Lymphatic Filariasis Research Articles

Mitragyna parvifolia as apotential therapeutic agent for lymphatic filariasis.

This study investigates the medicinal potential of Mitragyna parvifolia (M. parvifolia) leaves for the management of Lymphatic filariasis (LF). Phytochemical screening of the methanolic leaf extract revealed the presence of alkaloids, terpenoids, phenols, tannins, and flavonoids. The GC-MS analysis identified 24 phytoconstituents, including the major alkaloid "mitraphylline." Infrared spectroscopy confirmed the presence of various functional groups corresponding to the identified compounds. The extract exhibited significant antibacterial activity against Staphylococcus epidermidis, Bacillus cereus, and Salmonella typhi. In vitro macrofilaricidal screening demonstrated dose-dependent inhibition of worm motility and MTT reduction, indicating its potential as a macrofilaricidal agent. The larvicidal bioassay showed notable effectiveness against Culex quinquifasciatus larvae, with 1% concentration displaying the highest larvicidal activity. Concentration-dependent antioxidant activity was observed using the DPPH assay, with 100µg/ml showing the highest antioxidant potential. The findings suggest the potential of M. parvifolia leaves for LF management, supporting further research to identify active compounds and elucidate their mechanisms of action. The study highlights the plant's diverse bioactive compounds, antibacterial and macrofilaricidal activities, larvicidal efficacy, and significant antioxidant properties. Future investigations, including in vivo experiments and clinical trials, are warranted to validate the safety and efficacy of M. parvifolia as a potential therapeutic agent for LF.

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

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 an 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. 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. 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. 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.

Outcome Assessment of the implementation of Mass Drug Administration against Lymphatic Filariasis, in Kalaburagi (Gulbarga) District of Karnataka state: A Cross Sectional Survey.

Mass Drug Administration of Di-Ethyl Carbamazine and Albendazole is an effective strategy recommended by World Health Organization (WHO) to prevent transmission and eliminate Lymphatic Filariasis. Under the National Vector Borne Disease Control Programme in India, Mass Drug Administration (MDA) is carried out as a yearly activity in endemic areas to accelerate the progress towards elimination of lymphatic Filariasis. The study was carried with the objective to determine the coverage of Mass Drug Administration against Lymphatic Filariasis among the eligible population in Kalaburagi district and delineate the common reasons for non acceptance of MDA. Field based cross sectional survey was carried out in Kalaburagi. Cluster sampling of 4 clusters (3 rural and 1 urban) from four different taluks (one cluster from each taluk) of the district reporting high, medium and low coverage of MDA (as reported by District Malaria Office) Members from selected Households in all clusters were interviewed regarding MDA administration, Directly Observed treatment, side effects and any co morbidities which ruled out MDA administration. Responses documented as tally marks in assessment sheets shared by National Vector Borne Disease Control Programme office. Proportions, frequencies, and mean were calculated and inferential statistics were used. A total of 1263 individuals were assessed for Mass Drug administration from a total of 240 households (60 households in each cluster). The coverage of MDA varied from 90.33% in Heerapur in Kalaburagi Urban to 97.87% in Mogala thanda (Chittapur Taluk). MDA Coverage against Lymphatic Filariasis has improved when compared to previous reported studies carried out and it has also exceeded the coverage threshold as determined by programme for elimination of Lymphatic Filariasis.

Dual RNA-seq in filarial nematodes and Wolbachia endosymbionts using RNase H based ribosomal RNA depletion.

Lymphatic filariasis is caused by parasitic nematodes and is a leading cause of disability worldwide. Many filarial worms contain the bacterium Wolbachia as an obligate endosymbiont. RNA sequencing is a common technique used to study their molecular relationships and to identify potential drug targets against the nematode and bacteria. Ribosomal RNA (rRNA) is the most abundant RNA species, accounting for 80-90% of the RNA in a sample. To reduce sequencing costs, it is necessary to remove ribosomal reads through poly-A enrichment or ribosomal depletion. Bacterial RNA does not contain a poly-A tail, making it difficult to sequence both the nematode and Wolbachia from the same library preparation using standard poly-A selection. Ribosomal depletion can utilize species-specific oligonucleotide probes to remove rRNA through pull-down or degradation methods. While species-specific probes are commercially available for many commonly studied model organisms, there are currently limited depletion options for filarial parasites. Here, we performed total RNA sequencing from Brugia malayi containing the Wolbachia symbiont (wBm) and designed ssDNA depletion probes against their rRNA sequences. We compared the total RNA library to poly-A enriched, Terminator 5'-Phosphate-Dependent Exonuclease treated, NEBNext Human/Bacteria rRNA depleted and our custom nematode probe depleted libraries. The custom nematode depletion library had the lowest percentage of ribosomal reads across all methods, with a 300-fold decrease in rRNA when compared to the total RNA library. The nematode depletion libraries also contained the highest percentage of Wolbachia mRNA reads, resulting in a 16-1,000-fold increase in bacterial reads compared to the other enrichment and depletion methods. Finally, we found that the Brugia malayi depletion probes can remove rRNA from the filarial worm Dirofilaria immitis and the majority of rRNA from the more distantly related free living nematode Caenorhabditis elegans. These custom filarial probes will allow for future dual RNA-seq experiments between nematodes and their bacterial symbionts from a single sequencing library.

Sero-antigen prevalence of lymphatic filariasis and risk factors of podoconiosis in Busiriba sub-county, Kamwenge district, Southwestern Uganda, August-September 2018.

Given the neglected nature of filariasis, especially in Uganda where data are scarce, this cross-sectional study aimed to determine the sero-antigen prevalence of lymphatic filariasis and risk factors associated with non-lymphatic filariasis (podoconiosis) in Busiriba Sub-county, Kamwenge District, Uganda, during August-September 2018, to inform targeted elimination efforts. We enrolled 101 participants, among whom 35 (34.7%) had podoconiosis. The sero-antigen prevalence of lymphatic filariasis was 1.0%. Older age and walking barefoot were associated with increased podoconiosis risk. Specifically, individuals aged 25-49 years with had 7.38 times higher odds of podoconiosis (adjusted odds ratio [aOR] = 7.38, 95% CI: 1.36-40.13) compared to those under 25 years, while those aged ≥ 50 years had even higher odds (aOR = 8.49, 95%CI: 1.44-50.15). Additionally, individuals who reported walking barefoot had 14 times higher odds of podoconiosis (aOR = 14.08; 95% CI: 2.49-79.50).

Detection of microfilaria L3 and insecticide resistance among wild-caught mosquito vectors in endemic areas of lymphatic filariasis

Detection of microfilaria L3 and insecticide resistance among wild-caught mosquito vectors in endemic areas of lymphatic filariasis

Spatial distribution and environmental correlations of Culex pipiens pallens (Diptera: Culicidae) in Haidian district, Beijing.

Culex pipiens pallens Coquillett, 1898 (Diptera: Culicidae) was the dominant health threat to mosquito species in Beijing, and it is important to unravel the spatial distribution and environmental correlations of Cx. pipiens pallens in Beijing. 3S technology methods and spatial statistics were used to clarify the distribution pattern. Subsequently, linear and spatial regression were performed to detect the environmental factors linked with the density of Cx. pipiens pallens. The same "middle peak" spatial distribution pattern was observed for Cx. pipiens pallens density at the community, subdistrict, and loop area levels in our study area. In addition, there were various correlated environmental factors at the community and subdistrict scales. At the community scale, the summary values of the Modified Normalized Difference Water Index (MNDWI) in 2 km buffer zone (MNDWI_2K) were negatively correlated, and the summary values of Normalized Difference Built-up Index (NDBI) in 800 m buffer zone (NDBI_800) was positively correlated to the Cx. pipiens pallens density. However, the summary values of Normalized Difference Vegetation Index and Nighttime Light Index significantly affected Cx. pipiens pallens density at the subdistrict scale. Our findings provide insight into the spatial distribution pattern of Cx. pipiens pallens density and its associated environmental risk factors at different spatial scales in the Haidian district of Beijing for the first time. The results could be used to predict the Cx. pipiens pallens density as well as the risk of lymphatic filariasis (LF) infection, which would help implement prevention and control measures to prevent future risks of biting and LF transmission in Beijing.

Low schistosomiasis and soil-transmitted helminthiasis prevalence and intensities in selected communities in Davao de Oro and Davao del Norte, the Philippines: A setting for interruption of transmission?

Parasitic neglected tropical diseases, such as schistosomiasis and soil-transmitted helminthiasis (STH), remain as significant public health concerns in developing countries such as the Philippines. This study aimed to determine the prevalence and intensity of schistosomiasis and STH among school-age children (SAC) and adults in two co-endemic provinces in Mindanao in southern Philippines as part of monitoring of national control programs. Stool samples were collected, processed using Kato-Katz technique, and examined microscopically for presence of intestinal helminth ova. A total of 776 SAC and 526 adults participated in the study. Low schistosomiasis prevalence was generally observed in SAC (0.8%) and adults (0.4%). Generally low STH prevalence was reported in both SAC (3.9%) and adults (3.4%). Only three SAC had heavy intensity STH, which was not seen in adults. Results indicate a state of good morbidity control, which may be a result of effective implementation of mass drug administration (MDA) strategy for schistosomiasis, STH, and lymphatic filariasis in the last several years. The low prevalence and intensities of infections may also be partly attributed to the low diagnostic sensitivity of Kato-Katz technique in detecting low intensity intestinal helminth infections. While results of this study also indicate similarly low levels of both these infections in previous studies, sustaining high MDA coverage rates and addressing remaining challenges related to intensified case finding and treatment, improvements in safe water, sanitation, and hygiene, veterinary public health, and vector ecology and management will be necessary to interrupt transmission in these areas.

Diagnosis of filariasis: A case report of a reemerging neglected tropical disease

Filariasis is a neglected tropical disease (NTD) of humans caused by the helminthic filarial species Wuchereria (W.) bancrofti, Brugia (B.) timori, and B. malayi. Diverse species of mosquitoes transmit the microfilariae of these worms to cause filaria infection, with the disease presenting classical clinical manifestations such as lymphedema, adenolymphangitis, and hydrocele, which result in permanent disfigurement and psychosocial and economic stigmatization. These sequelae necessitate the need for proper identification and characterization of the etiological agent for therapy and prevention. In this study, we report a case of unilateral lymphedema in a 28-year-old gateman/farmer from the Sabon Gari Local Government Area of Kaduna State, Northern Nigeria. Microscopy of the patient’s blood sample demonstrated the presence of microfilariae, leading to PCR characterization to be W. bancrofti. Upon diagnosis, the patient was treated with tablets of doxycycline 200 mg daily and albendazole 200 mg bid for six weeks, followed by a single dose of ivermectin 150 mg/kg (15 mg) at the 4th week of initiating treatment. This treatment regimen was complemented by a combination of bed rest, use of compression bandage, and limb elevation at night, resulting in remarkable improvement of the patient’s health after six weeks. In conclusion, lymphatic filariasis diagnosis was microscopically confirmed by the demonstration of microfilaria in the blood film obtained at night, leading to molecular characterization by PCR to be W. bancrofti. This is a workup for treating filarial infections in patients with unilateral leg swelling and a history of living in or traveling to endemic areas. This should also be a wake-up call to policymakers and practitioners regarding the possible recrudescence of filariasis in Nigeria.

Towards Understanding the Microepidemiology of Lymphatic Filariasis at the Community Level in Ghana.

Studies on the distribution of lymphatic filariasis (LF) have mostly focused on reporting prevalence at the community level and distribution at the district levels. Understanding the distribution patterns at community levels may help in designing surveillance strategies. This study aimed to characterize the spatial distribution of LF infections in four hotspot communities in Ghana. The research, involving 252 participants, collected demographic data, mass drug administration (MDA) information, household GPS coordinates, and antigen detection test results. The LF prevalence varied significantly among the communities, with Asemda having the highest (33.33%) and Mempeasem having the lowest (4.44%). Females had lower odds of infection than males (OR = 2.67, p = 0.003 CI: 1.39-5.13). Spatial analysis using kernel density, Anselin Local Moran's, Getis-Ord Gi models, Ordinary Least Squares, and Geographic Weighted Regression revealed mixed patterns of spatial autocorrelation. This study identified LF hotspots, indicating clusters of high or low prevalence with some areas showing disparities between MDA coverage and LF positivity rates. Despite these hotspots, the overall distribution of LF appeared random, suggesting the importance of purposeful sampling in surveillance activities. These findings contribute valuable insights into the micro-epidemiology of LF, emphasizing the need for community-specific investigations to understand the factors influencing the effectiveness of MDA programs in controlling filarial infections. The study highlights the importance of refining surveillance strategies based on community-level distribution patterns.

The role of asymptomatic carriers on the dynamics of a lymphatic filariasis model incorporating control strategies

This study presents a mathematical model to investigate the patterns of transmission in lymphatic filariasis. The model considers chronic, acute, and asymptomatic individuals and integrates key control strategies. Random synthetic data is generated robustly through numerical solutions to closely replicate real-world scenarios and encompass uncertainties. The synthetic data adheres to a Gaussian distribution to ensure validity and reliability. Following the derivation of the basic and effective reproduction number using the next generation matrix approach, Latin Hypercube Sampling (LHS) and the Partial Rank Correlation Coefficient (PRCC) algorithm is utilized to assess the parameters that significantly influence the model outputs. The study examine the trajectories of different population compartments through numerical simulations over time, with particular emphasis on the role played by asymptomatic individuals in the transmission of the disease. To assess the potential for disease elimination, the study introduces a range of strategies involving protective measures, treatment interventions, and mosquito control. These strategies are determined through sensitivity analysis. The findings demonstrate that the simultaneous implementation of all control measures has a noteworthy effect in managing lymphatic filariasis. In conclusion, the proposed model enhances understanding of lymphatic filariasis dynamics and informs effective control strategies.

Assessment of participants’ perception on the use of mass drug administration in communities endemic to <i>Wuchereria bancrofti</i> Cobbold, 1877 in Northern Nigeria

Lymphatic filariasis (LF) is one of the neglected tropical diseases that cause permanent long term disability inform of hydrocoele, lymphoedema and elephantiasis that develop as a result of inflammation of the lymphatic system. This study aimed to assess the prevalence of lymphatic filariasis and perception of participants towards Mass Drug Administration (MDA) programme. The study was a community-based cross-sectional study for screening microfilariae of Wuchereria bancrofti in consenting participants. A total of 1010 participants’ from selected communities on the MDA programme in 5 Local Government Areas (LGAs) of Bauchi, Plateau and Kaduna states were enlisted into to the study. The communities were chosen based on the presence of the people living with LF according to the signs and symptoms. A well-structured adapted questionnaire was administered to collect participants’ information and their perception of the MDA programme. Microflaria of Wuchereria bancrofti were identified based on the sheathed nuclear, caudal nuclei and bent tail in Parasitology and Entomology Research Laboratory, Ahmadu Bello University, Zaria. Data was analysed using descriptive statistics, chi-squared and odds ratio. Participants with knowledge (294/1010; 29.11%) of the MDA programme were less than those without knowledge (716/1010; 70.89%) of the MDA. Similar, the prevalence of LF was higher in participants with knowledge (26.87%) of the MDA than in those without knowledge (25.14%). The status of participation showed that, those that participated (380/1010; 37.62%) in the MDA were lower than those did not participants (630/1010; 62.38%); the infection in participants that did not partook in the MDA programme had higher prevalence (29.68%) of LF than those that participated. Participants gave various reasons for not being part of the MDA programme ranging from absent (177/1010; 17.53%) at the time of the campaign to side effect (2/1010; 0.20%) of the drugs after taking it. However, those that gave reasons for not participating because Community Drug Distributors (CDD) did not come, had highest prevalence (40.74%) of LF compared to those that gave reasons as side effect (0.00%) for not taking the drugs. Overall LF prevalence of 25.64% was found in this study. There is poor knowledge of MDA programme among the participants in the communities examined. Similarly, microfilaria was present in some participants despite the MDA campaign in the selected states. Intensive awareness campaign and drug distribution need to be carried out in most of the remote communities in the affected states. Furthermore, members of the communities must be part of the CDDs for acceptability and effectiveness of the campaign.

The effects of selected neglected tropical diseases on economic performance at the macrolevel in Africa

BackgroundNeglected tropical diseases (NTDs) such as leprosy, lymphatic filariasis (LF), schistosomiasis and onchocerciasis are endemic in several African countries. These diseases can lead to severe pain and permanent disability, which can negatively affect the economic productivity of the affected person(s), and hence resulting into low economic performance at the macrolevel. Nonetheless, empirical evidence of the effects of these NTDs on economic performance at the macrolevel is sparse. This study therefore investigates the effects of the above-mentioned NTDs on economic performance at the macrolevel in Africa.MethodsThe study employs a panel design with data comprising 24 to 45 African countries depending on the NTD in question, over the period, 2002 to 2019. Gross domestic product (GDP) is used as the proxy for economic performance (Dependent variable) and the prevalence of the above-mentioned NTDs are used as the main independent variables. The random effects (RE), fixed effects (FE) and the instrumental variable fixed effects (IVFE) panel data regressions are used as estimation techniques.ResultsWe find that, an increase in the prevalence of the selected NTDs is associated with a fall in economic performance in the selected African countries, irrespective of the estimation technique used. Specifically, using the IVFE regression estimates, we find that a percentage increase in the prevalence of leprosy, LF, schistosomiasis and onchocerciasis is associated with a reduction in economic performance by 0.43%, 0.24%, 0.28% and 0.36% respectively, at either 1% or 5% level of significance.ConclusionThe findings highlight the need to increase attention and bolster integrated efforts or measures towards tackling these diseases in order to curb their deleterious effects on economic performance. Such measures can include effective mass drug administration (MDA), enhancing access to basic drinking water and sanitation among others.

Wolbachia and Lymphatic Filarial Nematodes and Their Implications in the Pathogenesis of the Disease.

Lymphatic filariasis (LF) is an infection of three closely related filarial worms such as Wuchereria bancrofti, Brugia malayi, and Brugia timori. These worms can cause a devastating disease that involves acute and chronic lymphoedema of the extremities, which can cause elephantiasis in both sexes and hydroceles in males. These important public health nematodes were found to have a mutualistic relationship with intracellular bacteria of the genus Wolbachia, which is essential for the development and survival of the nematode. The host's inflammatory response to parasites and possibly also to the Wolbachia endosymbiont is the cause of lymphatic damage and disease pathogenesis. This review tried to describe and highlight the mutualistic associations between Wolbachia and lymphatic filarial nematodes and the role of bacteria in the pathogenesis of lymphatic filariasis. Articles for this review were searched from PubMed, Google Scholar, and other databases. Article searching was not restricted by publication year; however, only English version full-text articles were included.

Evaluating Mosquito Biocontrol Effectiveness by Isolating and Characterizing Some Fungi Against Culex Pipiens and Anopheles Stephensi in Sothern Part of Iraq

Objectives: Isolation Aspergillus tamarii, Cladosporium herbarum, and Verticillium lecanii fungi from naturally infected Culex pipiens and Anopheles stephensi insects were morphologically and molecularly identified. Methods: In this study, populations of mosquitoes were cultured and examined to determine fungal infection and evaluated as potential agents against C. pipiens and A. stephensi. Results: A variety of fungal isolates demonstrated differing degrees of pathogenicity 24 hours after treatment against C. pipiens and A. stephensi eggs, four-instar mosquito larvae, and adults. and as a biological control, it was found that the fungal suspension of each of the used fungi affected the life roles of the two mosquitoes. as it was more than the fungus suspension A. tamarii, Cl. herbarum on V. lecanii. The highest percentage of eggs mortality were (36.72, 48.97) %, (29.14, 42.25) %, and (24.45, 35.70) % of C. pipiens and A. stephensi when using the highest concentration of 1*105 spore/ml, 3*105 spore/ml and 2*105 spore/ml of fungicide A. tamarii, C. herbarum, V.lecanii and respectively after 24 hours. The highest mortality rate was for the fourth larval stages, and the mosquito A. stephensi is more sensitive to type C. pipiens infection., as, in order (75.6, 67.19, 56.8) %, (74.18, 59.81, 50) %, and (65, 52,42.71) %. Conclusions: Results highlight the significance of a mosquito's natural fungal opponent. All isolates had an impact on adults and larvae, although they were less successful against eggs. Both have the potential to develop, particularly against the larvae of the primary arbovirus, malaria, and lymphatic filariasis vectors, A. stephensi, and C. pipiens.

Factors associated with never treatment and acceptability of mass drug administration for the elimination of lymphatic filariasis in Guyana, 2021.

Guyana remains one of four countries in the Americas endemic for lymphatic filariasis (LF). Elimination of LF requires repeated annual mass drug administration (MDA) with sufficient levels of coverage for success. This study assesses the acceptability and never treatment of LF MDA using data from a routine assessment survey in 2021. A subset of individuals, over 20 years of age (n = 2498), were selected to receive an expanded questionnaire to examine factors associated with acceptability and never treatment. Assessed factors include respondent demographics, knowledge, risk perceptions of LF, and opinions on the MDA programme. The majority (73%) of those with scores above the acceptability threshold (score ≥22.5) reported participating in MDA two or more times. Factors strongly and positively associated with scoring above the acceptability threshold include beliefs in importance of participation in MDA for their community (aOR = 2.8, 95%CI (1.1-7.2)), perception of importance of LF treatment (6.9 (3.2-14.7)), receiving treatment in 2021 (2.9 (1.5-5.4)), and the number of self-reported times taking treatment for LF (2.2 (1.1-4.4)). Ten percent of respondents participated in the MDA for the first time in 2021, while 15% reported never treatment during any round of LF MDA. Three factors were statistically associated with participation in MDA across the two levels of the models (level 1: took LF treatment once versus never, and level 2: took LF treatment twice versus never) included: 1) scoring above the acceptability threshold (aOR = 6.2, 95%CI(3.8-10.0)), 2) self-reported importance of participation in MDA for their community (7.1 (2.9-17.8)), and 3) personal beliefs that they should take LF treatment even if they are not sick (2.6 (1.7-3.9)). As Guyana moves closer to LF elimination, these results provide further insight and understanding into programmatic results and could inform further action following MDA activities-particularly if an approach is needed to address never treatment during MDA.

Subnational Projections of Lymphatic Filariasis Elimination Targets in Ethiopia to Support National Level Policy.

Lymphatic filariasis (LF) is a debilitating, poverty-promoting, neglected tropical disease (NTD) targeted for worldwide elimination as a public health problem (EPHP) by 2030. Evaluating progress towards this target for national programmes is challenging, due to differences in disease transmission and interventions at the subnational level. Mathematical models can help address these challenges by capturing spatial heterogeneities and evaluating progress towards LF elimination and how different interventions could be leveraged to achieve elimination by 2030. Here we used a novel approach to combine historical geo-spatial disease prevalence maps of LF in Ethiopia with 3 contemporary disease transmission models to project trends in infection under different intervention scenarios at subnational level. Our findings show that local context, particularly the coverage of interventions, is an important determinant for the success of control and elimination programmes. Furthermore, although current strategies seem sufficient to achieve LF elimination by 2030, some areas may benefit from the implementation of alternative strategies, such as using enhanced coverage or increased frequency, to accelerate progress towards the 2030 targets. The combination of geospatial disease prevalence maps of LF with transmission models and intervention histories enables the projection of trends in infection at the subnational level under different control scenarios in Ethiopia. This approach, which adapts transmission models to local settings, may be useful to inform the design of optimal interventions at the subnational level in other LF endemic regions.

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.

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. 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). 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. 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.

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

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. 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. 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. 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.

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

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. 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. 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. 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.