A general framework to support cost-efficient fecal egg count methods and study design choices for large-scale STH deworming programs-monitoring of therapeutic drug efficacy as a case study.

BACKGROUND: Soil-transmitted helminth (STH) control programs currently lack evidence-based recommendations for cost-efficient survey designs for monitoring and evaluation. Here, we present a framework to provide evidence-based recommendations, using a case study of therapeutic drug efficacy monitoring based on the examination of helminth eggs in stool. METHODS: We performed an in-depth analysis of the operational costs to process one stool sample for three diagnostic methods (Kato-Katz, Mini-FLOTAC and FECPAKG2). Next, we performed simulations to determine the probability of detecting a truly reduced therapeutic efficacy for different scenarios of STH species (Ascaris lumbricoides, Trichuris trichiura and hookworms), pre-treatment infection levels, survey design (screen and select (SS); screen, select and retest (SSR) and no selection (NS)) and number of subjects enrolled (100-5,000). Finally, we integrated the outcome of the cost assessment into the simulation study to estimate the total survey costs and determined the most cost-efficient survey design. PRINCIPAL FINDINGS: Kato-Katz allowed for both the highest sample throughput and the lowest cost per test, while FECPAKG2 required both the most laboratory time and was the most expensive. Counting of eggs accounted for 23% (FECPAKG2) or ≥80% (Kato-Katz and Mini-FLOTAC) of the total time-to-result. NS survey designs in combination with Kato-Katz were the most cost-efficient to assess therapeutic drug efficacy in all scenarios of STH species and endemicity. CONCLUSIONS/SIGNIFICANCE: We confirm that Kato-Katz is the fecal egg counting method of choice for monitoring therapeutic drug efficacy, but that the survey design currently recommended by WHO (SS) should be updated. Our generic framework, which captures laboratory time and material costs, can be used to further support cost-efficient choices for other important surveys informing STH control programs. In addition, it can be used to explore the value of alternative diagnostic techniques, like automated egg counting, which may further reduce operational costs. TRIAL REGISTRATION: ClinicalTrials.gov NCT03465488.

A descriptive qualitative case study of the experiences, perceptions and attitudes of pregnant women on Unguja island, Zanzibar, towards antischistosomal treatment.

Many countries exclude pregnant and lactating women from mass drug administration (MDA) programmes with praziquantel against schistosomiasis due to historic safety concerns over drug use during gestation and breast feeding. More than 10 years of empirical evidence from the field and a growing body of dedicated research has prompted the World Health Organisation and schistosomiasis control initiatives to advocate the inclusion of this vulnerable group into MDA. This qualitative descriptive case study explored, over a five-week period, the subjective experiences, perceptions, opinions, and attitudes of pregnant women attending government supported clinics on Unguja island, United Republic of Tanzania, towards praziquantel use during pregnancy in MDA programmes. The aim of the study was to identify and determine how to overcome potential barriers to effective use of MDA medications during pregnancy. Additionally, it was to determine trusted communication channels for future messaging and discover behavioural and community opportunities to increase participation of pregnant women in future MDA efforts. A 60 min, semi-structured qualitative interview was undertaken with 25 pregnant women recruited from 4 health centres on Unguja along with testing for Schistosoma haematobium infection. Using a modified-grounded theory approach, narrative data were transcribed, coded and analysed using a thematic analysis of the emergent themes. Women reported that they rely on traditional home remedies to stay healthy during pregnancy. Influenced by their mothers, husbands and neighbours, women predominately made medication choices during pregnancy and breastfeeding based on what they heard at home. Most women had been excluded from government MDA programmes in the past due to pregnancy. Women valued healthcare services for antenatal education and pregnancy advice. Women reported they would trust and follow direction from healthcare providers about taking praziquantel during pregnancy. Antenatal clinics offer an excellent opportunity to educate and expand praziquantel treatment to this cohort. Efforts should be augmented with training for providers and behavioural education for the community as a whole and family members of pregnant women.

Evaluation of integrated interventions layered on mass drug administration for urogenital schistosomiasis elimination: a cluster-randomised trial.

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.

Interrupting seasonal transmission of Schistosoma haematobium and control of soil-transmitted helminthiasis in northern and central Côte d'Ivoire: a SCORE study protocol.

BACKGROUND: To achieve a world free of schistosomiasis, the objective is to scale up control and elimination efforts in all endemic countries. Where interruption of transmission is considered feasible, countries are encouraged to implement a comprehensive intervention package, including preventive chemotherapy, information, education and communication (IEC), water, sanitation and hygiene (WASH), and snail control. In northern and central Côte d'Ivoire, transmission of Schistosoma haematobium is seasonal and elimination might be achieved. In a cluster-randomised trial, we will assess different treatment schemes to interrupt S. haematobium transmission and control soil-transmitted helminthiasis over a 3-year period. We will compare the impact of (i) arm A: annual mass drug administration (MDA) with praziquantel and albendazole before the peak schistosomiasis transmission season; (ii) arm B: annual MDA after the peak schistosomiasis transmission season; (iii) arm C: two yearly treatments before and after peak schistosomiasis transmission; and (iv) arm D: annual MDA before peak schistosomiasis transmission, coupled with chemical snail control using niclosamide. METHODS/DESIGN: The prevalence and intensity of S. haematobium and soil-transmitted helminth infections will be assessed using urine filtration and Kato-Katz thick smears, respectively, in six administrative regions in northern and central parts of Côte d'Ivoire. Once a year, urine and stool samples will be collected and examined from 50 children aged 5-8 years, 100 children aged 9-12 years and 50 adults aged 20-55 years in each of 60 selected villages. Changes in S. haematobium and soil-transmitted helminth prevalence and intensity will be assessed between years and stratified by intervention arm. In the 15 villages randomly assigned to intervention arm D, intermediate host snails will be collected three times per year, before niclosamide is applied to the selected freshwater bodies. The snail abundance and infection rates over time will allow drawing inference on the force of transmission. DISCUSSION: This cluster-randomised intervention trial will elucidate whether in an area with seasonal transmission, the four different treatment schemes can interrupt S. haematobium transmission and control soil-transmitted helminthiasis. Lessons learned will help to guide schistosomiasis control and elimination programmes elsewhere in Africa. TRIAL REGISTRATION: ISRCTN ISRCTN10926858 . Registered 21 December 2016. Retrospectively registered.

Study and implementation of urogenital schistosomiasis elimination in Zanzibar (Unguja and Pemba islands) using an integrated multidisciplinary approach.

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.