Triple-drug therapy with ivermectin, diethylcarbamazine and albendazole for the acceleration of lymphatic filariasis elimination in Kenya: Programmatic implementation and results of the first impact assessment.

The World Health Organization (WHO) endorsed the use of triple-drug mass drug administration (MDA) regimen with ivermectin, diethylcarbamazine (DEC) and albendazole (commonly abbreviated as IDA) to accelerate the elimination of lymphatic filariasis (LF) as a public health problem in settings where onchocerciasis is not co-endemic. The National Programme for Elimination of LF (NPELF) in Kenya was among the first adopters of the IDA-MDA and two annual rounds were provided in 2018 and 2019 to the residents of Lamu County and Jomvu sub-County in the coast region. This study documented the feasibility of successfully delivering the two rounds of IDA-MDA. An operational research study was undertaken to determine efficient sampling strategies, indicators, and the appropriate population groups that could be used for the monitoring and evaluation of LF programs using IDA-MDA for the elimination of the disease as a public health problem. Two cross-sectional surveys were conducted at baseline in 2018 before IDA-MDA and an impact assessment 17 months after the second round of IDA-MDA. The reported epidemiological treatment coverage was at least 80% in all implementation units during each round of IDA-MDA. Blood samples were tested for filarial antigenemia using commercial Filariasis Test Strips (FTS) and any individual found to be positive was tested again at night for the presence of microfilariae in finger prick blood smears using microscopy. The overall prevalence of circulating filarial antigen (CFA) was relatively low at the baseline survey with Jomvu having 1.39% (95% CI: 0.91, 2.11) and Lamu having 0.48% (95% CI: 0.21, 1.13). Significant reduction in CFA prevalence was observed during the impact assessment after the two annual rounds of mass treatment. The overall relative reduction (%) in CFA prevalence following the two rounds of MDA with IDA was significant in both Jomvu (52.45%, Z = -2.46, P < 0.02) and Lamu (52.71%, Z = -1.97, P < 0.05). Heterogeneity, however, was observed in the CFA prevalence reduction between random and purposive clusters, as well as between adult and child populations. The results of the impact assessment survey offered strong evidence that it was safe to stop the IDA-MDA in the two EUs because transmission appears to have been interrupted. It is also important to implement a post-treatment surveillance system which would enable efficient detection of any recrudescence of LF transmission at a sub-evaluation unit level. Our findings show that IDA-MDA may be considered for acceleration of LF elimination in other settings where onchocerciasis is not co-endemic.

Acceptance of Mass Drug Administration for Prophylaxis against Lymphatic Filariasis in a Tribal Endemic Area: A Descriptive Cross-sectional Study.

BACKGROUND: India is at a critical stage to eliminate filariasis. Uncovering the factors governing may help taking appropriate measures to achieve the goal. OBJECTIVES: This study evaluated the acceptance of "mass drug administration" (MDA) for prophylaxis against filariasis and the factors facilitating and interfering with it. MATERIALS AND METHODS: A cross-sectional study was conducted in a tribal endemic area of India from May 2022 to October 2022. A validated 29-item self-administered questionnaire was used to collect the data. Items were grouped under "knowledge," "social processes," "think and feel," "practical factors," and "motivation/hesitancy" domains. RESULTS: Of 101 participants, majority were aware of the disease (92.1%), its vector (74.3%), at least one disability caused (87.2%), and governmental scheme of MDA (69.3%). Two-thirds never received and 85.1% did not receive MDA within 1 year. 68.3% refused of distribution of MDA to their doorstep. Majority were concerned for getting MDA for self and their family/friends; however, 49.5% showed inability to take independent decision. More than 30% disagreed to get MDA had it been available. The region with the highest concerns for adverse drug effects showed minimum MDA consumption than others (P < 0.05). MDA acceptance/consumption was significantly associated with knowledge about disability caused, distribution of drugs by a health-care representative to doorstep, behavior of the representative, and concerns about potential adverse drug effects. CONCLUSION: MDA coverage was inadequate in the study population. Level of knowledge, practical difficulties in getting drugs, inapt thinking/concerns, motivation, awareness about disabilities caused, door-to-door drug distribution, and behavior of health-care representative(s), were identified as factors significantly affecting acceptance of MDA.

Efficacy of ivermectin and albendazole combination in suppressing transmission of lymphatic filariasis following mass administration in Tanzania: a prospective cohort study.

BACKGROUND: Preventive chemotherapy with ivermectin and albendazole (IA) in mass drug administration (MDA) programs for all at-risk populations is the core public health intervention to eliminate lymphatic filariasis (LF). Achieving this goal depends on drug effectiveness in reducing parasite reservoirs in the community to halt transmission. We assessed the efficacy of ivermectin and albendazole in clearing microfilariae and circulating filarial antigens (CFA) following MDA. METHODS: This community-based prospective study was conducted in Mkinga district, Tanga region, Tanzania, from November 2018 to June 2019. A total of 4115 MDA-eligible individuals were screened for CFA using Filarial test strips. CFA positives were re-examined for microfilariae by microscopy. CFA and microfilariae positive individuals were enrolled and received IA through MDA campaign. The status of microfilariae and CFA was monitored before MDA, and on day 7 and six-month following MDA. The primary efficacy outcomes were the clearance rates of microfilariae on day 7 and six-months, and CFA at 6 months of post-MDA. The McNemar test assessed the proportions of microfilariae positive pre- and post-MDA, while Chi-square tests were utilized to examine factors associated with CFA status six months post-MDA. RESULTS: Out of 4115 individuals screened, 239 (5.8%) tested positive for CFA, of whom 11 (4.6%) were also positive for microfilariae. Out of the ten microfilariae-positive individuals available for follow-up on day 7, nine tested negative, yielding a microfilariae clearance rate of 90% [95% confidence interval (CI): 59.6-98.2%]. Participants who tested negative for microfilariae on day 7 remained free of microfilariae six months after MDA. However, those who did not clear microfilariae on day-7 remained positive six-months post-MDA. The McNemar test revealed a significant improvement in microfilariae clearance on day 7 following MDA (P = 0.02). Out of 183 CFA-positive individuals who were available at 6-month follow-up, 160 (87.4%) remained CFA positive, while 23 became CFA negative. The CFA clearance rate at 6 months post-MDA was 12.6% (95% CI: 8.5-8.5%). There was no significant association of variability in ivermectin plasma exposure, measured by maximum concentration or area under the curve, and the clearance status of microfilariae or CFA post-MDA. CONCLUSIONS: Preventive chemotherapy with IA effectively clears microfilariae within a week. However, it is less effective in clearing CFA at six months of post-MDA. The low clearance rate for filarial antigenemia underscores the need for alternative drug combinations and additional preventive measures to achieve LF elimination by 2030.

A review of epidemiology of lymphatic filariasis in Nigeria.

Lymphatic filariasis is a neglected tropical disease that affects the lymphatic system of humans. The major etiologic agent is a nematode called Wuchereria bancrofti, but Brugia malayi and Brugia timoriare sometimes encountered as causative agents. Mosquitoes are the vectors while humans the definitive hosts respectively. The burden of the disease is heavier in Nigeria than in other endemic countries in Africa. This occurs with increasing morbidity and mortality at different locations within the country, the World Health Organization recommended treatments for lymphatic filariasis include the use of Albendazole (400mg) twice per year in co-endemic areas with loa loa, Ivermectin (200mcg/kg) in combination with Albendazole (400mg) in areas that are co-endemic with onchocerciasis, ivermectin (200mcg/kg) with diethylcarbamazine citrate (DEC) (6mg/kg) and albendazole (400mg) in areas without onchocerciasis. This paper covered a systematic review, meta-analysis, and scoping review on lymphatic filariasis in the respective geopolitical zones within the country. The literature used was obtained through online search engines including PubMed and Google Scholar with the heading "lymphatic filariasis in the name of the state", Nigeria. This review revealed an overall prevalence of 11.18% with regional spread of Northwest (1.59%), North Central and North East, (4.52%), South West (1.26%), and South-South with South East (3.81%) prevalence. The disease has been successfully eliminated in Argungu local government areas (LGAs) of Kebbi State, Plateau, and Nasarawa States respectively. Most clinical manifestations (31.12%) include hydrocele, lymphedema, elephantiasis, hernia, and dermatitis. Night blood samples are appropriate for microfilaria investigation. Sustained MDAs, the right testing methods, early treatment of infected cases, and vector control are useful for the elimination of lymphatic filariasis for morbidity management and disability prevention in the country. Regional control strategies, improved quality monitoring of surveys and intervention programs with proper records of morbidity and disability requiring intervention are important approaches for the timely elimination of the disease in Nigeria.

Ongoing transmission of lymphatic filariasis in Samoa 4.5 years after one round of triple-drug mass drug administration.

BACKGROUND: Lymphatic filariasis (LF) remains a significant global issue. To eliminate LF as a public health problem, the World Health Organization (WHO) recommends multiple rounds of mass drug administration (MDA). In certain scenarios, including when elimination targets have not been met with two-drug MDA, triple-drug MDA (using ivermectin, diethylcarbamazine and albendazole) is recommended. In this study, we report on antigen (Ag) and microfilaria (Mf) prevalence in eight primary sampling units (PSUs) in Samoa 4.5 years after one round of triple-drug MDA. METHODOLOGY: In 2023, community surveys were conducted in eight PSUs that had been surveyed previously in 2018 (between 1.5 and 3.5 months post triple-drug MDA) and 2019 (six to eight-months post triple-drug MDA). Fifteen houses were randomly selected in each PSU with household members aged ≥ 5 years invited to participate. Blood samples were tested for Ag and Mf. PRINCIPAL FINDINGS: Ag-positive participants were observed in six of the eight PSUs, and Ag prevalence was significantly above the 1% threshold in four PSUs. The presence of Mf-positive participants in five PSUs confirms the presence of residual active infections. CONCLUSIONS/SIGNIFICANCE: This study provides evidence of persistent LF transmission in Samoa 4.5 years after one round of triple-drug MDA, confirming that one round was insufficient for interruption of transmission in this setting. Our findings highlight the negative impact of delaying MDA rounds, for example, due to public health emergencies.

Modelling the cost of engage & treat and test & treat strategies towards the elimination of lymphatic filariasis in Ghana.

BACKGROUND: Despite several years of LF-MDA implementation, Ghana still has some districts with mf prevalence >1%, partly due to poor treatment coverage levels resulting from non-participation in MDA. To address the challenges, we implemented Engage & Treat (E&T) and Test & Treat (T&T) strategies for individuals who miss or refuse MDA respectively, in a hotspot district, enabling us to reach many of those who seldom, or never, take part in MDA. This financial cost study was undertaken to analyse data on the LF-MDA, E&T and T&T implementation in 2021 and the financial cost to inform the rollout of the E&T and T&T as mop-up strategies in future LF-MDAs. METHODS: This costing study analysed cost data from the 2021 LF-MDA implementation activities carried out by the Neglected Tropical Diseases (NTD) programme of the Ghana Health Service and the SENTINEL study, carried out in Ahanta West district for the two interventions (i.e., E&T and T&T). The 2021 Ghana Population and Housing Census data was used to estimate the LF-MDA-eligible population. The financial cost per person treated was estimated and these costs were applied to the projected population to obtain the financial cost for subsequent years. RESULTS: Implementing MDA mop-up strategies either through the E&T or T&T to improve coverage comes at an additional cost to the elimination goals. For example, in 2024 the projected cost per person treated by the routine LF-MDA is estimated at US$0.83. The cost using the integrated LF-MDA and the E&T, T&T led by the NTD programme or T&T integrated into the health system was estimated at US$1.62, US$2.88, and US$2.33, respectively, for the same year. Despite the increased cost, the proposed combined LF-MDA and mop-up strategies will have a higher estimated population treated for 2024 (i.e., 1,392,211) compared to the routine LF-MDA approach (i.e., 988,470) for the same year. CONCLUSION: Combining LF-MDA with E&T/T&T mop-up strategies, despite their high costs, may provide NTD Programmes with the options of improving treatment coverage and reaching the LF elimination target sooner, given that the routine LF-MDA alone approach has been implemented for many years with some districts yet to reach the elimination targets.

Investigating Dirofilaria immitis isolates infecting domestic canines and their susceptibility/resistance patterns to macrocyclic lactones in the northern region of the Mississippi Delta area (southeast Missouri).

Previous reports of macrocyclic lactone (ML) resistance in Dirofilaria immitis, the parasitic nematode which causes heartworm disease, have mainly been from the southern Mississippi Delta region. Southeast Missouri (SEMO), forming the northern boundary of this region, has not previously been well studied. The area is an ideal propagation region for heartworm infection and possibly for the spread of ML resistance. To assess whether D. immitis isolates infecting domestic canines in SEMO exhibit evidence of resistance to MLs, domestic canines, presented to veterinary facilities testing positive for heartworms through antigen and microfilariae (MF) examination, were utilized in the study. Using a descriptive epidemiological cross-sectional study, from March 2021 through February 2022, blood sample collection from 96 canines living in SEMO testing positive for heartworms were analyzed. MiSeq technology was utilized to sequence specific genetic markers associated with susceptibility/resistance for MLs in D. immitis isolates. Genomic data revealed most D. immitis isolates had genotypic profiles consistent with resistance to MLs. Of the 96 samples tested, 91 (94.8%) had a resistant genotype, 4 (4.2%) had a mixed genotype, and 1 sample (1%) genotyped as susceptible. While detailed and reliable medical histories were not available for most canines, detailed medical history from 2 canines indicated evidence of phenotypic resistance that was consistent with their genotypes. However, in vivo preventive tests are needed to confirm a high frequency of phenotypic ML resistance in D. immitis from this region. Increasing resistance patterns to MLs indicate the approach to heartworm prevention/treatment protocol should be reconsidered. New measures may be required to stop heartworm disease.

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.

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.

An Ensemble Framework for Projecting the Impact of Lymphatic Filariasis Interventions Across Sub-Saharan Africa at a Fine Spatial Scale.

BACKGROUND: Lymphatic filariasis (LF) is a neglected tropical disease targeted for elimination as a public health problem by 2030. Although mass treatments have led to huge reductions in LF prevalence, some countries or regions may find it difficult to achieve elimination by 2030 owing to various factors, including local differences in transmission. Subnational projections of intervention impact are a useful tool in understanding these dynamics, but correctly characterizing their uncertainty is challenging. METHODS: We developed a computationally feasible framework for providing subnational projections for LF across 44 sub-Saharan African countries using ensemble models, guided by historical control data, to allow assessment of the role of subnational heterogeneities in global goal achievement. Projected scenarios include ongoing annual treatment from 2018 to 2030, enhanced coverage, and biannual treatment. RESULTS: Our projections suggest that progress is likely to continue well. However, highly endemic locations currently deploying strategies with the lower World Health Organization recommended coverage (65%) and frequency (annual) are expected to have slow decreases in prevalence. Increasing intervention frequency or coverage can accelerate progress by up to 5 or 6 years, respectively. CONCLUSIONS: While projections based on baseline data have limitations, our methodological advancements provide assessments of potential bottlenecks for the global goals for LF arising from subnational heterogeneities. In particular, areas with high baseline prevalence may face challenges in achieving the 2030 goals, extending the "tail" of interventions. Enhancing intervention frequency and/or coverage will accelerate progress. Our approach facilitates preimplementation assessments of the impact of local interventions and is applicable to other regions and neglected tropical diseases.

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.

Improving access to melarsomine therapy: treating canine heartworm infection in a high-volume, outpatient community clinic setting.

BACKGROUND: Models that provide high-quality veterinary care for more affordable prices are emerging, but not well documented outside of wellness and preventative care. Effective treatment guidelines for heartworm disease have been developed by the American Heartworm Society; however, not all owners are able to access treatment due to the high costs associated with sick and emergency care services. METHODS: To increase access to high-quality adulticidal treatment of canine heartworm disease, we developed and implemented a technician-leveraged heartworm treatment protocol for high-volume, outpatient community clinic settings based on the American Heartworm Society guidelines. Modifications were few and included limited pre-treatment blood work, pre-injection sedation, post-injection pain medication, and a reduced exercise restriction period. We monitored retention rates for 556 dogs throughout treatment, evaluated treatment success (defined as no antigen detection 9 months post treatment) for patients that returned for post-treatment antigen testing, and reported on adverse reactions and therapy adherence throughout treatment. RESULTS: Of the patients that began adulticide therapy, 539/556 (97%) successfully completed the three-injection series. No microfilariae were detected in 99% (428/433) of those who returned for post-injection microfilaria testing. Among those that returned for or reported the results of post-injection antigen testing, no antigen was detected for 99% (245/248) and no microfilariae were detected for 99.5% (200/201). During the course of treatment, 483/539 (90%) of patients experienced at least one adverse reaction, with the most frequently reported types being behavioral and injection site reactions. 25/539 (4.6%) of owners sought additional medical care for adverse reactions at some point during the treatment course. The overall mortality rate was 1.3% (7/556). CONCLUSIONS: This study represents the first evaluation of a heartworm treatment protocol optimized for implementation in a high-volume, outpatient community clinic setting. Our findings align with those previously reported in private practice or tertiary referral centers, illustrating that through the inclusion of pre-treatment blood work, employing short-acting or reversible sedatives, ensuring proper analgesia, minimizing the use of ancillary diagnostics, reducing the duration of in-clinic monitoring while focusing on outpatient care, and maximizing technician involvement, we can deliver effective and safe melarsomine therapy at a more affordable cost to pet owners.

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.

Motivation-opportunity-ability-behaviour of community members and program implementers towards mass drug administration for lymphatic filariasis elimination in India: a systematic review and implementation priority.

Lymphatic filariasis (LF) is a significant public health issue in India. Despite 10-15 rounds of mass drug administration (MDA) in India, the global LF elimination target of 2030 appears challenging. To strengthen the program, community and provider perspectives on ways to bridge a gap in MDA are needed. Through the motivation-opportunity-ability-behaviour (MOAB) lens, we systematically reviewed the facilitators and barriers encountered in LF elimination in India. We followed Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. We searched PubMed, Embase, ProQuest and Google Scholar databases to explore factors related to MDA program implementation in India through 30 June 2021. We analysed the data using a thematic framework. We identified 576 studies; of these, 20 studies were included. This review revealed that the public health system for distributing MDA drugs in India created a better enabling environment, including zero out-of-pocket expenditure, door-step distribution of medicines and ample capacity-building training and follow-up. However, community members were unaware of the rationale for drug consumption, leading to a gap in drug distribution and consumption. Motivation is required among community members, which suggests capacity-building training for service providers to counsel the community.

A Landscape on Lymphatic Filariasis with its Effects and Recent Advanced Treatments.

Lymphatic filariasis is an infection caused by parasites that poses a significant health, social, and economic burden, affecting a vast population that exceeds 120 million individuals globally. The Etiology of the infection is attributed to three nematode parasites, namely Wuchereria bancrofti, B. timori, and Brugia malayi, as well as which are phylogenetically related. These parasites are transmitted to humans via mosquitoes belonging to the Anopheles, Aedes genera, and Culex. As per the estimation provided by the WHO, the current number of individuals infected with filariasis stands at approximately 120 million across 81 countries. Furthermore, it is estimated that around 1.34 billion individuals reside in regions that are endemic to filariasis, thereby putting them at risk of contracting the disease. Different synthetic drugs such as Ivermectin, Doxycycline, Albendazole, and Suramin are used in the treatment. Some natural plants are Azadirachta indica, Tinospora cordifolia, Zingiber officinal, as well as, some marine sources are also included for better treatment. We also touch briefly on a few additional filarial diseases. Although there are only a few medications available to treat filariasis, their frequent usage may result in drug resistance. Furthermore, there is no effective vaccination for the treatment of filariasis. Due to these restrictions, it has been crucial to create new anti-filarial medications, which motivates researchers to find novel pharmaceuticals with anti-filarial action. In this article, we examine the latest achievements in the anti-filarial area, including the many forms of filariasis and their historical contexts, elimination programmes, various therapeutic classes (both synthetic and natural), investigated product-derived targets as well as clinical investigations.

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.

The lymphatic filariasis treatment study landscape: A systematic review of study characteristics and the case for an individual participant data platform.

BACKGROUND: Lymphatic filariasis (LF) is a neglected tropical disease (NTD) targeted by the World Health Organization for elimination as a public health problem (EPHP). Since 2000, more than 9 billion treatments of antifilarial medicines have been distributed through mass drug administration (MDA) programmes in 72 endemic countries and 17 countries have reached EPHP. Yet in 2021, nearly 900 million people still required MDA with combinations of albendazole, diethylcarbamazine and/or ivermectin. Despite the reliance on these drugs, there remain gaps in understanding of variation in responses to treatment. As demonstrated for other infectious diseases, some urgent questions could be addressed by conducting individual participant data (IPD) meta-analyses. Here, we present the results of a systematic literature review to estimate the abundance of IPD on pre- and post-intervention indicators of infection and/or morbidity and assess the feasibility of building a global data repository. METHODOLOGY: We searched literature published between 1st January 2000 and 5th May 2023 in 15 databases to identify prospective studies assessing LF treatment and/or morbidity management and disease prevention (MMDP) approaches. We considered only studies where individual participants were diagnosed with LF infection or disease and were followed up on at least one occasion after receiving an intervention/treatment. PRINCIPAL FINDINGS: We identified 138 eligible studies from 23 countries, having followed up an estimated 29,842 participants after intervention. We estimate 14,800 (49.6%) IPD on pre- and post-intervention infection indicators including microfilaraemia, circulating filarial antigen and/or ultrasound indicators measured before and after intervention using 8 drugs administered in various combinations. We identified 33 studies on MMDP, estimating 6,102 (20.4%) IPD on pre- and post-intervention clinical morbidity indicators only. A further 8,940 IPD cover a mixture of infection and morbidity outcomes measured with other diagnostics, from participants followed for adverse event outcomes only or recruited after initial intervention. CONCLUSIONS: The LF treatment study landscape is heterogeneous, but the abundance of studies and related IPD suggest that establishing a global data repository to facilitate IPD meta-analyses would be feasible and useful to address unresolved questions on variation in treatment outcomes across geographies, demographics and in underrepresented groups. New studies using more standardized approaches should be initiated to address the scarcity and inconsistency of data on morbidity management.