An Updated Economic Assessment of Moxidectin Treatment Strategies for Onchocerciasis Elimination.

BACKGROUND: Concerns that annual mass administration of ivermectin, the predominant strategy for onchocerciasis control and elimination, may not lead to elimination of parasite transmission (EoT) in all endemic areas have increased interest in alternative treatment strategies. One such strategy is moxidectin. We performed an updated economic assessment of moxidectin- relative to ivermectin-based strategies. METHODS: We investigated annual and biannual community-directed treatment with ivermectin (aCDTI, bCDTI) and moxidectin (aCDTM, bCDTM) with minimal or enhanced coverage (65% or 80% of total population taking the drug, respectively) in intervention-naive areas with 30%, 50%, or 70% microfilarial baseline prevalence (representative of hypo-, meso-, and hyperendemic areas). We compared programmatic delivery costs for the number of treatments achieving 90% probability of EoT (EoT90), calculated with the individual-based stochastic transmission model EPIONCHO-IBM. We used the costs for 40 years of program delivery when EoT90 was not reached earlier. The delivery costs do not include drug costs. RESULTS: aCDTM and bCDTM achieved EoT90 with lower programmatic delivery costs than aCDTI with 1 exception: aCDTM with minimal coverage did not achieve EoT90 in hyperendemic areas within 40 years. With minimal coverage, bCDTI delivery costs as much or more than aCDTM and bCDTM. With enhanced coverage, programmatic delivery costs for aCDTM and bCDTM were lower than for aCDTI and bCDTI. CONCLUSIONS: Moxidectin-based strategies could accelerate progress toward EoT and reduce programmatic delivery costs compared with ivermectin-based strategies. The costs of moxidectin to national programs are needed to quantify whether delivery cost reductions will translate into overall program cost reduction.

Predictive Value of Microfilariae-Based Stop-MDA Thresholds After Triple Drug Therapy With IDA Against Lymphatic Filariasis in Treatment-Naive Indian Settings.

Mass drug administration (MDA) of antifilarial drugs is the main strategy for the elimination of lymphatic filariasis (LF). Recent clinical trials indicated that the triple-drug therapy with ivermectin, diethylcarbamazine, and albendazole (IDA) is much more effective against LF than the widely used two-drug combinations (albendazole plus either ivermectin or diethylcarbamazine). For IDA-based MDA, the stop-MDA decision is made based on microfilariae (mf) prevalence in adults. In this study, we assess how the probability of eventually reaching elimination of transmission depends on the critical threshold used in transmission assessment surveys (TAS-es) to define whether transmission was successfully suppressed and triple-drug MDA can be stopped. This analysis focuses on treatment-naive Indian settings. We do this for a range of epidemiological and programmatic contexts, using the established LYMFASIM model for transmission and control of LF. Based on our simulations, a single TAS, one year after the last MDA round, provides limited predictive value of having achieved suppressed transmission, while a higher MDA coverage increases elimination probability, thus leading to a higher predictive value. Every additional TAS, conditional on previous TAS-es being passed with the same threshold, further improves the predictive value for low values of stop-MDA thresholds. An mf prevalence threshold of 0.5% corresponding to TAS-3 results in ≥95% predictive value even when the MDA coverage is relatively low.

Reducing the Antigen Prevalence Target Threshold for Stopping and Restarting Mass Drug Administration for Lymphatic Filariasis Elimination: A Model-Based Cost-effectiveness Simulation in Tanzania, India and Haiti.

BACKGROUND: The Global Programme to Eliminate Lymphatic Filariasis (GPELF) aims to reduce and maintain infection levels through mass drug administration (MDA), but there is evidence of ongoing transmission after MDA in areas where Culex mosquitoes are the main transmission vector, suggesting that a more stringent criterion is required for MDA decision making in these settings. METHODS: We use a transmission model to investigate how a lower prevalence threshold (<1% antigenemia [Ag] prevalence compared with <2% Ag prevalence) for MDA decision making would affect the probability of local elimination, health outcomes, the number of MDA rounds, including restarts, and program costs associated with MDA and surveys across different scenarios. To determine the cost-effectiveness of switching to a lower threshold, we simulated 65% and 80% MDA coverage of the total population for different willingness to pay per disability-adjusted life-year averted for India ($446.07), Tanzania ($389.83), and Haiti ($219.84). RESULTS: Our results suggest that with a lower Ag threshold, there is a small proportion of simulations where extra rounds are required to reach the target, but this also reduces the need to restart MDA later in the program. For 80% coverage, the lower threshold is cost-effective across all baseline prevalences for India, Tanzania, and Haiti. For 65% MDA coverage, the lower threshold is not cost-effective due to additional MDA rounds, although it increases the probability of local elimination. Valuing the benefits of elimination to align with the GPELF goals, we find that a willingness to pay per capita government expenditure of approximately $1000-$4000 for 1% increase in the probability of local elimination would be required to make a lower threshold cost-effective. CONCLUSIONS: Lower Ag thresholds for stopping MDAs generally mean a higher probability of local elimination, reducing long-term costs and health impacts. However, they may also lead to an increased number of MDA rounds required to reach the lower threshold and, therefore, increased short-term costs. Collectively, our analyses highlight that lower target Ag thresholds have the potential to assist programs in achieving lymphatic filariasis goals.

How Does Treatment Coverage and Proportion Never Treated Influence the Success of Schistosoma mansoni Elimination as a Public Health Problem by 2030?

BACKGROUND: The 2030 target for schistosomiasis is elimination as a public health problem (EPHP), achieved when the prevalence of heavy-intensity infection among school-aged children (SAC) reduces to <1%. To achieve this, the new World Health Organization guidelines recommend a broader target of population to include pre-SAC and adults. However, the probability of achieving EPHP should be expected to depend on patterns in repeated uptake of mass drug administration by individuals. METHODS: We employed 2 individual-based stochastic models to evaluate the impact of school-based and community-wide treatment and calculated the number of rounds required to achieve EPHP for Schistosoma mansoni by considering various levels of the population never treated (NT). We also considered 2 age-intensity profiles, corresponding to a low and high burden of infection in adults. RESULTS: The number of rounds needed to achieve this target depends on the baseline prevalence and the coverage used. For low- and moderate-transmission areas, EPHP can be achieved within 7 years if NT ≤10% and NT <5%, respectively. In high-transmission areas, community-wide treatment with NT <1% is required to achieve EPHP. CONCLUSIONS: The higher the intensity of transmission, and the lower the treatment coverage, the lower the acceptable value of NT becomes. Using more efficacious treatment regimens would permit NT values to be marginally higher. A balance between target treatment coverage and NT values may be an adequate treatment strategy depending on the epidemiological setting, but striving to increase coverage and/or minimize NT can shorten program duration.

District-Level Forecast of Achieving Trachoma Elimination as a Public Health Problem By 2030: An Ensemble Modelling Approach.

Assessing the feasibility of 2030 as a target date for global elimination of trachoma, and identification of districts that may require enhanced treatment to meet World Health Organization (WHO) elimination criteria by this date are key challenges in operational planning for trachoma programmes. Here we address these challenges by prospectively evaluating forecasting models of trachomatous inflammation-follicular (TF) prevalence, leveraging ensemble-based approaches. Seven candidate probabilistic models were developed to forecast district-wise TF prevalence in 11 760 districts, trained using district-level data on the population prevalence of TF in children aged 1-9 years from 2004 to 2022. Geographical location, history of mass drug administration treatment, and previously measured prevalence data were included in these models as key predictors. The best-performing models were included in an ensemble, using weights derived from their relative likelihood scores. To incorporate the inherent stochasticity of disease transmission and challenges of population-level surveillance, we forecasted probability distributions for the TF prevalence in each geographic district, rather than predicting a single value. Based on our probabilistic forecasts, 1.46% (95% confidence interval [CI]: 1.43-1.48%) of all districts in trachoma-endemic countries, equivalent to 172 districts, will exceed the 5% TF control threshold in 2030 with the current interventions. Global elimination of trachoma as a public health problem by 2030 may require enhanced intervention and/or surveillance of high-risk districts.

How Does the Proportion of Never Treatment Influence the Success of Mass Drug Administration Programs for the Elimination of Lymphatic Filariasis?

BACKGROUND: Mass drug administration (MDA) is the cornerstone for the elimination of lymphatic filariasis (LF). The proportion of the population that is never treated (NT) is a crucial determinant of whether this goal is achieved within reasonable time frames. METHODS: Using 2 individual-based stochastic LF transmission models, we assess the maximum permissible level of NT for which the 1% microfilaremia (mf) prevalence threshold can be achieved (with 90% probability) within 10 years under different scenarios of annual MDA coverage, drug combination and transmission setting. RESULTS: For Anopheles-transmission settings, we find that treating 80% of the eligible population annually with ivermectin + albendazole (IA) can achieve the 1% mf prevalence threshold within 10 years of annual treatment when baseline mf prevalence is 10%, as long as NT <10%. Higher proportions of NT are acceptable when more efficacious treatment regimens are used. For Culex-transmission settings with a low (5%) baseline mf prevalence and diethylcarbamazine + albendazole (DA) or ivermectin + diethylcarbamazine + albendazole (IDA) treatment, elimination can be reached if treatment coverage among eligibles is 80% or higher. For 10% baseline mf prevalence, the target can be achieved when the annual coverage is 80% and NT ≤15%. Higher infection prevalence or levels of NT would make achieving the target more difficult. CONCLUSIONS: The proportion of people never treated in MDA programmes for LF can strongly influence the achievement of elimination and the impact of NT is greater in high transmission areas. This study provides a starting point for further development of criteria for the evaluation of NT.

Adolescents' Perspective Regarding a Community-Wide Mass Drug Administration Program for Soil-Transmitted Helminths in India.

This study was undertaken to understand the perspective of adolescents in endemic communities of India regarding soil-transmitted helminth (STH) infections and community-wide mass drug administration (cMDA). A multicountry community-based cluster-randomized trial, the Deworm3 trial, tested the feasibility of interrupting STH transmission with cMDA, where all individuals aged 1-99 are treated empirically with albendazole. Using a guideline based on the Consolidated Framework for Implementation Research, eight focus group discussions were conducted among 57 adolescents from the trial site in India and analyzed on ATLAS.ti 8.0 software using an a priori thematic codebook. Adolescents believed that adults could be a source of STH infection because they were not routinely dewormed like the children through the national deworming program. Perceived benefits of cMDA for all were better health and increased work efficiency. Perceived barriers to adults' participation in cMDA was their mistrust about the program, fear of side effects, perceived low risk of infection, and absence during drug distribution. To encourage adult participation in cMDAs, adolescents suggested community outreach activities, engaging village influencers and health workers, and tailoring drug distribution to when adults would be available. Adolescents were confident in their ability to be change agents within their households for treatment compliance. Adolescents provided insights into potential barriers and solutions to improve adult participation in cMDA, identified best practices of cMDA delivery, and suggested that they have unique roles as change agents to increase their household participation in cMDA.

A dynamic game of lymphatic filariasis prevention by voluntary use of insecticide treated nets.

Lymphatic filariasis (LF) has been targeted for elimination as a public health concern by 2030 with a goal to keep the prevalence of LF infections under the 1% threshold. While mass drug administration (MDA) is a primary strategy recommended by WHO, the use of insecticide treated nets (ITN) plays a crucial role as an alternative strategy when MDA cannot be used. In this paper, we use imitation dynamics to incorporate human behavior and voluntary use of ITN into the compartmental epidemiological model of LF transmission. We find the equilibrium states of the dynamics and the ITN usage as it depends on epidemiological parameters and the cost of ITNs. We investigate the conditions under which the voluntary use of ITNs can keep the LF prevalence under the 1% threshold. We found that when the cost of using the ITNs is about 105 smaller than the perceived cost of LF, then the voluntary use of ITNs will eliminate LF as a public health concern. Furthermore, when the ITNs are given away for free, our model predicts that over 80% of the population will use them which would eliminate LF completely in regions where Anopheles are the primary vectors.

Heterogeneity in elimination efforts could increase the risk of resurgence of lymphatic filariasis in Madagascar.

BACKGROUND: Progress in lymphatic filariasis (LF) elimination is spatially heterogeneous in many endemic countries, which may lead to resurgence in areas that have achieved elimination. Understanding the drivers and consequences of such heterogeneity could help inform strategies to reach global LF elimination goals by 2030. This study assesses whether differences in age-specific compliance with mass drug administration (MDA) could explain LF prevalence patterns in southeastern Madagascar and explores how spatial heterogeneity in prevalence and age-specific MDA compliance may affect the risk of LF resurgence after transmission interruption. METHODOLOGY: We used LYMFASIM model with parameters in line with the context of southeastern Madagascar and explored a wide range of scenarios with different MDA compliance for adults and children (40-100%) to estimate the proportion of elimination, non-elimination and resurgence events associated with each scenario. Finally, we evaluated the risk of resurgence associated with different levels of migration (2-6%) from surrounding districts combined with varying levels of LF microfilaria (mf) prevalence (0-24%) during that same study period. RESULTS: Differences in MDA compliance between adults and children better explained the observed heterogeneity in LF prevalence for these age groups than differences in exposure alone. The risk of resurgence associated with differences in MDA compliance scenarios ranged from 0 to 19% and was highest when compliance was high for children (e.g. 90%) and low for adults (e.g. 50%). The risk of resurgence associated with migration was generally higher, exceeding 60% risk for all the migration levels explored (2-6% per year) when mf prevalence in the source districts was between 9% and 20%. CONCLUSION: Gaps in the implementation of LF elimination programme can increase the risk of resurgence and undermine elimination efforts. In Madagascar, districts that have not attained elimination pose a significant risk for those that have achieved it. More research is needed to help guide LF elimination programme on the optimal strategies for surveillance and control that maximize the chances to sustain elimination and avoid resurgence.

Mass drug administration for neglected tropical disease control and elimination: a systematic review of ethical reasons.

BACKGROUND: Neglected tropical diseases (NTDs) are a diverse group of debilitating diseases and conditions afflicting more than one billion people in impoverished communities. Control of these diseases is crucial to achieve Sustainable Development Goal 3 and the pledge to 'leave no one behind'. Relying on large-scale delivery of wide-spectrum drugs to individuals in at-risk communities irrespective of their health status, mass drug administration is a core strategy for tackling half of the NTDs targeted by the latest WHO roadmap (2021-2030). However, ethical challenges surround its implementation and long-term impact. This systematic review aims to give a comprehensive picture of the variety of ethical reasons for and against mass drug administration for NTD control and elimination, facilitating further debate in ethics and policy. METHODS: PubMed and Web of Science Core Collection were searched for all relevant publications. Of the 486 retrieved records, 60 met the inclusion criteria for qualitative analysis. Ethical reasons discussing the topic at hand were extracted from full texts and synthesised through the Kuckartz method of qualitative content analysis. RESULTS: Data extraction revealed 61 ethical reasons, of which 20 (32.7%) had positive, 13 (21.3%) had ambivalent and 28 (45.9%) had negative implications regarding mass drug administration for NTDs. The health benefits and cost-effectiveness of the measure were extensively highlighted. However, equity, autonomy and sustainability emerged as the domains with the most pressing ethical concerns. Many issues related to implementation are yet to be adequately addressed in policy documents. CONCLUSIONS: This is the first systematic review of ethical reasons pertaining to mass drug administration for NTD control and elimination. Due to the diversity of included studies, no general recommendations can be made. Instead, context-specific strategies seem necessary. Alternative approaches tackling socioecological determinants of ill health are needed for long-term sustainability. Future research could benefit from contributions of non-Western philosophies and perspectives by local researchers.

Albendazole metabolites excretion in human saliva as a biomarker to assess treatment compliance in mass drug administration (MDA) anthelmintic programs.

Soil-transmitted-helminth (STH) infections continue to be a persistent global public health problem. Control strategies for STH have been based on the use of mass drug administration (MDA). Coverage and compliance assessment is critical to understanding the true effectiveness of albendazole (ABZ) in those MDA programs. The aims of this work were to characterize the pattern of albendazole and metabolites excretion in human saliva, and to develop a saliva-based biomarker (HPLC drug/metabolite detection) useful to accurately estimate the coverage/compliance in MDA campaigns. The study subjects were 12 healthy volunteers treated with a single oral dose of ABZ (400 mg). Saliva and blood (dried blood spot, DBS) samples were taken previously and between 2 and 72 h post-treatment. The samples were analyzed by HPLC with UV detection, C18 reversed-phase column. ABZ sulphoxide was the main analyte recovered up to 72 h p.t. in blood and saliva. The concentration profiles measured in the blood (DBS samples) were higher (P < 0.05) than those in saliva, however, this ABZ-metabolite was recovered longer in saliva. The in vivo measurement of drugs/metabolites in saliva samples from ABZ-treated volunteers offers strong scientific evidence to support the use of saliva as a valid biological sample for assessing compliance in MDA programs.

Elimination of transmission of onchocerciasis (river blindness) with long-term ivermectin mass drug administration with or without vector control in sub-Saharan Africa: a systematic review and meta-analysis.

BACKGROUND: WHO has proposed elimination of transmission of onchocerciasis (river blindness) by 2030. More than 99% of cases of onchocerciasis are in sub-Saharan Africa. Vector control and mass drug administration of ivermectin have been the main interventions for many years, with varying success. We aimed to identify factors associated with elimination of onchocerciasis transmission in sub-Saharan Africa. METHODS: For this systematic review and meta-analysis we searched for published articles reporting epidemiological or entomological assessments of onchocerciasis transmission status in sub-Saharan Africa, with or without vector control. We searched MEDLINE, PubMed, Web of Science, Embase, Cochrane Central Register of Controlled Trials, African Index Medicus, and Google Scholar databases for all articles published from database inception to Aug 19, 2023, without language restrictions. The search terms used were "onchocerciasis" AND "ivermectin" AND "mass drug administration". The three inclusion criteria were (1) focus or foci located in Africa, (2) reporting of elimination of transmission or at least 10 years of ivermectin mass drug administration in the focus or foci, and (3) inclusion of at least one of the following assessments: microfilarial prevalence, nodule prevalence, Ov16 antibody seroprevalence, and blackfly infectivity prevalence. Epidemiological modelling studies and reviews were excluded. Four reviewers (NM, AJ, AM, and TNK) extracted data in duplicate from the full-text articles using a data extraction tool developed in Excel with columns recording the data of interest to be extracted, and a column where important comments for each study could be highlighted. We did not request any individual-level data from authors. Foci were classified as achieving elimination of transmission, being close to elimination of transmission, or with ongoing transmission. We used mixed-effects meta-regression models to identify factors associated with transmission status. This study is registered in PROSPERO, CRD42022338986. FINDINGS: Of 1525 articles screened after the removal of duplicates, 75 provided 282 records from 238 distinct foci in 19 (70%) of the 27 onchocerciasis-endemic countries in sub-Saharan Africa. Elimination of transmission was reported in 24 (9%) records, being close to elimination of transmission in 86 (30%) records, and ongoing transmission in 172 (61%) records. I2 was 83·3% (95% CI 79·7 to 86·3). Records reporting 10 or more years of continuous mass drug administration with 80% or more therapeutic coverage of the eligible population yielded significantly higher odds of achieving elimination of transmission (log-odds 8·5 [95% CI 3·5 to 13·5]) or elimination and being close to elimination of transmission (42·4 [18·7 to 66·1]) than those with no years achieving 80% coverage or more. Reporting 15-19 years of ivermectin mass drug administration (22·7 [17·2 to 28·2]) and biannual treatment (43·3 [27·2 to 59·3]) were positively associated with elimination and being close to elimination of transmission compared with less than 15 years and no biannual mass drug administration, respectively. Having had vector control without vector elimination (-42·8 [-59·1 to -26·5]) and baseline holoendemicity (-41·97 [-60·6 to -23·2]) were associated with increased risk of ongoing transmission compared with no vector control and hypoendemicity, respectively. Blackfly disappearance due to vector control or environmental change contributed to elimination of transmission. INTERPRETATION: Mass drug administration duration, frequency, and coverage; baseline endemicity; and vector elimination or disappearance are important determinants of elimination of onchocerciasis transmission in sub-Saharan Africa. Our findings underscore the importance of improving and sustaining high therapeutic coverage and increasing treatment frequency if countries are to achieve elimination of onchocerciasis transmission. FUNDING: The Bill & Melinda Gates Foundation and Neglected Tropical Diseases Modelling Consortium, UK Medical Research Council, and Global Health EDCTP3 Joint Undertaking. TRANSLATIONS: For the Swahili, French, Spanish and Portuguese translations of the abstract see Supplementary Materials section.

Risk factors for non-participation in ivermectin and dihydroartemisinin-piperaquine mass drug administration for malaria control in the MASSIV trial.

BACKGROUND: Mass Drug Administration (MDA) has become a mainstay for the control of several diseases over the last two decades. Successful implementation of MDA programmes requires community participation and can be threatened by systematic non-participation. Such concerns are particularly pertinent for MDA programmes against malaria, as they require multi-day treatment over several consecutive months. Factors associated with non-participation to the MDA campaign with ivermectin (IVM) and dihydroartemisinin-piperaquine (DHP) implemented within the MASSIV cluster randomized trial were determined. METHODS: Coverage data was extracted from the MASSIV trial study database, with every datapoint being a directly observed therapy (DOT). A complete month of MDA was classified as receiving all three daily doses of treatment. For both ivermectin and DHP, ordinal logistic regression was used to identify individual and household level variables associated with non-participation. RESULTS: For ivermectin, 51.5% of eligible participants received all 3 months of treatment while 30.7% received either one or two complete months. For DHP, 56.7% of eligible participants received all 3 months of treatment and 30.5% received either one or two complete months. Children aged 5-15 years and adults aged more than 50 years were more likely to receive at least one complete month of MDA than working age adults, both for ivermectin (aOR 4.3, 95% CI 3.51-5.28 and aOR of 2.26, 95% CI 1.75-2.95) and DHP (aOR 2.47, 95%CI 2.02-3.02 and aOR 1.33, 95%CI 1.01-1.35), respectively. Members of households where the head received a complete month of MDA were more likely to themselves have received a complete month of MDA, both for ivermectin (aOR 1.71, 95%CI 1.35-2.14) and for DHP (aOR 1.64, 95%CI 1.33-2.04). CONCLUSION: Personal and household-level variables were associated with participation in the MDA programme for malaria control. Specific strategies to (increase participation amongst some groups may be important to ensure maximum impact of MDA strategies in achieving malaria elimination. TRIAL REGISTRATION: The MASSIV trial is registered under NCT03576313.

Modeling the persistence of Opisthorchis viverrini worm burden after mass-drug administration and education campaigns with systematic adherence.

Opisthorchis viverrini is a parasitic liver fluke contracted by consumption of raw fish, which affects over 10 million people in Southeast Asia despite sustained control efforts. Chronic infections are a risk factor for the often fatal bile duct cancer, cholangiocarcinoma. Previous modeling predicted rapid elimination of O. viverrini following yearly mass drug administration (MDA) campaigns. However, field data collected in affected populations shows persistence of infection, including heavy worm burden, after many years of repeated interventions. A plausible explanation for this observation is systematic adherence of individuals in health campaigns, such as MDA and education, with some individuals consistently missing treatment. We developed an agent-based model of O. viverrini which allows us to introduce various heterogeneities including systematic adherence to MDA and education campaigns at the individual level. We validate the agent-based model by comparing it to a previously published population-based model. We estimate the degree of systematic adherence to MDA and education campaigns indirectly, using epidemiological data collected in Lao PDR before and after 5 years of repeated MDA, education and sanitation improvement campaigns. We predict the impact of interventions deployed singly and in combination, with and without the estimated systematic adherence. We show how systematic adherence can substantially increase the time required to achieve reductions in worm burden. However, we predict that yearly MDA campaigns alone can result in a strong reduction of moderate and heavy worm burden, even under systematic adherence. We predict latrines and education campaigns to be particularly important for the reduction in overall prevalence, and therefore, ultimately, elimination. Our findings show how systematic adherence can explain the observed persistence of worm burden; while emphasizing the benefit of interventions for the entire population, even under systematic adherence. At the same time, the results highlight the substantial opportunity to further reduce worm burden if patterns of systematic adherence can be overcome.

Quantifying the impact of interventions against Plasmodium vivax: A model for country-specific use.

In order to evaluate the impact of various intervention strategies on Plasmodium vivax dynamics in low endemicity settings without significant seasonal pattern, we introduce a simple mathematical model that can be easily adapted to reported case numbers similar to that collected by surveillance systems in various countries. The model includes case management, vector control, mass drug administration and reactive case detection interventions and is implemented in both deterministic and stochastic frameworks. It is available as an R package to enable users to calibrate and simulate it with their own data. Although we only illustrate its use on fictitious data, by simulating and comparing the impact of various intervention combinations on malaria risk and burden, this model could be a useful tool for strategic planning, implementation and resource mobilization.

"Our desire is to make this village intestinal worm free": Identifying determinants of high coverage of community-wide mass drug administration for soil transmitted helminths in Benin, India, and Malawi.

BACKGROUND: Soil-transmitted helminth infections (STH) are associated with substantial morbidity in low-and-middle-income countries, accounting for 2.7 million disability-adjusted life years annually. Current World Health Organization guidelines recommend controlling STH-associated morbidity through periodic deworming of at-risk populations, including children and women of reproductive age (15-49 years). However, there is increasing interest in community-wide mass drug administration (cMDA) which includes deworming adults who serve as infection reservoirs as a method to improve coverage and possibly to interrupt STH transmission. We investigated determinants of cMDA coverage by comparing high-coverage clusters (HCCs) and low-coverage clusters (LCCs) receiving STH cMDA in three countries. METHODS: A convergent mixed-methods design was used to analyze data from HCCs and LCCs in DeWorm3 trial sites in Benin, India, and Malawi following three rounds of cMDA. Qualitative data were collected via 48 community-level focus group discussions. Quantitative data were collected via routine activities nested within the DeWorm3 trial, including annual censuses and coverage surveys. The Consolidated Framework for Implementation Research (CFIR) guided coding, theme development and a rating process to determine the influence of each CFIR construct on cMDA coverage. RESULTS: Of 23 CFIR constructs evaluated, we identified 11 constructs that differentiated between HCCs and LCCs, indicating they are potential drivers of coverage. Determinants differentiating HCC and LCC include participant experiences with previous community-wide programs, communities' perceptions of directly observed therapy (DOT), perceptions about the treatment uptake behaviors of neighbors, and women's agency to make household-level treatment decisions. CONCLUSION: The convergent mixed-methods study identified barriers and facilitators that may be useful to NTD programs to improve cMDA implementation for STH, increase treatment coverage, and contribute to the successful control or elimination of STH. TRIAL REGISTRATION: The parent trial was registered at clinicaltrials.gov (NCT03014167).

Effectiveness of ivermectin mass drug administration in the control of soil-transmitted helminth infections in endemic populations: a systematic review and meta-analysis.

BACKGROUND: Current soil-transmitted helminth (STH) control guidelines endorse the use of albendazole or mebendazole for school-based targeted preventive chemotherapy (PC), yet their reduced efficacy against Strongyloides stercoralis and Trichuris trichiura presents significant limitations. Emerging evidence indicates that community-wide PC [or mass drug administration (MDA)] using ivermectin, commonly used in other neglected tropical disease (NTD) control programs, may play an important role in controlling these parasites. We conducted a systematic review and meta-analysis to evaluate the effectiveness of ivermectin PC in reducing STH prevalence in endemic populations. METHODS: We searched Pubmed, EMBASE, and Web of Science on February 14, 2023, for studies that investigated the effectiveness of ivermectin PC, either alone or in combination with other anthelmintic drugs, on STH infections, and provided a measure of STH prevalence before and after PC. We calculated pooled prevalence reductions for each STH using random-effects meta-analyses. Our protocol is available on PROSPERO (registration number CRD42023401219). RESULTS: A total of 21 were eligible for the systematic review, of which 15 were eligible for meta-analysis. All studies delivered ivermectin through MDA. The pooled prevalence reduction of S. stercoralis following MDA with ivermectin alone was 84.49% (95% CI 54.96-94.66) across five studies and 81.37% (95% CI 61.62-90.96) across seven studies with or without albendazole. The prevalence reduction of T. trichiura was 49.93% (95% CI 18.23-69.34) across five studies with ivermectin alone, and 89.40% (95% CI 73.66-95.73) across three studies with the addition of albendazole. There was high heterogeneity for all syntheses (I2 > 65%). CONCLUSIONS: This study underscores the key role of ivermectin-based MDA in addressing limitations in current global STH guidelines in terms of limited efficacy against S. stercoralis and T. trichiura. Based on these findings, revising international STH guidelines to include ivermectin is a promising option to progress the control and eventual elimination of STHs and other NTDs.

Spatial heterogeneity in mass drug administration from a longitudinal epidemiological study assessing transmission interruption of soil transmitted helminths in the Wolaita zone of southern Ethiopia (Geshiyaro Project).

OBJECTIVES: Deworming programmes of soil-transmitted helminths are generally monitored and evaluated by aggregating drug coverage and infection levels at a district level. However, heterogeneity in drug coverage at finer spatial scales means indicators may remain above thresholds for elimination as a public health problem or of transmission in some areas. This paper aims to highlight the misleading information that aggregating data at larger spatial scales can have for programme decision making. METHODS: Drug coverage data from the Geshiyaro project were compared at two spatial scales with reference to the World Health Organisation's targets. District (woreda) and village (kebele) level were compared. The association between infection levels and drug coverage was analysed by fitting a weighted least-squares function to the mean intensity of infection (eggs per gram of faeces) against drug coverage. RESULTS: The data show clearly that when the evaluation of coverage is aggregated to the district level, information on heterogeneity at a finer spatial scale is lost. Infection intensity decreases significantly (p = 0.0023) with increasing drug coverage. CONCLUSION: Aggregating data at large spatial scales can result in prematurely ceasing deworming, prompting rapid infection bounce-back. There is a strong need to define context-specific spatial scales for monitoring and evaluating intervention programmes.

Mass drug administration campaigns: comparing two approaches for schistosomiasis and soil-transmitted helminths prevention and control in selected Southern Malawi districts.

BACKGROUND: Mass drug administration is one of the key interventions recommended by WHO to control certain NTDs. With most support from donors, health workers distribute antihelminthic drugs annually in Malawi. Mean community coverage of MDA from 2018 to 2020 was high at 87% for praziquantel and 82% for albendazole. However, once donor support diminishes sustaining these levels will be challenging. This study intended to compare the use of the community-directed intervention approach with the standard practice of using health workers in delivery of MDA campaigns. METHODS: This was a controlled implementation study carried out in three districts, where four health centres and 16 villages in each district were selected and randomly assigned to intervention and control arms which implemented MDA campaigns using the CDI approach and the standard practice, respectively. Cross-sectional and mixed methods approach to data collection was used focusing on quantitative data for coverage and knowledge levels and qualitative data to assess perceptions of health providers and beneficiaries at baseline and follow-up assessments. Quantitative and qualitative data were analyzed using IBM SPSS software version 26 and NVivo 12 for Windows, respectively. RESULTS: At follow-up, knowledge levels increased, majority of the respondents were more knowledgeable about what schistosomiasis was (41%-44%), its causes (41%-44%) and what STH were (48%-64%), while knowledge on intermediate host for schistosomiasis (19%-22%), its types (9%-13%) and what causes STH (15%-16%) were less known both in intervention and control arm communities. High coverage rates for praziquantel were registered in intervention (83%-89%) and control (86%-89%) communities, intervention (59%-79) and control (53%-86%) schools. Costs for implementation of the study indicated that the intervention arm used more resources than the control arm. Health workers and community members perceived the use of the CDI approach as a good initiative and more favorable over the standard practice. CONCLUSIONS: The use of the CDI in delivery of MDA campaigns against schistosomiasis and STH appears feasible, retains high coverages and is acceptable in intervention communities. Despite the initial high costs incurred, embedding into community delivery platforms could be considered as a possible way forward addressing the sustainability concern when current donor support wanes. TRIAL REGISTRATION: Pan-African Clinical Trials Registry PACTR202102477794401, date: 25/02/2021.

Assessment of microfilaremia in 'hotspots' of four lymphatic filariasis endemic districts of Nepal during post-MDA surveillance.

BACKGROUND: The lymphatic filariasis (LF) elimination program in all sixty-three endemic districts of Nepal was based on annual mass drug administration (MDA) using a combination of diethylcarbamazine (DEC) and albendazole for at least 5 years. The MDA program was started in the Parsa district of the Terai region and at least six rounds of MDA were completed between 2003 and 2017 in all filariasis endemic districts of Central Nepal. Transmission Assessment Survey (TAS) report indicated that circulating filarial antigen (CFA) prevalence was below the critical value i.e., ≤ 2% in selected LF endemic districts of Central Nepal. Based on the TAS report, antigen-positive cases were found clustered in the foci of those districts which were considered as "hotspots". Hence the present study was designed to assess microfilaremia in hotspots of four endemic districts of Central Nepal after the MDA program. METHODOLOGY AND PRINCIPAL FINDINGS: The present study assessed microfilaremia in hotspots of four endemic districts i.e. Lalitpur and Dhading from the hilly region and Bara and Mahottari from the Terai region of Central Nepal. Night blood samples (n = 1722) were collected by finger prick method from the eligible sample population irrespective of age and sex. Community people's participation in the MDA program was ensured using a structured questionnaire and chronic clinical manifestation of LF was assessed using standard case definition. Two districts one each from the hilly region (Lalitpur district) and Terai region (Bara district) showed improved microfilaria (MF) prevalence i.e. below the critical level (<1%) while the other two districts are still over the critical level. There was a significantly high prevalence of MF in male (p = <0.05) and ≥41 years of age group (p = <0.05) community people in the hotspots of four endemic districts. People who participated in the previous rounds of the MDA program have significantly low MF prevalence. The upper confidence limit of MF prevalence in all hotspots of four districts was above the critical level (>1%). Chronic clinical manifestation of LF showed significant association with the older age group (≥41 years) but not with sex. CONCLUSIONS: The study revealed LF transmission improved in hotspots of two districts while continued in others but the risk of LF resurgence cannot be ignored since the upper confidence level of MF prevalence is over 1% in all the hotspots studied districts. High MF prevalence is well correlated with the number of MDA rounds but not with the MDA coverage. Community people involved in MDA drug uptake in any previous and last rounds have significantly less MF infection. Hence it is recommended that before deciding to stop the MDA rounds it is essential to conduct the MF survey at the hotspots of the sentinel sites.