Identifying research questions for HIV, tuberculosis, tuberculosis-HIV, malaria, and neglected tropical diseases through the World Health Organization guideline development process: a retrospective analysis, 2008-2018.

OBJECTIVES: World Health Organization (WHO) guidelines for health programmes and healthcare delivery are the foundation of its technical leadership in public health and essential to decision-making globally. A key function of guideline development is to identify areas in which further evidence is needed because filling these gaps will lead to future improvements in population health. The objective of this study was to examine the knowledge gaps and research questions for addressing those gaps generated through the WHO guideline development process, with the goal of informing future strategies for improving and strengthening the guideline development process. STUDY DESIGN: We did a systematic, retrospective analysis of research questions identified in the published guidelines. METHODS: We analyzed guidelines published between January 1, 2008, and December 31, 2018, by the Communicable Diseases Cluster in five disease areas: tuberculosis (TB), HIV, malaria, TB-HIV, and neglected tropical diseases (NTDs). Research questions were extracted independently by two researchers. We analyzed the distribution of research questions by disease and by topic category and did a qualitative assessment of optimum practice for research question generation during the guideline development process. RESULTS: A total of 48 guidelines were included: 26 on HIV, 1 on malaria, 11 on TB, 5 on TB/HIV, and 5 on NTDs. Overall, 36 (75%) guidelines encompassed a total of 360 explicit research questions; the remainder did not contain specific research questions. The number of research questions that focused on TB was 49, TB/HIV was 38, HIV was 250, and NTDs was 23. The number of research questions that focused on diagnosis was 43 (11.9%) of 360, prevention was 62 (17.2%), treatment was 103 (28.6%), good practice was 12 (3.3%), service delivery was 86 (23.8%), and other areas was 54 (15%). Research questions were often not formulated in a specific or actionable way and were hard to identify in the guideline. Examples of good practice identified by the review team involved the generation of specific and narrowly defined research questions, with accompanying recommendations for appropriate study design. CONCLUSIONS: The WHO must strengthen its approach to identifying and presenting research questions during the guideline development process. Ensuring access to research questions is a key next step in adding value to the guideline development process.

Preventive chemotherapy in human helminthiasis: theoretical and operational aspects.

Preventive chemotherapy (PC), the large-scale distribution of anthelminthic drugs to population groups at risk, is the core intervention recommended by the WHO for reducing morbidity and transmission of the four main helminth infections, namely lymphatic filariasis, onchocerciasis, schistosomiasis and soil-transmitted helminthiasis. The strategy is widely implemented worldwide but its general theoretical foundations have not been described so far in a comprehensive and cohesive manner. Starting from the information available on the biological and epidemiological characteristics of helminth infections, as well as from the experience generated by disease control and elimination interventions across the world, we extrapolate the fundamentals and synthesise the principles that regulate PC and justify its implementation as a sound and essential public health intervention. The outline of the theoretical aspects of PC contributes to a thorough understanding of the different facets of this strategy and helps comprehend opportunities and limits of control and elimination interventions directed against helminth infections.

Population genetics of Schistosoma haematobium: development of novel microsatellite markers and their application to schistosomiasis control in Mali.

The recent implementation of mass drug administration (MDA) for control of uro-genital schistosomiasis has identified an urgent need for molecular markers to both directly monitor the impact of MDA, for example to distinguish re-infections from uncleared infections, as well as understand aspects of parasite reproduction and gene flow which might predict evolutionary change, such as the development and spread of drug resistance. We report the development of a novel microsatellite tool-kit allowing, for the first time, robust genetic analysis of individual S. haematobium larvae collected directly from infected human hosts. We genotyped the parasite populations of 47 children from 2 schools in the Ségou region of Mali, the first microsatellite study of this highly neglected parasite. There was only limited evidence of population subdivision between individual children or between the two schools, suggesting that few barriers to gene flow exist in this population. Complex relationships between parasite reproductive success, infection intensity and host age and gender were identified. Older children and boys harboured more diverse infections, as measured by the number of unique adult genotypes present. Individual parasite genotypes had variable reproductive success both across hosts, a pre-requisite for evolutionary selection, and, phenotypically, in hosts of different ages and genders. These data serve as a baseline against which to measure the effect of treatment on parasite population genetics in this region of Mali, and the tools developed are suitable to further investigate this important pathogen, and its close relatives, throughout their range.

Moderate and high endemicity of schistosomiasis is a predictor of the endemicity of soil-transmitted helminthiasis: a systematic review.

The authors conducted a systematic literature review with the following aims: to investigate how frequently soil-transmitted helminthiasis (STH) infections are endemic where schistosomiasis is present; and to assess the correlation between the risk level of schistosomiasis and that of STH. Among 155 sites on which data were collected and analyzed, schistosomiasis was present in 130, all of which were also co-endemic for STH, whereas 25 sites were endemic only for STH. Ninety percent (117 out of 130) of the areas eligible for preventive chemotherapy (PC) against schistosomiasis are also eligible for PC against STH. This fact provides managers of control programmes with the operationally important indication that use of available information on endemicity of schistosomiasis is a valid tool to predict the presence of STH in the same geographical area and to estimate the need of PC for STH. The implementation of this tool is expected to save financial and human resources and help accelerate the scale-up of PC throughout the world.

Estimation of the cost of large-scale school deworming programmes with benzimidazoles.

This study estimates the cost of distributing benzimidazole tablets in the context of school deworming programmes: we analysed studies reporting the cost of school deworming from seven countries in four WHO regions. The estimated cost for drug procurement to cover one million children (including customs clearance and international transport) is approximately US$20000. The estimated financial costs (including the cost of training of personnel, drug transport, social mobilization and monitoring) is, on average, equivalent to US$33000 per million school-age children with minimal variation in different countries and continents. The estimated economic costs of distribution (including the time spent by teachers, and health personnel at central, provincial and district level) to cover one million children approximately corresponds to US$19000. This study shows the minimal cost of school deworming activities, but also shows the significant contribution (corresponding to a quarter of the entire cost of the programme) provided by health and education systems in endemic countries even in the case of drug donations and donor support of distribution costs.

The Schistosomiasis Control Initiative (SCI): rationale, development and implementation from 2002-2008.

Schistosomiasis remains one of the most prevalent parasitic diseases in developing countries. After malaria, schistosomiasis is the most important tropical disease in terms of human morbidity with significant economic and public health consequences. Although schistosomiasis has recently attracted increased focus and funding for control, it has been estimated that less than 20% of the funding needed to control the disease in Africa is currently available. In this article the following issues are discussed: the rationale, development and objectives of the Schistosomiasis Control Initiative (SCI)-supported programmes; the management approaches followed to achieve implementation by each country; mapping, monitoring and evaluation activities with quantifiable impact of control programmes; monitoring for any potential drug resistance; and finally exit strategies within each country. The results have demonstrated that morbidity due to schistosomiasis has been reduced by the control programmes. While challenges remain, the case for the control of schistosomiasis has been strengthened by research by SCI teams and the principle that a national programme using 'preventive chemotherapy' can be successfully implemented in sub-Saharan Africa, whenever the resources are available. SCI and partners are now actively striving to raise further funds to expand the coverage of integrated control of neglected tropical diseases (NTDs) in sub-Saharan Africa.

Soil-transmitted helminths and haemoglobin status among Afghan children in World Food Programme assisted schools.

In recent years there have been major socio-economic changes within Afghanistan such that the present public health burden of soil-transmitted helminths (STH), especially that within school-aged children, remains to be determined. A baseline parasitological survey was therefore carried out in four defined areas of Afghanistan to better assess the distribution, prevalence and intensity of STH infections prior to a nationwide de-worming campaign beginning within World Food Programme assisted schools. A cross-sectional examination of 1001 children aged between 8 and 15 years old revealed that approximately half (47.2%) were infected with at least one STH. Infections with Ascaris lumbricoides were most widespread (40.9%) and elevated prevalences were detected in urban environments; for example, schoolchildren in Kabul were more likely to be infected (OR=2.2, 95% CI 1.6-3.0) than elsewhere and these infections were often of higher intensity (OR=7.6, 95% CI 4.9-11.8). Trichuris trichiura (9.9%) and hookworms (0.7%), previously unknown from Afghanistan, were encountered. The blood haemoglobin concentration of surveyed children was also assessed: 4% resulted to be anaemic (Hb<11 g dl(-1)), and 0.4% to be severely anaemic (Hb<7 g dl(-1)).