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.

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.

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.

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.

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.

Coverage and compliance of mass drug administration (MDA) programme for elimination of lymphatic filariasis in an endemic district of eastern Uttar Pradesh, India.

BACKGROUND & OBJECTIVES: Lymphatic filariasis is targeted for elimination in India through mass drug administration (MDA) with diethylcarbamazine (DEC) combined with albendazole (ABZ). To assess the coverage, compliance and causes for non-compliance towards MDA in an endemic district of Uttar Pradesh (U.P.), north India. METHODS: A cross-sectional coverage evaluation survey was conducted in 24 rural and 6 urban clusters of Ghazipur district in eastern U.P. using multi-stage random sampling technique with probability proportional to estimated size (PPES). Data was collected in a semi-structured Performa from all the individuals in the selected households by interview technique. Bivariate analysis was performed to identify the factors associated with non-consumption of MDA drugs. RESULTS: A total of 1422 individuals were surveyed from 30 randomly selected subunits of which 1401 (98.5%) were eligible for MDA at the time of the round. Majority of the participants were in the age-group of 15-59 years (67.0%) and were males (53.3%). The overall coverage of MDA (both drugs) among the eligible population in Ghazipur district was 58.5%. Compliance among those who had received both the drugs was 61.6% with effective coverage of 36.0%. The coverage was significantly higher in rural areas compared to the urban clusters (p<0.0001). The most common reason quoted for not consuming drugs was fear of side effects (34.9%). However, the incidence of adverse events among those who consumed the drugs was only 2.5%. None of the socio-demographic variables showed a significant association with the compliance to the drugs. INTERPRETATION & CONCLUSION: Coverage and compliance of MDA in Ghazipur district of U.P., India was found to be below satisfactory levels. Targeted Information Education and Communication (IEC) campaigns focusing on the safety of drugs and the necessity of MDA, and mass mobilization with effective monitoring and supervision is the need of the hour for effective coverage of MDA Programme.

Spatial predictive risk mapping of lymphatic filariasis residual hotspots in American Samoa using demographic and environmental factors.

BACKGROUND: American Samoa successfully completed seven rounds of mass drug administration (MDA) for lymphatic filariasis (LF) from 2000-2006. The territory passed the school-based transmission assessment surveys in 2011 and 2015 but failed in 2016. One of the key challenges after the implementation of MDA is the identification of any residual hotspots of transmission. METHOD: Based on data collected in a 2016 community survey in persons aged ≥8 years, Bayesian geostatistical models were developed for LF antigen (Ag), and Wb123, Bm14, Bm33 antibodies (Abs) to predict spatial variation in infection markers using demographic and environmental factors (including land cover, elevation, rainfall, distance to the coastline and distance to streams). RESULTS: In the Ag model, females had a 26.8% (95% CrI: 11.0-39.8%) lower risk of being Ag-positive than males. There was a 2.4% (95% CrI: 1.8-3.0%) increase in the odds of Ag positivity for every year of age. Also, the odds of Ag-positivity increased by 0.4% (95% CrI: 0.1-0.7%) for each 1% increase in tree cover. The models for Wb123, Bm14 and Bm33 Abs showed similar significant associations as the Ag model for sex, age and tree coverage. After accounting for the effect of covariates, the radii of the clusters were larger for Bm14 and Bm33 Abs compared to Ag and Wb123 Ab. The predictive maps showed that Ab-positivity was more widespread across the territory, while Ag-positivity was more confined to villages in the north-west of the main island. CONCLUSION: The findings may facilitate more specific targeting of post-MDA surveillance activities by prioritising those areas at higher risk of ongoing transmission.

Lymphatic filariasis endgame strategies: Using GEOFIL to model mass drug administration and targeted surveillance and treatment strategies in American Samoa.

American Samoa underwent seven rounds of mass drug administration (MDA) for lymphatic filariasis (LF) from 2000-2006, but subsequent surveys found evidence of ongoing transmission. American Samoa has since undergone further rounds of MDA in 2018, 2019, and 2021; however, recent surveys indicate that transmission is still ongoing. GEOFIL, a spatially-explicit agent-based LF model, was used to compare the effectiveness of territory-wide triple-drug MDA (3D-MDA) with targeted surveillance and treatment strategies. Both approaches relied on treatment with ivermectin, diethylcarbamazine, and albendazole. We simulated three levels of whole population coverage for 3D-MDA: 65%, 73%, and 85%, while the targeted strategies relied on surveillance in schools, workplaces, and households, followed by targeted treatment. In the household-based strategies, we simulated 1-5 teams travelling village-to-village and offering antigen (Ag) testing to randomly selected households in each village. If an Ag-positive person was identified, treatment was offered to members of all households within 100m-1km of the positive case. All simulated interventions were finished by 2027 and their effectiveness was judged by their 'control probability'-the proportion of simulations in which microfilariae prevalence decreased between 2030 and 2035. Without future intervention, we predict Ag prevalence will rebound. With 3D-MDA, a 90% control probability required an estimated ≥ 4 further rounds with 65% coverage, ≥ 3 rounds with 73% coverage, or ≥ 2 rounds with 85% coverage. While household-based strategies were substantially more testing-intensive than 3D-MDA, they could offer comparable control probabilities with substantially fewer treatments; e.g. three teams aiming to test 50% of households and offering treatment to a 500m radius had approximately the same control probability as three rounds of 73% 3D-MDA, but used < 40% the number of treatments. School- and workplace-based interventions proved ineffective. Regardless of strategy, reducing Ag prevalence below the 1% target threshold recommended by the World Health Organization was a poor indicator of the interruption of LF transmission, highlighting the need to review blanket elimination targets.

Heartworm adulticide treatment: a tropical perspective.

Dirofilaria immitis (the canine heartworm) is widespread in the tropics, with prevalence surpassing 30% in high-risk areas. In addition to the suitable climatic conditions that favour mosquito abundance and filarial larva development, there is low compliance with the recommended year-round use of preventives in these transmission hotspots. This represents a major concern, considering that melarsomine (first-line heartworm adulticide) is unavailable in several tropical countries, resulting in the so-called slow-kill protocol being the only available adulticide treatment option. In this article, the members of TroCCAP (Tropical Council for Companion Animal Parasites) review the current distribution of heartworm in the tropics and the availability of melarsomine, and discuss alternatives for the management of heartworm infections in dogs.

Contextual determinants of mass drug administration performance: Modelling fourteen years of lymphatic filariasis treatments in West Africa.

BACKGROUND: Effective mass drug administration (MDA) is the cornerstone in the elimination of lymphatic filariasis (LF) and a critical component in combatting all neglected tropical diseases for which preventative chemotherapy is recommended (PC-NTDs). Despite its importance, MDA coverage, however defined, is rarely investigated systematically across time and geography. Most commonly, investigations into coverage react to unsatisfactory outcomes and tend to focus on a single year and health district. Such investigations omit more macro-level influences including sociological, environmental, and programmatic factors. The USAID NTD database contains measures of performance from thousands of district-level LF MDA campaigns across 14 years and 10 West African countries. Specifically, performance was measured as an MDA's epidemiological coverage, calculated as persons treated divided by persons at risk. This analysis aims to explain MDA coverage across time and geography in West Africa using sociological, environmental, and programmatic factors. METHODOLOGY: The analysis links epidemiological coverage data from 3,880 LF MDAs with contextual, non-NTD data via location (each MDA was specific to a health district) and time (MDA month, year). Contextual data included rainfall, temperature, violence or social unrest, COVID-19, the 2014 Ebola outbreak, road access/isolation, population density, observance of Ramadan, and the number of previously completed MDAs. PRINCIPAL FINDINGS: We fit a hierarchical linear regression model with coverage as the dependent variable and performed sensitivity analyses to confirm the selection of the explanatory factors. Above average rainfall, COVID-19, Ebola, violence and social unrest were all significantly associated with lower coverage. Years of prior experience in a district and above average temperature were significantly associated with higher coverage. CONCLUSIONS/SIGNIFICANCE: These generalized and context-focused findings supplement current literature on coverage dynamics and MDA performance. Findings may be used to quantify typically anecdotal considerations in MDA planning. The model and methodology are offered as a tool for further investigation.

Comparing antigenaemia- and microfilaraemia as criteria for stopping decisions in lymphatic filariasis elimination programmes in Africa.

BACKGROUND: Mass drug administration (MDA) is the main strategy towards lymphatic filariasis (LF) elimination. Progress is monitored by assessing microfilaraemia (Mf) or circulating filarial antigenaemia (CFA) prevalence, the latter being more practical for field surveys. The current criterion for stopping MDA requires <2% CFA prevalence in 6- to 7-year olds, but this criterion is not evidence-based. We used mathematical modelling to investigate the validity of different thresholds regarding testing method and age group for African MDA programmes using ivermectin plus albendazole. METHODOLGY/PRINCIPAL FINDINGS: We verified that our model captures observed patterns in Mf and CFA prevalence during annual MDA, assuming that CFA tests are positive if at least one adult worm is present. We then assessed how well elimination can be predicted from CFA prevalence in 6-7-year-old children or from Mf or CFA prevalence in the 5+ or 15+ population, and determined safe (>95% positive predictive value) thresholds for stopping MDA. The model captured trends in Mf and CFA prevalences reasonably well. Elimination cannot be predicted with sufficient certainty from CFA prevalence in 6-7-year olds. Resurgence may still occur if all children are antigen-negative, irrespective of the number tested. Mf-based criteria also show unfavourable results (PPV <95% or unpractically low threshold). CFA prevalences in the 5+ or 15+ population are the best predictors, and post-MDA threshold values for stopping MDA can be as high as 10% for 15+. These thresholds are robust for various alternative assumptions regarding baseline endemicity, biological parameters and sampling strategies. CONCLUSIONS/SIGNIFICANCE: For African areas with moderate to high pre-treatment Mf prevalence that have had 6 or more rounds of annual ivermectin/albendazole MDA with adequate coverage, we recommend to adopt a CFA threshold prevalence of 10% in adults (15+) for stopping MDA. This could be combined with Mf testing of CFA positives to ensure absence of a significant Mf reservoir for transmission.

Assessment of factors related to individuals who were never treated during mass drug administration for lymphatic filariasis in Ambon City, Indonesia.

BACKGROUND: One challenge to achieving Lymphatic filariasis (LF) elimination is the persistent coverage-compliance gap during annual mass drug administration (MDA) and the risk of ongoing transmission among never treated individuals. Our analysis examined factors associated with individuals who were never treated during MDA. METHODS: Data were derived from two cross-sectional surveys conducted in Waihaong and Air Salobar Health Center in 2018 and 2019. We analyzed information from 1915 respondents aged 18 years or above. The study outcome was individuals who self-reported never treatment during any round of MDA. All potential predictors were grouped into socio-demographic, health system, therapy and individual factors. Logistic regression analyses were used to examine factors associated with never treatment in any year of MDA. RESULTS: Nearly half (42%) of respondents self-reported they were never treated during any round of MDA. Factors associated with increased odds of never treatment were respondents working in formal sectors (aOR = 1.75, p = 0.040), living in the catchment area of Waihaong Health Center (aOR = 2.33, p = 0.029), and those perceiving the possibility of adverse events after swallowing LF drugs (aOR = 2.86, p<0.001). Respondents reporting difficulty swallowing all the drugs (aOR = 3.12, p<0.001) and having difficulties remembering the time to swallow the drugs (aOR = 1.53, p = 0.049) also had an increased odds of never treatment. The highest odds of never treatment were associated with respondents reporting almost none of their family members took LF drugs (aOR = 3.93, p<0.001). Respondents confident that they knew how to swallow LF drugs had a reduced odds (aOR = 0.26, p<0.001) of never treatment. CONCLUSIONS: Efforts to reassure community members about adverse events, specific instructions on how to take LF drugs, and improving awareness that MDA participation is part of one's contribution to promoting community health are essential drivers for uptake with LF drugs during MDA.

Factors Associated with the Acceptability of Mass Drug Administration for Filariasis: A Systematic Review.

Mass drug administration (MDA) has been implemented as a tool to eliminate lymphatic filariasis. Acceptability among susceptible populations is crucial to achieving MDA effective coverage. This systematic review aims to present and systematically determine the factors associated with the acceptability of MDA. Articles related to factors associated with acceptability were collected electronically from three different databases (Scopus, Web of Science, and PubMed). Four pairs of independent reviewers screened the titles and abstracts of the collected data, stored in EndnoteX7, against the inclusion criteria. Afterwards, the included articles have been critically appraised to assess the quality of the studies using the Mixed Method Appraisal Tool (MMAT). Of the 68 articles identified, 11 were included in the final review. Knowledge, awareness, attitude and perceptions, communications, delivery and accessibility of MDA, gender, and age are the factors associated with MDA acceptability. Community acceptance remains a challenge in the implementation of MDA. To expand MDA coverage in all endemic countries, there is a strong need to address the factors influencing community acceptance of MDA.

Diethylcarbamazine citrate-fortified salt for lymphatic filariasis elimination in India.

Lymphatic filariasis (LF) is a vector-borne neglected tropical disease, causing permanent disability. The disease is debilitating and widespread, leading to tremendous productivity and economic loss. The Government of India (GOI) prioritized the elimination of LF through the annual mass drug administration (MDA) programme in 2004 and continued with a single dose of diethylcarbamazine citrate (DEC), 6 mg/kg of body weight, plus albendazole annually over a period of 5-6 years. The GOI had set the target to achieve LF elimination by 2015 and now by 2030. The progress so far has been suboptimal. Much remains to be done as about 84 per cent of the total 328 endemic districts are still under MDA. The major challenge in implementing MDA is poor compliance. It is necessary to have a feasible alternative strategy addressing the above challenge to achieve the desired goal of LF elimination. At this juncture, a well-researched approach, i.e. the use of DEC-fortified salt, also advocated by the World Health Organization, as a unique form of MDA, is proposed. As per this strategy, a low dose of DEC (0.2% w/w) is added to the cooking salt at the manufacturing facility of iodized salt and consumed by the LF-endemic communities for about two years. Many examples of successful use of this strategy for LF elimination in small- and large-scale trials have been documented in India and several other endemic countries in the world. Implementing DEC-iodine-fortified salt is a safe, less expensive, more efficient and prompt approach for achieving the elimination of LF in India. Adverse effects are none or minor and self-limiting. The DEC-fortified salt strategy can easily piggyback on the existing countrywide deployment of iodized salt under the National Iodine Deficiency Disorders Control Programme (NIDDCP), which has achieved a great success in reducing iodine-deficiency disorders such as hypothyroidism. This existing robust programme can be leveraged to launch DEC-fortified salt for the community. If implemented appropriately, this strategy will ensure the complete cessation of LF transmission within two years from its introduction. If the said strategy is implemented in 2022, it is expected that India will be able to achieve the LF elimination by 2024, much before the global target of 2030.

No evidence of lymphatic filariasis transmission in Bamako urban setting after three mass drug administration rounds.

Lymphatic filariasis (LF) elimination activities started in Mali in 2005 in the most endemic areas and reached countrywide coverage in 2009. In 2004, the district of Bamako was endemic for LF with a prevalence of 1.5%. The current study was designed to determine LF endemicity level in the urban area of Bamako after three rounds of ivermectin and albendazole mass drug administration (MDA). A cross-sectional study was conducted in 2011 in Bamako city, consisting of human prevalence and entomological surveys. Volunteers aged 14 years and above were invited to participate and tested for evidence of Wuchereria bancrofti using night time blood thick smear microfilarial count and blood spots for LF antibodies using the SD BIOLINE Oncho/LF IgG4 Biplex rapid test (Ov16/Wb123). Mosquitoes were collected using CDC light and gravid traps and tested using molecular methods. Poolscreen software v2.0 was used to estimate vector transmission potential. Of the 899 volunteers, one (0.11%) was found to be positive for LF using the Oncho/LF IgG4 Biplex rapid test, and none was found to have Wuchereria bancrofti microfilariae. No mosquitoes were found infected among 6174 Culex spp. (85.2%), 16 Anopheles gambiae s.l. (An. gambiae s.l.) (0.2%), 26 Aedes spp. (0.4%), 858 Ceratopogonidae (11.8%) and 170 other insects not identified (2.3%) tested. Our data indicate that there was no active LF transmission in the low prevalence urban district of Bamako after three MDA rounds. These data helped the National LF programme move forward towards the elimination goal.

The compliance and revenue benefits of ProHeart Vs monthly heartworm disease preventives in the US.

The aim of the current study was to understand how the canine heartworm disease preventive ProHeart® 12 (extended-release injectable moxidectin, PH 12), impacts heartworm preventive purchase compliance and veterinary practice revenue over time compared to monthly heartworm disease preventives. This was a preliminary observational purchase compliance and revenue study based on a retrospective review of transaction data from 4,615 general practices across the United States. The review period was from September 2018 to August 2020. Anonymous transaction records of over 13 million canine patients were analyzed. Of these, only 3.5 million (25.7%) patients purchased any heartworm preventive, as has been presented in other studies. Practices that implemented PH 12 demonstrated the most growth in canine heartworm prevention revenue, patients, and patient compliance levels during the 12-month observation period, compared to previous year. These practices saw year over year growth in percent patients receiving heartworm protection, as well as 10% and 15% growth in the proportion of preventive patients compliant for more than 6 months and 12 months respectively. In contrast, practices that did not bring on PH 12 and only dispensed monthly heartworm preventives saw a decline in the proportion of canine preventive patients that were compliant for more than 6 months. Similarly, PH 12 practices experienced 15% growth in preventive revenue, and practices that did not bring on PH 12 only experienced 3.9% growth in preventive revenue. PH 12 was single-handedly responsible for all growth in patients compliant for more than 6 months in this study. Growth in protection of canine patients with PH 12 proves a helpful tool where mitigation strategies have thus far failed to curb increasing canine heartworm disease prevalence in the US.

Step towards elimination of Wuchereria bancrofti in Southwest Tanzania 10 years after mass drug administration with Albendazole and Ivermectin.

BACKGROUND: Lymphatic filariasis is a mosquito transmitted parasitic infection in tropical regions. Annual mass treatment with ivermectin and albendazole is used for transmission control of Wuchereria bancrofti, the infective agent of lymphatic filariasis in many African countries, including Tanzania. METHODOLOGY: In a general population study in Southwest Tanzania, individuals were tested for circulating filarial antigen, an indicator of W. bancrofti adult worm burden in 2009 before mass drug administration commenced in that area. Seven annual rounds with ivermectin and albendazole were given between 2009 and 2015 with a population coverage of over 70%. Participants of the previous study took part in a follow-up activity in 2019 to measure the effect of this governmental activity. FINDINGS: One thousand two hundred and ninety nine inhabitants of Kyela district in Southwest Tanzania aged 14 to 65 years who had participated in the study activities in 2009 were revisited in 2010/11 and 2019. Among this group, the prevalence of lymphatic filariasis of the 14-65 years olds in 2009 was 35.1%. A follow-up evaluation in 2010/11 had shown a reduction to 27.7%. In 2019, after 7 years of annual treatment and an additional three years of surveillance, the prevalence had dropped to 1.7%, demonstrating successful treatment by the national control programme. Risk factors for W. bancrofti-infection were the occupation as farmer, male sex, and older age. Most infected individuals in the 2019 follow-up study already had a positive test for filarial antigen in 2009 and/or 2010/11. CONCLUSIONS: This data supports the findings of the Tanzanian Neglected Tropical Disease Control Programme (NTDCP), who conducted Transmission Assessment Surveys and found an impressive reduction in the prevalence of LF in children. Our results complement this data by showing a similar decrease in prevalence of LF in the adult population in the same area. The elimination of LF seems achievable in the near future.

Modelling lymphatic filariasis elimination in American Samoa: GEOFIL predicts need for new targets and six rounds of mass drug administration.

BACKGROUND: As part of the global effort to eliminate the debilitating mosquito-borne disease lymphatic filariasis (LF), seven rounds of two-drug (diethylcarbamazine and albendazole) mass drug administration (MDA) were conducted in American Samoa over 2000-2006. However subsequent surveys demonstrated ongoing transmission prompting further rounds of three-drug (diethylcarbamazine, albendazole, and ivermectin) MDA starting in 2018. METHODS: We extend GEOFIL, a spatially-explicit agent-based model of LF transmission to predict the probability and timing of the local elimination or resurgence of LF for different MDA scenarios starting in 2018: two-drug vs. three-drug MDA, two to seven annual rounds, and population coverage rates of 55-75%. We developed an interactive visualisation comparing the effect of MDA strategies on different outcomes. RESULTS: At least six annual rounds of three-drug MDA treating 75% of the population were required to achieve LF elimination in American Samoa by 2035 in > 50% of simulations. In scenarios where MDA did not achieve elimination, prevalence doubled approximately every three years, even if MDA reduced antigen prevalence to <1% (the target recommended by the World Health Organisation). Prevalence in six- and seven-year-old children was approximately one quarter of the prevalence in the general population. CONCLUSION: The three rounds of three-drug MDA conducted in 2018, 2019, and 2021 may have come close to WHO targets but are unlikely to interrupt LF transmission in American Samoa without further interventions. The recommended post-MDA surveillance strategy of testing primarily six and seven-year-old children will delay detection of resurgence compared to population representative surveys. The recommended elimination targets (reducing antigen prevalence below 0.5%, 1%, or 2%) may not be sufficient to interrupt transmission in countries with LF epidemiology like American Samoa. Alternative surveillance strategies and interventions designed to identify and eliminate spatially localized residual transmission may need to be considered. Interactive visualisations may assist decision-makers to choose locally appropriate strategies.