Accelerating Progress Towards the 2030 Neglected Tropical Diseases Targets: How Can Quantitative Modeling Support Programmatic Decisions?

Over the past decade, considerable progress has been made in the control, elimination, and eradication of neglected tropical diseases (NTDs). Despite these advances, most NTD programs have recently experienced important setbacks; for example, NTD interventions were some of the most frequently and severely impacted by service disruptions due to the coronavirus disease 2019 (COVID-19) pandemic. Mathematical modeling can help inform selection of interventions to meet the targets set out in the NTD road map 2021-2030, and such studies should prioritize questions that are relevant for decision-makers, especially those designing, implementing, and evaluating national and subnational programs. In September 2022, the World Health Organization hosted a stakeholder meeting to identify such priority modeling questions across a range of NTDs and to consider how modeling could inform local decision making. Here, we summarize the outputs of the meeting, highlight common themes in the questions being asked, and discuss how quantitative modeling can support programmatic decisions that may accelerate progress towards the 2030 targets.

Addressing a silent and neglected scourge in sexual and reproductive health in Sub-Saharan Africa by development of training competencies to improve prevention, diagnosis, and treatment of female genital schistosomiasis (FGS) for health workers.

BACKGROUND: Schistosomiasis is an acute and chronic disease caused by parasitic worms, that can take two main forms: intestinal or urogenital. If left untreated, the urogenital form can lead to female genital schistosomiasis (FGS) in women and girls; frequently resulting in severe reproductive health complications which are often misdiagnosed as sexually-transmitted infections (STIs) or can be confused with cervical cancer. Despite its impact on women's reproductive health, FGS is typically overlooked in medical training and remains poorly recognized with low awareness both in affected communities and in health professionals. FGS has been described as the one of the most neglected sexual and reproductive health issues in sub-Saharan Africa (Swai in BMC Infect Dis 6:134, 2006; Kukula in PLoS Negl Trop Dis 13:e0007207; Joint United Nations Programme on HIV/AIDS (UNAIDS) 2019). Increased knowledge and awareness of FGS is required to end this neglect, improve women's reproductive health, and decrease the burden of this preventable and treatable neglected tropical disease. METHODS: We conducted interactive virtual workshops, in collaboration with the World Health Organization (WHO), engaging 64 participants with medical and public health backgrounds from around the world to establish standardized skills (or competencies) for prevention, diagnosis, and treatment of FGS at all levels of the health system. The competencies were drafted in small groups, peer-reviewed, and finalized by participants. RESULTS: This participatory process led to identification of 27 skills needed for FGS prevention, diagnosis, and management for two categories of health workers; those working in a clinical setting, and those working in a community setting. Among them, ten relate to the diagnosis of FGS including three that involve a pelvic exam and seven that do not. Six constitute the appropriate behaviors required to treat FGS in a clinical setting. Eleven address the community setting, with six relating to the identification of women at risk and five relating to prevention. CONCLUSION: Defining the skills necessary for FGS management is a critical step to prepare for proper diagnosis and treatment of women and girls in sub-Saharan Africa by trained health professionals. The suggested competencies can now serve as the foundation to create educative tools and curricula to better train health care workers on the prevention, diagnosis, and management of FGS.

Association of schistosomiasis and HIV infections: A systematic review and meta-analysis.

BACKGROUND: Female genital schistosomiasis (FGS) affects up to 56 million women in sub-Saharan Africa and may increase risk of HIV infection. METHODS: To assess the association of schistosomiasis with HIV infection, peer-reviewed literature published until 31 December 2018 was examined and a pooled estimate for the odds ratio was generated using Bayesian random effects models. RESULTS: Of the 364 abstracts that were identified, 26 were included in the summary. Eight reported odds ratios of the association between schistosomiasis and HIV; one reported a transmission hazard ratio of 1.8 (95% CI, 1.2-2.6) among women and 1.4 (95% CI, 1.0-1.9) among men; 11 described the prevalence of schistosomiasis among HIV-positive people (range, 1.5-36.6%); and six reported the prevalence of HIV among people with schistosomiasis (range, 5.8-57.3%). Six studies were selected for quantitative analysis. The pooled estimate for the odds ratio of HIV among people with schistosomiasis was 2.3 (95% CI, 1.2-4.3). CONCLUSIONS: A significant association of schistosomiasis with HIV was found. However, a specific summary estimate for FGS could not be generated. A research agenda was provided to determine the effect of FGS on HIV infection. The WHO's policy on mass drug administration for schistosomiasis may prevent HIV.

Correction: Female genital schistosomiasis and HIV/AIDS: Reversing the neglect of girls and women.

[This corrects the article DOI: 10.1371/journal.pntd.0007025.].

A Multicountry Comparison of Three Coverage Evaluation Survey Sampling Methodologies for Neglected Tropical Diseases.

Coverage evaluation surveys (CESs) are an important complement to routinely reported drug coverage estimates following mass drug administration for neglected tropical diseases (NTDs). Although the WHO recommends the routine use of CESs, they are rarely implemented. Reasons for this low uptake are multifaceted; one is uncertainty on the best sampling method. We conducted a multicountry study to compare the statistical characteristics, cost, time, and complexity of three commonly used CES sampling methods: the Expanded Program on Immunization's (EPI's) 30 × 7 cluster survey, a stratified design with systematic sampling within strata to enable lot quality assurance sampling (S-LQAS) decision rules, and probability sampling with segmentation (PSS). The three CES methods were used in Burkina Faso, Honduras, Malawi, and Uganda, and results were compared across the country sites. All three CES methods were found to be feasible. The S-LQAS approach took the least amount of time to complete and, consequently, was the least expensive; however, all three methods cost less than $5,000 per district. The PSS design resulted in an unbiased, equal-probability sample of the target populations. By contrast, the EPI approach had inherent bias related to the selection of households. Because of modifications needed to maintain feasibility, the S-LQAS method also resulted in a non-probability sample with less precision than the other two methods. Given the comparable cost and time of the three sampling methods and the statistical advantages of the PSS method, the PSS method was deemed to be the best for CESs in NTD programs.

Comparison of World Health Organization and Demographic and Health Surveys data to estimate sub-national deworming coverage in pre-school aged children.

BACKGROUND: The key metric for monitoring the progress of deworming programs in controlling soil-transmitted helminthiasis (STH) is national drug coverage reported to the World Health Organization (WHO). There is increased interest in utilizing geographically-disaggregated data to estimate sub-national deworming coverage and equity, as well as gender parity. The Demographic and Health Surveys (DHS) offer a potential source of sub-national data. This study aimed to compare deworming coverage routinely reported to WHO and estimated by DHS in pre-school aged children to inform global STH measurement and evaluation. METHODOLOGY: We compared sub-national deworming coverage in pre-school aged children reported to WHO and estimated by DHS aligned geospatially and temporally. We included data from Burundi (2016-2017), Myanmar (2015-2016), and the Philippines (2017) based on data availability. WHO provided data on the date and sub-national coverage per mass drug administration reported by Ministries of Health. DHS included maternally-reported deworming status within the past 6 months for each child surveyed. We estimated differences in sub-national deworming coverage using WHO and DHS data, and performed sensitivity analyses. PRINCIPAL FINDINGS: We compared data on pre-school aged children from 13 of 18 districts in Burundi (N = 6,835 in DHS), 11 of 15 districts in Myanmar (N = 1,462 in DHS) and 16 of 17 districts in the Philippines (N = 7,594 in DHS) following data exclusion. The national deworming coverages estimated by DHS in Burundi, Myanmar, and the Philippines were 75.5% (95% CI: 73.7%-77.7%), 47.0% (95% CI: 42.7%-51.3%), and 48.0% (95% CI: 46.0%-50.0%), respectively. The national deworming coverages reported by WHO in Burundi, Myanmar, and the Philippines were 80.1%, 93.6% and 75.7%, respectively. The mean absolute differences in district-level coverage reported to WHO and estimated by DHS in Burundi, Myanmar, and the Philippines were 9.5%, 41.5%, and 24.6%, respectively. Across countries, coverage reported to WHO was frequently higher than DHS estimates (32 of 40 districts). National deworming coverage from DHS estimates were similar by gender within countries. CONCLUSIONS AND SIGNIFICANCE: Agreement of deworming coverage reported to WHO and estimated by DHS data was heterogeneous across countries, varying from broadly compatible in Burundi to largely discrepant in Myanmar. DHS data could complement deworming data reported to WHO to improve data monitoring practices and serve as an independent sub-national source of coverage data.

Ruling out early trimester pregnancy when implementing community-based deworming programs.

BACKGROUND: Large-scale deworming programs have, to date, mostly targeted preschool- and school-age children. As community-based deworming programs become more common, deworming will be offered to women of reproductive age. The World Health Organization recommends preventive chemotherapy be administered to pregnant women only after the first trimester. It is therefore important for deworming programs to be able to identify women in early pregnancy. Our objective was to validate a short questionnaire which could be used by deworming program managers to identify and screen out women in early pregnancy. METHODOLOGY/PRINCIPAL FINDINGS: In May and June 2018, interviewers administered a questionnaire, followed by a pregnancy test, to 1,203 adult women living in the Peruvian Amazon. Regression analyses were performed to identify questions with high predictive properties (using the pregnancy test as the gold standard). Test parameters were computed at different decision tree nodes (where nodes represented questions). With 106 women confirmed to be pregnant, the positive predictive value of asking the single question 'Are you pregnant?' was 100%, at a 'cost' of a false negative rate of 1.9% (i.e. 21 women were incorrectly identified as not pregnant when they were truly pregnant). Additional questions reduced the false negative rate, but increased the false positive rate. Rates were dependent on both the combination and the order of questions. CONCLUSIONS/SIGNIFICANCE: To identify women in early pregnancy when deworming programs are community-based, both the number and order of questions are important. The local context and cultural acceptability of different questions should inform this decision. When numbers are manageable and resources are available, pregnancy tests can be considered at different decision tree nodes to confirm pregnancy status. Trade-offs in terms of efficiency and misclassification rates will need to be considered to optimize deworming coverage in women of reproductive age.

Monitoring equity in universal health coverage with essential services for neglected tropical diseases: an analysis of data reported for five diseases in 123 countries over 9 years.

BACKGROUND: A service coverage index has recently been proposed to monitor progress towards universal health coverage (UHC), and baseline results for 2015 are available. However, evidence on equity in that progress is scarce. The service coverage index did not consider services for neglected tropical diseases (NTDs), a group of preventable diseases defined by WHO member states on the basis of the disproportionate burden they place on their poorest, remotest, and otherwise most marginalised communities. Because of the much-needed equity lens that it could provide, NTD service coverage should not be neglected in efforts to monitor UHC progress. METHODS: We developed an index focused on coverage of services for NTDs, comparable in methods to the UHC service coverage index. On the basis of data availability, we focused on preventive chemotherapy, which was recently included in the highest-priority package of essential UHC interventions. We used data reported to WHO since 2008 for the five NTDs amenable to preventive chemotherapy (lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiases, and trachoma) to develop an NTD service coverage index based on the geometric mean of coverage rates for individual NTD services with regularly reported data. We then compared this NTD service coverage index with the UHC service coverage index. A high UHC index value and a low NTD index value suggest that a country might not be adequately prioritising interventions for the poor. We measured Spearman rank-order correlation (ρ) of the NTD service coverage index with income inequality, as measured by the Gini coefficient (range of 0-1), where values of the Gini coefficient close to 1 indicate higher income inequality, and a negative correlation was evidence of socioeconomic barriers to health service coverage for people who are least well off. FINDINGS: At least 123 countries can monitor NTD service coverage by use of a simple index. The median national NTD index was 32 in 2016, an increase from 3 in 2012, and from 0 in 2008. In 2015, the NTD index was lower than the UHC index in 81 of the 113 countries for which both NTD and UHC indices are available, by up to 80 points. The NTD index was negatively but weakly correlated with income inequality; this correlation was strongest in the African Region (ρ=-0·46 in 2008, ρ=-0·32 in 2015), suggesting that high-income inequality, although associated with low coverage of services targeting the poor, does not preclude the extension of that coverage. INTERPRETATION: The NTD index can be used to measure equity in progress towards UHC. A broader NTD index including services for other NTDs could be developed at regional and country levels. Comparing the NTD and UHC service coverage indices reveals that some countries that are performing well by the measure of the UHC service coverage index still have work to do in prioritising services for their poorest and otherwise most marginalised communities. Our results offer hope that socioeconomic barriers to health service coverage can be overcome. FUNDING: None.

Contributions of non-governmental organizations to WHO targets for control of soil-transmitted helminthiases.

Soil-transmitted helminthiases (STH) may affect up to 1 billion children globally. The World Health Organization (WHO) recommends regular preventive chemotherapy for at-risk individuals. The WHO Preventive Chemotherapy (PCT) Databank tracks annual treatments reported by national Ministries of Health (MOHs) to evaluate progress to coverage goals. Non-governmental organizations (NGOs) deliver STH treatments; the extent to which they are included in MOH reports to the WHO is unclear. The Global NGO Deworming Inventory solicited treatment reports from NGOs to compare with the PCT Databank. In 2010, NGOs delivered 65.4 million STH treatments, which is an estimated 25.1% of the total delivered. Of these treatments, 23.3 million (35.6%) were not reported to the WHO; 22.3 million (95.7%) were from countries that had not submitted STH treatment reports to the WHO. Reporting from NGOs to MOHs and from MOHs to the WHO should be strengthened to ensure that progress to WHO treatment goals is monitored with better completeness and assessed accurately.

Examining the relationship between urogenital schistosomiasis and HIV infection.

BACKGROUND: Urogenital schistosomiasis, caused by infection with Schistosoma haematobium, is widespread and causes substantial morbidity on the African continent. The infection has been suggested as an unrecognized risk factor for incident HIV infection. Current guidelines recommend preventive chemotherapy, using praziquantel as a public health tool, to avert morbidity due to schistosomiasis. In individuals of reproductive age, urogenital schistosomiasis remains highly prevalent and, likely, underdiagnosed. This comprehensive literature review was undertaken to examine the evidence for a cause-effect relationship between urogenital schistosomiasis and HIV/AIDS. The review aims to support discussions of urogenital schistosomiasis as a neglected yet urgent public health challenge. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a systematic search of the literature including online databases, clinical guidelines, and current medical textbooks. We describe plausible local and systemic mechanisms by which Schistosoma haematobium infection could increase the risk of HIV acquisition in both women and men. We also detail the effects of S. haematobium infection on the progression and transmissibility of HIV in co-infected individuals. We briefly summarize available evidence on the immunomodulatory effects of chronic schistosomiasis and the implications this might have for populations at high risk of both schistosomiasis and HIV. CONCLUSIONS/SIGNIFICANCE: Studies support the hypothesis that urogenital schistosomiasis in women and men constitutes a significant risk factor for HIV acquisition due both to local genital tract and global immunological effects. In those who become HIV-infected, schistosomal co-infection may accelerate HIV disease progression and facilitate viral transmission to sexual partners. Establishing effective prevention strategies using praziquantel, including better definition of treatment age, duration, and frequency of treatment for urogenital schistosomiasis, is an important public health priority. Our findings call attention to this pressing yet neglected public health issue and the potential added benefit of scaling up coverage of schistosomal treatment for populations in whom HIV infection is prevalent.