detection and guide therapeutic studies. Objective To investigate the ability of transcriptomics and proteomics profiling of plasma and metabolomics analysis of urine to identify early biological measurements associated with PTB. Design, Setting, and Participants This diagnostic/prognostic study analyzed plasma and urine samples collected from May 2014 to June 2017 from pregnant women in 5 biorepository cohorts in low- and middle-income countries (LMICs; ie, Matlab, Bangladesh; Lusaka, Zambia; Sylhet, Bangladesh; Karachi, Pakistan; and Pemba, Tanzania). These cohorts were established to study maternal and fetal outcomes and were supported by the Alliance for Maternal and Newborn Health Improvement and the Global Alliance to Prevent Prematurity and Stillbirth biorepositories. Data were analyzed from December 2018 to July 2019. Exposures Blood and urine specimens that were collected early during pregnancy (median sampling time of 13.6 weeks of gestation, according to ultrasonography) were processed, stored, and shipped to the laboratories under uniform protocols. Plasma samples were assayed for targeted measurement of proteins and untargeted cell-free ribonucleic acid profiling; urine samples were assayed for metabolites. Main Outcomes and Measures The PTB phenotype was defined as the delivery of a live infant before completing 37 weeks of gestation. Results Of the 81 pregnant women included in this study, 39 had PTBs (48.1%) and 42 had term pregnancies (51.9%) (mean [SD] age of 24.8 [5.3] years). Univariate analysis demonstrated functional biological differences across the 5 cohorts. A cohort-adjusted machine learning algorithm was applied to each biological data set, and then a higher-level machine learning modeling combined the results into a final integrative model. The integrated model was more accurate, with an area under the receiver operating characteristic curve (AUROC) of 0.83 (95% CI, 0.72-0.91) compared with the models derived for each independent biological modality (transcriptomics AUROC, 0.73 [95% CI, 0.61-0.83]; metabolomics AUROC, 0.59 [95% CI, 0.47-0.72]; and proteomics AUROC, 0.75 [95% CI, 0.64-0.85]). Primary features associated with PTB included an inflammatory module as well as a metabolomic module measured in urine associated with the glutamine and glutamate metabolism and valine, leucine, and isoleucine biosynthesis pathways. Conclusions and Relevance This study found that, in LMICs and high PTB settings, major biological adaptations during term pregnancy follow a generalizable model and the predictive accuracy for PTB was augmented by combining various omics data sets, suggesting that PTB is a condition that manifests within multiple biological systems. These data sets, with machine learning partnerships, may be a key step in developing valuable predictive tests and intervention candidates for preventing PTB.

Schistosomiasis, a neglected tropical disease of medical and veterinary importance, transmitted through specific freshwater snail intermediate hosts, is targeted for elimination in several endemic regions in sub-Saharan Africa. Multi-disciplinary methods are required for both human and environmental diagnostics to certify schistosomiasis elimination when eventually reached. Molecular xenomonitoring protocols, a DNA-based detection method for screening disease vectors, have been developed and trialed for parasites transmitted by hematophagous insects, such as filarial worms and trypanosomes, yet few have been extensively trialed or proven reliable for the intermediate host snails transmitting schistosomes. Here, previously published universal and Schistosoma-specific internal transcribed spacer (ITS) rDNA primers were adapted into a triplex PCR primer assay that allowed for simple, robust, and rapid detection of Schistosoma haematobium and Schistosoma bovis in Bulinus snails. We showed this two-step protocol could sensitively detect DNA of a single larval schistosome from experimentally infected snails and demonstrate its functionality for detecting S. haematobium infections in wild-caught snails from Zanzibar. Such surveillance tools are a necessity for succeeding in and certifying the 2030 control and elimination goals set by the World Health Organization.

The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was created in 2008 to answer questions of importance to program managers working to reduce the burden of schistosomiasis in Africa. In the past, intermediate host snail monitoring and control was an important part of integrated schistosomiasis control. However, in Africa, efforts to control snails have declined dramatically over the last 30 years. A resurgence of interest in the control of snails has been prompted by the realization, backed by a World Health Assembly resolution (WHA65.21), that mass drug administration alone may be insufficient to achieve schistosomiasis elimination. SCORE has supported work on snail identification and mapping and investigated how xenomonitoring techniques can aid in the identification of infected snails and thereby identify potential transmission areas. Focal mollusciciding with niclosamide was undertaken in Zanzibar and Côte d’Ivoire as a part of elimination studies. Two studies involving biological control of snails were conducted: one explored the association of freshwater riverine prawns and snail hosts in Côte d’Ivoire and the other assessed the current distribution of Procambarus clarkii, the invasive Louisiana red swamp crayfish, in Kenya and its association with snail hosts and schistosomiasis transmission. SCORE also supported modeling studies on the importance of snail control in achieving elimination and a meta-analysis of the impact of molluscicide-based snail control programs on human schistosomiasis prevalence and incidence. SCORE’s snail control studies contributed to increased investment in building capacity, and specimens collected during SCORE research deposited in the Schistosomiasis Collections at the Natural History Museum (SCAN) will provide a valuable resource for the years to come.

Preventive chemotherapy is the current strategy to control soil-transmitted helminth infections (caused by Ascaris lumbricoides, hookworm, and Trichuris trichiura). But, to improve efficacy and avoid emerging resistance, new drugs are warranted. Tribendimidine has shown good anthelmintic efficacy and is therefore a frontrunner for monotherapy and combination chemotherapy.We did a randomised, controlled, single-blinded, non-inferiority trial on Pemba Island, Tanzania, and in Côte d'Ivoire. We recruited adolescents aged 15-18 years from four primary schools on Pemba, and school attendees and non-schoolers from two districts in Côte d'Ivoire. Only hookworm-positive participants were randomly assigned (1:1:1:1) to single, oral doses of tribendimidine 400 mg plus placebo (tribendimidine monotherapy), tribendimidine 400 mg plus ivermectin 200 μg/kg, tribendimidine 400 mg plus oxantel pamoate 25 mg/kg, or albendazole 400 mg plus oxantel pamoate 25 mg/kg. Randomisation was done via a computer-generated list in block sizes of four or eight. Participants were asked to provide two stool samples on 2 consecutive days at baseline and again 14-21 days at follow-up. The primary outcome was the difference in egg-reduction rates (ERRs; ie, the geometric mean reduction) in hookworm egg counts between treatment groups, measured by the Kato-Katz technique. Differences in coadministrated treatment groups were assessed for non-inferiority with a margin of -3% to albendazole plus oxantel pamoate based on the available-case population, analysed by intention to treat. Safety was assessed 3 h and 24 h after treatment. This study is registered with ISRCTN (number 14373201).Between July 26, and Dec 23, 2016, we treated 636 hookworm-positive participants, and outcome data were available for 601 participants (151 assigned to tribendimidine monotherapy, 154 to tribendimidine plus ivermectin, 148 to tribendimidine plus oxantel pamoate, and 148 to albendazole plus oxantel pamoate). Tribendimidine plus ivermectin was non-inferior to albendazole plus oxantel pamoate (ERRs 99·5% [95% CI 99·2-99·7] vs 96·0% [93·9-97·4]; difference 3·52 percentage points [2·05-5·65]). Likewise, tribendimidine plus oxantel pamoate was non-inferior to albendazole plus oxantel pamoate (ERRs 96·5% [95% CI 94·9 to 97·6] vs 96·0% [93·9 to 97·4]; difference 0·48 percentage points [-1·61 to 2·88]). 3 h after treatment, headache (n=50 [8%]) and vertigo (n=37 [6%]) were the most widely reported symptoms; 24 h after treatment, 50 (8%) patients reported vertigo and 41 (7%) reported headache. Mainly mild adverse events were reported with peak numbers (n=111 [18%]) at 24 h after treatment. Three participants had moderate adverse events 3 h after treatment: two (1%) had vertigo and one (1%) had headache, and two had moderate adverse events 24 h after treatment: one (1%) had vomiting and one (1%) had vomiting plus diarrhoea.Tribendimidine in combination with either ivermectin or oxantel pamoate had a similar, non-inferior efficacy profile as albendazole plus oxantel pamoate, hence tribendimidine will be a useful addition to the depleted anthelmintic drug armamentarium.Swiss National Science Foundation.

Accurate diagnosis of urogenital schistosomiasis is crucial for disease surveillance and control. Routine diagnostic methods, however, lack sensitivity when assessing patients with low levels of infection still able to maintain pathogen transmission. Therefore, there is a need for highly sensitive diagnostic tools that can be used at the point-of-care in endemic areas. Recombinase polymerase amplification (RPA) is a rapid and sensitive diagnostic tool that has been used to diagnose several pathogens at the point-of-care. Here, the analytical performance of a previously developed RPA assay (RT-ShDra1-RPA) targeting the Schistosoma haematobium Dra1 genomic region was assessed using commercially synthesised S. haematobium Dra1 copies and laboratory-prepared samples spiked with S. haematobium eggs. Clinical performance was also assessed by comparing diagnostic outcomes with that of a reference diagnostic standard, urine-egg microscopy. The RT-ShDra1-RPA was able to detect 1 &times, 101 copies of commercially synthesised Dra1 DNA as well as one S. haematobium egg within laboratory-spiked ddH2O samples. When compared with urine-egg microscopy, the overall sensitivity and specificity of the RT-ShDra1-RPA assay was 93.7% (&plusmn, 88.7&ndash, 96.9) and 100% (&plusmn, 69.1&ndash, 100), respectively. Positive and negative predictive values were 100% (&plusmn, 97.5&ndash, 100) and 50% (&plusmn, 27.2&ndash, 72.8), respectively. The RT-ShDra1-RPA therefore shows promise as a rapid and highly sensitive diagnostic tool able to diagnose urogenital schistosomiasis at the point-of-care.

BackgroundIn clinical research, obtaining informed consent from participants is an ethical and legal requirement. Conveying the information concerning the study can be done using multiple methods yet this step commonly relies exclusively on the informed consent form alone. While this is legal, it does not ensure the participant’s true comprehension. New effective methods of conveying consent information should be tested. In this study we compared the effect of different methods on the knowledge of caregivers of participants of a clinical trial on Pemba Island, Tanzania.MethodsA total of 254 caregivers were assigned to receive (i) a pamphlet (n = 63), (ii) an oral information session (n = 62) or (iii) a pamphlet and an oral information session (n = 64) about the clinical trial procedures, their rights, benefits and potential risks. Their post-intervention knowledge was assessed using a questionnaire. One group of caregivers had not received any information when they were interviewed (n = 65).ResultsIn contrast to the pamphlet, attending an information session significantly increased caregivers’ knowledge for some of the questions. Most of these questions were either related to the parasite (hookworm) or to the trial design (study procedures).ConclusionsIn conclusion, within our trial on Pemba Island, a pamphlet was found to not be a good form of conveying clinical trial information while an oral information session improved knowledge. Not all caregivers attending an information session responded correctly to all questions; therefore, better forms of communicating information need to be found to achieve a truly informed consent.

Background Preventive chemotherapy is the main strategy to control soil-transmitted helminth (STH) infections. Albendazole and mebendazole are ubiquitously used, but they are not sufficiently effective against Trichuris trichiura. Moxidectin might be a useful addition to the small drug armamentarium. However, the optimal dosage of moxidectin alone and in combination with albendazole against T. trichiura and other STHs has not yet been determined. Methods A Phase II, randomized, placebo-controlled, dose-finding trial was conducted in 2 secondary schools on Pemba Island, Tanzania. Using a computer-generated list, T. trichiura–infected adolescents were randomly assigned to 7 treatment arms: 8, 16, or 24 mg of moxidectin monotherapy; 8, 16, or 24 mg of moxidectin plus 400 mg of albendazole combination therapy; or placebo. The primary outcome was cure rate (CR) against T. trichiura, analyzed 13 to 20 days after treatment by quadruple Kato-Katz thick smears. Results A total of 290 adolescents were enrolled (41 or 42 per arm). CRs against T. trichiura were 43, 46, and 44% for 8, 16, and 24 mg of moxidectin alone, respectively; 60, 62, and 66% for the same moxidectin dosages plus 400 mg of albendazole, respectively; and 12% for placebo. The moxidectin-albendazole arms also revealed higher CRs and egg reduction rates against hookworm than the monotherapy arms. Moxidectin and its combination with albendazole were well tolerated. Conclusions Moxidectin-albendazole is superior to moxidectin. There is no benefit of using doses above 8 mg, which is the recommended dose for onchocerciasis. The moxidectin-albendazole combination of 8 mg plus 400 mg should be investigated further to develop recommendations for appropriate control of STH infections. Clinical Trials Registration NCT03501251.

The AMANHI Biobank cohort is a large cohort of pregnant women and their babies in sub-Saharan Africa and South Asia aimed at studying the interactions between genes and a wide range of varying environmental exposures on key pregnancy and birth outcomes. The cohort is well characterized for clinical, epidemiological and socio-economic information with harmonized data collection across all sites. The samples were collected and stored following standard operating procedures and provide an excellent opportunity for biological characterization. The cohort includes a total of 10 001 women enrolled between May 2014 and June 2018 across Sylhet-Bangladesh, Karachi-Pakistan and Pemba Island-Tanzania, who have given birth to 9938 babies. Follow-up included three to four visits during pregnancy: at baseline, at 24–28 weeks, at 32–36 weeks and after 37 completed weeks of gestational age to collect routine epidemiological data and biological samples, and two additional visits after birth: between 1 and 6 days after birth and the second one between 42 and 60 days of age, in which the newborn’s samples were taken. The data set comprises a wide range of phenotypical data and environmental measures, biological samples, as well as a multiplicity of outcomes from the mother, the fetus and the neonate. The AMANHI biobank data is available at the Department for Maternal, Newborn, Child and Adolescent Health, and Ageing at the World Health Organization, which is the coordination centre of the study. Queries regarding the data and potential collaborations can be sent to Dr Rajiv Bahl (bahlr@who.int).

Strongyloides stercoralis, although endemic in many countries, is not included in helminth control programs. Few data are available on the prevalence and morbidity linked to this infection. We compared data from two studies conducted in 1998 and 2013 on Pemba Island, Tanzania, involving 525 and 509 schoolchildren, respectively. In 1998, the diagnostic method used was Harada Mori, whereas in 2013 diagnosis was made by both Koga agar plate and Baermann methods. The prevalence registered was 41% in 1998 and 7% in 2013. This data suggest that the prevalence of S. stercoralis on Pemba was significantly reduced 7 years after the last ivermectin administration for preventive chemotherapy and underlines the importance and impact of large-scale preventive chemotherapy, which often goes beyond its actual target. Preventive chemotherapy with ivermectin should be recommended in areas where S. stercoralis is endemic.

Improved tuberculosis (TB) prevention and control depend critically on the development of a simple, readily accessible rapid triage test to stratify TB risk. We hypothesized that a blood protein-based host response signature for active TB (ATB) could distinguish it from other TB-like disease (OTD) in adult patients with persistent cough, thereby providing a foundation for a point-of-care (POC) triage test for ATB. Three adult cohorts consisting of ATB suspects were recruited. A bead-based immunoassay and machine learning algorithms identified a panel of four host blood proteins, interleukin-6 (IL-6), IL-8, IL-18, and vascular endothelial growth factor (VEGF), that distinguished ATB from OTD. An ultrasensitive POC-amenable single-molecule array (Simoa) panel was configured, and the ATB diagnostic algorithm underwent blind validation in an independent, multinational cohort in which ATB was distinguished from OTD with receiver operator characteristic-area under the curve (ROC-AUC) of 0.80 [95% confidence interval (CI), 0.75 to 0.85], 80% sensitivity (95% CI, 73 to 85%), and 65% specificity (95% CI, 57 to 71%). When host antibodies against TB antigen Ag85B were added to the panel, performance improved to 86% sensitivity and 69% specificity. A blood-based host response panel consisting of four proteins and antibodies to one TB antigen can help to differentiate ATB from other causes of persistent cough in patients with and without HIV infection from Africa, Asia, and South America. Performance characteristics approach World Health Organization (WHO) target product profile accuracy requirements and may provide the foundation for an urgently needed blood-based POC TB triage test.

Background The Zanzibar Elimination of Schistosomiasis Transmission (ZEST) project aimed to eliminate urogenital schistosomiasis as a public health problem from Pemba and to interrupt Schistosoma haematobium transmission from Unguja in 5 years. Methodology A repeated cross-sectional cluster-randomized trial was implemented from 2011/12 till 2017. On each island, 45 shehias were randomly assigned to receive one of three interventions: biannual mass drug administration (MDA) with praziquantel alone, or in combination with snail control or behavior change measures. In cross-sectional surveys, a single urine sample was collected from ~9,000 students aged 9- to 12-years and from ~4,500 adults aged 20- to 55-years annually, and from ~9,000 1st year students at baseline and the final survey. Each sample was examined for S. haematobium eggs by a single urine filtration. Prevalence and infection intensity were determined. Odds of infection were compared between the intervention arms. Principal findings Prevalence was reduced from 6.1% (95% confidence interval (CI): 4.5%-7.6%) to 1.7% (95% CI: 1.2%-2.2%) in 9- to 12-year old students, from 3.9% (95% CI: 2.8%-5.0%) to 1.5% (95% CI: 1.0%-2.0%) in adults, and from 8.8% (95% CI: 6.5%-11.2%) to 2.6% (95% CI: 1.7%-3.5%) in 1st year students from 2011/12 to 2017. In 2017, heavy infection intensities occurred in 0.4% of 9- to 12-year old students, 0.1% of adults, and 0.8% of 1st year students. Considering 1st year students in 2017, 13/45 schools in Pemba and 4/45 schools in Unguja had heavy infection intensities >1%. There was no significant difference in prevalence between the intervention arms in any study group and year. Conclusions/Significance Urogenital schistosomiasis was eliminated as public health problem from most sites in Pemba and Unguja. Prevalence was significantly reduced, but transmission was not interrupted. Continued interventions that are adaptive and tailored to the micro-epidemiology of S. haematobium in Zanzibar are needed to sustain and advance the gains made by ZEST., Author summary Schistosomiasis is a disease caused by parasitic blood flukes of the genus Schistosoma. The highest burden is concentrated in sub-Saharan Africa. On the Zanzibar islands, urogenital schistosomiasis has been successfully controlled over the past decades. The Zanzibar Elimination of Schistosomiasis Transmission (ZEST) project implemented from 2011/12 through 2017 aimed to eliminate urogenital schistosomiasis as a public health problem from Pemba and to interrupt S. haematobium transmission from Unguja in 5 years. In a cluster-randomized trial, we investigated the impact of biannual treatment of the population with praziquantel alone or combined with snail control or behavior change interventions. After five years of interventions, the overall S. haematobium prevalence was reduced to

Background More than 1.5 billion people are infected with soil-transmitted helminths (Ascaris lumbricoides, hookworm, Strongyloides stercoralis, and Trichuris trichiura), causing an estimated global burden in excess of 3 million disability-adjusted life years. However, the relationship between soil-transmitted helminth infection, adverse health consequences, and beneficial effects of deworming are not well understood. Methodology We pursued a detailed longitudinal clinical evaluation of school-age children to evaluate morbidity associated with soil-transmitted helminth infection and responses to treatment. This exploratory study was embedded into a randomized controlled trial. Overall, 434 children, aged 7–14 years, underwent a detailed medical history, physical examination, stool microscopy for soil-transmitted helminths, and hemoglobin (Hb) measurement at baseline. Medical history and stool examination were repeated at 3 and 18 weeks posttreatment. Additionally, Hb measurement was performed at the 18-week treatment follow-up. Logistic regression was employed to assess clinical factors associated with soil-transmitted helminth infection at baseline, and longitudinal data analysis to examine change in health outcomes following treatment over time. Principal findings All enrolled children were infected with T. trichiura, and randomized into four different treatment interventions. None of the medical history, physical examination, and laboratory (i.e., Hb) findings were associated with A. lumbricoides, hookworm, or S. stercoralis infection at baseline. A composite of physical exam findings for anemia, including pallor of the conjunctiva, nail beds, and palmar creases predicted lower Hb values (-3.8 g/dl, 95% confidence interval (CI): -6.9, -0.6 g/dl). When examining longitudinal trends, we did not find improvements to Hb or face Wong-Baker Likert scale among children with soil-transmitted helminth infection compared to those without infection, although there was a slight trend toward improving Hb values after treating hookworm infection. Conclusions/significance Our study demonstrates the challenges of measuring morbidity in the context of soil-transmitted helminth infection and treatment, thus confirming the mainly subtle morbidity effects of infection., Author summary Soil-transmitted helminth infections frequently affect children and impoverished individuals in low-resource settings and are associated with negative health effects. We attempted to measure morbidity in school-age children from Pemba Island, Tanzania who are infected with soil-transmitted helminths but with relatively low risk for other infections known to cause chronic morbidity, such as malaria and schistosomiasis. We used a composite of clinical history, physical examination, and hemoglobin measurements. Our study was embedded into a randomized controlled trial, and by design, all individuals were infected with whipworms (Trichuris trichiura). A detailed clinical evaluation for morbidity in school-age children was not associated with an infection of roundworms (Ascaris lumbricoides), hookworm, or threadworms (Strongyloides stercoralis) but demonstrated the utility of the clinical examination to detect anemia. Indeed, anemia slightly trended toward resolution after deworming. While many metrics for soil-transmitted helminth infection-related morbidity may have been masked by ongoing deworming campaigns, simple physical exam findings for anemia can be useful to highlight individuals that require further evaluation.

Background Accurate diagnosis of urogenital schistosomiasis is vital for surveillance and control programmes. While a number of diagnostic techniques are available there is a need for simple, rapid and highly sensitive point-of-need (PON) tests in areas where infection prevalence and intensity are low. Recombinase Polymerase Amplification (RPA) is a sensitive isothermal molecular diagnostic technology that is rapid, portable and has been used at the PON for several pathogens. Results A real time fluorescence RPA assay (RT-ShDra1-RPA) targeting the Schistosoma haematobium Dra1 genomic repeat region was developed and was able to detect 1 fg of S. haematobium gDNA. Results were obtained within 10 minutes using a small portable battery powered tube scanner device that incubated reactions at 40 °C, whilst detecting DNA amplification and fluorescence over time. The assay’s performance was evaluated using 20 urine samples, with varying S. haematobium egg counts, from school children from Pemba Island, Zanzibar Archipelago, Tanzania. Prior to RPA analysis, samples were prepared using a quick crude field DNA extraction method, the Speed Extract Kit (Qiagen, Manchester, UK). Positive assay results were obtained from urine samples with egg counts of 1–926 eggs/10 ml, except for two samples, which had inconclusive results. These two samples had egg counts of two and three eggs/10 ml of urine. Conclusions The RT-ShDra1-RPA assay proved robust for S. haematobium gDNA detection and was able to amplify and detect S. haematobium DNA in urine samples from infected patients. The assay’s speed and portability, together with the use of crude sample preparation methods, could advance the rapid molecular diagnosis of urogenital schistosomiasis at the PON within endemic countries.

Summary Background Elimination of schistosomiasis as a public health problem and interruption of transmission in selected areas are targets set by WHO for 2025. Our aim was to assess biannual mass drug administration (MDA) applied alone or with complementary snail control or behaviour change interventions for the reduction of Schistosoma haematobium prevalence and infection intensity in children from Zanzibar and to compare the effect between the clusters. Methods In a 5-year repeated cross-sectional cluster-randomised trial, 90 shehias (small administrative regions; clusters) in Zanzibar eligible owing to available natural open freshwater bodies and public primary schools were randomly allocated (ratio 1:1:1) to receive one of three interventions: biannual MDA with praziquantel alone (arm 1) or in combination with snail control (arm 2), or behaviour change activities (arm 3). Neither participants nor field or laboratory personnel were blinded to the intervention arms. From 2012 to 2017, annually, a single urine sample was collected from approximately 100 children aged 9–12 years in the main public primary school of each shehia. The primary outcome was S haematobium infection prevalence and intensity in 9–12-year-old children after 5 years of follow-up. This study is completed and was registered with the ISRCTN, number 48837681. Findings The trial was done from Nov 1, 2011, through to Dec 31, 2017 and recruitment took place from Nov 2, 2011, until May 17, 2017. At baseline we enrolled 8278 participants, of whom 2899 (35%) were randomly allocated to arm 1, 2741 (33%) to arm 2, and 2638 (32%) to arm 3. 120 (4·2%) of 2853 in arm 1, 209 (7·8%) of 2688 in arm 2, and 167 (6·4%) of 2613 in arm 3 had S haematobium infections at baseline. Heavy infections (≥50 eggs per 10 mL of urine) were found in 126 (1·6%) of 8073 children at baseline. At the 5-year endline survey, 46 (1·4%) of 3184 in arm 1, 56 (1·7%) of 3217 (odds ratio [OR] 1·2 [95% CI 0·6–2·7] vs arm 1) in arm 2, and 58 (1·9%) of 3080 (1·3 [0·6–2·9]) in arm 3 had S haematobium infections. Heavy infections were detected in 33 (0·3%) of 9462 children. Interpretation Biannual MDA substantially reduced the S haematobium prevalence and infection intensity but was insufficient to interrupt transmission. Although snail control or behaviour change activities did not significantly boost the effect of MDA in our study, they might enhance interruption of transmission when tailored to focal endemicity and applied for a longer period. It is now necessary to focus on reducing prevalence in remaining hotspot areas and to introduce new methods of surveillance and public health response so that the important gains can be maintained and advanced. Funding University of Georgia Research Foundation Inc and Bill & Melinda Gates Foundation.

Summary Background The recommended anthelmintics show low efficacy in a single-dose regimen against Trichuris trichiura . Moxidectin, a new treatment for river blindness, might complement the drug armamentarium for the treatment and control of soil-transmitted helminthiasis. However, its efficacy against T trichiura has not yet been studied. The aim of the study was to assess the efficacy of moxidectin alone and in co-administrations against T trichiura infection. Methods A randomised, single-blind, non-inferiority trial was done in two primary schools and one secondary school in Pemba, Tanzania. Adolescents aged 12–18 years who tested positive for T trichiura were randomly assigned (5:5:3:3) with a computer-generated sequence to receive moxidectin (8 mg) plus albendazole (400 mg), albendazole (400 mg) plus oxantel pamoate (25 mg/kg; reference treatment), moxidectin (8 mg) plus tribendimidine (200 mg or 400 mg), or moxidectin (8 mg) alone. Study group assignments were masked from participants and laboratory technicians. The primary outcome was non-inferiority with a 2 percentage point margin for egg reduction rate (ERR) against T trichiura assessed as the relative change in the geometric mean egg counts from baseline to 14–21 days after treatment with the Kato-Katz method, based on the available case population. Cure rates (CR) and tolerability (assessed 3, 24, and 48 h post treatment) were secondary outcomes. The study is registered at ISRCTN (number 20398469) and is closed to accrual. Findings 701 students were enrolled between April 1, and Aug 7, 2017. Primary outcome data were available for 634 students. We observed ERRs of 98·5% for moxidectin plus albendazole and 99·8% for albendazole plus oxantel pamoate, resulting in an absolute difference of −1·2 percentage points (95% CI −1·8 to −0·8), meeting the non-inferiority margin. 100 (51%) of 197 students receiving moxidectin plus albendazole and 166 (83%) of 200 receiving albendazole plus oxantel pamoate were cured, indicating a difference of 32 percentage points (odds ratio 5·3, 95% CI 3·3 to 8·7). ERRs were 91·6% for moxidectin–tribendimidine and 83·2% for moxidectin. Only mild adverse events (mainly headache and stomach pain) were reported. The largest number of adverse events (126 [20%] of 632 students) was observed 24 h post treatment, with no difference among the individual treatment arms (ranging from 23 [19%] of 118 students treated with moxidectin to 38 [19%] of 199 with moxidectin plus albendazole). Interpretation Moxidectin plus albendazole showed non-inferiority to albendazole plus oxantel pamoate in terms of ERR; however, albendazole plus oxantel pamoate showed a considerably higher cure rate. Dose-optimisation studies with moxidectin and moxidectin plus albendazole should be considered since the efficacy of the dose used for the treatment of onchocerciasis (8 mg) in this study might not be optimal for the treatment of T trichiura infections. Funding Thrasher Foundation.

Background Single-dose mebendazole is widely used in preventive chemotherapy against the soil-transmitted helminths (STHs) Ascaris lumbricoides, hookworm and Trichuris trichiura, yet it shows limited efficacy against hookworm and T. trichiura infections. The use of adapted treatment regimens might provide a strategy to control and eliminate STH infections in STH-persistent settings. We evaluated the safety and efficacy of the multiple dose mebendazole regimen (3 days 100 mg bid) versus a single dose of 500 mg mebendazole in a setting with high STH prevalence and high drug pressure. Methods This randomised, double-blind clinical trial took place in a primary school on Pemba Island, Tanzania, in school-aged children (6–12 years). Using a computer random number generator (block size 10), hookworm-positive children were randomly assigned (1:1) to either a single or multiple dose regimen of mebendazole by an independent statistician. Two stool samples were collected at baseline and follow-up (18 to 22 days after treatment) for Kato-Katz analysis. The primary outcome was cure rate (CR) against hookworm. Secondary outcomes were egg reduction rate (ERR) against hookworm, CRs and ERRs against A. lumbricoides and T. trichiura, and tolerability assessed 3, 24 and 48 h post-treatment. Participants, investigators, caregivers, outcome assessors and the trial statistician were blinded. This trial is registered with ClinicalTrials.gov, number NCT03245398. Findings 93 children were assigned to each treatment arm. 185 children completed treatment and provided follow-up stool samples. CR against hookworm was significantly higher in the multiple dose (98%) than in the single dose arm (13%, OR 389.1, 95% CI 95.2 to 2885.7%, p

Objectives: The AMANHI study aims to seek for biomarkers as predictors of important pregnancy-related outcomes, and establish a biobank in developing countries for future research as new methods and technologies become available.Methods: AMANHI is using harmonised protocols to enrol 3000 women in early pregnancies (8-19 weeks of gestation) for population-based follow-up in pregnancy up to 42 days postpartum in Bangladesh, Pakistan and Tanzania, with collection taking place between August 2014 and June 2016. Urine pregnancy tests will be used to confirm reported or suspected pregnancies for screening ultrasound by trained sonographers to accurately date the pregnancy. Trained study field workers will collect very detailed phenotypic and epidemiological data from the pregnant woman and her family at scheduled home visits during pregnancy (enrolment, 24-28 weeks, 32-36 weeks & 38+ weeks) and postpartum (days 0-6 or 42-60). Trained phlebotomists will collect maternal and umbilical blood samples, centrifuge and obtain aliquots of serum, plasma and the buffy coat for storage. They will also measure HbA1C and collect a dried spot sample of whole blood. Maternal urine samples will also be collected and stored, alongside placenta, umbilical cord tissue and membrane samples, which will both be frozen and prepared for histology examination. Maternal and newborn stool (for microbiota) as well as paternal and newborn saliva samples (for DNA extraction) will also be collected. All samples will be stored at -80°C in the biobank in each of the three sites. These samples will be linked to numerous epidemiological and phenotypic data with unique study identification numbers.Importance of the study: AMANHI biobank proves that biobanking is feasible to implement in LMICs, but recognises that biobank creation is only the first step in addressing current global challenges.

We evaluated the Newton Nm1, a commercially available handheld light microscope and compared it with conventional light microscopy for the diagnosis of soil-transmitted helminth infections. A total of 91 Kato-Katz thick smears were examined by experienced microscopists and helminth eggs were counted and expressed as eggs per gram of stool (EPG). Mean egg counts were significantly higher with the conventional light microscope (5,190 EPG versus 2,386 EPG for Ascaris lumbricoides; 826 versus 456 for Trichuris trichiura; both P < 0.05). Using regression coefficients and accounting for intensity of infection, we found that the agreement between the two devices was excellent for both species (κ = 0.90, 95% confidence interval = 0.82–0.99 for A. lumbricoides and κ = 0.96, 95% CI = 0.91–1.00 for T. trichiura). The Newton Nm1 microscope may be a useful tool for the detection and quantification of soil-transmitted helminth infection in clinical, epidemiologic, and public health settings.

BACKGROUND Infections with soil-transmitted helminths (Ascaris lumbricoides, hookworm, and Trichuris trichiura) are widespread and often occur concomitantly. These parasiticworm infections are typically treated with albendazole or mebendazole, but both drugs show low efficacy against T. trichiura. Albendazole is the drug of choice against hookworm. METHODS In this double-blind trial conducted on Pemba Island, Tanzania, we randomly assigned children, 6 to 14 years of age, to receive one of four treatments: oxantel pamoate at a dose of 20 mg per kilogram of body weight, plus 400 mg of albendazole, administered on consecutive days; oxantel pamoate at a single dose of 20 mg per kilogram; albendazole at a single dose of 400 mg; or mebendazole at a single dose of 500 mg. We assessed the efficacy and safety profile of oxantel pamoate– albendazole when used in the treatment of T. trichiura infection (primary outcome) and concomitant soil-transmitted helminth infection (secondary outcome). Efficacy was determined by means of assessment of the cure rate and egg-reduction rate. Adverse events were assessed four times after treatment. RESULTS Complete data were available for 458 children, of whom 450 were infected with T. trichiura, 443 with hookworm, and 293 with A. lumbricoides. The cure rate of T. trichiura infection was significantly higher with oxantel pamoate–albendazole than with mebendazole (31.2% vs. 11.8%, P = 0.001), as was the egg-reduction rate (96.0% [95% confidence interval {CI}, 93.5 to 97.6] vs. 75.0% [95% CI, 64.2 to 82.0]). The cure rate with albendazole (2.6%) and the egg-reduction rate with albendazole (45.0%; 95% CI, 32.0 to 56.4) were significantly lower than the rates with mebendazole (P = 0.02 for the comparison of cure rates). Oxantel pamoate had low efficacy against hookworm and A. lumbricoides. Adverse events (mainly mild) were reported by 30.9% of all children. CONCLUSIONS Treatment with oxantel pamoate–albendazole resulted in higher cure and eggreduction rates for T. trichiura infection than the rates with standard therapy. (Funded by the Medicor Foundation and the Swiss National Science Foundation; Current Controlled Trials number, ISRCTN54577342.)

Soil-transmitted helminth infections are a major public health problem. An accurate diagnosis is important in order to identify individuals and communities in need of intervention, and for monitoring drug efficacy and potential emergence of resistance. We compared the accuracy of the Kato-Katz method and ether-concentration technique for the diagnosis of soil-transmitted helminth infections within a randomised controlled trial. Quadruplicate Kato-Katz thick smears (duplicate Kato-Katz from two stool samples each) were examined before (baseline) and 3 weeks after treatment (follow-up). Additionally, at baseline and follow-up, the first stool sample was subjected to an ether-concentration method. We determined the prevalence, sensitivity, negative predictive value, diagnostic agreement and cure rates for single and duplicate Kato-Katz thick smears from the first stool sample, quadruplicate Kato-Katz thick smears produced from two stool samples and single ether-concentration as compared to our 'gold' standard (i.e. quadruplicate Kato-Katz plus ether-concentration). Quadruplicate Kato-Katz revealed a higher sensitivity than single ether-concentration for Trichuris trichiura at baseline (94.3 % vs. 88.5 %, p = 0.002) and follow-up (93.8 % vs. 83.5 %, p < 0.001). In contrary, at follow-up, ether-concentration showed a higher sensitivity than quadruplicate Kato-Katz for Ascaris lumbricoides diagnosis (86.7 % vs. 46.7 %, p = 0.012). The ether-concentration method showed similar or slightly higher sensitivity than the Kato-Katz technique based on a single stool sample for all soil-transmitted helminth infections. The estimated cure rates were heavily dependent on the diagnostic technique and sampling effort. In conclusion, data on the prevalence of soil-transmitted helminth infections and the efficacy of anthelminthics are greatly influenced by the diagnostic method and sampling effort. The ether-concentration technique is a valuable alternative to the Kato-Katz method for helminth diagnosis.

We created a mobile phone microscope and assessed its accuracy for the diagnosis of soil-transmitted helminths compared with conventional microscopy. Mobile phone microscopy has a sensitivity of 69.4% for detecting any helminth egg and sensitivities of 81.0%, 54.4%, and 14.3% for the diagnosis of Ascaris lumbricoides, Trichuris trichiura and hookworm respectively.

Purpose: Based on health care records and trachoma rapid assessments, trachoma was suspected to be endemic in Kaskazini A and Micheweni districts of Zanzibar. This study aimed to investigate the prevalence of trachomatous inflammation–follicular (TF), and trachomatous trichiasis (TT) in each of those districts. Methods: The survey was undertaken in Kaskazini A and Micheweni districts on Unguja and Pemba Islands, respectively. A multi-stage cluster random sampling design was applied, whereby 25 census enumeration areas (clusters) and 30 households per cluster were included. Consenting eligible participants (children aged 1–9 years and people aged 15 years and older) were examined for trachoma using the World Health Organization simplified grading system. Results: A total of 1673 households were surveyed and 6407 participants (98.0% of those enumerated) were examined for trachoma. Examinees included a total of 2825 children aged 1–9 years and 3582 people aged 15 years and older. TF prevalence in 1–9-year-olds was 2.7% (95% confidence interval, CI, 2.7–4.1%) in Kazkazini A and 11.4% (95% CI 6.6–16.5%) in Micheweni. Among people aged 15 years and older, TT prevalence was 0.01% (95% CI 0.00–0.04%) in Kazkazini A and 0.21% (95% CI 0.08–0.39%) in Micheweni. Conclusion: Trachoma is a public health problem in Micheweni district, where implementation of all four components of the SAFE strategy (surgery, antibiotics, facial cleanliness, and environmental improvement), including mass drug administration with azithromycin, is required. These findings will facilitate planning for trachoma elimination.

To estimate neonatal mortality, particularly within 24 hours of birth, in six low- and lower-middle-income countries.We analysed epidemiological data on a total of 149 570 live births collected between 2007 and 2013 in six prospective randomized trials and a cohort study from predominantly rural areas of Bangladesh, Ghana, India, Pakistan, the United Republic of Tanzania and Zambia. The neonatal mortality rate and mortality within 24 hours of birth were estimated for all countries and mortality within 6 hours was estimated for four countries with available data. The findings were compared with published model-based estimates of neonatal mortality.Overall, the neonatal mortality rate observed at study sites in the six countries was 30.5 per 1000 live births (range: 13.6 in Zambia to 47.4 in Pakistan). Mortality within 24 hours was 14.1 per 1000 live births overall (range: 5.1 in Zambia to 20.1 in India) and 46.3% of all neonatal deaths occurred within 24 hours (range: 36.2% in Pakistan to 65.5% in the United Republic of Tanzania). Mortality in the first 6 hours was 8.3 per 1000 live births, i.e. 31.9% of neonatal mortality.Neonatal mortality within 24 hours of birth in predominantly rural areas of six low- and lower-middle-income countries was higher than model-based estimates for these countries. A little under half of all neonatal deaths occurred within 24 hours of birth and around one third occurred within 6 hours. Implementation of high-quality, effective obstetric and early newborn care should be a priority in these settings.Estimer la mortalité néonatale, en particulier dans les 24 heures suivant la naissance, dans six pays à revenu faible et intermédiaire - tranche inférieure.Nous avons analysé des données épidémiologiques portant sur un total de 149 570 naissances vivantes qui avaient été recueillies entre 2007 et 2013 lors de six essais prospectifs randomisés et d'une étude de cohorte réalisés dans des zones majoritairement rurales du Bangladesh, du Ghana, d'Inde, du Pakistan, de Tanzanie et de Zambie. Le taux de mortalité néonatale ainsi que la mortalité dans les 24 heures suivant la naissance ont été estimés pour tous ces pays; la mortalité dans les 6 heures suivant la naissance a été estimée pour quatre pays sur lesquels nous avions des données. Les résultats ont été comparés aux estimations de la mortalité néonatale publiées, qui ont été établies d'après des modèles.Globalement, le taux de mortalité néonatale observé sur les sites étudiés dans les six pays était de 30,5 pour 1000 naissances vivantes (de 13,6 en Zambie à 47,4 au Pakistan). La mortalité globale dans les 24 heures suivant la naissance était de 14,1 pour 1000 naissances vivantes (de 5,1 en Zambie à 20,1 en Inde) et 46,3% de l'ensemble des décès néonataux étaient survenus dans les 24 heures (de 36,2% au Pakistan à 65,5% en Tanzanie). Le taux de mortalité dans les 6 heures suivant la naissance était de 8,3 pour 1000 naissances vivantes, soit 31,9% de la mortalité néonatale totale.La mortalité néonatale dans les 24 heures suivant la naissance dans des zones majoritairement rurales de six pays à revenu faible et intermédiaire-tranche inférieure était supérieure aux estimations établies d'après des modèles pour ces pays. Un peu moins de la moitié des décès néonataux étaient survenus dans les 24 heures suivant la naissance et environ un tiers dans les 6 heures. La mise en place de soins obstétriques et néonataux efficaces et de haute qualité devrait être une priorité dans ces pays.Calcular la mortalidad neonatal, especialmente durante las 24 horas posteriores al nacimiento, en países con ingresos bajos y países con ingresos medios más bajos.Se analizaron datos epidemiológicos de un total de 149 570 nacidos vivos recopilados entre 2007 y 2013 en seis ensayos aleatorizados prospectivos y un estudio de cohortes de zonas principalmente rurales de Bangladesh, Ghana, India, Pakistán, la República Unida de Tanzanía y Zambia. Se calculó la tasa de mortalidad neonatal y la mortalidad durante las 24 horas posteriores al nacimiento en todos los países y se estimó la tasa de mortalidad en 6 horas en cuatro países con información disponible. Los resultados se compararon con estimaciones publicadas basadas en modelos de mortalidad neonatal.En general, la tasa de mortalidad neonatal observada en los lugares de estudio de los seis países fue de 30,5 por cada 1 000 nacidos vivos (alcance: 13,6 en Zambia a 47,4 en Pakistán). En conjunto, la mortalidad durante las primeras 24 horas fue de 14,1 por cada 1 000 nacidos vivos (alcance: 5,1 en Zambia a 20,1 en India) y el 46,3% de todas las muertes neonatales se produjo durante las primeras 24 horas (alcance: 36,2% en Pakistán a 65,5% en la República Unida de Tanzanía). La mortalidad en las primeras 6 horas fue de 8,3 por cada 1 000 nacidos vivos, es decir, un 31,9% de mortalidad neonatal.La mortalidad neonatal durante las 24 horas posteriores al nacimiento en zonas principalmente rurales de seis países con ingresos bajos y países con ingresos medios más bajos fue superior a las estimaciones basadas en modelos realizadas para estos países. Algo menos de la mitad de todas las muertes neonatales se produjeron durante las 24 horas posteriores al nacimiento y cerca de un tercio durante las primeras 6 horas de vida. En estos lugares, la implementación de obstetricia eficaz y de alta calidad y la atención a recién nacidos debería ser una prioridad.تقدير معدل وفيات الأطفال حديثي الولادة، وبالأخص في غضون 24قمنا بتحليل البيانات الوبائية لإجمالي 149,570عمومًا، كان معدل وفيات الأطفال حديثي الولادة الذي لوحظ في مواقع الدراسة في ستة بلدان يبلغ 30.5 لكل 1000 من المواليد على قيد الحياة (نطاق القياس: 13.6 في زامبيا إلى 47.4إن معدل الوفيات للأطفال حديثي الولادة في غضون 24旨在评估 6 个中低收入国家的新生儿死亡率、尤其是出生后 24 小时内的死亡率。.我们一共对 149 570 名新出生婴儿的流行病学数据进行了分析，该数据来自于 2007 年至 2013 年对巴基斯坦、印度、加纳、孟加拉国、坦桑尼亚联合共和国及赞比亚主要乡村地区进行的 6 项前瞻性随机试验和一项队列研究。 我们对所有国家的新生儿死亡率以及新生儿出生后 24 小时内的死亡率进行了评估，并对拥有可用数据的 4 个国家的新生儿出生后 6 小时内的死亡率进行了评估。 我们将调查结果与已发布的、基于模型的新生儿死亡率估算结果进行了比较。.总体而言， 6 个国家的研究地的实际新生儿死亡率为每 1000 名新出生婴儿中有 30.5 名死亡（范围： 从赞比亚的 13.6 到巴基斯坦的 47.4）。 新生儿出生后 24 小时内死亡率为每 1000 名新出生婴儿中共有 14.1 名死亡（范围： 从赞比亚的 5.1 到印度的 20.1），且 46.3% 的新生儿死亡案例发生在婴儿出生后 24 小时内（范围： 从巴基斯坦的 36.2% 到坦桑尼亚联合共和国的 65.5%）。 婴儿出生后 6 小时内的死亡率为每 1000 名新出生婴儿中有 8.3 名死亡，即新生儿死亡率为 31.9%。.6 个中低收入国家主要乡村地区的新生儿出生后 24 小时内的死亡率均高于这些国家的基于模型的估算结果。 略低于一半的新生儿死亡案例发生在婴儿出生后 24 小时内，而大约三分之一的案例发生在婴儿出生后 6 小时内。 上述国家应将实施优质、有效的产科护理和早期新生儿护理视为工作重点。.Дать оценку смертности новорожденных, особенно в первые 24 часа жизни, в шести странах с низким уровнем дохода и уровнем дохода ниже среднего.Проведен анализ эпидемиологических данных, полученных в результате рождения 149 570 живых детей в промежутке с 2007 по 2013 год, на основании шести проспективных рандомизированных исследований и одного когортного исследования в преимущественно сельских регионах Бангладеша, Ганы, Замбии, Индии, Объединенной Республики Танзании и Пакистана. Были рассчитаны показатели смертности новорожденных в первые 24 часа для всех стран, а оценка смертности в первые шесть часов была получена для четырех стран с доступными данными. Результаты сравнили с опубликованными показателями смертности новорожденных, рассчитанными на основе моделирования.В целом показатель смертности новорожденных, наблюдаемый в центрах проведения исследования шести стран, составил 30,5 на 1000 рождений живых детей (от 13,6 в Замбии до 47,4 в Пакистане). Смертность в течение первых суток в целом составляла 14,1 на 1000 рождений живых детей (диапазон: от 5,1 в Замбии до 20,1 в Индии) или 46,3% от всех смертей новорожденных (от 36,2% в Пакистане до 65,5% в Объединенной Республике Танзания). Смертность в первые шесть часов составляла 8,3 на 1000 рождений живых детей или 31,9% от всех смертей новорожденных.Смертность новорожденных в первые 24 часа в преимущественно сельских регионах шести стран с низким уровнем дохода и уровнем дохода ниже среднего была выше, чем показатели, рассчитанные на основе моделирования для этих же стран. Чуть менее половины всех смертей новорожденных произошли в течение 24 часов после рождения, и около трети произошли в течение первых шести часов. Поэтому внедрение высококачественной эффективной акушерской помощи и ухода за новорожденными должно стать первостепенной задачей.

Objectives This study evaluates the diagnostic accuracy of Haemoglobin Colour Scale (HCS), compared with clinical diagnosis, to detect anaemia and severe anaemia in preschool-age children attending primary healthcare clinics in rural Zanzibar. Methods In all participants, haemoglobin (Hb) concentration was independently estimated by clinical examination for palmar pallor, HCS and HemoCue™. HemoCue was considered the reference method. Data collection was integrated into the usual health services and performed by local healthcare workers (HCWs). Sensitivity, specificity, positive and negative predictive values were calculated for HCS and clinical examination for palmar pallor. The limits of agreement between HCS and HemoCue, and inter-observer variability for HCS, were also defined. Results A total of 799 children age 2–59 months were recruited to the study. The prevalence of anaemia (Hb 0.1) or specificity (P > 0.1) between HCS and palmar pallor to detect severe anaemia. Conclusions Haemoglobin Colour Scale does not improve the capacity of HCWs to diagnose anaemia in this population. Accuracy is limited by considerable variability in the performances of test operators. However, optimizing the training protocol for those using the test may improve performance. Objectifs: Cette etude evalue la precision diagnostique de l’echelle de couleur de l’hemoglobine (HCS), par rapport au diagnostic clinique, pour detecter l’anemie et l’anemie severe chez les enfants d’âge prescolaire frequentant les cliniques de soins primaires dans les zones rurales de Zanzibar. Methodes: Chez tous les participants, la concentration d’hemoglobine (Hb) a ete estimee de facon independante par un examen clinique de la pâleur palmaire, les methodes HCS et HemoCueTM. HemoCue a ete consideree comme la methode de reference. La collecte des donnees a ete integree dans les services de sante habituels et realisee par les agents de sante locaux. La sensibilite, la specificite, les valeurs predictives positives et negatives ont ete calculees pour HCS et l’examen clinique de la pâleur palmaire. Les limites de concordance entre HCS et HemoCue, et la variabilite inter observateur pour HCS, ont egalement ete definies. Resultats: 799 enfants âges de 2 a 59 mois ont ete recrutes dans l’etude. La prevalence de l’anemie (Hb 0,1) ou de specificite (p > 0,1) entre HCS et la pâleur palmaire pour la detection de l’anemie severe. Conclusions: HCS n’ameliore pas la capacite des agents de la santea diagnostiquer l’anemie dans cette population. La precision est limitee par la variabilite considerable dans les performances des operateurs du test. Cependant, l’optimisant du protocole de formation pour ceux qui utilisent le test pourrait ameliorer les performances. Objetivos: Este estudio evalua la precision diagnostica de la escala de color de la hemoglobina (ECH), comparada con el diagnostico clinico, para la deteccion de anemia y de anemia severa en ninos en edad pre-escolar atendidos en centros de atencion primaria en zonas rurales de Zanzibar. Metodos: En todos los participantes la concentracion de hemoglobina (Hb) se estimaba independientemente mediante el metodo clinico de palidez palmar, ECH y HemoCueTM. Se considero el HemoCue como metodo de referencia. La recolecta de datos se integro en los servicios sanitarios usuales y fue realizada por los trabajadores sanitarios locales. Se calculo la sensibilidad, la especificidad, el valor predictivo positivo y negativo para ECH y el metodo clinico de palidez palmar. Tambien se definieron los limites de concordancia entre ECH y HemoCue, y la variabilidad interobservador para ECH. Resultados: Se reclutaron 799 ninos con edades entre los 2 y 59 meses. La prevalencia de anemia (Hb 0.1) o especificidad (p > 0.1) del ECH y la palidez palmar como metodos para detectar la anemia severa. Conclusiones: La ECH no mejora la capacidad de los trabajadores sanitarios para diagnosticar la anemia en esta poblacion. La precision esta limitada por una variabilidad considerable en el desempeno de quien realiza la prueba. Sin embargo, optimizar los protocolos de entrenamiento de aquellos que utilizan la prueba podria mejorar su desempeno.

Biannual mass drug administration (MDA) with praziquantel and additional interventions to eliminate urogenital schistosomiasis has been implemented on the Zanzibar islands, United Republic of Tanzania, since 2012. We aimed to assess the coverage of school-based treatment (SBT) and community-wide treatment (CWT), to validate the coverage reported by the Zanzibar Ministry of Health (MoH) and to identify reasons for non-compliance. We conducted a post-MDA cross-sectional survey in 93 schools and 92 communities on Pemba and Unguja islands in early 2014, 3–5 months after the last MDA round. Pupils and adults were asked whether they had received and taken the praziquantel treatment provided in the last SBT or CWT, respectively, and the observed and reported coverage were compared. Reasons for non-compliance were recorded in a pretested questionnaire and assessed in qualitative interviews. Urine samples of participants were examined for Schistosoma haematobium eggs with a single urine filtration. Around 8000 pupils and 4000 adults were included in the analysis. Our survey revealed a SBT coverage of 85.2 % in Pemba and of 86.9 % in Unguja, which was in line with MoH reports from Pemba (84.3 %) and higher than reports from Unguja (63.9 %). However, 15 among the 48 schools surveyed in Unguja had not received SBT. Among the interviewed adults, 53.6 % in Pemba and 64.9 % in Unguja had received praziquantel during CWT, which was less than the 59.0 % and 67.7 %, respectively, indicated by MoH reports. Moreover, only 43.8 % and 54.0 % of adults in Pemba and Unguja, respectively, had taken all the tablets as recommended. The main reasons for not receiving or taking praziquantel were absence during CWT, no drug distributor coming, being busy, fear of adverse events, pregnancy, breastfeeding or feeling healthy. To increase coverage and compliance in Zanzibar, SBT should target all schools and mobilization, sensitization and implementation of the CWT need to be improved. To reach elimination of urogenital schistosomiasis transmission in Zanzibar and elsewhere, a very high treatment coverage and compliance at national and local level is key and additional control measures such as snail control and behaviour change interventions will need to be implemented area wide. ISRCTN48837681 .

Background Preventive chemotherapy with albendazole or mebendazole is the current strategy to control soil-transmitted helminth (STH) infections (i.e. Ascaris lumbricoides, hookworm and Trichuris trichiura). STH reinfections, in particular A. lumbricoides and T. trichiura occur rapidly after treatment with the standard drugs. However, their low efficacy against T. trichiura, made an accurate assessment of reinfection patterns impossible. Methods In 2013 a randomised controlled trial was conducted on Pemba Island, Tanzania. School-aged children diagnosed positive for T. trichiura, were randomly allocated to (i) albendazole-ivermectin; (ii) albendazole-mebendazole; (iii) albendazole-oxantel pamoate; or (iv) mebendazole. Here we report the efficacy [cure rates (CR) and egg-reduction rates (ERR)], reinfection rates and new infections determined 18 weeks post-treatment. Results For a total of 405 children complete baseline and follow-up data were available. Similar to the efficacy determined after 3 weeks, 18 weeks after treatment albendazole-oxantel pamoate showed a significantly higher efficacy against T. trichiura (CR: 54.0 %, 95 % CI: 43.7–64.0; ERR: 98.6 %, 95 % CI: 97.8–99.2) compared to the other treatment arms. Children treated with albendazole-oxantel pamoate or albendazole-ivermectin had fewer moderate infections compared to children treated with albendazole. The reinfection rates 18 weeks post-treatment among all treatment arms were 37.2 % for T. trichiura (95 % CI: 28.3–46.8), 34.6 % for A. lumbricoides (95 % CI: 27.3–42.3) and 25.0 % for hookworms (95 % CI: 15.5–36.6). Conclusion The moderate reinfection rates with STHs 18 weeks post-treatment support the concept of regular anthelminthic treatment in highly endemic settings. Combination chemotherapy might achieve decreased morbidity in children since in the albendazole plus oxantel pamoate and albendazole plus ivermectin treatment arms only few moderate T. trichiura infections remained. Further trials should investigate the long term efficacy of albendazole-oxantel pamoate (i.e. 6 and 12 month post-treatment) and after several rounds of treatment in order to develop recommendations for appropriate control approaches for STH infections. Trial registration Current Controlled Trials ISRCTN80245406 Electronic supplementary material The online version of this article (doi:10.1186/s13071-016-1406-8) contains supplementary material, which is available to authorized users.

Summary Background In low-income countries, including the east African region, a third of neonatal deaths are due to infections. A substantial proportion of these have been attributed to sepsis, which can result from umbilical cord infections. Evidence from Asia suggests that chlorhexidine application to the neonatal umbilical cord reduces mortality, but no data from Africa are available. We aimed to assess the effect of umbilical cord cleansing with 4% chlorhexidine solution on neonatal mortality and omphalitis in rural settings of sub-Saharan Africa. Methods We did a community-based randomised controlled trial on Pemba Island, Zanzibar, Tanzania. All eligible babies (aged 1 h to 48 h, without congenital malformations) from hospital-based and community-based deliveries on Pemba Island were enrolled. Participants were randomly assigned to either 4% free chlorhexidine for cord care or to dry cord care using a computer-generated random sequence. For babies allocated to the chlorhexidine group, mothers or caretakers were advised to apply the solution to the cord every day until 3 days after the cord had dropped off. Cord stumps were examined for redness, pus, swelling, and foul odour on day 0, 1, 4, 10, and 28. The primary outcome for this study was mortality until day 28 on an intention-to-treat basis. The trial is registered with ClinicalTrials.gov, number NCT01528852. Findings Between May 19, 2011, and Aug 31, 2014, 36 911 newborn babies were enrolled into the chlorhexidine (n=18 015) and dry cord care study (n=18 896) groups. 17 468 (96·9%) of 18 015 neonates in the chlorhexidine group were available for complete follow-up (28 days) compared with 18 384 (97·3%) of 18 896 neonates in the dry cord care group. Mortality rate in the chlorhexidine group (10·5 deaths per 1000 livebirths) was not significantly lower than that in the dry cord care group (11·7 per 1000 livebirths; relative risk 0·90, 0·74–1·09; p=0·27). Interpretation Our findings do not support the use of chlorhexidine for reduction of neonatal mortality in this east African setting, which might not justify a change in the WHO policy. To inform global policy, a detailed meta-analysis and pooled analysis needs to be undertaken using data from both African and Asian settings. Funding Bill & Melinda Gates Foundation.

Summary Background Commonly used drugs for preventive chemotherapy against soil-transmitted helminths (ie, albendazole and mebendazole) show low efficacy against Trichuris trichiura . Recent studies with oxantel pamoate revealed good cure rates and high egg-reduction rates against T trichiura . We aimed to assess the nature of the dose–response relation to determine the optimum dose. Methods We did a parallel, randomised, placebo-controlled, single-blind trial with oxantel pamoate in school-aged children (aged 6–14 years) infected with T trichiura on Pemba Island, Tanzania. Children were asked to provide two stool samples and children positive for T trichiura were eligible to participate in the trial. Children were excluded if they suffered from any systematic illness. Children were randomly assigned to six different oxantel pamoate doses (5–30 mg/kg) or a placebo. Randomisation was stratified by baseline infection intensity using random block sizes of seven and 14. The primary endpoints were cure rates and egg-reduction rates against T trichiura , both analysed by available case. Drug safety was assessed 2 h and 24 h after treatment. The trial is registered at www.isrctn.com, number ISRCTN86603231. Findings Between Oct 14, and Nov 28, 2014, we enrolled 480 participants and randomly assigned 350 children to the different oxantel pamoate doses or the placebo. 5 mg/kg oxantel pamoate was the minimum effective dose (10 of 46 children cured [cure rate 22%, 95% CI 11–36]; egg-reduction rate 85·0%, 64·5–92·9). An increased probability of being cured and reduced egg counts with escalating doses was recorded. At 25 mg/kg oxantel pamoate 27 of 45 children were cured (cure rate 60%, 95% CI 44–65) with an egg-reduction rate of 97·5% (94·4–98·9), and at 30 mg/kg 27 of 46 children were cured (59%, 43–73) with an egg-reduction rate of 98·8% (96·8–99·6). Oxantel pamoate was well tolerated across all treatment groups; only mild adverse events were reported by the participants 2 h (27 [10%]) and 24 h (12 [4%]) after treatment. Interpretation Our dose-finding study revealed an excellent tolerability profile of oxantel pamoate in children infected with T trichiura . An optimum therapeutic dose range of 15–30 mg/kg oxantel pamoate was defined. With a weight independent dose of 500 mg oxantel pamoate 95% of children aged 7–14 years in sub-Saharan Africa would receive doses of 11·7–32·0 mg/kg. Future research should include studies with oxantel pamoate in younger children and on different continents with the ultimate goal to be able to add oxantel pamoate to soil-transmitted helminth control programmes. Funding Swiss National Science Foundation.

Background Kato-Katz is a widely used method for the diagnosis of soil-transmitted helminth infection. Fecal samples cannot be preserved, and hence, should be processed on the day of collection and examined under a microscope within 60 min of slide preparation. Mini-FLOTAC is a technique that allows examining fixed fecal samples. We assessed the performance of Mini-FLOTAC using formalin-fixed stool samples compared to Kato-Katz and determined the dynamics of prevalence and intensity estimates of soil-transmitted helminth infection over a 31-day time period. Methodology The study was carried out in late 2013 on Pemba Island, Tanzania. Forty-one children were enrolled and stool samples were subjected on the day of collection to a single Kato-Katz thick smear and Mini-FLOTAC examination; 12 aliquots of stool were fixed in 5% formalin and subsequently examined by Mini-FLOTAC up to 31 days after collection. Principal Findings The combined results from Kato-Katz and Mini-FLOTAC revealed that 100% of children were positive for Trichuris trichiura, 85% for Ascaris lumbricoides, and 54% for hookworm. Kato-Katz and Mini-FLOTAC techniques found similar prevalence estimates for A. lumbricoides (85% versus 76%), T. trichiura (98% versus 100%), and hookworm (42% versus 51%). The mean eggs per gram of stool (EPG) according to Kato-Katz and Mini-FLOTAC was 12,075 and 11,679 for A. lumbricoides, 1,074 and 1,592 for T. trichiura, and 255 and 220 for hookworm, respectively. The mean EPG from day 1 to 31 of fixation was stable for A. lumbricoides and T. trichiura, but gradually declined for hookworm, starting at day 15. Conclusions/Significance The findings of our study suggest that for a qualitative diagnosis of soil-transmitted helminth infection, stool samples can be fixed in 5% formalin for at least 30 days. However, for an accurate quantitative diagnosis of hookworm, we suggest a limit of 15 days of preservation. Our results have direct implication for integrating soil-transmitted helminthiasis into transmission assessment surveys for lymphatic filariasis., Author Summary Soil-transmitted helminths are parasitic worms (hookworm, roundworm, and whipworm) that affect hundreds of millions of people. Kato-Katz is the most widely used technique for the diagnosis of soil-transmitted helminth infection. It requires the collection, processing, and microscopic examination of stool samples within the same day. In remote areas, laboratories are often far away from where stool samples are being collected, which makes it difficult to examine the samples on the same day. Mini-FLOTAC is an alternative to Kato-Katz technique that allows analysis of fixed stool samples several days after collection. We assessed the accuracy of the Mini-FLOTAC with fixed stool samples. The study was carried out in late 2013 on Pemba Island and 41 children participated. Fresh stool samples were first examined by Kato-Katz and then fixed in formalin and examined by Mini-FLOTAC (12 examinations within one month). We found that for a qualitative diagnosis (presence or absence of infection) stool samples can be fixed for 31 days. However, for an accurate quantitative diagnosis of hookworm eggs, stool samples should not be stored for more than 15 days, as egg counts decline. Our results have implications for integrating soil-transmitted helminth surveys with other neglected tropical diseases.

Summary Background Existing anthelmintic drugs (eg, albendazole and mebendazole) have low efficacy against the intestinal nematode species Trichuris trichiura and the drug pipeline is exhausted. We aimed to investigate the strategy of combination chemotherapy with existing drugs to establish whether their efficacy could be enhanced and broadened. Methods In this randomised controlled trial, we compared three drug combinations and one standard drug alone in children aged 6–14 years in two schools on Pemba Island, Tanzania infected with T trichiura and concomitant intestinal nematodes. We assigned children, via a randomisation list with block sizes of either four or eight, to orally receive albendazole (400 mg) plus ivermectin (200 μg/kg); albendazole (400 mg) plus mebendazole (500 mg); albendazole (400 mg) plus oxantel pamoate (20 mg/kg); or mebendazole (500 mg) alone. The primary endpoints were the proportion of children cured of T trichiura infection and the reduction of T trichiura eggs in stool based on geometric means, both analysed by available case. This study is registered with ISRCTN, number ISRCTN80245406. Findings We randomly assigned 440 eligible children infected with T trichiura between Sept 2, and Oct 18, 2013, to one of the four treatment groups (110 children per group). Data for 431 children were included in the analysis for the primary endpoints. Albendazole plus oxantel pamoate (74 of 108 children cured [68·5%, 95% CI 59·6–77·4]; egg reduction 99·2%, 98·7–99·6) and albendazole plus ivermectin (30 of 109 cured [27·5%, 19·0–36·0]; egg reduction 94·5%, 91·7–96·3) were significantly more effective against T trichiura than mebendazole alone (nine of 107 cured [8·4%, 3·1–13·8]; egg reduction 58·5%, 45·2–70·9). Albendazole plus mebendazole had similar low efficacy (nine of 107 cured [8·4%, 3·1–13·8; egg reduction 51·6%, 35·0–65·3) to mebendazole alone. About a fifth of the children reported adverse events, which were mainly mild. Abdominal cramps and headache were the most common adverse events after treatment; abdominal cramps were reported by 13 (12·0%) children for albendazole plus ivermectin, 10 (9·3%) for albendazole plus mebendazole, 20 (18·2%) for albendazole plus oxantel pamoate, and 16 (14·5%) for mebendazole; headaches were reported by 5 (4·6%) children for albendazole plus ivermectin, 6 (5·6%) for albendazole plus mebendazole, 12 (10·9%) for albendazole plus oxantel pamoate, and 7 (6·4%) for mebendazole. Interpretation Our head-to-head comparison of three combination chemotherapies showed the highest efficacy for albendazole plus oxantel pamoate for the treatment of infection with T trichiura . Further studies should investigate the combination of albendazole plus oxantel pamoate so that it can be considered for soil-transmitted helminthiasis control programmes. Funding Medicor Foundation and Swiss National Science Foundation.

Background An accurate diagnosis of soil-transmitted helminthiasis is important for individual patient management, for drug efficacy evaluation and for monitoring control programmes. The Kato-Katz technique is the most widely used method detecting soil-transmitted helminth eggs in faecal samples. However, detailed analyses of quality control, including false-positive and faecal egg count (FEC) estimates, have received little attention. Methods Over a 3-year period, within the frame of a series of randomised controlled trials conducted in Pemba, United Republic of Tanzania, 10% of randomly selected Kato-Katz thick smears were re-read for Trichuris trichiura and Ascaris lumbricoides eggs. In case of discordant result (i.e. positive versus negative) the slides were re-examined a third time. A result was assumed to be false-positive or false-negative if the result from the initial reading did not agree with the quality control as well as the third reading. We also evaluated the general agreement in FECs between the first and second reading, according to internal and World Health Organization (WHO) guidelines. Results From the 1,445 Kato-Katz thick smears subjected to quality control, 1,181 (81.7%) were positive for T. trichiura and 290 (20.1%) were positive for A. lumbricoides. During quality control, very low rates of false-positive results were observed; 0.35% (n = 5) for T. trichiura and 0.28% (n = 4) for A. lumbricoides. False-negative readings of Kato-Katz thick smears were obtained in 28 (1.94%) and 6 (0.42%) instances for T. trichiura and A. lumbricoides, respectively. A high frequency of discordant results in FECs was observed (i.e. 10.0-23.9% for T. trichiura, and 9.0-11.4% for A. lumbricoides). Conclusions Our analyses show that the rate of false-positive diagnoses of soil-transmitted helminths is low. As the probability of false-positive results increases after examination of multiple stool samples from a single individual, the potential influence of false-positive results on epidemiological studies and anthelminthic drug efficacy studies should be determined. Existing WHO guidelines for quality control might be overambitious and might have to be revised, specifically with regard to handling disagreements in FECs.

Background Gaining and sustaining control of schistosomiasis and, whenever feasible, achieving local elimination are the year 2020 targets set by the World Health Organization. In Zanzibar, various institutions and stakeholders have joined forces to eliminate urogenital schistosomiasis within 5 years. We report baseline findings before the onset of a randomized intervention trial designed to assess the differential impact of community-based praziquantel administration, snail control, and behavior change interventions. Methodology In early 2012, a baseline parasitological survey was conducted in ∼20,000 people from 90 communities in Unguja and Pemba. Risk factors for schistosomiasis were assessed by administering a questionnaire to adults. In selected communities, local knowledge about schistosomiasis transmission and prevention was determined in focus group discussions and in-depths interviews. Intermediate host snails were collected and examined for shedding of cercariae. Principal Findings The baseline Schistosoma haematobium prevalence in school children and adults was 4.3% (range: 0–19.7%) and 2.7% (range: 0–26.5%) in Unguja, and 8.9% (range: 0–31.8%) and 5.5% (range: 0–23.4%) in Pemba, respectively. Heavy infections were detected in 15.1% and 35.6% of the positive school children in Unguja and Pemba, respectively. Males were at higher risk than females (odds ratio (OR): 1.45; 95% confidence interval (CI): 1.03–2.03). Decreasing adult age (OR: 1.04; CI: 1.02–1.06), being born in Pemba (OR: 1.48; CI: 1.02–2.13) or Tanzania (OR: 2.36; CI: 1.16–4.78), and use of freshwater (OR: 2.15; CI: 1.53–3.03) showed higher odds of infection. Community knowledge about schistosomiasis was low. Only few infected Bulinus snails were found. Conclusions/Significance The relatively low S. haematobium prevalence in Zanzibar is a promising starting point for elimination. However, there is a need to improve community knowledge about disease transmission and prevention. Control measures tailored to the local context, placing particular attention to hot-spot areas, high-risk groups, and individuals, will be necessary if elimination is to be achieved., Author Summary Schistosomiasis is a chronic and debilitating disease caused by parasitic worms. It negatively impacts on the health and wellbeing of mainly rural dwellers in tropical and sub-tropical countries. The World Health Organization recently put forward an ambitious goal for the year 2020: to control schistosomiasis globally. Interruption of transmission and elimination of schistosomiasis are encouraged whenever resources allow. After careful consideration, the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) selected the Zanzibar archipelago to learn how best to eliminate schistosomiasis. We report the baseline findings of a 5-year program. Parasitological examination of about 20,000 people on Unguja and Pemba islands revealed a low overall prevalence of Schistosoma haematobium (7%). Nevertheless, hot-spots with high prevalence (>20%) and high-risk groups (males, young adults, people born in Pemba or mainland Tanzania, and people using natural freshwater) were identified. The community knowledge about schistosomiasis transmission and prevention was poor. Few of the collected intermediate host snails shed S. haematobium cercariae. A multi-arm randomized trial is now being implemented to determine the differential impact of mass deworming, snail control, and behavior change interventions. Lessons learned from this schistosomiasis elimination program will be important for other settings.

Background The diagnostic accuracy of three faecal egg count techniques (Kato-Katz, McMaster and FLOTAC) to assess albendazole efficacy against soil-transmitted helminth (STH) infections was compared. Methods The study is registered with Current Controlled Trials [identifier: ISRCTN90088840]. During September-November 2009, 304 school-aged children on Pemba Island, Tanzania, were screened and those infected with Ascaris lumbricoides, hookworm or Trichuris trichiura were treated with a single dose of albendazole (400 mg). Twenty-one days post-treatment, children provided a single stool sample which was examined using the same diagnostic methods. All stool samples were divided into two aliquots and one was fixed in 5% formalin and examined using FLOTAC and McMaster approximately 6 months after collection. Results Using fresh stool samples, comparable prevalences were demonstrated for the three methods at baseline (90-92.2% for T. trichiura, 41.1-52.8% for hookworm, 32.9-37.2% for A. lumbricoides); FLOTAC was the most sensitive method at baseline and follow-up. Albendazole showed high cure rate (CR) against A.lumbricoides (90-97%), moderate CR against hookworm (63-72%) and very low CR against T.trichiura (6-9%), regardless of the technique used. Egg counts (eggs per gram) at baseline were similar for A. lumbricoides and for hookworm among the three methods, and higher using McMaster and Kato-Katz compared with FLOTAC for T. trichiura. All methods were similar for hookworm and A. lumbricoides egg reduction rate (ERR) estimation, but Kato-Katz indicated a significantly higher ERR than McMaster and FLOTAC for T. trichiura. Preserved stool samples revealed consistently lower FECs at baseline and follow-up for all STHs. Conclusion Further development and validation of standard protocols for anthelminthic drug efficacy evaluation must be pursued

Background Pathogenic intestinal protozoa infections are common in school-aged children in the developing world and they are frequently associated with malabsorption syndromes and gastrointestinal morbidity. Since diagnosis of these parasites is difficult, prevalence data on intestinal protozoa is scarce. Methods We collected two stool samples from school-aged children on Pemba Island, Tanzania, as part of a randomized controlled trial before and 3 weeks after treatment with (i) single-dose albendazole (400 mg); (ii) single-dose nitazoxanide (1,000 mg); (iii) nitazoxanide-albendazole combination (1,000 mg–400 mg), with each drug given separately on two consecutive days; and (iv) placebo. Formalin-fixed stool samples were examined for the presence of intestinal protozoa using an ether-concentration method to determine the prevalence and estimate cure rates (CRs). Results Almost half (48.7%) of the children were diagnosed with at least one of the (potentially) pathogenic protozoa Giardia intestinalis, Entamoeba histolytica/E. dispar and Blastocystis hominis. Observed CRs were high for all treatment arms, including placebo. Nitazoxanide showed a significant effect compared to placebo against the non-pathogenic protozoon Entamoeba coli. Conclusions Intestinal protozoa infections might be of substantial health relevance even in settings where they are not considered as a health problem. Examination of a single stool sample with the ether-concentration method lacks sensitivity for the diagnosis of intestinal protozoa, and hence, care is indicated when interpreting prevalence estimates and treatment effects.

Background Schistosomiasis is a parasitic infection that continues to be a major public health problem in many developing countries being responsible for an estimated burden of at least 1.4 million disability-adjusted life years (DALYs) in Africa alone. Importantly, morbidity due to schistosomiasis has been greatly reduced in some parts of the world, including Zanzibar. The Zanzibar government is now committed to eliminate urogenital schistosomiasis. Over the next 3–5 years, the whole at-risk population will be administered praziquantel (40 mg/kg) biannually. Additionally, snail control and behaviour change interventions will be implemented in selected communities and the outcomes and impact measured in a randomized intervention trial. Methods/Design In this 5-year research study, on both Unguja and Pemba islands, urogenital schistosomiasis will be assessed in 45 communities with urine filtration and reagent strips in 4,500 schoolchildren aged 9–12 years annually, and in 4,500 first-year schoolchildren and 2,250 adults in years 1 and 5. Additionally, from first-year schoolchildren, a finger-prick blood sample will be collected and examined for Schistosoma haematobium infection biomarkers. Changes in prevalence and infection intensity will be assessed annually. Among the 45 communities, 15 were randomized for biannual snail control with niclosamide, in concordance with preventive chemotherapy campaigns. The reduction of Bulinus globosus snail populations and S. haematobium-infected snails will be investigated. In 15 other communities, interventions triggering behaviour change have been designed and will be implemented in collaboration with the community. A change in knowledge, attitudes and practices will be assessed annually through focus group discussions and in-depth interviews with schoolchildren, teachers, parents and community leaders. In all 45 communities, changes in the health system, water and sanitation infrastructure will be annually tracked by standardized questionnaire-interviews with community leaders. Additional issues potentially impacting on study outcomes and all incurring costs will be recordedand monitored longitudinally. Discussion Elimination of schistosomiasis has become a priority on the agenda of the Zanzibar government and the international community. Our study will contribute to identifying what, in addition to preventive chemotherapy, needs to be done to prevent, control, and ultimately eliminate schistosomiasis, and to draw lessons for current and future schistosomiasis elimination programmes in Africa and elsewhere. Trial registration ISRCTN48837681

Background Entering data on case report forms and subsequently digitizing them in electronic media is the traditional way to maintain a record keeping system in field studies. Direct data entry using an electronic device avoids this two-step process. It is gaining in popularity and has replaced the paper-based data entry system in many studies. We report our experiences with paper- and PDA-based data collection during a fever surveillance study in Pemba Island, Zanzibar, Tanzania. Methods Data were collected on a 14-page case report paper form in the first period of the study. The case report paper forms were then replaced with handheld computers (personal digital assistants or PDAs). The PDAs were used for screening and clinical data collection, including a rapid assessment of patient eligibility, real time errors, and inconsistency checking. Results A comparison of paper-based data collection with PDA data collection showed that direct data entry via PDA was faster and 25% cheaper. Data was more accurate (7% versus 1% erroneous data) and omission did not occur with electronic data collection. Delayed data turnaround times and late error detections in the paper-based system which made error corrections difficult were avoided using electronic data collection. Conclusions Electronic data collection offers direct data entry at the initial point of contact. It has numerous advantages and has the potential to replace paper-based data collection in the field. The availability of information and communication technologies for direct data transfer has the potential to improve the conduct of public health research in resource-poor settings.

Background The Kato-Katz thick smear (Kato-Katz) is the diagnostic method recommended for monitoring large-scale treatment programs implemented for the control of soil-transmitted helminths (STH) in public health, yet it is difficult to standardize. A promising alternative is the McMaster egg counting method (McMaster), commonly used in veterinary parasitology, but rarely so for the detection of STH in human stool. Methodology/Principal Findings The Kato-Katz and McMaster methods were compared for the detection of STH in 1,543 subjects resident in five countries across Africa, Asia and South America. The consistency of the performance of both methods in different trials, the validity of the fixed multiplication factor employed in the Kato-Katz method and the accuracy of these methods for estimating ‘true’ drug efficacies were assessed. The Kato-Katz method detected significantly more Ascaris lumbricoides infections (88.1% vs. 75.6%, p0.32) in FEC between both methods, and indicated no significant difference in FEC, except for A. lumbricoides, where the Kato-Katz resulted in significantly higher FEC (14,197 eggs per gram of stool (EPG) vs. 5,982 EPG). For the Kato-Katz, the fixed multiplication factor resulted in significantly higher FEC than the multiplication factor adjusted for mass of feces examined for A. lumbricoides (16,538 EPG vs. 15,396 EPG) and T. trichiura (1,490 EPG vs. 1,363 EPG), but not for hookworm. The McMaster provided more accurate efficacy results (absolute difference to ‘true’ drug efficacy: 1.7% vs. 4.5%). Conclusions/Significance The McMaster is an alternative method for monitoring large-scale treatment programs. It is a robust (accurate multiplication factor) and accurate (reliable efficacy results) method, which can be easily standardized., Author Summary Currently, in public health, the reduction in the number of eggs excreted in stools after drug administration is used to monitor the efficacy of drugs against parasitic worms. Yet, studies comparing diagnostic methods for the enumeration of eggs in stool are few. We compared the Kato-Katz thick smear (Kato-Katz) and McMaster egg counting (McMaster) methods, which are commonly used diagnostic methods in public and animal health, respectively, for the diagnosis and enumeration of eggs of roundworms, whipworms and hookworms in 1,536 stool samples from children in five trials across Africa, Asia and South America. The Kato-Katz method was the most sensitive for the detection of roundworms, but there was no significant difference in sensitivity between the methods for hookworms and whipworms. The sensitivity of the methods differed across the trials and magnitude of egg counts. The Kato-Katz method resulted in significantly higher egg counts, but these were subject to lack of accuracy caused by intrinsic properties of this method. McMaster provided more reliable estimates of drug efficacies. We conclude that the McMaster is an alternative method for monitoring large-scale treatment programs. It allows accurate monitoring of drug efficacy and can be easily performed under field conditions.

Background Typhoid fever remains a significant health problem in many developing countries. A rapid test with a performance comparable to that of blood culture would be highly useful. A rapid diagnostic test for typhoid fever, Tubex®, is commercially available that uses particle separation to detect immunoglobulin M directed towards Salmonella Typhi O9 lipopolysaccharide in sera. Methods We assessed the sensitivity and specificity of the Tubex test among Tanzanian children hospitalized with febrile illness using blood culture as gold standard. Evaluation was done considering blood culture confirmed S. Typhi with non-typhi salmonella (NTS) and non - salmonella isolates as controls as well as with non-salmonella isolates only. Results Of 139 samples tested with Tubex, 33 were positive for S. Typhi in blood culture, 49 were culture-confirmed NTS infections, and 57 were other non-salmonella infections. Thirteen hemolyzed samples were excluded. Using all non - S. Typhi isolates as controls, we showed a sensitivity of 79% and a specificity of 89%. When the analysis was repeated excluding NTS from the pool of controls we showed a sensitivity of 79% and a specificity of 97%. There was no significant difference in the test performance using the two different control groups (p > 0.05). Conclusion This first evaluation of the Tubex test in an African setting showed a similar performance to those seen in some Asian settings. Comparison with the earlier results of a Widal test using the same samples showed no significant difference (p > 0.05) for any of the performance indicators, irrespective of the applied control group.

Background The diagnosis of typhoid fever is confirmed by culture of Salmonella enterica serotype Typhi (S. typhi). However, a more rapid, simpler, and cheaper diagnostic method would be very useful especially in developing countries. The Widal test is widely used in Africa but little information exists about its reliability. Methods We assessed the performance of the Widal tube agglutination test among febrile hospitalized Tanzanian children. We calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of various anti-TH and -TO titers using culture-confirmed typhoid fever cases as the "true positives" and all other febrile children with blood culture negative for S. typhi as the "true negatives." Results We found that 16 (1%) of 1,680 children had culture-proven typhoid fever. A single anti-TH titer of 1:80 and higher was the optimal indicator of typhoid fever. This had a sensitivity of 75%, specificity of 98%, NPV of 100%, but PPV was only 26%. We compared our main findings with those from previous studies. Conclusion Among febrile hospitalized Tanzanian children with a low prevalence of typhoid fever, a Widal titer of ≥ 1:80 performed well in terms of sensitivity, specificity, and NPV. However a test with improved PPV that is similarly easy to apply and cost-efficient is desirable.

We have previously shown a reduction in anaemia and wasting malnutrition in infants, Author Summary Infants and very young children commonly become infected with intestinal nematode infections. However, the worm burdens are generally very light, so a beneficial effect of deworming on wasting malnutrition and anaemia in this age group which we have demonstrated was unexpected and the mechanism unclear. To investigate this, we have, for the first time, determined whether such worm infections in infants induce significant immune reactions which might be detrimental to nutrition and growth e.g. by inducing inflammation in the gut or by cytokine effects on erythropoiesis. We also determined if such responses are modulated by regular deworming over a 9 month period. Peripheral blood cells from infants infected with Ascaris and hookworms in particular responded to stimulation with worm antigens, producing predominantly Th2 cytokines. Although the Th2 cytokine responses in the periphery were not significantly altered by deworming, the levels of eosinophils, which are regulated by the Th2 cytokine, IL-5, were lower after treatment. It is possible that eosinophils play a role in gut pathology leading to wasting malnutrition and anaemia in the very young and that this effect is reduced by deworming.