Health workers' perspectives on school-based mass drug administration control programs for soil-transmitted helminthiasis and schistosomiasis in Ogun State, Nigeria.

BACKGROUND: Soil-transmitted helminthiasis (STH) and schistosomiasis (SCH) are among the most prevalent neglected tropical diseases (NTDs), affecting 1.5 billion globally, with a significant burden in sub-Saharan Africa, particularly Nigeria. These diseases impair health and contribute to socio-economic challenges, especially in children, undermining educational and future economic prospects. The 2030 NTD Roadmap highlights Mass Drug Administration (MDA) as a critical strategy for controlling these NTDs, targeting vulnerable populations like school-age children. Despite some successes, challenges persist, indicating the need for deeper insights into program implementation. This study focuses on the perspectives of health workers implementing MDA in selected local government areas (LGAs) of Ogun State, Nigeria, aiming to identify challenges and enablers that align with the broader NTD 2030 goals. METHODOLOGY/PRINCIPAL FINDINGS: The study used a qualitative research approach involving focus group discussions and in-depth interviews with health workers engaged in neglected tropical disease control programs in Ogun State, Nigeria, between July and September 2022. A semi-structured questionnaire guided the exploration of ideas, and the data were analyzed using the QRS Nvivo 12 software package. The study found that the school-based MDA control program's efficacy largely relies on strong collaborations and partnerships, particularly with educators, community heads, and other stakeholders. These alliances and strategic communication methods, like town announcements and media campaigns, have been pivotal in reaching communities. However, the program does grapple with hurdles such as parental misconceptions, limited funds, insufficient staffing, and misalignment with the Ministry of Education. It is recommended to boost funding, foster early stakeholder involvement, enhance mobilization techniques, and consider introducing a monitoring card system similar to immunization. CONCLUSIONS/SIGNIFICANCE: The MDA Integrated Control Programs for STH and SCH in Ogun State schools demonstrate a holistic approach, integrating knowledge, collaboration, communication, and feedback. Health workers have shown commitment and adeptness in their roles. However, achieving maximum efficacy requires addressing critical barriers, such as parental misconceptions and funding challenges. Adopting the recommended strategies, including proactive communication, increased remuneration, and introducing a tracking system, can significantly enhance the program's reach and impact. The involvement of all stakeholders, from health workers to community leaders and parents, is essential for the program's sustainability and success.

Molecular markers of artemisinin resistance during falciparum malaria elimination in Eastern Myanmar.

BACKGROUND: Artemisinin resistance in Plasmodium falciparum threatens global malaria elimination efforts. To contain and then eliminate artemisinin resistance in Eastern Myanmar a network of community-based malaria posts was instituted and targeted mass drug administration (MDA) with dihydroartemisinin-piperaquine (three rounds at monthly intervals) was conducted. The prevalence of artemisinin resistance during the elimination campaign (2013-2019) was characterized. METHODS: Throughout the six-year campaign Plasmodium falciparum positive blood samples from symptomatic patients and from cross-sectional surveys were genotyped for mutations in kelch-13-a molecular marker of artemisinin resistance. RESULT: The program resulted in near elimination of falciparum malaria. Of 5162 P. falciparum positive blood samples genotyped, 3281 (63.6%) had K13 mutations. The prevalence of K13 mutations was 73.9% in 2013 and 64.4% in 2019. Overall, there was a small but significant decline in the proportion of K13 mutants (p < 0.001). In the MDA villages there was no significant change in the K13 proportions before and after MDA. The distribution of different K13 mutations changed substantially; F446I and P441L mutations increased in both MDA and non-MDA villages, while most other K13 mutations decreased. The proportion of C580Y mutations fell from 9.2% (43/467) before MDA to 2.3% (19/813) after MDA (p < 0.001). Similar changes occurred in the 487 villages where MDA was not conducted. CONCLUSION: The malaria elimination program in Kayin state, eastern Myanmar, led to a substantial reduction in falciparum malaria. Despite the intense use of artemisinin-based combination therapies, both in treatment and MDA, this did not select for artemisinin resistance.

Mixed-method evaluation study of a targeted mass drug administration of long-acting anti-malarials among children aged 3 months to 15 years in the Bossangoa sub-prefecture, Ouham, Central African Republic, during the COVID-19 pandemic.

BACKGROUND: In 2020, during the COVID-19 pandemic, Médecins Sans Frontières (MSF) initiated three cycles of dihydroartemisin-piperaquine (DHA-PQ) mass drug administration (MDA) for children aged three months to 15 years within Bossangoa sub-prefecture, Central African Republic. Coverage, clinical impact, and community members perspectives were evaluated to inform the use of MDAs in humanitarian emergencies. METHODS: A household survey was undertaken after the MDA focusing on participation, recent illness among eligible children, and household satisfaction. Using routine surveillance data, the reduction during the MDA period compared to the same period of preceding two years in consultations, malaria diagnoses, malaria rapid diagnostic test (RDT) positivity in three MSF community healthcare facilities (HFs), and the reduction in severe malaria admissions at the regional hospital were estimated. Twenty-seven focus groups discussions (FGDs) with community members were conducted. RESULTS: Overall coverage based on the MDA card or verbal report was 94.3% (95% confidence interval (CI): 86.3-97.8%). Among participants of the household survey, 2.6% (95% CI 1.6-40.3%) of round 3 MDA participants experienced illness in the preceding four weeks compared to 30.6% (95% CI 22.1-40.8%) of MDA non-participants. One community HF experienced a 54.5% (95% CI 50.8-57.9) reduction in consultations, a 73.7% (95% CI 70.5-76.5) reduction in malaria diagnoses, and 42.9% (95% CI 36.0-49.0) reduction in the proportion of positive RDTs among children under five. A second community HF experienced an increase in consultations (+ 15.1% (- 23.3 to 7.5)) and stable malaria diagnoses (4.2% (3.9-11.6)). A third community HF experienced an increase in consultations (+ 41.1% (95% CI 51.2-31.8) and malaria diagnoses (+ 37.3% (95% CI 47.4-27.9)). There were a 25.2% (95% CI 2.0-42.8) reduction in hospital admissions with severe malaria among children under five from the MDA area. FGDs revealed community members perceived less illness among children because of the MDA, as well as fewer hospitalizations. Other indirect benefits such as reduced household expenditure on healthcare were also described. CONCLUSION: The MDA achieved high coverage and community acceptance. While some positive health impact was observed, it was resource intensive, particularly in this rural context. The priority for malaria control in humanitarian contexts should remain diagnosis and treatment. MDA may be additional tool where the context supports its implementation.

Prolonged mass azithromycin distributions and macrolide resistance determinants among preschool children in Niger: A sub-study of a cluster-randomized trial (MORDOR).

BACKGROUND: Randomized controlled trials found that twice-yearly mass azithromycin administration (MDA) reduces childhood mortality, presumably by reducing infection burden. World Health Organization (WHO) issued conditional guidelines for mass azithromycin administration in high-mortality settings in sub-Saharan Africa given concerns for antibiotic resistance. While prolonged twice-yearly MDA has been shown to increase antibiotic resistance in small randomized controlled trials, the objective of this study was to determine if macrolide and non-macrolide resistance in the gut increases with the duration of azithromycin MDA in a larger setting. METHODS AND FINDINGS: The Macrolide Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) study was conducted in Niger from December 2014 to June 2020. It was a cluster-randomized trial of azithromycin (A) versus placebo (P) aimed at evaluating childhood mortality. This is a sub-study in the MORDOR trial to track changes in antibiotic resistance after prolonged azithromycin MDA. A total of 594 communities were eligible. Children 1 to 59 months in 163 randomly chosen communities were eligible to receive treatment and included in resistance monitoring. Participants, staff, and investigators were masked to treatment allocation. At the conclusion of MORDOR Phase I, by design, all communities received an additional year of twice-yearly azithromycin treatments (Phase II). Thus, at the conclusion of Phase II, the treatment history (1 letter per 6-month period) for the participating communities was either (PP-PP-AA) or (AA-AA-AA). In Phase III, participating communities were then re-randomized to receive either another 3 rounds of azithromycin or placebo, thus resulting in 4 treatment histories: Group 1 (AA-AA-AA-AA-A, N = 51), Group 2 (PP-PP-AA-AA-A, N = 40), Group 3 (AA-AA-AA-PP-P, N = 27), and Group 4 (PP-PP-AA-PP-P, N = 32). Rectal swabs from each child (N = 5,340) were obtained 6 months after the last treatment. Each child contributed 1 rectal swab and these were pooled at the community level, processed for DNA-seq, and analyzed for genetic resistance determinants. The primary prespecified outcome was macrolide resistance determinants in the gut. Secondary outcomes were resistance to beta-lactams and other antibiotic classes. Communities recently randomized to azithromycin (groups 1 and 2) had significantly more macrolide resistance determinants than those recently randomized to placebo (groups 3 and 4) (fold change 2.18, 95% CI 1.5 to 3.51, Punadj < 0.001). However, there was no significant increase in macrolide resistance in communities treated 4.5 years (group 1) compared to just the most recent 2.5 years (group 2) (fold change 0.80, 95% CI 0.50 to 1.00, Padj = 0.010), or between communities that had been treated for 3 years in the past (group 3) versus just 1 year in the past (group 4) (fold change 1.00, 95% CI 0.78 to 2.35, Padj = 0.52). We also found no significant differences for beta-lactams or other antibiotic classes. The main limitations of our study were the absence of phenotypic characterization of resistance, no complete placebo arm, and no monitoring outside of Niger limiting generalizability. CONCLUSIONS: In this study, we observed that mass azithromycin distribution for childhood mortality among preschool children in Niger increased macrolide resistance determinants in the gut but that resistance may plateau after 2 to 3 years of treatment. Co-selection to other classes needs to be monitored. TRIAL REGISTRATION: NCT02047981 https://classic.clinicaltrials.gov/ct2/show/NCT02047981.

Praziquantel-related visual disorders among recipients in mass drug administration campaigns in schistosomiasis endemic settings: Systematic review and meta-analysis protocol.

BACKGROUND: Hundreds of millions of doses of Praziquantel (PZQ) have been administered to persons with and without schistosomiasis living in schistosomiasis endemic settings, through the mass drug administration (MDA) strategy which started in the early 2000s. A recent publication suggested high risk of PZQ-related visual disorders, raising public health concerns. We aim to systematically synthesize evidence on the magnitude of PZQ-related visual disorders. METHODS: We will search PubMed, Google Scholar, CINAHL, SCOPUS, CENTRAL and LILACS from 1977 (when the first human clinical trials on PZQ started) to 31st May 2024, with no language restrictions. The key search terms will include "Praziquantel", "PZQ", "visual disorder", "adverse events", "side effects", "blurry vision" and "visual impairment" together with alternative terms and synonyms. All the countries endemic for schistosomiasis will be included as search terms. We will also search HINARI, Africa Journals Online, Thesis Databases and Preprint Repositories. Where necessary, we will contact expert researchers working in the field of schistosomiasis, UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR), pharmaceutical industries, country-specific Food and Drug Authorities (FDAs) and the European Medicines Agency databases. We will search Conference Proceedings and reference lists of relevant studies for additional studies. At least two authors will independently select studies, extract data and assess risk of bias in the included studies. Any disagreements or discrepancies will be resolved through discussion between the reviewers. Heterogeneity will be explored graphically, and statistically using the I2-statistic. We will conduct random-effects meta-analysis when heterogeneity is appreciable, and express dichotomous outcomes (visual adverse events including excessive lacrimation, blurry vision and visual impairments) as risk ratio (RR) or Odds Ratio (OR) with their 95% confidence interval (CI). We will perform subgroup analysis to assess the impact of heterogeneity, and sensitivity analyses to test the robustness of the effect estimates. The overall level of evidence will be assessed using GRADE. EXPECTED OUTCOMES: The present review expects to identify and categorize visual disorders occurring after administration of PZQ, alone or in combination with other drugs. By synthesizing the data from multiple studies, the review aims to present a quantitative assessment of the risk or odds of experiencing a visual disorder in different populations after ingesting PZQ. The review will also generate insights into whether PZQ in combination with other drugs are associated with increased odds of visual disorders and whether the occurrence of visual disorders correlates with dosage or treatment duration. Policymakers, public health experts and stakeholders could rely on the review findings to deliver context-sensitive preventive chemotherapy programs by adjusting drug combinations or dosing schedules to reduce risk of visual adverse effects in populations treated with PZQ. The review aims to identify gaps in the current evidence regarding visual disorders following PZQ administration in schistosomiasis endemic settings which can serve as the basis for future research on important but unanswered questions. DISSEMINATION AND PROTOCOL REGISTRATION: The findings of this study will be disseminated through stakeholder forums, conferences, and peer-review publications. The review protocol has been registered in the International Prospective Register for Systematic Reviews (PROSPERO)- CRD42023417963.

Effects of paediatric schistosomiasis control programmes in sub-Saharan Africa: A systematic review.

Preventive chemotherapy by mass drug administration is globally recommended as the primary method of reaching the elimination of schistosomiasis, especially in the high risk-paediatric population. This systematic review provides a summary of the effects of paediatric schistosomiasis control programs on eliminating schistosomiasis in sub-Saharan Africa. A systematic search was conducted in PubMed, EBSCOhost, and other databases to obtain studies regarding the effects of paediatric schistosomiasis control programmes in sub-Saharan Africa. 3455 studies were screened for eligibility, included articles reported on both paediatrics control programmes and schistosomiasis, and articles were excluded when they did not report on schistosomiasis control programmes in paediatrics exclusively. 40 selected studies were critically appraised using the JBI critical appraisal tools for relevance and 30 studies were included in the study. An in-depth quantitative descriptive analysis was conducted, and a comprehensive narrative summary explained the results within the scope of the review questions. The results show that despite preventive chemotherapy lowering schistosomiasis prevalence, chances of re-infection are high in endemic areas. Preventive chemotherapy without complementary interventions including safe water provision and proper sanitation, snail control and health education on the aetiology of schistosomiasis, transmission pattern and control practices might not eliminate schistosomiasis.

Onchocerciasis in the Cameroon-Chad border area after more than 20 years of annual mass ivermectin distribution.

BACKGROUND: The main vectors of onchocerciasis in Africa are Simulium damnosum sensu lato, which transmit the causative agent Onchocerca volvulus. The force of transmission is driven by the vector density, hence influencing the disease prevalence and intensity. Onchocerciasis is currently targeted for elimination using mass drug administration (MDA) of ivermectin, a potent microfilaricide. MDA in Cameroon began in 1987 in the Vina Valley, an endemic cross-border area with Chad, known for high vector densities and precontrol endemicity. Evaluations in 2008-2010 in this area showed ongoing transmission, while border areas in Chad were close to interrupting transmission. This study aimed to evaluate transmission in this area after several rounds of MDA since the last evaluation surveys. METHODS: Black flies were collected by human landing catches at seven border sites in Cameroon, twice a week, from August 2021 to March 2022. A fraction of the flies was dissected for parity assessment and identification of Onchocerca larval stages. The transmission indices were estimated. Black fly larvae were also collected from the breeding sites at the fly catching sites and identified to species level by cytotaxonomy. RESULTS: A total of 14,303 female flies were collected, and 6918 were dissected. Of these, 4421 (64.0%) were parous. The total biting rates were high, reaching up to 16,407 bites/person/study period, and transmission potential (third-stage larvae (L3) from head/all L3) were 367/702, 146/506, 51/55, 20/32, 0/3, 0/0, and 0/0 infective larvae/person, respectively, for Mbere-Tchad, Babidan, Hajam/V5, Gor, Djeing, Touboro, and Koinderi. Infectivity rates (L3 from head) were 16.00, 12.75, 5.15, and 4.07 infective females (L3H)/1000 parous flies for Haijam, Mbere-Tchad, Babidan, and Gor, respectively. These values exceed the World Health Organization (WHO) thresholds of ≤ 20 annual transmission potential (ATP) or < 1 infective female/1000 parous females. The major vectors identified were Simulium damnosum sensu stricto, S. squamosum, and for the first time in the area, S. yahense. CONCLUSIONS: More than 20 years of MDA has not eliminated onchocerciasis in the study area; hence, this area is a potential source of reintroduction of onchocerciasis in Chad and would require alternative treatment strategies. Many factors such as MDA efficiency, effectiveness of ivermectin, and cytospecies composition may be contributing to transmission persistence.

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 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.

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.

Entomological assessment in 'hotspots' of four lymphatic filariasis endemic districts, Central Nepal during post-MDA surveillance.

BACKGROUND OBJECTIVES: Annual mass drug administration (MDA) is the main strategy to interrupt the transmission of lymphatic filariasis (LF) in the community. The main aim of monitoring the MDA program, for its effectiveness and interruption of LF is the post-MDA surveillance using antigen survey in children born after MDA. The latest technique of new research suggests that xenomonitoring is an effective tool for monitoring LF intervention. The objective of this study was to assess the W. bancrofti infection/or infectivity in vector mosquitoes by xenomonitoring during post-MDA surveillance. METHODS: A descriptive cross-sectional study was conducted in the hotspots of selected four districts of Central Nepal. A gravid trap technique was used for sampling mosquitoes. Infection/or infectivity was determined via the dissection of vector mosquitoes. Anopheles, Aedes, Armigerus and Culex species were collected from hotspots of four endemic districts, two from the hilly region (Lalitpur and Dhading) and two from Terai region (Bara and Mahottari) of Central Nepal. RESULTS: A total of 4450 mosquitoes belonging to four genera, Anopheles, Culex, Armigeres, and Aedes were collected from four hotspots. The distribution of Culex quinquefasciatus was found to be the highest, 88.9% (n=3955/4450) followed by Cx. vishnui (4.5%), Armigeres sp (5.8%), An. culicifascies (0.2%), Aedes spp (0.8%). The proportion of female mosquitoes trapped is significantly higher. A total of 3344 parous Cx. quinquefasciatus mosquitoes were dissected for any larval stage of W. bancrofti. We could not find any filarial infection in dissected mosquito samples. INTERPRETATION CONCLUSION: We conclude that the gravid trap is an efficient tool for the collection of gravid Cx. quinquefasciatus mosquitoes for xenomonitoring studies of filariasis endemic regions. Vector composition indicated a maximum number of vector mosquitoes of lymphatic filariasis were trapped compared with the other three species. Distribution and density of Cx. quinquefasciatus was found highest in four hotspots of endemic districts. None of the Cx. quinquefasciatus dissected were found to be infected by larval forms of filaria. Since the low levels of infection persistence in the human population in these hot spots, vector infection and infectivity can't be ignored. Microscopic xenomonitoring at a low level of infection persistent is less likely to be efficient so molecular xenomonitoring along with a large sample should be required in each of the hot spots of the districts. Additionally, area is receptive so further vector control intervention should be required to reduce the risk of resurgence of infection.

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.

Progress towards elimination of onchocerciasis in the Region du Sud-Ouest of Burkina Faso which was previously subject to a recrudescence event after vector control.

BACKGROUND: The Sud-Ouest region of Burkina Faso (especially the Bougouriba valley) has been historically problematic with respect to onchocerciasis control, with a recrudescence of infections after vector control carried out the WHO Onchocerciasis Control Programme was halted in 1989. After 1996, mass drug administration of ivermectin was instigated to control the recrudescence so that it would no longer constitute a public health problem. However, in 2010 WHO changed its recommended policy from control to elimination, and in 2013 biannual Community-Directed Treatment with Ivermectin (CDTI) was instigated. Epidemiological surveys were carried-out in 2011 and 2018 to determine whether CDTI was producing a decline in infection levels and progress towards elimination. METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional study was conducted across 20 villages in four health districts in 2011 and 29 villages in 2018. Individuals aged five years and above were examined by skin-snip, and the prevalence and microfilarial load was determined for each village. In 2011, 75% of villages had some infections and 20% had prevalences >5%, with a mean prevalence across all villages of 2.63% (range 0.0-9.7%), and community microfilarial load ranging from 0 to 0.25 microfilariae per biopsy. In 2018, nine villages (= 31% of total) had some infections, with prevalences ranging from 0.41% to 3.54%, and a mean prevalence across all villages of 0.37%. Community microfilarial load ranged from 0 to 0.1. Amongst those people found to be microfilarial positive, 87% had a history of migration. CONCLUSIONS/SIGNIFICANCE: The endemicity of onchocerciasis infection in the Sud-Ouest region has declined to low levels and seems to be progressing towards elimination. Our findings indicated that biannual CDTI is having good effect, but it should continue for a number of years to ensure elimination of transmission. However, progress towards elimination has a troublesome history in this region, and it would be advisable to select more sentinel villages to have confidence in any future epidemiological and entomological surveys, especially Stop-MDA surveys. With positive individuals migrating between countries, cross-border collaboration needs more attention to ensure effective treatment for onchocerciasis elimination.

Impact of conflict on the elimination targets of lymphatic filariasis, schistosomiasis and soil-transmitted helminths in Cabo Delgado province, Mozambique.

BACKGROUND: Mozambique has one of the highest burdens of neglected tropical diseases in Africa. Lymphatic filariasis, schistosomiasis and soil-transmitted helminths are being targeted for elimination as part of integrated mass drug administration campaigns. The progress made towards interruption of transmission has been affected by recent conflict in Cabo Delgado province. The aim of this paper was to determine the potential impact of this crisis on the neglected tropical diseases programme and the challenges in reaching the elimination goals of 2030. METHODOLOGY: A desk-based secondary data analysis was conducted on publicly available sources of neglected tropical diseases, conflict incidents, internally displaced persons and geographical access between 2020 and 2022. Data were summarised and mapped using GIS software. A combined risk stratified assessment at district level was developed with five classifications i) Very high-risk; ii) High-risk; iii) Medium to high-risk; iv) Medium risk; and v) Not at risk due to conflict absence but co-endemic. RESULTS: Lymphatic filariasis, schistosomiasis and soil-transmitted helminths were co-endemic in 115 out of 156 (74%) districts. Between 2020 and 2022 a total of 1,653 conflict-related incidents were reported, most of them in Cabo Delgado province (n = 1,397, 85%). A five-fold increase of internally displaced persons was recorded from April 2020 (n = 172,186) to November 2022 (n = 935,130). Geographical accessibility also deteriorated across the province with an increase from five (29%) in 2021 to seven (41%) districts in 2022 classified as hard-to-reach. The combined risk stratification identified that most districts in Cabo Delgado province had medium to high-risk (n = 7; 41%); very high-risk (n = 5, 29%); medium risk (n = 3, 18%); high-risk (n = 2, 12%). CONCLUSION: Most of the districts of Cabo Delgado were considered to be at risk of not meeting the neglected tropical diseases road map 2030 targets due to the humanitarian crisis ongoing. There is the need for practical strategies and funding to overcome these hostile challenges.

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.

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.

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.

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.