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

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

How Does 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.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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

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

Wolbachia depletion blocks transmission of lymphatic filariasis by preventing chitinase-dependent parasite exsheathment.

Lymphatic filariasis is a vector-borne neglected tropical disease prioritized for global elimination. The filarial nematodes that cause the disease host a symbiotic bacterium, Wolbachia, which has been targeted using antibiotics, leading to cessation of parasite embryogenesis, waning of circulating larvae (microfilariae [mf]), and gradual cure of adult infection. One of the benefits of the anti-Wolbachia mode of action is that it avoids the rapid killing of mf, which can drive inflammatory adverse events. However, mf depleted of Wolbachia persist for several months in circulation, and thus patients treated with antibiotics are assumed to remain at risk for transmitting infections. Here, we show that Wolbachia-depleted mf rapidly lose the capacity to develop in the mosquito vector through a defect in exsheathment and inability to migrate through the gut wall. Transcriptomic and Western blotting analyses demonstrate that chitinase, an enzyme essential for mf exsheathment, is down-regulated in Wolbachia-depleted mf and correlates with their inability to exsheath and escape the mosquito midgut. Supplementation of in vitro cultures of Wolbachia-depleted mf with chitinase enzymes restores their ability to exsheath to a similar level to that observed in untreated mf. Our findings elucidate a mechanism of rapid transmission-blocking activity of filariasis after depletion of Wolbachia and adds to the broad range of biological processes of filarial nematodes that are dependent on Wolbachia symbiosis.

Lymphatic filariasis elimination status: Wuchereria bancrofti infections in human populations and factors contributing to continued transmission after seven rounds of mass drug administration in Masasi District, Tanzania.

BACKGROUND: Lymphatic filariasis (LF) affects more than 120 million people globally. In Tanzania, nearly six million people are estimated to live with clinical manifestations of the disease. The National LF control program was established in 2000 using Mass drug administration (MDA) of Ivermectin and Albendazole to individuals aged 5years and above. This study assessed the infection status in individuals aged 15 years and above who are eligible for participation in MDA. The level of compliance to MDA and the reasons for non-compliance to MDA were also assessed. METHODS: A community based cross-sectional study was conducted in two villages of Masasi District. A total of 590 participants aged 15 years and above were screened for the circulating filarial antigen (CFA) using the rapid diagnostic test. Night blood samples from CFA positive individuals were further analyzed for detection and quantification of Wuchereria bancrofti microfilaria (Mf) using the counting chamber technique. A pre-tested questionnaire was administered to collect information on compliance to MDA and the factors affecting continued transmission. Data were analyzed using SPSS Version 20. Chi-square test was used to compare the prevalence of CFA by gender and village where a P-value ≤0.05 was considered statistically significant. RESULTS: Out of 590 participants, 30 (5.1%) were positive for CFA and one (0.2%) was found positive for microfilaria of Wuchereria bancrofti. Compliance during the last round of MDA, in the year 2019 was 56% which is below the minimum coverage recommended by WHO. Absence from home during MDA and perceptions of being free from hydrocele or elephantiasis were the major reasons for non-compliance. CONCLUSION: There is a significant decline in LF transmission in Masasi District after seven rounds of MDA. However, the presence of individuals who are persistently non-compliant may delay elimination of LF in the District.

Simulating the effect of evaluation unit size on eligibility to stop mass drug administration for lymphatic filariasis in Haiti.

BACKGROUND: The Transmission Assessment Survey (TAS) is a decision-making tool to determine when transmission of lymphatic filariasis is presumed to have reached a level low enough that it cannot be sustained even in the absence of mass drug administration. The survey is applied over geographic areas, called evaluation units (EUs); existing World Health Organization guidelines limit EU size to a population of no more than 2 million people. METHODOLOGY/PRINCIPAL FINDINGS: In 2015, TASs were conducted in 14 small EUs in Haiti. Simulations, using the observed TAS results, were performed to understand the potential programmatic impact had Haiti chosen to form larger EUs. Nine "combination-EUs" were formed by grouping adjacent EUs, and bootstrapping was used to simulate the expected TAS results. When the combination-EUs were comprised of at least one "passing" and one "failing" EU, the majority of these combination-EU would pass the TAS 79% - 100% of the time. Even in the case when both component EUs had failed, the combination-EU was expected to "pass" 11% of the time. Simulations of mini-TAS, a strategy with smaller power and hence smaller sample size than TAS, resulted in more conservative "passing" and "failing" when implemented in original EUs. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate the high potential for misclassification when the average prevalence of lymphatic filariasis in the combined areas differs with regards to the TAS threshold. Of particular concern is the risk of "passing" larger EUs that include focal areas where prevalence is high enough to be potentially self-sustaining. Our results reaffirm the approach that Haiti took in forming smaller EUs. Where baseline or monitoring data show a high or heterogeneous prevalence, programs should leverage alternative strategies like mini-TAS in smaller EUs, or consider gathering additional data through spot check sites to advise EU formation.

Prevalence of soil-transmitted helminth infections, schistosomiasis, and lymphatic filariasis before and after preventive chemotherapy initiation in the Philippines: A systematic review and meta-analysis.

OBJECTIVE: To estimate the impact of preventive chemotherapy on the prevalence and intensity of soil-transmitted helminth (STH) infections, schistosomiasis, and lymphatic filariasis in the Philippines, using systematic review and meta-analysis. METHODS: We included reports reporting prevalence of STH infections, schistosomiasis, or lymphatic filariasis in the Philippines published until 31 March 2021. Peer-reviewed studies were identified in electronic databases. Grey literature reports by the University of the Philippines and the Department of Health were also included. Pooled infection prevalence, before and after the initiation of preventive chemotherapy, stratified by age group, was calculated using the inverse variance heterogeneity model. FINDINGS: A total of 109 reports were included in the review and meta-analysis. Overall prevalence of moderate-heavy intensity Ascaris lumbricoides (6.6%) and Trichuris trichiura (2.7%) infection after initiation of preventive chemotherapy were significantly lower than the prevalence prior to initiation (23.6% for A. lumbricoides and 12.2% for T. trichiura). Prevalence reductions were also found in school and preschool-age children for A. lumbricoides and T. trichiura. Studies conducted after preventive chemotherapy initiation had significantly lower overall prevalence of moderate-heavy intensity schistosomiasis (3.1% vs 0.2%) and of schistosomiasis in school-age children (30.5% vs 1%). Pooled prevalence of lymphatic filariasis prior to preventive chemotherapy initiation was 3.2% across 12 provinces, while currently only two provinces still have prevalence of more than 1%. There were no published studies reporting prevalence of lymphatic filariasis after initiation of preventive chemotherapy. Heterogeneity was high with I2 mostly above 90%. CONCLUSION: The burden of STH infections and schistosomiasis in children were significantly lower in studies conducted following the initiation of preventive chemotherapy. Eliminating morbidity and interrupting transmission, however, may require expanded control initiatives including community-wide treatment, and improved water, sanitation, and hygiene. Lymphatic filariasis burden has decreased since the implementation of preventive chemotherapy, with all but two provinces having reached the elimination of lymphatic filariasis as a public health problem.

Impact of Semi-Annual Albendazole on Lymphatic Filariasis and Soil-Transmitted Helminth Infection: Parasitological Assessment after 14 Rounds of Community Treatment.

Between October 2012 and October 2015, we conducted a community trial to assess the impact of semi-annual (twice yearly) community treatment with albendazole on lymphatic filariasis in Seke Pembe, a village in the Republic of the Congo. Semi-annual community treatment with albendazole has been continued in the community since October 2015. We conducted an additional parasitological assessment survey in October 2019, 6 months after the 14th round of semi-annual treatment. Between October 2012 and October 2015, Wuchereria bancrofti antigenemia and microfilaremia rates in the community had decreased from 17.3% to 4.7% and from 5.3% to 0.3%, respectively. In October 2019, the antigenemia rate had decreased further to 2.8% (19 of 687). No microfilariae were found in night blood smears from persons with circulating filarial antigenemia (0 of 16), suggesting that W. bancrofti transmission has been interrupted in Seke Pembe. Semi-annual albendazole treatments also reduced significantly infection rates with soil-transmitted helminths.

A strong effect of individual compliance with mass drug administration for lymphatic filariasis on sustained clearance of soil-transmitted helminth infections.

BACKGROUND: The impact of semiannual mass drug administration (MDA) with albendazole (ALB; 400 mg) alone on lymphatic filariasis (LF) and soil-transmitted helminth (STH) infections was assessed during two trials conducted from 2012 to 2018 in the Republic of Congo and the Democratic Republic of Congo. The collected data were analyzed to evaluate the effect of compliance with ALB treatment on STH infections. METHODS: STH infections were diagnosed with duplicate Kato-Katz thick smears and the results are reported as eggs per gram of stool. All subjects with at least two STH infection assessments were included in the analyses. We used parametric survival models to assess the influence of compliance with ALB treatment on the probability of (i) achieving sustained clearance of an STH infection, and (ii) acquiring an STH infection during the follow-up. RESULTS: Out of 2658 subjects included in the trials, data on 202 participants (701 person-years; PY) with hookworm infection, 211 (651 PY) with Ascaris lumbricoides infection and 270 (1013 PY) with Trichuris trichiura infection were available to calculate the probability of achieving sustained clearance of infection. The effect of ALB was dose related for all three STH. For hookworm, the time required for sustained clearance was longer (4.3 years, P < 0.001) for participants who took zero doses per year and shorter (3.4 years, P = 0.112) for participants who took two doses per year compared to those who took one dose per year (3.7 years). For Ascaris, the time required to obtain sustained clearance followed the same pattern: 6.1 years (P < 0.001) and 3.2 years (P = 0.004) vs 3.6 years for, zero, two and one dose per year, respectively. For Trichuris, less time was required for sustained clearance (4.2 years, P < 0.001) for fully compliant participants, i.e. those who took two doses per year, than for those who only took one dose per year (5.0 years). ALB was more effective in achieving sustained clearance of STH infection in subjects with light baseline infection intensities compared to those with higher egg counts. CONCLUSION: Our results illustrate the importance of MDA compliance at the level of the individual with respect to the STH benefit provided by semiannual ALB MDA, which is used for the elimination of LF in Central Africa.

Strengthening data collection for neglected tropical diseases: What data are needed for models to better inform tailored intervention programmes?

Locally tailored interventions for neglected tropical diseases (NTDs) are becoming increasingly important for ensuring that the World Health Organization (WHO) goals for control and elimination are reached. Mathematical models, such as those developed by the NTD Modelling Consortium, are able to offer recommendations on interventions but remain constrained by the data currently available. Data collection for NTDs needs to be strengthened as better data are required to indirectly inform transmission in an area. Addressing specific data needs will improve our modelling recommendations, enabling more accurate tailoring of interventions and assessment of their progress. In this collection, we discuss the data needs for several NTDs, specifically gambiense human African trypanosomiasis, lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths (STH), trachoma, and visceral leishmaniasis. Similarities in the data needs for these NTDs highlight the potential for integration across these diseases and where possible, a wider spectrum of diseases.

Simulating a Transmission Assessment Survey: An evaluation of current methods used in determining the elimination of the neglected tropical disease, Lymphatic Filariasis.

INTRODUCTION: The World Health Organization (WHO) recommends Transmission Assessment Surveys (TAS) to determine when an evaluation unit (EU) (a designated population survey area) has achieved elimination of transmission of the vector-borne macroparasitic disease Lymphatic Filariasis (LF). These determinations are based on combining data from multiple survey units within an EU; it is unclear how underlying cluster-level variation influences the outcome of the TAS at EU level. We simulate LF infection distribution in an EU and compare three methods for assessing whether LF elimination has occurred based on currently recommended decision thresholds and sampling methods. METHODS: We simulate an EU divided into clusters of varying size and disease prevalence. We produce 1000 samples according to LF TAS examples and WHO guidelines and compare three decision-making approaches: lot quality assurance sampling (LQAS) (recommended by WHO), one-sided interval estimate (CI), and nth order statistic (MAX). Summary statistics demonstrating the "pass" rate for the EU under different disease transmission conditions are generated using a versatile SAS® macro. RESULTS: As the prevalence of LF decreases, the LQAS and CI approaches produce increased likelihood of a pass outcome for an EU while some cluster units may still have a high likelihood of transmission. The MAX provides an alternative that increases the likelihood of determining a pass only once the whole area has a low likelihood of transmission. LQAS and CI approaches designed to estimate the LF prevalence in the EU miss hotspots that will continue to transmit infection while the MAX approach focuses on identifying clusters with high risk of transmission. CONCLUSIONS: The current TAS methodology has a flaw that may result in false predictions of LF transmission interruption throughout an EU. Modifying the TAS methodology to address results from extreme clusters rather than being based on mean prevalence over an EU will result in greater success for global elimination of LF.

Interruption of lymphatic filariasis transmission in Manaus, a former focus of Wuchereria bancrofti in the Western Brazilian Amazon / Interrupción de la transmisión de la filariasis linfática en Manaos, anteriormente un foco de Wuchereria bancrofti en la Amazonia occidental de Brasil / Interrupção da transmissão da filariose linfática em Manaus, anteriormente um foco de Wuchereria bancrofti na parte leste da Amazônia brasileira

ABSTRACT Objective. To confirm the absence of Wuchereria bancrofti autochthonous cases in Manaus, a former focus of lymphatic filariasis in the Western Brazilian Amazon. Methods. A field survey was carried out in 2016 using immunochromatographic rapid tests (ICT card) for the detection of circulating filarial antigens in blood. The sample included a group of 3 000 schoolchildren aged 6 to 10 years enrolled in schools from different urban areas of Manaus (including the former lymphatic filariasis focus in the city) and a group of 709 adolescents and adults, between the ages of 11 and 85 years, born and raised in different areas of Manaus. Results. All of the individuals tested negative for W. bancrofti antigen. Conclusions. Although Manaus was once considered endemic, this focus no longer seems to be active for lymphatic filariasis transmission. The results of this study could support the certification by the World Health Organization of the lymphatic filariasis transmission elimination exercise in Brazil.

RESUMEN Objetivo. Confirmar la ausencia de casos autóctonos de Wuchereria bancrofti en Manaos, anteriormente un foco de filariasis linfática en la Amazonia occidental de Brasil. Métodos. En el 2016 se llevó a cabo una encuesta en el terreno con pruebas rápidas inmunocromatográficas (tiras inmunocromatográficas) para detectar antígenos filáricos circulantes en sangre. La muestra constó de un grupo de 3 000 escolares de 6 a 10 años matriculados en escuelas de diferentes zonas urbanas de Manaos (incluida la zona que anteriormente era el foco de filariasis linfática en la ciudad) y de un grupo de 709 adolescentes y adultos, de edades comprendidas entre 11 y 85 años, nacidos y criados en diferentes áreas de Manaos. Resultados. Todas las personas dieron negativo en la prueba de antígeno de Wuchereria bancrofti. Conclusiones. Aunque hubo un tiempo en que Manaos se consideraba zona endémica, parece que este foco de transmisión de la filariasis linfática ya no está activo. Los resultados de este estudio podrían brindar apoyo a la certificación de la Organización Mundial de la Salud respecto de los esfuerzos realizados en Brasil para eliminar la transmisión de la filariasis linfática.

RESUMO Objetivo. Confirmar a ausência de casos autóctones de Wuchereria bancrofti em Manaus, anteriormente um foco da filariose linfática na parte leste da Amazônia brasileira. Métodos. Uma pesquisa de campo foi realizada em 2016 com o uso de teste rápido por imunocromatografia (cartão ICT) para detecção de antígenos de microfilárias circulantes no sangue. A amostra estudada consistiu de um grupo de 3 000 crianças escolares entre 6 e 10 anos de idade matriculados em escolas de diferentes áreas da zona urbana de Manaus (englobando a área anteriormente com o foco de filariose linfática) e um grupo de 709 adolescentes e adultos entre 11 e 85 anos de idade nascidos e crescidos em diferentes áreas de Manaus. Resultados. Todos os indivíduos pesquisados tiveram teste negativo para o antígeno da W. bancrofti. Conclusões. Apesar de Manaus ter sido anteriormente uma área endêmica, parece que não existe mais foco ativo de transmissão da filariose linfática na cidade. Os resultados deste estudo podem servir para embasar a certificação pela Organização Mundial da Saúde da eliminação da transmissão da filariose linfática no Brasil.

Potential strategies for strengthening surveillance of lymphatic filariasis in American Samoa after mass drug administration: Reducing 'number needed to test' by targeting older age groups, hotspots, and household members of infected persons.

Under the Global Programme to Eliminate Lymphatic Filariasis (LF), American Samoa conducted mass drug administration (MDA) from 2000-2006. Despite passing Transmission Assessment Surveys (TAS) in 2011/2012 and 2015, American Samoa failed TAS-3 in 2016, with antigen (Ag) prevalence of 0.7% (95%CI 0.3-1.8%) in 6-7 year-olds. A 2016 community survey (Ag prevalence 6.2% (95%CI 4.4-8.5%) in age ≥8 years) confirmed resurgence. Using data from the 2016 survey, this study aims to i) investigate antibody prevalence in TAS-3 and the community survey, ii) identify risk factors associated with being seropositive for Ag and anti-filarial antibodies, and iii) compare the efficiency of different sampling strategies for identifying seropositive persons in the post-MDA setting. Antibody prevalence in TAS-3 (n = 1143) were 1.6% for Bm14 (95%CI 0.9-2.9%), 7.9% for Wb123 (95%CI 6.4-9.6%), and 20.2% for Bm33 (95%CI 16.7-24.3%); and in the community survey (n = 2507), 13.9% for Bm14 (95%CI 11.2-17.2%), 27.9% for Wb123 (95%CI 24.6-31.4%), and 47.3% for Bm33 (95%CI 42.1-52.6%). Multivariable logistic regression was used to identify risk factors for being seropositive for Ag and antibodies. Higher Ag prevalence was found in males (adjusted odds ratio [aOR] 3.01), age ≥18 years (aOR 2.18), residents of Fagali'i (aOR 15.81), and outdoor workers (aOR 2.61). Ag prevalence was 20.7% (95%CI 9.7-53.5%) in households of Ag-positive children identified in TAS-3. We used NNTestav (average number needed to test to identify one positive) to compare the efficiency of the following strategies for identifying persons who were seropositive for Ag and each antibody: i) TAS of 6-7 year-old children, ii) population representative surveys of older age groups, and iii) targeted surveillance of subpopulations at higher risk of being seropositive (older ages, householders of Ag-positive TAS children, and known hotspots). For Ag, NNTestav ranged from 142.5 for TAS, to <5 for households of index children. NNTestav was lower in older ages, and highest for Ag, followed by Bm14, Wb123 and Bm33 antibodies. We propose a multi-stage surveillance strategy, starting with population-representative sampling (e.g. TAS or population representative survey of older ages), followed by strategies that target subpopulations and/or locations with low NNTestav. This approach could potentially improve the efficiency of identifying remaining infected persons and residual hotspots. Surveillance programs should also explore the utility of antibodies as indicators of transmission.

Supporting elimination of lymphatic filariasis in Samoa by predicting locations of residual infection using machine learning and geostatistics.

The global elimination of lymphatic filariasis (LF) is a major focus of the World Health Organization. One key challenge is locating residual infections that can perpetuate the transmission cycle. We show how a targeted sampling strategy using predictions from a geospatial model, combining random forests and geostatistics, can improve the sampling efficiency for identifying locations with high infection prevalence. Predictions were made based on the household locations of infected persons identified from previous surveys, and environmental variables relevant to mosquito density. Results show that targeting sampling using model predictions would have allowed 52% of infections to be identified by sampling just 17.7% of households. The odds ratio for identifying an infected individual in a household at a predicted high risk compared to a predicted low risk location was 10.2 (95% CI 4.2-22.8). This study provides evidence that a 'one size fits all' approach is unlikely to yield optimal results when making programmatic decisions based on model predictions. Instead, model assumptions and definitions should be tailored to each situation based on the objective of the surveillance program. When predictions are used in the context of the program objectives, they can result in a dramatic improvement in the efficiency of locating infected individuals.

Molecular xenomonitoring of diurnally subperiodic Wuchereria bancrofti infection in Aedes (Downsiomyia) niveus (Ludlow, 1903) after nine rounds of Mass Drug Administration in Nancowry Islands, Andaman and Nicobar Islands, India.

A group of four human inhabited Nancowry Islands in Nicobar district in the Andaman and Nicobar Islands, India having a population of 7674 is the lone focus of diurnally sub-periodic Wuchereria bancrofti (DspWB) that is transmitted by Aedes niveus (Ludlow). Microfilaria (Mf) prevalence was above 1% even after nine rounds of Mass Drug Administration (MDA) with DEC and albendazole. Molecular xenomonitoring (MX) was conducted to identify appropriate vector sampling method and assess the impact. BioGents Sentinel traps, gravid traps and human baited double bed nettraps were used in three locations in each village to collect Aedes niveus female mosquitoes. Subsequently daytime man landing collections (MLC) were carried out in all the 25 villages in the islands. Collections were compared in terms of the number of vector mosquitoes captured per trap collection. Females of Ae. niveus were pooled, dried and processed for detecting filarial parasite DNA using RT-PCR assay. Vector infection rate was estimated using PoolScreen software. Only 393 female mosquitoes including 44 Ae. niveus (11.2%) were collected from 459 trap collections using three trapping devices. From 151 MLCs, 2170 Ae. niveus female mosquitoes were collected. The average prevalence of W. bancrofti DNA was 0.43%. Estimated upper 95% CI exceeded the provisional prevalence threshold of 0.1% in all the villages, indicating continued transmission as observed in Mf survey. MLCs could be the choice, for now, to sample Ae. niveus mosquitoes. The PCR assay used in MX for nocturnally periodic bancroftian filariasis could be adopted for DspWB. The vector-parasite MX, can be used to evaluate interventions in this area after further standardization of the protocol.

Defining a prevalence level to describe the elimination of Lymphatic Filariasis (LF) transmission and designing monitoring & evaluating (M&E) programmes post the cessation of mass drug administration (MDA).

The global decline in prevalence of lymphatic filariasis has been one of the major successes of the WHO's NTD programme. The recommended strategy of intensive, community-wide mass drug administration, aims to break localised transmission by either reducing the prevalence of microfilaria positive infections to below 1%, or antigen positive infections to below 2%. After the threshold is reached, and mass drug administration is stopped, geographically defined evaluation units must pass Transmission Assessment Surveys to demonstrate that transmission has been interrupted. In this study, we use an empirically parameterised stochastic transmission model to investigate the appropriateness of 1% microfilaria-positive prevalence as a stopping threshold, and statistically evaluate how well various monitoring prevalence-thresholds predict elimination or disease resurgence in the future by calculating their predictive value. Our results support the 1% filaremia prevalence target as appropriate stopping criteria. However, because at low prevalence-levels random events dominate the transmission dynamics, we find single prevalence measurements have poor predictive power for predicting resurgence, which suggests alternative criteria for restarting MDA may be beneficial.

Elimination of Lymphatic Filariasis in Shandong Province, China, 1957-2015.

China used to be one of the most heavily endemic countries for lymphatic filariasis (LF) in the world. Bancroftian filariasis, which is caused by the filarioid nematode Wuchereria bancrofti, is the only filariasis in Shandong Province. A total of 864 endemic counties (cities) in 16 provinces/autonomous regions/municipalities with a total population of 330 million people were at risk of infection. Shandong Province was a highly LF-endemic area in the 1950s, the epidemiological investigation of LF conducted in 1957 indicated that the disease was endemic in 74 counties and the highest microfilaria rate was up to 26%. There were ∼5 million people in the province infected with LF; among which almost 2.5 million people had lymphedema, elephantiasis, or hydrocele. Through vigorous prevention and scientific research, Shandong Province was the first to propose to treat LF with fortified diethylcarbamazine salt, more than 25 million people in the province had taken the salt, and more than 3 million people took intermittent medication. After more than 50 years of unremitting efforts, Shandong Province basically eliminated LF in 1983 and became the first province in China that successfully eradicated LF in 2004, which has played an important role in accelerating the elimination of filariasis in the country in 2007 and has made tremendous contributions to social and economic development of China. Since 1980, Shandong Province has carried out extensive international cooperation as the WHO Collaborating Center for Lymphatic Filariasis. This article is intended to share the experience in eliminating LF to other parts of the world and improve public health capacity in regions such as Africa and Oceania where the disease is still endemic for interest.

The Epitome of Novel Techniques and Targeting Approaches in Drug Delivery for Treating Lymphatic Filariasis.

BACKGROUND: Lymphatic filariasis is a pervasive and life-threatening disease for human beings. Currently, 893 million people in 49 countries worldwide affected by lymphatic filariasis as per WHO statistics. The concealed aspects of lymphatic diseases such as delayed disease detection, inappropriate disease imaging, the geographical outbreak of infection, and lack of preventive chemotherapy have brought this epidemic to the edge of Neglected Tropical Diseases. Many medications and natural bioactive substances have seen to promote filaricidal activity against the target parasitic species. However, the majority of failures have occurred in pharmaceutical and pharmacokinetic issues. OBJECTIVE: The purpose of the study is to focus on the challenges and therapeutic issues in the treatment of filariasis. The review brings novel techniques and therapeutic approaches for combating lymphatic filariasis. It also offers significant developments and opportunities for such therapeutic interventions. CONCLUSION: Through this review, an attempt has made to critically evaluate the avenues of innovative pharmaceuticals and molecular targeting approaches to bring an integrated solution to combat lymphatic filariasis.

Development of a molecular xenomonitoring protocol to assess filariasis transmission.

According to the World Health Organization, lymphatic filariasis (LF), a mosquito-borne neglected tropical disease (NTD), should be eliminated as a public health concern by the end of 2020. To this end, the goals of the Global Programme to Eliminate Lymphatic Filariasis (GPELF) include interrupting transmission through mass drug administration (MDA). After two decades, several countries have implemented MDA and are now ready to confirm whether transmission has been interrupted. The method for detecting the parasites in mosquito vectors known as xenomonitoring is a non-invasive tool for assessing the current transmission status of the filarial nematode Wuchereria bancrofti (which is responsible for 90% of cases) by their vectors. There are several methods available for detection of the worm in mosquito samples, such as dissection or polymerase chain reaction (PCR). However, most of these techniques still produce a considerable number of false-negative results. The present study describes a new duplex PCR protocol, which is an improvement on the traditional PCR methodology, enhanced by introducing the actin gene as an endogenous control gene. After adjusting the mosquito pool size, DNA extraction, and WbCx PCR duplex design, we achieved a reliable and sensitive molecular xenomonitoring protocol. This assay was able to eliminate 5% of false negative samples and detected less than one Wb larvae. This high sensitivity is particularly valuable after MDA, when prevalence declines. This new method could reduce the number of false-negative samples, which will enable us to improve our ability to generate accurate results and aid the monitoring strategies used by LF elimination programmes.