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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 (n = 7; 41%) in Cabo Delgado province had medium to high-risk; 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 2021–2030 targets due to the humanitarian crisis ongoing. There is the need for practical strategies and funding to overcome these hostile challenges. Author summary: Neglected tropical diseases (NTDs) are a group of diseases that usually affect the most vulnerable population in tropical countries. Mozambique has been tackling lymphatic filariasis, schistosomiasis and soil-transmitted helminths for two decades with the aim of eliminating them through large-scale distribution of drugs to interrupt transmission. In recent years, internal conflict has emerged and led to an escalating humanitarian crisis in the endemic province of Cabo Delgado which has hampered elimination efforts. This study aimed to shed light on the situation and to determine the potential impact on the Mozambique NTDs' programme. We used a range of open-source data on NTDs, conflict, internally displaced persons and geographical access to summarise, describe, and map the situation at the district level in the most affected province. We used this data to also examine their geographical overlap and to develop a risk assessment tool to highlight the high risk and most vulnerable areas. We found that between 2021–2022 more than 1,300 conflict incidents occurred, and almost 1 million people were displaced in Cabo Delgado province with many districts having limited geographical access which impacted the NTDs programme's ability to work. The study highlights the important challenges of conflict and displacement of vulnerable populations, and the need for support and set of guidelines for NTDs endemic programmes to use to help to overcome key barriers and meet the targets of elimination set by the World Health Organization for 2030. [ABSTRACT FROM AUTHOR]

Background: Lymphatic filariasis (LF) is a parasitic disease transmitted by mosquitoes, causing severe pain, disfiguring, and disabling clinical conditions such as lymphoedema and hydrocoele. LF is a global public health problem affecting 72 countries, primarily in Africa and Asia. Since 2000, the World Health Organization (WHO) has led the Global Programme to Eliminate Lymphatic Filariasis (GPELF) to support all endemic regions. This paper focuses on the achievements of the Malawi LF Elimination Programme between 2000 and 2020 to eliminate LF as a public health problem, making it the second sub-Saharan country to receive validation from the WHO. Methodology/principal findings: The Malawi LF Programme addressed the widespread prevalence of LF infection and disease across the country, using the recommended WHO GPELF strategies and operational research initiatives in collaboration with key national and international partners. First, to stop the spread of infection (i.e., interrupt transmission) and reduce the circulating filarial antigen prevalence from as high as 74.4% to below the critical threshold of 1–2% prevalence, mass drug administration (MDA) using a two-drug regime was implemented at high coverage rates (>65%) of the total population, with supplementary interventions from other programmes (e.g., malaria vector control). The decline in prevalence was monitored and confirmed over time using several impact assessment and post-treatment surveillance tools including the standard sentinel site, spot check, and transmission assessment surveys and alternative integrated, hotspot, and easy-access group surveys. Second, to alleviate suffering of the affected populations (i.e., control morbidity) the morbidity management and disability prevention (MMDP) package of care was implemented. Specifically, clinical case estimates were obtained via house-to-house patient searching activities; health personnel and patients were trained in self-care protocols for lymphoedema and/or referrals to hospitals for hydrocoele surgery; and the readiness and quality of treatment and services were assessed with new survey tools. Conclusions: Malawi's elimination of LF will ensure that future generations are not infected and suffer from the disfiguring and disabling disease. However, it will be critical that the Malawi LF Elimination programme remains vigilant, focussing on post-elimination surveillance and MMDP implementation and integration into routine health systems to support long-term sustainability and ongoing success. Summary: Lymphatic filariasis, also known as elephantiasis, is a disabling, disfiguring, and painful disease caused by a parasite that infected mosquitoes transmit to millions of people worldwide. Since 2000, the Global Programme to Eliminate Lymphatic Filariasis (GPELF) has supported endemic countries such as Malawi in south-eastern Africa, to eliminate the disease as a public health problem. The Malawi National LF Elimination Programme has worked tirelessly over the past two decades to implement the GPELF recommended strategies to interrupt the transmission with a two-drug regime, and to alleviate suffering in patients with lymphoedema and/or hydrocoele through morbidity management and disability prevention. Additionally, the LF Programme has collaborated with national and international stakeholders to implement a range of supplementary operational research projects to address outstanding knowledge gaps and programmatic barriers. In 2020, the World Health Organisation validated that Malawi had successfully eliminated LF as a public health problem, making it the second country in sub-Saharan Africa to achieve this, which is remarkable given that Malawi previously had very high infection rates. The LF Programme now remains vigilant, putting its efforts towards post-elimination surveillance and the continued implementation of care for patients with chronic conditions. Malawi's elimination of LF will ensure that future generations are not affected by this devastating disease. [ABSTRACT FROM AUTHOR]

Background: Moxidectin is a macrocyclic lactone registered for the treatment of human onchocerciasis. The drug has a good safety profile, large volume of distribution and a long elimination half-life. This paper reports tolerability data from the first use of moxidectin in persons with Wuchereria bancrofti infection. Methods: In this randomized, open-label, masked-observer superiority trial, adults with Wuchereria bancrofti microfilaremia in Côte d'Ivoire were randomized to 1 of 4 treatment arms: ivermectin + albendazole (IA), moxidectin + albendazole (MoxA), ivermectin + diethylcarbamazine (DEC) + albendazole (IDA), or moxidectin + DEC + albendazole (MoxDA). As part of a larger efficacy trial, all participants were closely monitored for 7 days after treatment. Results: One hundred sixty-four individuals were treated, and monitored for treatment emergent adverse events (TEAE). Eighty-seven participants (53%) experienced one or more mild (grade 1) or moderate (grade 2) TEAE. Four participants had transient Grade 3 hematuria after treatment (3 after IDA and 1 after IA). There were no serious adverse events. There were no significant differences in frequency or types of TEAE between treatment groups (IA = 22/41 (53%), MoxA = 24/40 (60%), IDA = 18/41 (44%), MoxDA = 15/42 (36%), p = 0.530). Fifty-nine participants (36%) had multiple TEAE, and 8.5% had a one or more grade 2 (moderate) TEAE. Grade 2 TEAE were more frequent after triple drug treatments (IDA, 14.6%; MoxDA, 9.5%) than after two-drug treatments (IA, 7.3%; MoxA, 2.5%). There was no difference in TEAEs based on baseline Mf counts (OR 0.69 (0.33, 1.43), p-value 0.319). Conclusion: All treatment regimens were well tolerated. We observed no difference in safety parameters between regimens that contained ivermectin or moxidectin. Trial registration: Clinicaltrials.gov, NCT04410406. Author summary: Lymphatic Filariasis (LF) is a mosquito-borne parasitic infection caused predominantly by Wuchereria bancrofti. Infection can lead to significant lymphatic dysfunction, including hydroceles and lymphedema, which can progress to elephantiasis. The World Health Organization's Global Programme to Eliminate LF (GPELF) recommends mass drug administration (MDA) in endemic populations to eliminate the disease. GPELF recommendations for MDA include ivermectin (IVM) plus albendazole (IA) in sub-Saharan Africa where onchocerciasis is present. In 2018 the US Food and Drug Administration approved use of moxidectin for treatment of onchocerciasis. Moxidectin is a macrocytic lactone, similar to IVM, but more lipophilic, with a larger volume of distribution and longer half-life. Onchocerciasis studies found moxidectin to be superior to IVM for clearance of microfiladermia in people with onchocerciasis, with a treatment emergent adverse event (TEAE) profile similar to that of ivermectin. Moxidectin has not yet been studied, alone or in combination with other antihelminthic drugs. This is a safety evaluation of the first trial of moxidectin combination therapy for LF, which shows that moxidectin combination regimens are well tolerated in Wuchereria bancrofti-infected patients, with a TEAE profile comparable to standard ivermectin containing regimens. [ABSTRACT FROM AUTHOR]

Due to the success of the Global Programme to Eliminate Lymphatic Filariasis (GPELF) many countries have either eliminated the disease as a public health problem or are scheduled to achieve this elimination status in the coming years. The World Health Organization (WHO) recommend that the Transmission Assessment Survey (TAS) is used routinely for post-mass drug administration (MDA) surveillance but it is considered to lack sensitivity in low prevalence settings and not be suitable for post-validation surveillance. Currently there is limited evidence to support programme managers on the design of appropriate alternative strategies to TAS that can be used for post-validation surveillance, as recommended by the WHO. We searched for human and mosquito LF surveillance studies conducted between January 2000 and December 2018 in countries which had either completed MDA or had been validated as having eliminated LF. Article screening and selection were independently conducted. 44 papers met the eligibility criteria, summarising evidence from 22 countries and comprising 83 methodologically distinct surveillance studies. No standardised approach was reported. The most common study type was community-based human testing (n = 42, 47.2%), followed by mosquito xenomonitoring (n = 23, 25.8%) and alternative (non-TAS) forms of school-based human testing (n = 19, 21.3%). Most studies were cross-sectional (n = 61, 73.5%) and used non-random sampling methods. 11 different human diagnostic tests were described. Results suggest that sensitivity of LF surveillance can be increased by incorporating newer human diagnostic tests (including antibody tests) and the use of mosquito xenomonitoring may be able to help identify and target areas of active transmission. Alternative sampling methods including the addition of adults to routine surveillance methods and consideration of community-based sampling could also increase sensitivity. The evidence base to support post-validation surveillance remains limited. Further research is needed on the diagnostic performance and cost-effectiveness of new diagnostic tests and methodologies to guide policy decisions and must be conducted in a range of countries. Evidence on how to integrate surveillance within other routine healthcare processes is also important to support the ongoing sustainability of LF surveillance. Author summary: Lymphatic filariasis (LF) is a mosquito-borne disease, which can result in complications including swelling affecting the limbs (lymphoedema) or scrotum (hydrocele). LF can be eliminated by mass drug administration (MDA) which involves whole communities taking drug treatment at regular intervals. After MDA programmes, country programmes conduct the Transmission Assessment Survey (TAS), which tests school children for LF. It is important to continue testing for LF after elimination because there can be a 10-year period between becoming infected and developing symptoms, but it is thought that the use of TAS in such settings is likely to be too expensive and also not sensitive enough to detect low-level infections. Our study assesses the results from 44 studies in areas of low LF prevalence that have investigated methods of surveillance for LF which differ from the standardised TAS approach. These include both human and mosquito studies. Results show that there is currently no standardised approach to testing, but that surveillance can be made more sensitive through the use of new diagnostic tests, such as antibody testing, and also by targeting higher risk populations. However, further research is needed to understand whether these approaches work in a range of settings and whether they are affordable on the ground. [ABSTRACT FROM AUTHOR]

Background: American Samoa completed seven rounds of mass drug administration from 2000–2006 as part of the Global Programme to Eliminate Lymphatic Filariasis (LF). However, resurgence was confirmed in 2016 through WHO-recommended school-based transmission assessment survey and a community-based survey. This paper uses data from the 2016 community survey to compare different spatial and non-spatial methods to characterise clustering and hotspots of LF. Method: Non-spatial clustering of infection markers (antigen [Ag], microfilaraemia [Mf], and antibodies (Ab [Wb123, Bm14, Bm33]) was assessed using intra-cluster correlation coefficients (ICC) at household and village levels. Spatial dependence, clustering and hotspots were examined using semivariograms, Kulldorf's scan statistic and Getis-Ord Gi* statistics based on locations of surveyed households. Results: The survey included 2671 persons (750 households, 730 unique locations in 30 villages). ICCs were higher at household (0.20–0.69) than village levels (0.10–0.30) for all infection markers. Semivariograms identified significant spatial dependency for all markers (range 207–562 metres). Using Kuldorff's scan statistic, significant spatial clustering was observed in two previously known locations of ongoing transmission: for all markers in Fagali'i and all Abs in Vaitogi. Getis-Ord Gi* statistic identified hotspots of all markers in Fagali'i, Vaitogi, and Pago Pago-Anua areas. A hotspot of Ag and Wb123 Ab was identified around the villages of Nua-Seetaga-Afao. Bm14 and Bm33 Ab hotspots were seen in Maleimi and Vaitogi-Ili'ili-Tafuna. Conclusion: Our study demonstrated the utility of different non-spatial and spatial methods for investigating clustering and hotspots, the benefits of using multiple infection markers, and the value of triangulating results between methods. Author summary: Lymphatic filariasis is a parasitic infection caused by thread-like filarial nematodes and transmitted by mosquitoes. Lymphatic filariasis was endemic in American Samoa and seven rounds of mass drug administration were distributed between 2000 and 2006. Routine blood surveys in 2011 and 2015 did not identify any evidence of ongoing transmission. However, research studies conducted at around the same time showed evidence of residual hotspots and ongoing transmission, which was confirmed by both school-based and community-based surveys in 2016. This study analysed data from the 2016 community survey to identify clusters and hotspots using both non-spatial and spatial analytical methods. The findings confirmed previously known locations of ongoing lymphatic filariasis transmission in American Samoa and identified other potential hotspots that warrant further investigation. We demonstrated the utility of different non-spatial and spatial methods for investigating clustering and hotspots, and different information provided by each method. Noting the added value of these methods, they could potentially be considered as additional tools for improving lymphatic filariasis surveillance and optimising operational activities for elimination programmes, particularly for identifying areas of ongoing transmission or resurgence that may not be identified through current surveillance strategies. [ABSTRACT FROM AUTHOR]

Background: The success of programs to eliminate lymphatic filariasis (LF) depends in large part on their ability to achieve and sustain high levels of compliance with mass drug administration (MDA). This paper reports results from a comprehensive review of factors that affect compliance with MDA. Methodology/Principal Findings: Papers published between 2000 and 2012 were considered, and 79 publications were included in the final dataset for analysis after two rounds of selection. While results varied in different settings, some common features were associated with successful programs and with compliance by individuals. Training and motivation of drug distributors is critically important, because these people directly interact with target populations, and their actions can affect MDA compliance decisions by families and individuals. Other important programmatic issues include thorough preparation of personnel, supplies, and logistics for implementation and preparation of the population for MDA. Demographic factors (age, sex, income level, and area of residence) are often associated with compliance by individuals, but compliance decisions are also affected by perceptions of the potential benefits of participation versus the risk of adverse events. Trust and information can sometimes offset fear of the unknown. While no single formula can ensure success MDA in all settings, five key ingredients were identified: engender trust, tailor programs to local conditions, take actions to minimize the impact of adverse events, promote the broader benefits of the MDA program, and directly address the issue of systematic non-compliance, which harms communities by prolonging their exposure to LF. Conclusions/Significance: This review has identified factors that promote coverage and compliance with MDA for LF elimination across countries. This information may be helpful for explaining results that do not meet expectations and for developing remedies for ailing MDA programs. Our review has also identified gaps in understanding and suggested priority areas for further research. Author Summary: Lymphatic filariasis (LF, also known as "elephantiasis") is a deforming and disabling disease that is caused by roundworm parasites that are transmitted by mosquitoes. The Global Programme to Eliminate Lymphatic Filariasis is the largest public health intervention program attempted to date based on mass drug administration (MDA). MDA does not cure filarial infections, but it can reduce or interrupt transmission of new infections by clearing larval parasites from human blood so that they are not available for mosquitoes. High levels of participation are required for this strategy to work; guidelines from the World Health Organization call for at least 65% of the eligible population to take the medications annually for four to six years. MDA presents logistical challenges that require cooperation between donors, health ministries, and communities. The success of MDA depends on coverage (drug delivery) and compliance (people ingesting antifilarial drugs), which depends on individual interactions between drug distributors and the people who live in LF-endemic areas. This paper focuses on this last step of implementation with a comprehensive review of published and unpublished information on factors that affect compliance with MDA at the level of the individual. We have also provided an outline of current gaps in understanding and recommendations for further research. [ABSTRACT FROM AUTHOR]

Background: The Bangladesh Lymphatic Filariasis (LF) Elimination Programme has made significant progress in interrupting transmission through mass drug administration (MDA) and has now focussed its efforts on scaling up managing morbidity and preventing disability (MMDP) activities to deliver the minimum package of care to people affected by LF clinical conditions. This paper highlights the Bangladesh LF Programme's success in conducting a large-scale cross-sectional survey to determine the number of people affected by lymphoedema and hydrocoele, which enabled clinical risk maps to be developed for targeted interventions across the 34 endemic districts (19 high endemic; 15 low endemic). Methodology/Principal findings: In the 19 high endemic districts, 8,145 community clinic staff were trained to identify and report patients in their catchment area. In the 15 low endemic districts, a team of 10 trained field assistants conducted active case finding with cases reported via a SMS mHealth tool. Disease burden and prevalence maps were developed, with morbidity hotspots identified at sub-district level based on a combination of the highest prevalence rates per 100,000 and case-density rates per square kilometre (km2). The relationship between morbidity and baseline microfilaria (mf) prevalence was also examined. In total 43,678 cases were identified in the 19 high endemic districts; 30,616 limb lymphoedema (70.1%; female 55.3%), 12,824 hydrocoele (29.4%), and 238 breast/female genital swelling (0.5%). Rangpur Division reported the highest cases numbers and prevalence of lymphoedema (26,781 cases, 195 per 100,000) and hydrocoele (11661 cases, 169.6 per 100,000), with lymphoedema predominately affecting females (n = 21,652). Rangpur and Lalmonirhat Districts reported the highest case numbers (n = 11,199), and prevalence (569 per 100,000) respectively, with five overlapping lymphoedema and hydrocoele sub-district hotspots. In the 15 low endemic districts, 732 cases were identified; 661 lymphoedema (90.2%; female 39.6%), 56 hydrocoele (7.8%), and 15 both conditions (2.0%). Spearman's correlation analysis found morbidity and mf prevalence significantly positively correlated (r = 0.904; p<0.01). Conclusions/Significance: The Bangladesh LF Programme has developed one of the largest, most comprehensive country databases on LF clinical conditions in the world. It provides an essential database for health workers to identify local morbidity hotspots, deliver the minimum package of care, and address the dossier elimination requirements. Author summary: The Global Programme to Eliminate Lymphatic Filariasis (GPELF) requires lymphatic filariasis (LF) endemic countries, such as Bangladesh, to estimate the number of lymphoedema and hydrocoele cases in order to deliver the minimum package of care required to control morbidity and reduce patient suffering. This paper highlights the Bangladesh LF Elimination Programme's progress in training more than 8000 community health workers to identify more than 44,000 cases across 34 endemic districts where approximately 70 million people are at risk. The morbidity data collected enabled the creation of a national database and a series of risk maps of lymphoedema and hydrocoele to be developed, which highlighted the significant burden in northern Rangpur Division, especially of lymphoedema among female patients. The Bangladesh LF Elimination Programme's efforts to identify LF cases across all endemic districts represents one of the most comprehensive national databases on LF clinical cases in the world. It provides an informative database for health workers to use in the delivery of the minimum package of care and a template for other countries to adopt and develop national strategies to manage morbidity and prevent disability as recommended by GPELF. [ABSTRACT FROM AUTHOR]

Leprosy, podoconiosis, and lymphatic filariasis (LF) are among the priority neglected tropical diseases (NTDs) in Ethiopia. The disability, psychosocial, and mental health status of people affected by these NTDs are still overlooked in global NTD discourse. The objective of this systematic review was to synthesize the existing evidence describing the disability, psychosocial, and mental health status of people affected by leprosy, podoconiosis, and LF prior to developing a holistic physical and psychosocial care package for these individuals. We searched papers reporting on disability, psychosocial, and mental health status linked to these 3 NTDs. The protocol was registered in PROSPERO with registration number CRD42019128400. Peer-reviewed articles were searched and extracted from Medline, PsycINFO, Global Health, and Embase. Articles published in English, irrespective of the year of publication, using a quantitative study methodology, were included. Abstracts and full texts were reviewed by 2 reviewers. Data were extracted and narratively summarized, as the studies were heterogeneous and used different outcome measures. Out of 1,318 titles/abstracts screened and 59 full text studies reviewed, 24 fulfilled the inclusion criteria. Fourteen studies provided evidence of the disability associated with leprosy, podoconiosis, or LF. Ten studies provided evidence on the association between the 3 NTDs and mental health or psychosocial outcomes. The prevalence of grade 2 disability varied from 3.9% to 86%. The most commonly reported mental health impacts were depression and mental distress. A high burden of mental illness was reported, varying from 12.6% to 71.7%; the suicidal ideation was also high (18.5%). In conclusion, disability and poor psychosocial and mental health status are associated with leprosy, podoconiosis, and LF. For optimum management of these NTDs, holistic care including both physical and psychosocial interventions is vital. Author summary: Podoconiosis, lymphatic filariasis (LF), and leprosy are neglected tropical diseases (NTDs) that are commonly found among disadvantaged rural and some poor urban communities. These diseases lead to disabilities of the leg, which may result in reduced productivity. The longer the duration of the disease, the more severe the disability. People affected by these diseases also commonly experience stigma and discrimination, which, in turn, affect health-seeking behavior. Due to this disability, stigma, and discrimination, people affected by these 3 NTDs have a poor quality of life. We also found a range of mental health problems related to these 3 NTDs. Among these, the most common were mental distress and depression. As all 3 NTDs are associated with poor physical, psychosocial, and mental health outcomes, management should be holistic, incorporating physical, psychosocial, and mental health interventions. Following this review, we are working on the development of a holistic integrated care package for people affected by leprosy, podoconiosis, and LF in northwestern Ethiopia. [ABSTRACT FROM AUTHOR]

Background: Samoa conducted eight nationwide rounds of mass drug administration (MDA) for lymphatic filariasis (LF) between 1999 and 2011, and two targeted rounds in 2015 and 2017 in North West Upolu (NWU), one of three evaluation units (EUs). Transmission Assessment Surveys (TAS) were conducted in 2013 (failed in NWU) and 2017 (all three EUs failed). In 2018, Samoa was the first in the world to distribute nationwide triple-drug MDA using ivermectin, diethylcarbamazine, and albendazole. Surveillance and Monitoring to Eliminate LF and Scabies from Samoa (SaMELFS Samoa) is an operational research program designed to evaluate the effectiveness of triple-drug MDA on LF transmission and scabies prevalence in Samoa, and to compare the usefulness of different indicators of LF transmission. This paper reports results from the 2018 baseline survey and aims to i) investigate antigen (Ag) prevalence and spatial epidemiology, including geographic clustering; ii) compare Ag prevalence between two different age groups (5–9 years versus ≥10 years) as indicators of areas of ongoing transmission; and iii) assess the prevalence of limb lymphedema in those aged ≥15 years. Methods: A community-based cluster survey was conducted in 30 randomly selected and five purposively selected clusters (primary sampling units, PSUs), each comprising one or two villages. Participants were recruited through household surveys (age ≥5 years) and convenience surveys (age 5–9 years). Alere Filariasis Test Strips (FTS) were used to detect Ag, and prevalence was adjusted for survey design and standardized for age and gender. Adjusted Ag prevalence was estimated for each age group (5–9, ≥10, and all ages ≥5 years) for random and purposive PSUs, and by region. Intraclass correlation (ICC) was used to quantify clustering at regions, PSUs, and households. Results: A total of 3940 persons were included (1942 children aged 5–9 years, 1998 persons aged ≥10 years). Adjusted Ag prevalence in all ages ≥5 years in randomly and purposively selected PSUs were 4.0% (95% CI 2.8–5.6%) and 10.0% (95% CI 7.4–13.4%), respectively. In random PSUs, Ag prevalence was lower in those aged 5–9 years (1.3%, 95% CI 0.8–2.1%) than ≥10 years (4.7%, 95% CI 3.1–7.0%), and poorly correlated at the PSU level (R2 = 0.1459). Adjusted Ag prevalence at PSUs ranged from 0% to 10.3% (95% CI 5.9–17.6%) in randomly selected and 3.8% (95% CI 1.3–10.8%) to 20.0% (95% CI 15.3–25.8%) in purposively selected PSUs. ICC for Ag-positive individuals was higher at households (0.46) compared to PSUs (0.18) and regions (0.01). Conclusions: Our study confirmed ongoing transmission of LF in Samoa, in accordance with the 2017 TAS results. Ag prevalence varied significantly between PSUs, and there was poor correlation between prevalence in 5–9 year-olds and older ages, who had threefold higher prevalence. Sampling older age groups would provide more accurate estimates of overall prevalence, and be more sensitive for identifying residual hotspots. Higher prevalence in purposively selected PSUs shows local knowledge can help identify at least some hotspots. Author summary: Lymphatic filariasis (LF), a disease caused by infection with worms transmitted by mosquitoes, has long been present in Samoa. Since the 1960s, Samoa has attempted to control the disease through many rounds of annual administration of two deworming drugs to the whole population. However, Samoa recently observed that LF transmission was still occurring, prompting mass drug administration (MDA) with three drugs in 2018. Here, we report the baseline survey of an operational research program to evaluate the triple drug MDA. The survey assessed prevalence and geographical distribution of LF in the population, compared prevalence by age groups, and investigated the burden of elephantiasis (swollen limbs caused by long-term LF infection). The study confirmed ongoing transmission, with 4% of those aged ≥5 years showing antigen in their blood as evidence of infection. Antigen prevalence was more than three times higher in those aged ≥10 years (4.7%) than in 5–9 year-old children (1.3%). Infection was highly clustered within households and villages, with up to 20% of residents infected in known hotspot villages. Future surveillance strategies should consider that i) testing older age groups would provide more accurate indication of LF transmission, and ii) local knowledge can help identify transmission hotspots. [ABSTRACT FROM AUTHOR]

The Global Programme to Eliminate Lymphatic Filariasis has made considerable progress but is experiencing challenges in meeting targets in some countries. Recent World Health Organization guidelines have recommended two rounds of triple-drug therapy with ivermectin, diethylcarbamazine (DEC), and albendazole (IDA), in areas where mass drug administration (MDA) results with two drugs (DEC and albendazole) have been suboptimal, as is the case in Samoa. In August 2018, Samoa was the first country in the world to implement countrywide triple-drug MDA. This paper aims to describe Samoa's experience with program coverage and adverse events (AEs) in the first round of triple-drug MDA. We conducted a large cross-sectional community survey to assess MDA awareness, reach, compliance, coverage and AEs in September/October 2018, 7–11 weeks after the first round of triple-drug MDA. In our sample of 4420 people aged ≥2 years (2.2% of the population), age-adjusted estimates indicated that 89.0% of the eligible population were offered MDA, 83.9% of the eligible population took MDA (program coverage), and 80.2% of the total population took MDA (epidemiological coverage). Overall, 83.8% (2986/3563) reported that they did not feel unwell at all after taking MDA. Mild AEs (feeling unwell but able to do normal everyday things) were reported by 13.3% (476/3563) and moderate or severe AEs (feeling unwell and being unable to do normal everyday activities such as going to work or school) by 2.9% (103/3563) of participants. This study following the 2018 triple-drug MDA in Samoa demonstrated a high reported program awareness and reach of 90.8% and 89.0%, respectively. Age-adjusted program coverage of 83.9% of the total population showed that MDA was well accepted and well tolerated by the community. Author summary: Lymphatic filariasis is a disease caused by worms and transmitted between humans by mosquitoes. A global program underway aims to eliminate lymphatic filariasis as a public health problem by distributing two deworming drugs to the whole population once a year for at least five years. In some countries, including Samoa, this strategy has not been sufficient to eliminate transmission. A new drug has been added, and in 2018, Samoa was the first country in the world to distribute triple-drug mass drug administration (MDA) using ivermectin, diethylcarbamazine, and albendazole. This study reports on the coverage achieved (percentage of people who reported taking the drugs) and adverse events after taking the drugs. The study was a large community survey of over 4000 people, done 7–11 weeks after the distribution of the first round of triple-drug MDA. We found that the program reached and offered MDA to approximately 90% of the whole population, and approximately 80% of the whole population swallowed the drugs. We also collected data on whether people felt unwell after taking the pills, and found that 84% of people taking the pills did not feel unwell at all, while 13% reported feeling unwell afterwards but were able to do normal everyday activities, and 3% reported that they had felt unwell and that it stopped them doing normal everyday activities, such as going to school or work. [ABSTRACT FROM AUTHOR]

Achieving elimination of lymphatic filariasis (LF) as a public health problem requires a minimum of five effective rounds of mass drug administration (MDA) and demonstrating low prevalence in subsequent assessments. The first assessments recommended by the World Health Organization (WHO) are sentinel and spot-check sites—referred to as pre-transmission assessment surveys (pre-TAS)—in each implementation unit after MDA. If pre-TAS shows that prevalence in each site has been lowered to less than 1% microfilaremia or less than 2% antigenemia, the implementation unit conducts a TAS to determine whether MDA can be stopped. Failure to pass pre-TAS means that further rounds of MDA are required. This study aims to understand factors influencing pre-TAS results using existing programmatic data from 554 implementation units, of which 74 (13%) failed, in 13 countries. Secondary data analysis was completed using existing data from Bangladesh, Benin, Burkina Faso, Cameroon, Ghana, Haiti, Indonesia, Mali, Nepal, Niger, Sierra Leone, Tanzania, and Uganda. Additional covariate data were obtained from spatial raster data sets. Bivariate analysis and multilinear regression were performed to establish potential relationships between variables and the pre-TAS result. Higher baseline prevalence and lower elevation were significant in the regression model. Variables statistically significantly associated with failure (p-value ≤0.05) in the bivariate analyses included baseline prevalence at or above 5% or 10%, use of Filariasis Test Strips (FTS), primary vector of Culex, treatment with diethylcarbamazine-albendazole, higher elevation, higher population density, higher enhanced vegetation index (EVI), higher annual rainfall, and 6 or more rounds of MDA. This paper reports for the first time factors associated with pre-TAS results from a multi-country analysis. This information can help countries more effectively forecast program activities, such as the potential need for more rounds of MDA, and prioritize resources to ensure adequate coverage of all persons in areas at highest risk of failing pre-TAS. Author summary: Achieving elimination of lymphatic filariasis (LF) as a public health problem requires a minimum of five rounds of mass drug administration (MDA) and being able to demonstrate low prevalence in several subsequent assessments. LF elimination programs implement sentinel and spot-check site assessments, called pre-TAS, to determine whether districts are eligible to implement more rigorous population-based surveys to determine whether MDA can be stopped or if further rounds are required. Reasons for failing pre-TAS are not well understood and have not previously been examined with data compiled from multiple countries. For this analysis, we analyzed data from routine USAID and WHO reports from Bangladesh, Benin, Burkina Faso, Cameroon, Ghana, Haiti, Indonesia, Mali, Nepal, Niger, Sierra Leone, Tanzania, and Uganda. In a model that included multiple variables, high baseline prevalence and lower elevation were significant. In models comparing only one variable to the outcome, the following were statistically significantly associated with failure: higher baseline prevalence at or above 5% or 10%, use of the FTS, primary vector of Culex, treatment with diethylcarbamazine-albendazole, lower elevation, higher population density, higher Enhanced Vegetation Index, higher annual rainfall, and six or more rounds of mass drug administration. These results can help national programs plan MDA more effectively, e.g., by focusing resources on areas with higher baseline prevalence and/or lower elevation. [ABSTRACT FROM AUTHOR]

Background: Neglected Tropical Diseases (NTDs) not only cause health and life expectancy loss, but can also lead to economic consequences including reduced ability to work. This article describes a systematic literature review of the effect on the economic productivity of individuals affected by one of the five worldwide most prevalent NTDs: lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths (ascariasis, trichuriasis, and hookworm infection) and trachoma. These diseases are eligible to preventive chemotherapy (PCT). Methodology/Principal Findings: Eleven bibliographic databases were searched using different names of all NTDs and various keywords relating to productivity. Additional references were identified through reference lists from relevant papers. Of the 5316 unique publications found in the database searches, thirteen papers were identified for lymphatic filariasis, ten for onchocerciasis, eleven for schistosomiasis, six for soil-transmitted helminths and three for trachoma. Besides the scarcity in publications reporting the degree of productivity loss, this review revealed large variation in the estimated productivity loss related to these NTDs. Conclusions: It is clear that productivity is affected by NTDs, although the actual impact depends on the type and severity of the NTD as well as on the context where the disease occurs. The largest impact on productivity loss of individuals affected by one of these diseases seems to be due to blindness from onchocerciasis and severe schistosomiasis manifestations; productivity loss due to trachoma-related blindness has never been studied directly. However, productivity loss at an individual level might differ from productivity loss at a population level because of differences in the prevalence of NTDs. Variation in estimated productivity loss between and within diseases is caused by differences in research methods and setting. Publications should provide enough information to enable readers to assess the quality and relevance of the study for their purposes. [ABSTRACT FROM AUTHOR]

Introduction: Sri Lanka implemented the National Programme for Elimination of Lymphatic Filariasis (NPELF) in its endemic regions in 2002. Five annual rounds of mass drug administration using the two-drug combination diethylcarbamazine (DEC) and albendazole led to sustained reductions in infection rates below threshold levels. In 2016, WHO validated that Sri Lanka eliminated lymphatic filariasis as a public health problem. Objective: To explore the impact of the NPELF on lymphatic filariasis morbidity in Sri Lanka. Methods: Passive Case Detection (PCD) data maintained in filaria clinic registries from 2006–2022 for lymphoedema and hospital admission data for managing hydroceles/spermatoceles from 2007–2022 were analyzed. The morbidity status in 2022 and trends in overall and district-wise PCD rates were assessed. Poisson log-linear models were used to assess the trends in PCD for endemic regions, including district-wise trends and hospital admissions for the management of hydroceles/spermatoceles. Results: In 2022, there were 566 new lymphoedema case visits. The mean (SD) age was 53.9 (16.0) years. The staging was done for 94% of cases, of which 79% were in the early stages (57.3% and 21.4% in stages two and one, respectively). Western Province had the highest caseload (52%), followed by the Southern (32%) and Northwestern (16%) Provinces, respectively. The reported lymphoedema PCD rate in 2022 was 0.61 per 10,000 endemic population. The overall PCD rate showed a decline of 7.6% (95%CI: 4.9% - 10.3%) per year (P < 0.0001) from 2007 to 2022. A steady decline was observed in Colombo, Gampaha and Kurunegala districts, while Kalutara remained static and other districts showed a decline in recent years. Further, admissions for inpatient management of hydroceles/spermatoceles showed a declining trend after 2015. Conclusions: The PCD rates of lymphoedema and hydroceles/spermatoceles showed a declining trend in Sri Lanka after the implementation of the NPELF. Author summary: In the year 2000, the World Health Organization initiated the mass drug administration program to eliminate lymphatic filariasis. Sri Lanka implemented the program for five years (2002–2006), offering yearly single doses of anti-filarial treatment to the eligible population of all eight endemic districts. In 2016, Sri Lanka was acknowledged as having eliminated lymphatic filariasis as a public health problem. This study explored the impact of the mass drug administration program on lymphoedema and hydrocele/spermatoceles passive case detection rates using filaria clinic and hospital admission data. A reduction in new lymphoedema case visits to filaria clinics and hospital admissions for hydrocele/spermatoceles management was noted two decades after implementing mass anti-filarial treatment in Sri Lanka. [ABSTRACT FROM AUTHOR]

The World Health Organization (WHO) endorsed the use of triple-drug mass drug administration (MDA) regimen with ivermectin, diethylcarbamazine (DEC) and albendazole (commonly abbreviated as IDA) to accelerate the elimination of lymphatic filariasis (LF) as a public health problem in settings where onchocerciasis is not co-endemic. The National Programme for Elimination of LF (NPELF) in Kenya was among the first adopters of the IDA-MDA and two annual rounds were provided in 2018 and 2019 to the residents of Lamu County and Jomvu sub-County in the coast region. This study documented the feasibility of successfully delivering the two rounds of IDA-MDA. An operational research study was undertaken to determine efficient sampling strategies, indicators, and the appropriate population groups that could be used for the monitoring and evaluation of LF programs using IDA-MDA for the elimination of the disease as a public health problem. Two cross-sectional surveys were conducted at baseline in 2018 before IDA-MDA and an impact assessment 17 months after the second round of IDA-MDA. The reported epidemiological treatment coverage was at least 80% in all implementation units during each round of IDA-MDA. Blood samples were tested for filarial antigenemia using commercial Filariasis Test Strips (FTS) and any individual found to be positive was tested again at night for the presence of microfilariae in finger prick blood smears using microscopy. The overall prevalence of circulating filarial antigen (CFA) was relatively low at the baseline survey with Jomvu having 1.39% (95% CI: 0.91, 2.11) and Lamu having 0.48% (95% CI: 0.21, 1.13). Significant reduction in CFA prevalence was observed during the impact assessment after two annual rounds of treatment. The overall relative reduction (%) in CFA prevalence following the two rounds of MDA with IDA was significant in both Jomvu (52.45%, Z = -2.46, P < 0.02) and Lamu (52.71%, Z = -1.97, P < 0.05). Heterogeneity, however, was observed in the CFA prevalence reduction between random and purposive clusters, as well as between adult and child populations. The results of the impact assessment survey offered strong evidence that it was safe to stop the IDA-MDA in the two EUs because transmission appears to have been interrupted. It is also important to implement a post-treatment surveillance system which would enable efficient detection of any recrudescence of LF transmission at a sub-evaluation unit level. Our findings show that IDA-MDA may be considered for acceleration of LF elimination in other settings where onchocerciasis is not co-endemic. Author summary: Preventive chemotherapy with antifilarial drugs is currently the mainstay public health intervention recommended for the elimination of lymphatic filariasis (commonly known as elephantiasis) in endemic countries. Two-drug regimen mass drug administration of albendazole plus either diethylcarbamazine or ivermectin has been used widely in most countries since the launch of the Global Programme to Eliminate Lymphatic Filariasis by the World Health Organization in 2000. Safety and efficacy clinical studies conducted in Papua New Guinea have shown that co-administration of three antifilarial drugs namely, ivermectin, diethylcarbamazine and albendazole is superior to the two-drug regimen diethylcarbamazine and albendazole in clearance of microfilariae from the bloodstream. Consequently, the triple-drug regimen was endorsed for accelerating efforts to eliminate lymphatic filariasis as a public health problem in areas where onchocerciasis is not co-endemic. The aim of this study was to assess the feasibility of delivering mass treatment with the triple-drug regimen under programmatic conditions. An operational research study was conducted to determine the optimal sampling strategies, indicator (or set of indicators), and study populations for monitoring and evaluation of lymphatic filariasis elimination programs using the triple-drug regimen mass treatment. Two rounds of mass treatment with the triple-drug regimen were given to the residents of Lamu County (comprising of Lamu East and Lamu West sub-counties) and Jomvu sub-County (in Mombasa) in November 2018 and November 2019. The programme epidemiological treatment coverage was at least 80% in each implementation unit during the two treatment rounds. The preventive treatment resulted in significant reductions in the prevalence of the disease with the number of positive cases being fewer than the threshold recommended for areas where transmission is likely to be no longer sustainable. [ABSTRACT FROM AUTHOR]

Introduction: The Global Strategy to Eliminate Lymphatic Filiariasis (GFELF) through Mass Drug Administration (MDA) has been implemented in Ghana since the year 2000 and transmission has been interrupted in 76 of 98 endemic districts. To improve the MDA in the remaining districts with microfilaria (MF) prevalence above the 1% threshold for the interruption of transmission, there is a need to identify and implement appropriate quality improvement (QI) strategies. This paper describes the use of intervention mapping to select QI strategies to improve an existing evidence-based MDA program in Northern Ghana. Methods: Due to the complexities associated with implementing evidence-based programs (EBP) such as the lymphatic filariasis MDA and variability in the context, an initial assessment to identify implementation bottlenecks associated with the quality of implementation of lymphatic filariasis MDA in the Bole District of Ghana was conducted using a mixed methods approach. Based on the findings of the initial assessment, a context specific QI strategy was designed and operationalized using intervention mapping strategy in terms of seven domains: actor, the action, action targets, temporality, dose, implementation outcomes addressed, and theoretical justification. Results: The initial needs assessment shows that the persistent transmission of lymphatic filariasis in the Bole District is characterized by high levels of refusal to ingest the drug, high levels of reported adverse drug reactions, low MDA coverage at community level, poor adherence to the MDA protocol and non-participants’ responsiveness. Conclusion: This study has shown that it is feasible to develop a context specific QI strategy for an existing evidence-based intervention based on an initial needs assessment through stakeholder participation using the IM approach. However, working (towards) QI requires more time than is usually available in public health service. Sufficient theoretical knowledge of implementation research and experience with technical IM experts must be available. [ABSTRACT FROM AUTHOR]

Introduction: Molecular xenomonitoring (MX)—pathogen detection in the mosquito rather than human—is a promising tool for lymphatic filariasis (LF) surveillance. In the Recife Metropolitan Region (RMR), the last LF focus in Brazil, Culex quinquefasciatus mosquitoes have been implicated in transmitting Wuchereria bancrofti parasites. This paper presents findings on the ideal mosquito collection method, mosquito dispersion, W. bancrofti infection in mosquitoes and W. bancrofti antigen in humans to aid MX development. Methods: Experiments occurred within two densely populated urban areas of Olinda, RMR, in July and August 2015. U.S. Centers for Disease Control and Prevention (CDC) light traps were compared to battery-powered aspirators as collection methods, and mosquito dispersion was measured by mosquito mark release recapture (MMRR). Female Cx. quinquefasciatus were tested by PCR for W. bancrofti infection, and study area residents were screened by rapid tests for W. bancrofti antigen. Results: Aspirators caught 2.6 times more total Cx. quinquefasciatus, including 38 times more blood-fed and 5 times more gravid stages, than CDC light traps. They also collected 123 times more Aedes aegypti. Of the 9,644 marked mosquitoes released, only ten (0.01%) were recaptured, nine of which were < 50m (34.8m median, 85.4m maximum) from the release point. Of 9,169 unmarked mosquitoes captured in the MMR, 38.3% were unfed, 48.8% blood-fed, 5.5% semi-gravid, and 7.3% gravid. PCR on 182 pools (1,556 mosquitoes) found no evidence of W. bancrofti infection in Cx. quinquefasciatus. Rapid tests on 110 of 111 eligible residents were all negative for W. bancrofti antigen. Conclusions: Aspirators were more effective than CDC light traps at capturing Ae. aegypti and all but unfed stages of Cx. quinquefasciatus. Female Cx. quinquefasciatus traveled short (< 86m) distances in this urban area. Lack of evidence for W. bancrofti infection in mosquitoes and antigen in humans in these fine-scale studies does not indicate that LF transmission has ceased in the RMR. A MX surveillance system should consider vector-specific collection methods, mosquito dispersion, and spatial scale but also local context, environmental factors such as sanitation, and host factors such as infection prevalence and treatment history. [ABSTRACT FROM AUTHOR]

Background: The goal of the global lymphatic filariasis (LF) program is to eliminate the disease as a public health problem by the year 2020. The WHO mapping protocol that is used to identify endemic areas in need of mass drug administration (MDA) uses convenience-based sampling. This rapid mapping has allowed the global program to dramatically scale up treatment, but as the program approaches its elimination goal, it is important to ensure that all endemic areas have been identified and have received MDA. In low transmission settings, the WHO mapping protocol for LF mapping has several limitations. To correctly identify the LF endemicity of woredas, a new confirmatory mapping tool was developed to test older school children for circulating filarial antigen (CFA) in settings where it is uncertain. Ethiopia is the first country to implement this new tool. In this paper, we present the Ethiopian experience of implementing the new confirmatory mapping tool and discuss the implications of the results for the LF program in Ethiopia and globally. Methods: Confirmatory LF mapping was conducted in 1,191 schools in 45 woredas, the implementation unit in Ethiopia, in the regions of Tigray, Amhara, Oromia, SNNP, Afar and Harari, where the results of previous mapping for LF using the current WHO protocol indicated that LF endemicity was uncertain. Within each woreda schools were selected using either cluster or systematic sampling. From selected schools, a total of 18,254 children were tested for circulating filarial antigen (CFA) using the immuno-chromatographic test (ICT). Results: Of the 18,254 children in 45 woredas who participated in the survey, 28 (0.16%) in 9 woredas tested CFA positive. According to the confirmatory mapping threshold, which is ≥2% CFA in children 9–14 years of age, only 3 woredas out of the total 45 had more CFA positive results than the threshold and thus were confirmed to be endemic; the remaining 42 woredas were declared non-endemic. These results drastically decreased the estimated total population living in LF-endemic woredas in Ethiopia and in need of MDA by 49.1%, from 11,580,010 to 5,893,309. Conclusion: This study demonstrated that the new confirmatory mapping tool for LF can benefit national LF programs by generating information that not only can confirm where LF is endemic, but also can save time and resources by preventing MDA where there is no evidence of ongoing LF transmission. [ABSTRACT FROM AUTHOR]

Background: Despite several years of LF-MDA implementation, Ghana still has some districts with mf prevalence >1%, partly due to poor treatment coverage levels resulting from non-participation in MDA. To address the challenges, we implemented 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. Methods: This costing study analysed cost data from the 2021 LF-MDA implementation activities carried out by the Neglected Tropical Diseases (NTD) programme of the Ghana Health Service and the SENTINEL study, carried out in Ahanta West district for the two interventions (i.e., E&T and T&T). The 2021 Ghana Population and Housing Census data was used to estimate the LF-MDA-eligible population. The financial cost per person treated was estimated and these costs were applied to the projected population to obtain the financial cost for subsequent years. Results: Implementing MDA mop-up strategies either through the E&T or T&T to improve coverage comes at an additional cost to the elimination goals. For example, in 2024 the projected cost per person treated by the routine LF-MDA is estimated at US$0.83. The cost using the integrated LF-MDA and the E&T, T&T led by the NTD programme or T&T integrated into the health system was estimated at US$1.62, US$2.88, and US$2.33, respectively, for the same year. Despite the increased cost, the proposed combined LF-MDA and mop-up strategies will have a higher estimated population treated for 2024 (i.e., 1,392,211) compared to the routine LF-MDA approach (i.e., 988,470) for the same year. Conclusion: Combining LF-MDA with E&T/T&T mop-up strategies, despite their high costs, may provide NTD Programmes with the options of improving treatment coverage and reaching the LF elimination target sooner, given that the routine LF-MDA alone approach has been implemented for many years with some districts yet to reach the elimination targets. Author summary: In Ghana, despite many years of efforts to eliminate lymphatic filariasis (LF) through mass drug administration (MDA), some districts still have a prevalence of infection above the threshold required to eliminate the disease as a public health problem. This is partly because not everyone in these districts is participating in the MDA program. To tackle this challenge, new strategies called Engage & Treat (E&T) and Test & Treat (T&T) were implemented in a hotspot district. These strategies focus on reaching individuals who either miss or refuse MDA, ensuring that even those who rarely or never participate are covered. A financial cost study was undertaken to analyze the data from LF-MDA, E&T, and T&T implementations in 2021 to understand the financial implications for future LF-MDA efforts. The study looked at the cost data from LF-MDA activities conducted by the Neglected Tropical Diseases (NTD) program of the Ghana Health Service and the SENTINEL study in the Ahanta West district for the E&T and T&T interventions. Population data from the 2021 Ghana Population and Housing Census were used to estimate the LF-MDA-eligible population in the country. The study found that implementing these strategies, either through E&T or T&T, to improve coverage comes with an additional cost to the LF elimination goals. For example, in 2024, the projected cost per person treated by the routine LF-MDA alone is estimated at US$0.83. However, when combining LF-MDA with E&T or T&T, the costs increase to US$1.62, US$2.88, and US$2.33, respectively, for the same year. Despite the higher costs, the combined LF-MDA and mop-up strategies are estimated to treat a larger population in 2024 (1,392,211) compared to the routine LF-MDA approach (988,470) for the same year. In summary, although the combined LF-MDA and mop-up strategies have higher costs, they may offer NTD Programs the option to improve treatment coverage and achieve the LF elimination target sooner. This is particularly important as the routine LF-MDA alone approach has been in place for many years, with some districts still facing challenges in reaching elimination targets. [ABSTRACT FROM AUTHOR]

Background: More than 20 million people are infected with L. loa, and around 40 million live in high or intermediate-risk areas in West- and Central Africa. Although loiasis is associated with significant morbidity and excess mortality, little is known about the perception of loiasis by affected communities. This study assessed the knowledge, attitudes, and practices in the rural population of Sindara, Gabon, a region characterized by high loiasis prevalence. Methods: A community-based cross-sectional survey was conducted in Gabon between January and June 2022. During systematic door-to-door visits, randomly selected inhabitants were invited to participate in this questionnaire based survey. Venous blood was collected at midday from all participants for microscopic detection of filarial infection and clinical signs of loiasis were assessed. Results: A total of 150 participants were recruited, of which 66% were infected by L. loa. While almost everyone had some knowledge about L. loa, 72% of the participants understood that L. loa is a parasitic worm. The transmission of L. loa via the deer fly was known to only 21% of participants. The most frequently mentioned clinical symptoms attributed to loiasis were itching (84%), eye worm migration (59%), and conjunctivitis-like symptoms (53%). Participants who experienced migratory loiasis had better knowledge of loiasis and considered it as more serious. Traditional and herbal medicine was reported most often as an available treatment option (72%). While the formal healthcare sector was mentioned as the preferred treatment provider, 60% of the reported infections were treated by traditional medical practitioners. Conclusion: Loiasis is in general well known by this community residing in a region of high L. loa transmission. Important gaps in knowledge were discovered foremost regarding the mode of transmission. The available healthcare system does not seem to provide adequate management for loiasis. Author summary: Loiasis is a filarial disease highly prevalent in parts of Western- and Central Africa. For a long time, the disease has been considered to be a relatively benign condition, but recent studies have shown that loiasis causes significant morbidity and excess mortality. In the present study, we investigated the perception of loiasis in a highly affected community in rural Gabon to better understand the community perspective on this infectious disease. While L. loa as a disease is known to most inhabitants, the mode of transmission and prevention modalities are only poorly understood. This lack of knowledge leaves the communities with inadequate means to prevent onward transmission of this filarial disease. The contribution from media, schools and healthcare institutions in providing information about loiasis is inadequate, and the available healthcare system is insufficient to provide the necessary care for loiasis. A better understanding of loiasis by the affected communities is desirable to empower inhabitants of high-transmission regions to better protect themselves from loiasis. Improved understanding of the disease by the healthcare sector is necessary to improve the management of loiasis. [ABSTRACT FROM AUTHOR]

Background: Entomological surveillance of lymphatic filariasis and malaria infections play an important role in the decision-making of national programs to control, or eliminate these both diseases. In areas where both diseases prevalence is low, a large number of mosquitoes need to be sampled to determine vectors infection rate. To do this, efficient mosquito collection methods must be used. This study is part in this framework, to assess appropriate mosquito collection methods for lymphatic filariasis xenomonitoring in a coexistence context with malaria in Burkina Faso. Methodology/Principal findings: Mosquito collections were performed between August and September 2018 in four villages (Koulpissi, Seiga, and Péribgan, Saptan), distributed in East and South-West health regions of Burkina Faso. Different collection methods were used: Human Landing Catches (HLC) executed indoor and outdoor, Window Exit-Trap, Double Net Trap (DNT) and Pyrethrum Spray Catches (PSC). Molecular analyses were performed to identify Anopheles gambiae s.l. sibling species and to detect Wuchereria bancrofti and Plasmodium falciparum infection in Anopheles mosquitoes. A total of 3 322 mosquitoes were collected among this, Anopheles gambiae s.l. was the vector caught in largest proportion (63.82%). An. gambiae s.l. sibling species molecular characterization showed that An. gambiae was the dominant specie in all villages. The Human Landing Catches (indoor and outdoor) collected the highest proportion of mosquitoes (between 61.5% and 82.79%). For the sampling vectors infected to W. bancrofti or P. falciparum, PSC, HLC and Window Exit-Trap were found the most effective collection methods. Conclusions/Significance: This study revealed that HLC indoor and outdoor remained the most effective collection method. Likewise, the results showed the probability to use Window Exit-Trap and PSC collection methods to sample Anopheles infected. Author summary: In Burkina Faso, the monitoring and evaluation scheme to assess the impact of lymphatic filariasis and malaria interventions is relied only on parasitological tests. While nowadays, the most simple and direct measure of vector borne diseases is xenomonitoring. When the both diseases prevalence is low in human population, sampling large numbers of mosquitoes is necessary for xenomonitoring. This study was undertaken in this context to assess the efficiency of four mosquito collection methods for xenomonitoring LF and malaria. Mosquito collections were performed between August and September 2018 in four villages, distributed in East and South-West health regions of Burkina Faso. Human Landing Catches (HLC), Window Exit-Trap, Double Net Trap (DNT) and Pyrethrum Spray Catches (PSC) were evaluated. The results showed that HLC remained the most effective collection method by collecting the highest number of Anopheles (2 388; 71.88% of total). Across the study, mosquito infection rate for W. bancrofti and P. falciparum were 0.004 and 0.13 respectively. To collect vectors infected it was found that Window Exit-Trap and PSC were efficient. In conclusion, HLC has been shown to be appropriate for collecting large number of mosquitoes. Likewise, Window Exit-Trap and PSC can be useful for malaria and lymphatic filariasis xenomonitoring. [ABSTRACT FROM AUTHOR]

The Global Program to Eliminate Lymphatic Filariasis (GPELF) advocates for the treatment of entire endemic communities, in order to achieve its elimination targets. LF is predominantly a rural disease, and achieving the required treatment coverage in these areas is much easier compared to urban areas that are more complex. In Ghana, parts of the Greater Accra Region with Accra as the capital city are also endemic for LF. Mass Drug Administration (MDA) in Accra started in 2006. However, after four years of treatment, the coverage has always been far below the 65% epidemiologic coverage for interrupting transmission. As such, there was a need to identify the reasons for poor treatment coverage and design specific strategies to improve the delivery of MDA. This study therefore set out to identify the opportunities and barriers for implementing MDA in urban settings, and to develop appropriate strategies for MDA in these settings. An experimental, exploratory study was undertaken in three districts in the Greater Accra region. The study identified various types of non-rural settings, the social structures, stakeholders and resources that could be employed for MDA. Qualitative assessment such as in-depth interviews (IDIs) and focus group discussions (FGDs) with community leaders, community members, health providers, NGOs and other stakeholders in the community was undertaken. The study was carried out in three phases: pre-intervention, intervention and post-intervention phases, to assess the profile of the urban areas and identify reasons for poor treatment coverage using both qualitative and quantitative research methods. The outcomes from the study revealed that, knowledge, attitudes and practices of community members to MDA improved slightly from the pre-intervention phase to the post-intervention phase, in the districts where the interventions were readily implemented by health workers. Many factors such as adequate leadership, funding, planning and community involvement, were identified as being important in improving implementation and coverage of MDA in the study districts. Implementing MDA in urban areas therefore needs to be given significant consideration and planning, if the required coverage rates are to be achieved. This paper, presents the recommendations and strategies for undertaking MDA in urban areas. [ABSTRACT FROM AUTHOR]

Background: The monitoring and evaluation of lymphatic filariasis (LF) has largely relied on the detection of antigenemia and antibodies in human populations. Molecular xenomonitoring (MX), the detection of parasite DNA/RNA in mosquitoes, may be an effective complementary method, particularly for detecting signals in low-level prevalence areas where Culex is the primary mosquito vector. This paper investigated the application of a household-based sampling method for MX in Tamil Nadu, India. Methods: MX surveys were conducted in 2010 in two evaluation units (EUs): 1) a hotspot area, defined as sites with community microfilaria prevalence ≥1%, and 2) a larger area that also encompassed the hotspots. Households were systematically selected using a sampling interval proportional to the number of households in the EU. Mosquito pools were collected and analyzed by real-time polymerase chain reaction (qPCR). Two independent samples were taken in each EU to assess reproducibility of results. Follow-up surveys were conducted in 2012. Results: In 2010, the proportion of positive pools in the hotspot EU was 49.3% compared to 23.4% in the overall EU. In 2012, pool positivity was significantly reduced to 24.3% and 6.5%, respectively (p<0.0001). Pool positivity based on independent samples taken from each EU in 2010 and 2012 were not significantly different except for the hotspot EU in 2012 (p = 0.009). The estimated prevalence of infection in mosquitoes, measured by PoolScreen, declined from 2.2–2.7% in 2010 to 0.6–1.2% in 2012 in the hotspot area and from 0.9–1.1% to 0.2–0.3% in the larger area. Conclusions: The household-based sampling strategy for MX led to mostly reproducible results and supported the observed LF infection trends found in humans. MX has the potential to be a cost-effective, non-invasive monitoring and evaluation tool with sensitive detection of infection signals in low prevalence settings. Further investigation and application of this sampling strategy for MX are recommended to support its adoption as a standardized method for global LF elimination programs. [ABSTRACT FROM AUTHOR]

Background: Bangladesh had one of the highest burdens of lymphatic filariasis (LF) at the start of the Global Programme to Eliminate Lymphatic Filariasis (GPELF) with an estimated 70 million people at risk of infection across 34 districts. In total 19 districts required mass drug administration (MDA) to interrupt transmission, and 15 districts were considered low endemic. Since 2001, the National LF Programme has implemented MDA, reduced prevalence, and been able to scale up the WHO standard Transmission Assessment Survey (TAS) across all endemic districts as part of its endgame surveillance strategy. This paper presents TAS results, highlighting the momentous geographical reduction in risk of LF and its contribution to the global elimination target of 2020. Methodology/Principal findings: The TAS assessed primary school children for the presence of LF antigenaemia in each district (known as an evaluation unit—EU), using a defined critical cut-off threshold (or ‘pass’) that indicates interruption of transmission. Since 2011, a total of 59 TAS have been conducted in 26 EUs across the 19 endemic MDA districts (99,148 students tested from 1,801 schools), and 22 TAS in the 15 low endemic non-MDA districts (36,932 students tested from 663 schools). All endemic MDA districts passed TAS, except in Rangpur which required two further rounds of MDA. In total 112 students (male n = 59; female n = 53), predominately from the northern region of the country were found to be antigenaemia positive, indicating a recent or current infection. However, the distribution was geographically sparse, with only two small focal areas showing potential evidence of persistent transmission. Conclusions/Significance: This is the largest scale up of TAS surveillance activities reported in any of the 73 LF endemic countries in the world. Bangladesh is now considered to have very low or no risk of LF infection after 15 years of programmatic activities, and is on track to meet elimination targets. However, it will be essential that the LF Programme continues to develop and maintain a comprehensive surveillance strategy that is integrated into the health infrastructure and ongoing programmes to ensure cost-effectiveness and sustainability. [ABSTRACT FROM AUTHOR]

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. Author summary: Lymphatic filariasis is a neglected tropical disease that causes disability to human beings and is caused by a group of filarial nematodes such as W. bancrofti, Brugia malayi, and Brugia timori while these parasites are transmitted by different species of vector mosquitoes. Nepal government started the MDA program in 2003 and has completed 6–11 rounds of anti-filarial medicine with DEC and albendazole between 2007 and 2022 in selected endemic districts of Central Nepal. TAS report showed a low level of infection (<2%) in all study districts. Interestingly we found that the antigen-positive cases were clustered in foci. We defined those circulating filarial antigen (CFA) positive clustered areas as hotspots and assessed MF infection among the adult community people after the MDA program. The result revealed evidence of MF prevalence above threshold in the hotspots of two districts one each from the hilly region (Dhading district) and Terai region (Mahottari district) even after the completion of the MDA program. In those areas, alternative treatment strategies should be employed to reduce the active infection which can serve as reservoirs for recrudescence transmission. Hence it is urgently needed to identify and screen MF infection among community individuals of hotspots after completion of the MDA program even in other districts. [ABSTRACT FROM AUTHOR]

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. Principle 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. Author summary: Lymphatic filariasis (LF) is a debilitating parasitic disease that the World Health Organization (WHO) has earmarked for elimination by 2030 through a combination of mass distribution of anti-parasitic medicines and disease management approaches. Great strides have been made towards the elimination of LF as a public health problem, but nearly 900 million people still require treatment every year. In recent years, new combinations of medicines have been shown to improve the treatment of LF, yet there remain substantial gaps in understanding of apparent variability in treatment success and on the best treatment and management approaches to alleviate chronic morbidity. Some of these questions could be addressed through the development of a LF global data platform, which would enable pooled analyses of all available individual participant data. Here, we present the results of a systematic literature review of the LF treatment study landscape. We estimate the abundance of individual data on treatment of infection and morbidity and describe the characteristics of the studies and participants that have generated these data. We argue that collating and curating these data into a data LF platform could help to fill gaps in understanding of the best ways to treat infection and disease and enhance prospects of eliminating LF by 2030. [ABSTRACT FROM AUTHOR]

Background: Ethiopia is assumed to have the highest burden of podoconiosis globally, but the geographical distribution and environmental limits and correlates are yet to be fully investigated. In this paper we use data from a nationwide survey to address these issues. Methodology: Our analyses are based on data arising from the integrated mapping of podoconiosis and lymphatic filariasis (LF) conducted in 2013, supplemented by data from an earlier mapping of LF in western Ethiopia in 2008–2010. The integrated mapping used woreda (district) health offices’ reports of podoconiosis and LF to guide selection of survey sites. A suite of environmental and climatic data and boosted regression tree (BRT) modelling was used to investigate environmental limits and predict the probability of podoconiosis occurrence. Principal Findings: Data were available for 141,238 individuals from 1,442 communities in 775 districts from all nine regional states and two city administrations of Ethiopia. In 41.9% of surveyed districts no cases of podoconiosis were identified, with all districts in Affar, Dire Dawa, Somali and Gambella regional states lacking the disease. The disease was most common, with lymphoedema positivity rate exceeding 5%, in the central highlands of Ethiopia, in Amhara, Oromia and Southern Nations, Nationalities and Peoples regional states. BRT modelling indicated that the probability of podoconiosis occurrence increased with increasing altitude, precipitation and silt fraction of soil and decreased with population density and clay content. Based on the BRT model, we estimate that in 2010, 34.9 (95% confidence interval [CI]: 20.2–51.7) million people (i.e. 43.8%; 95% CI: 25.3–64.8% of Ethiopia’s national population) lived in areas environmentally suitable for the occurrence of podoconiosis. Conclusions: Podoconiosis is more widespread in Ethiopia than previously estimated, but occurs in distinct geographical regions that are tied to identifiable environmental factors. The resultant maps can be used to guide programme planning and implementation and estimate disease burden in Ethiopia. This work provides a framework with which the geographical limits of podoconiosis could be delineated at a continental scale. [ABSTRACT FROM AUTHOR]

Background: The prevalence of Wuchereria bancrofti, which causes lymphatic filariasis (LF) in The Gambia was among the highest in Africa in the 1950s. However, surveys conducted in 1975 and 1976 revealed a dramatic decline in LF endemicity in the absence of mass drug administration (MDA). The decline in prevalence was partly attributed to a significant reduction in mosquito density through the widespread use of insecticidal nets. Based on findings elsewhere that vector control alone can interrupt LF, we asked the question in 2013 whether the rapid scale up in the use of insecticidal nets in The Gambia had interrupted LF transmission. Methodology/Principal Finding: We present here the results of three independently designed filariasis surveys conducted over a period of 17 years (1997–2013), and involving over 6000 subjects in 21 districts across all administrative divisions in The Gambia. An immunochromatographic (ICT) test was used to detect W. bancrofti antigen during all three surveys. In 2001, tests performed on stored samples collected between 1997 and 2000, in three divisions, failed to show positive individuals from two divisions that were previously highly endemic for LF, suggesting a decline towards extinction in some areas. Results of the second survey conducted in 2003 showed that LF was no longer endemic in 16 of 21 districts surveyed. The 2013 survey used a WHO recommended LF transmission verification tool involving 3180 6–7 year-olds attending 60 schools across the country. We demonstrated that transmission of W. bancrofti has been interrupted in all 21 districts. Conclusions: We conclude that LF transmission may have been interrupted in The Gambia through the extensive use of insecticidal nets for malaria control for decades. The growing evidence for the impact of malaria vector control activities on parasite transmission has been endorsed by WHO through a position statement in 2011 on integrated vector management to control malaria and LF. Author Summary: The prevalence of lymphatic filariasis (LF), in The Gambia was among the highest in Africa in the 1950s when about 50% of the adult population was positive for microfilaraemia. However, surveys conducted in 1975 and 1976 revealed a dramatic decline in LF endemicity in the absence of systematic treatment with anti-filaria medicines. This decline in LF prevalence in all villages was partly attributed to a significant drop in human-mosquito contact through a sustained reduction in rainfall in the 1960s and 1970s and the widespread use of insecticidal nets to protect against malaria. We asked the question in 2013 whether the rapid scale up in the use of insecticidal nets for malaria control in Gambia had resulted in the interruption of LF transmission. In this paper we present the results of three independently designed filariasis surveys conducted over a period of 17 years (1997–2013), and involving over 6000 subjects in 21 districts across all administrative divisions in the country. In 2001, tests performed to detect circulating filarial antigens (CFA) in serum samples collected between 1997 and 2000, in three divisions, failed to show positive individuals from two that were previously highly endemic for the LF. Results of the second survey conducted in 2003 indicated that five of the 21 districts were slightly endemic for LF with CFA rates of 1% or 2% but MDA was never implemented in The Gambia. The results of our final survey conducted in 2013 were unequivocal in confirming the absence of transmission of LF in all 21 districts surveyed using WHO recommended statistically robust and validated tool known as transmission assessment survey (TAS). The Gambia achieving a non-endemic status for LF represents a significant step in the efforts to shrink the filariasis endemicity map and demonstrates the value of cross sector approaches in disease control. [ABSTRACT FROM AUTHOR]

Background: Co-endemicity of neglected tropical diseases (NTDs) necessitates that these diseases should be considered concomitantly to understand the relationship between pathology and to support disease management and control programs. The aims of the study were to assess the prevalence of filarial infection in asymptomatic Leishmania donovani infected individuals and the correlation of Wuchereria bancrofti infection with progression to clinical visceral leishmaniasis (VL) in Bihar, India. Methodology/Principal findings: Within the Muzaffarpur-TMRC Health and Demographic Surveillance System (HDSS) area, a cohort of Leishmania seropositive (n = 476) or seronegative individuals (n = 1130) were sampled annually for three years for filarial infection and followed for progression to clinical VL. To corroborate the results from the cohort study, we also used a retrospective case-control study of 36 VL cases and 71 controls selected from a subset of the HDSS population to investigate the relationship between progression to clinical VL and the prevalence of filarial infection at baseline. Our findings suggest a higher probability of progression to clinical VL in individuals with a history of filarial infection: in both the cohort and case-control studies, progression to clinical VL was higher among filaria infected individuals (RR = 2.57, p = 0.056, and OR = 2.52, p = 0.046 respectively). Conclusion: This study describes that progression to clinical VL disease is associated with serological evidence of prior infection with W. bancrofti. The integration of disease programs for Leishmania and lymphatic filariasis extend beyond the relationship of sequential or co-infection with disease burden. To ensure elimination targets can be reached and sustained, we suggest areas of co-endemicity would benefit from overlapping vector control activities, health system networks and surveillance infrastructure. Author summary: India has committed to eliminate two neglected tropical diseases (NTDs) as a public health problem: visceral leishmaniasis (VL) and lymphatic filariasis (LF), both of which are transmitted by vectors and are caused by the parasites Leishmania donovani and Wuchereria bancrofti, respectively. Notably, the majority of L. donovani infections do not lead to a clinical event of VL and asymptomatic infections significantly outnumber the clinical cases. While mixed infections with Leishmania parasites and those causing lymphatic filariasis have been reported, the influence of the immune response triggered by filarial infection on the clinical manifestations and progression of both disorders is not well understood. The Muzaffarpur-TMRC Health and Demographic Surveillance System (HDSS) in Bihar is a well-established demographic platform in an area with the highest incidence of L. donovani infections in India which is also co-endemic for lymphatic filariasis. We used both cohort and case-control study designs within the HDSS population to assess the prevalence of filarial infection in blood samples and examine the association between filarial infection and the progression to clinical VL. Our findings strongly suggest there is an increased risk of progression to clinical VL in individuals with a history of infection with W. bancrofti: in both the study designs, progression to clinical VL was higher among filaria-infected individuals. These results highlight that the co-endemicity of these NTDs necessitates an integrated approach in diagnosis and disease management to ensure elimination targets can be achieved and sustained. [ABSTRACT FROM AUTHOR]

The use of antibiotics targeting the obligate bacterial endosymbiont Wolbachia of filarial parasites has been validated as an approach for controlling filarial infection in animals and humans. Availability of genomic sequences for the Wolbachia (wBm) present in the human filarial parasite Brugia malayi has enabled genome-wide searching for new potential drug targets. In the present study, we investigated the cell division machinery of wBm and determined that it possesses the essential cell division gene ftsZ which was expressed in all developmental stages of B. malayi examined. FtsZ is a GTPase thereby making the protein an attractive Wolbachia drug target. We described the molecular characterization and catalytic properties of Wolbachia FtsZ. We also demonstrated that the GTPase activity was inhibited by the natural product, berberine, and small molecule inhibitors identified from a high-throughput screen. Furthermore, berberine was also effective in reducing motility and reproduction in B. malayi parasites in vitro. Our results should facilitate the discovery of selective inhibitors of FtsZ as a novel anti-symbiotic approach for controlling filarial infection. Note: The nucleotide sequences reported in this paper are available in GenBank™ Data Bank under the accession number wAlB-FtsZ (JN616286). Author Summary: Filarial nematode parasites are responsible for a number of devastating diseases in humans and animals. These include lymphatic filariasis and onchocerciasis that afflict 150 million people in the tropics and threaten the health of over one billion. The parasites possess intracellular bacteria, Wolbachia, which are needed for worm survival. Clearance of these bacteria with certain antibiotics leads to parasite death. These findings have pioneered the approach of using antibiotics to treat and control filarial infections. In the present study, we have investigated the cell division process in Wolbachia for new drug target discovery. We have identified the essential cell division protein FtsZ, which has a GTPase activity, as an attractive Wolbachia drug target. We describe the molecular characterization and catalytic properties of the enzyme and demonstrate that the GTPase activity is inhibited by the natural product, berberine, and small molecule inhibitors identified from a high-throughput screen. We also found that berberine was effective in reducing motility and reproduction in B. malayi parasites in vitro. Our results should facilitate the discovery of selective inhibitors of FtsZ as a novel antibiotic approach for controlling filarial infection. [ABSTRACT FROM AUTHOR]

Objective: We sought to evaluate the relationship between onchocerciasis prevalence and that of epilepsy using available data collected at community level. Design: We conducted a systematic review and meta-regression of available data. Data Sources: Electronic and paper records on subject area ever produced up to February 2008. Review Methods: We searched for population-based studies reporting on the prevalence of epilepsy in communities for which onchocerciasis prevalence was available or could be estimated. Two authors independently assessed eligibility and study quality and extracted data. The estimation of point prevalence of onchocerciasis was standardized across studies using appropriate correction factors. Variation in epilepsy prevalence was then analyzed as a function of onchocerciasis endemicity using random-effect logistic models. Results: Eight studies from west (Benin and Nigeria), central (Cameroon and Central African Republic) and east Africa (Uganda, Tanzania and Burundi) met the criteria for inclusion and analysis. Ninety-one communities with a total population of 79,270 individuals screened for epilepsy were included in the analysis. The prevalence of epilepsy ranged from 0 to 8.7% whereas that of onchocerciasis ranged from 5.2 to 100%. Variation in epilepsy prevalence was consistent with a logistic function of onchocerciasis prevalence, with epilepsy prevalence being increased, on average, by 0.4% for each 10% increase in onchocerciasis prevalence. Conclusion: These results give further evidence that onchocerciasis is associated with epilepsy and that the disease burden of onchocerciasis might have to be re-estimated by taking into account this relationship. Author Summary: Epilepsy is particularly common in tropical areas. One main reason is that many endemic infections have neurological consequences. In addition, the medical, social and demographic burden of epilepsy remains substantial in these countries where it is often seen as a contagious condition and where the aetiology is often undetermined. For several decades, field researchers had reported some overlapping between the geographical distributions of epilepsy and onchocerciasis, a parasitic disease caused by the filarial worm Onchocerca volvulus which afflicts some 40 million persons worldwide. Here, we conducted a statistical analysis of all the data available on the relationship between the two conditions to determine whether the proportion of people suffering from epilepsy in a community could be related to the frequency of onchocerciasis. The combined results of the eight studies carried out in west, central and east Africa indicate a close epidemiological association between the two diseases. Should a causative relationship be demonstrated, onchocerciasis, which is known as "river blindness" because of its most serious sequela and the distribution of its vectors, could thus also be called "river epilepsy". More research is needed to determine the mechanisms explaining this association and to assess the burden of onchocerciasis-associated epilepsy. [ABSTRACT FROM AUTHOR]

Background: Scabies is a common skin infestation caused by the Sarcoptes scabei mite. Ivermectin, one of three drugs used in mass drug administration (MDA) for lymphatic filariasis, is also effective for treating scabies. Ivermectin-based MDA was first conducted in Samoa in August 2018, with ivermectin being offered to those aged ≥5 years. Here, we report scabies prevalence in Samoa after MDA. Methods: We conducted household surveys 1.5–3.5 months (Survey 1) and 6–8 months (Survey 2) after the 2018 MDA in 35 primary sampling units. We conducted clinical examination for scabies-like rash and used International Alliance for the Control of Scabies classification criteria. We estimated scabies prevalence by age, gender and region. Multivariable logistic regression was used to assess factors associated with prevalence. Results: We surveyed 2868 people (499 households) and 2796 people (544 households) aged 0–75 years in Surveys 1 and 2, respectively. Scabies prevalence increased from 2.4% (95% CI 2.1–2.7%) to 4.4% (95% CI 4.0–4.9%) between surveys. Scabies was associated with younger age (0–4 years: aOR 3.5 [2.9–4.2]; 5–15 years: aOR 1.6 [1.4–1.8] compared to ≥16 years), female gender (aOR 1.2 [95% CI 1.1–1.4]; region (aOR range from 1.4 [1.1–1.7] to 2.5 [2.1–3.1] between regions), large households (aOR 2.6 [2.0–3.4] households ≥13), and not taking MDA in 2018 (aOR 1.3 [95% CI 1.1–1.6]). Conclusions: We found moderate prevalence of scabies in two population-representative surveys conducted within 8 months of the 2018 MDA for lymphatic filariasis. Prevalence appeared to increase between the surveys, and ongoing surveillance is recommended, particularly in young children. Author summary: Scabies is a common skin disease that is caused by a small mite that burrows into the skin. It can be treated by a drug called ivermectin, which was given to every person aged 5 years and over in Samoa in 2018 to treat a different disease, known as lymphatic filariasis. We wanted to understand how common scabies was in the people of Samoa and so did two surveys where we visited people's houses that we randomly selected. We and asked people in each household questions about scabies symptoms and looked at their skin for signs of scabies. We surveyed 2868 people in 499 households in the first survey and 2796 in 544 households in the second survey. We found that 2.4% of people in the first survey and 4.4% of people in the second survey had scabies. We also found that some people were more likely to have scabies: younger children, women, people living in some regions of Samoa, people living with more people in their household, and people who didn't take the medicine for lymphatic filariasis in 2018. [ABSTRACT FROM AUTHOR]

Background: Lymphatic filariasis (LF) is a vector-borne parasitic disease which affects 70 million people worldwide and causes life-long disabilities. In Bangladesh, there are an estimated 44,000 people suffering from clinical conditions such as lymphoedema and hydrocoele, with the greatest burden in the northern Rangpur division. To better understand the factors associated with this distribution, this study examined socio-economic and environmental factors at division, district, and sub-district levels. Methodology: A retrospective ecological study was conducted using key socio-economic (nutrition, poverty, employment, education, house infrastructure) and environmental (temperature, precipitation, elevation, waterway) factors. Characteristics at division level were summarised. Bivariate analysis using Spearman's rank correlation coefficient was conducted at district and sub-district levels, and negative binomial regression analyses were conducted across high endemic sub-districts (n = 132). Maps were produced of high endemic sub-districts to visually illustrate the socio-economic and environmental factors found to be significant. Results: The highest proportion of rural population (86.8%), poverty (42.0%), tube well water (85.4%), and primary employment in agriculture (67.7%) was found in Rangpur division. Spearman's rank correlation coefficient at district and sub-district level show that LF morbidity prevalence was significantly (p<0.05) positively correlated with households without electricity (district rs = 0.818; sub-district rs = 0.559), households with tube well water (sub-district rs = 0.291), households without toilet (district rs = 0.504; sub-district rs = 0.40), mean annual precipitation (district rs = 0.695; sub-district rs = 0.503), mean precipitation of wettest quarter (district rs = 0.707; sub-district rs = 0.528), and significantly negatively correlated with severely stunted children (district rs = -0.723; sub-district rs = -0.370), mean annual temperature (district rs = -0.633.; sub-district rs = 0.353) and mean temperature (wettest quarter) ((district rs = -0.598; sub-district rs = 0.316) Negative binomial regression analyses at sub-district level found severely stunted children (p = <0.001), rural population (p = 0.002), poverty headcount (p = 0.001), primary employment in agriculture (p = 0.018), households without toilet (p = <0.001), households without electricity (p = 0.002) and mean temperature (wettest quarter) (p = 0.045) to be significant. Conclusions: This study highlights the value of using available data to identify key drivers associated with high LF morbidity prevalence, which may help national LF programmes better identify populations at risk and implement timely and targeted public health messages and intervention strategies. Author summary: Lymphatic Filariasis (LF) is particularly associated with poverty and living in a rural area, where disease transmitting mosquito vectors thrive. To better understand the socio-economic and environmental factors associated with the LF morbidity prevalence distribution in Bangladesh, this study examined publicly available data and used descriptive, statistical, and mapping methods to highlight key associations. Results found that high risk populations were those living in rural areas, employed in agriculture, with high levels of poverty, and houses without electricity or toilets, and where temperatures in the rainy season were lower than other regions of the country. These findings will help to inform public health messages and implement interventions for people affected by LF morbidity, but also to help reduce any current and future risk of transmission. This will support progress to achieving WHO elimination targets, leading to a future free of suffering for people affected by LF associated morbidity. [ABSTRACT FROM AUTHOR]

Background: Onchocerciasis, also known as "river blindness", is caused by the bite of infected female blackflies (genus Simuliidae) that transmit the parasite Onchocerca volvulus. A high onchocerciasis microfarial load increases the risk to develop epilepsy in children between the ages of 3 and 18 years. In resource-limited settings in Africa where onchocerciasis has been poorly controlled, high numbers of onchocerciasis-associated epilepsy (OAE) are reported. We use mathematical modeling to predict the impact of onchocerciasis control strategies on the incidence and prevalence of OAE. Methodology: We developed an OAE model within the well-established mathematical modelling framework ONCHOSIM. Using Latin-Hypercube Sampling (LHS), and grid search technique, we quantified transmission and disease parameters using OAE data from Maridi County, an onchocerciasis endemic area, in southern Republic of South Sudan. Using ONCHOSIM, we predicted the impact of ivermectin mass drug administration (MDA) and vector control on the epidemiology of OAE in Maridi. Principal findings: The model estimated an OAE prevalence of 4.1% in Maridi County, close to the 3.7% OAE prevalence reported in field studies. The OAE incidence is expected to rapidly decrease by >50% within the first five years of implementing annual MDA with good coverage (≥70%). With vector control at a high efficacy level (around 80% reduction of blackfly biting rates) as the sole strategy, the reduction is slower, requiring about 10 years to halve the OAE incidence. Increasing the efficacy levels of vector control, and implementing vector control simultaneously with MDA, yielded better results in preventing new cases of OAE. Conclusions/Significances: Our modeling study demonstrates that intensifying onchocerciasis eradication efforts could substantially reduce OAE incidence and prevalence in endemic foci. Our model may be useful for optimizing OAE control strategies. Author summary: Onchocerciasis is a parasitic disease caused by the filarial worm Onchocerca volvulus, which is transmitted by Simuliidae black flies. This disease is most common in Africa and South America. Onchocerca volvulus is thought to infect approximately 35 million Africans these days. Adult female worms infect people and form subcutaneous nodules, releasing thousands of microfilariae per day, causing itching, dermatitis, blindness, and epilepsy. Despite the fact that the association between onchocerciasis and epilepsy was already mentioned in a study from Mexico in 1938, this association was only reported around 1991 in Africa in the Mbam valley in Cameroon. Onchocerciasis-associated epilepsy (OAE) is characterised by seizures that start between the ages of 3 and 18 years in previously healthy children with a high degree of O. volvulus infection. Raising awareness about OAE will increase adherence to community-directed treatment with ivermectin (CDTI), particularly in high-prevalence areas, while also motivating funders and stakeholders to keep fighting onchocerciasis. Here, we create an OAE model within the framework of ONCHOSIM that is parametrized using South Sudan data and investigate how different control measures such as CDTI and vector control might help reduce OAE in the future. [ABSTRACT FROM AUTHOR]

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. Author summary: Elimination of lymphatic filariasis, and of certain other neglected tropical diseases, depends critically on the successful treatment of the population through a series of typically annual mass drug administration (MDA) campaigns. When an MDA falls short of expectations in terms of population treated, organizers can learn and adapt the next round of MDA to improve performance. Because this learning is often based on anecdotal evidence or surveys specific to a narrow geography, there is an opportunity in the literature to augment our understanding of what impacts MDA performance, particularly in terms of more contextual factors and trends or patterns that reach across multiple years and regions. In this analysis we linked a performance measure from 3,880 MDA campaigns across 10 West African countries to contextual factors such as 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. We hope the findings themselves will better equip MDA organizers in decision-making and offer this mixed-level model as an approach to better understanding coverage dynamics in West Africa and elsewhere. [ABSTRACT FROM AUTHOR]

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. 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 (41%) 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. Author summary: Lymphatic filariasis (LF) remains an important public health issues in endemic areas in Indonesia. One potential challenge to achieving LF elimination is the risk posed by never treatment during mass drug administration (MDA). Although Ambon City in Maluku Province, Indonesia, initiated its annual MDA in 2009, the microfilaria rate in 2016 still exceeded the threshold for elimination as a public health problem. In 2018 and 2019, we conducted a community-based study in the catchment areas of Air Salobar and Waihaong Health Centers, Ambon to improve treatment coverage and reduce the coverage-compliance gap in MDA for LF. Using data from the two cross-sectional surveys, our analysis examined factors associated with never treatment. We found the role of employment, healthcare catchment area, perceived possibility of side effects after swallowing LF drugs, difficulties in swallowing and remembering when to swallow all LF drugs and knowledge of how to swallow LF drugs were associated with the likelihood of never treatment. Recommendations to improve MDA uptake include the need to reassure community members about side effects, provide specific instructions on how to take LF drugs, and promote the message that MDA participation is part of one's contribution to community health. [ABSTRACT FROM AUTHOR]

Background: Community presence of loiasis must be determined before mass drug administration programmes for lymphatic filariasis and onchocerciasis can be implemented. However, taking human blood samples for loiasis surveillance is invasive and operationally challenging. A xenosurveillance approach based on the molecular screening of mosquitoes and their excreta/feces (E/F) for Loa loa DNA may provide a non-invasive method for detecting the community presence of loiasis. Methods: We collected 770 wild mosquitoes during a pilot study in a known loiasis transmission area in Mbalmayo, Cameroon. Of these, 376 were preserved immediately while 394 were kept in pools to collect 36-hour E/F samples before processing. Carcasses and E/F were screened for L. loa DNA. To demonstrate this method's potential for integrated disease surveillance, the samples were further tested for Wuchereria bancrofti, Mansonella perstans, and Plasmodium falciparum. Results: Despite limited sample numbers, L. loa DNA was detected in eight immediately-stored mosquitoes (2.13%; 95% CI 1.08 to 4.14), one carcass stored after providing E/F (0.25%; 95% CI 0.04 to 1.42), and three E/F samples (estimated prevalence 0.77%; 95% CI 0.15 to 2.23%). M. perstans and P. falciparum DNA were also detected in carcasses and E/F samples, while W. bancrofti DNA was detected in E/F. None of the carcasses positive for filarial worm DNA came from pools that provided a positive E/F sample, supporting the theory that, in incompetent vectors, ingested parasites undergo a rapid, complete expulsion in E/F. Conclusions: Mosquito xenosurveillance may provide a useful tool for the surveillance of loiasis alongside other parasitic diseases. Author summary: Loiasis is a typically-mild filarial worm disease. In contrast, lymphatic filariasis (LF) and onchocerciasis are diseases of significant public health concern. LF and onchocerciasis are primarily controlled by administering chemotherapeutics to entire at-risk human populations. However, individuals with heavy loiasis infections are at risk of severe adverse events when treated with these drugs. Accurate loiasis surveillance is therefore critical to the safe implementation of these programmes. Screening humans to detect parasites in the blood is invasive and expensive at large scale. Recently, however, several studies have demonstrated the potential of collecting wild blood-feeding insects such as mosquitoes and screening them for the presence of human blood-borne parasites. To explore the potential of mosquito screening as a non-invasive tool for loiasis surveillance, we collected mosquitoes in a known loiasis transmission area in Cameroon. We tested the samples for parasites that cause loiasis, and concurrently screened for the parasites that cause malaria, LF and mansonellosis to determine the potential for integrated disease surveillance. The DNA of all four parasites were identified using these methods. The findings suggest mosquito screening may provide a useful tool for the surveillance of loiasis alongside other parasitic diseases. [ABSTRACT FROM AUTHOR]

Lymphatic filariasis (LF) is a mosquito-borne parasitic neglected tropical disease. In 2000, WHO launched the Global Programme to Eliminate Lymphatic Filariasis (GPELF) as a public health problem. In 2020, new goals for 2030 were set which includes a reduction to 0 of the total population requiring Mass Drug Administrations (MDA), a primary tool of GPELF. We develop a mathematical model to study what can happen at the end of MDA. We use a game-theoretic approach to assess the voluntary use of insect repellents in the prevention of the spread of LF through vector bites. Our results show that when individuals use what they perceive as optimal levels of protection, the LF incidence rates will become high. This is in striking difference to other vector-borne NTDs such as Chagas or zika. We conclude that the voluntary use of the protection alone will not be enough to keep LF eliminated as a public health problem and a more coordinated effort will be needed at the end of MDA. Author summary: We adapt a compartmental ODE model of lymphatic filariasis (LF) transmission and focus our attention on what happens after Mass Drug Administrations (MDA) is terminated. We add a game-theoretic component to the model and study whether LF transmission can be substantially interrupted by voluntary use of personal protection strategies such as using insect repellents. We identify optimal voluntary protection levels and demonstrate that LF incidence rates will become too high. [ABSTRACT FROM AUTHOR]

Background: Loiasis–a filarial disease endemic in Central and West Africa–is increasingly recognized as significant individual and public health concern. While the understanding of the disease characteristics remains limited, significant morbidity and excess mortality have been demonstrated. Here, we characterize clinical and hematological findings in a large cohort from Gabon. Methods: Loiasis-related clinical manifestations and microfilaremia, hemoglobin and differential blood counts were recorded prospectively during a cross-sectional survey. For analysis, participants were categorized into distinct infection states by the diagnostic criteria of eye worm history and microfilaremia. Results: Analysis of data from 1,232 individuals showed that occurrence of clinical and hematological findings differed significantly between the infection states. Eye worm positivity was associated with a wide range of clinical manifestations while microfilaremia by itself was not. Loa loa infection was associated with presence of eosinophilia and absolute eosinophil counts were associated with extent of microfilaremia (p-adj. = 0.012, ß-estimate:0.17[0.04–0.31]). Conclusions: Loiasis is a complex disease, causing different disease manifestations in patients from endemic regions. The consequences for the affected individuals or populations as well as the pathophysiological consequences of correlating eosinophilia are largely unknown. High-quality research on loiasis should be fostered to improve patient care and understanding of the disease. Author summary: Loiasis is a parasitic disease, endemic in parts of Western and Central Africa. While the disease has traditionally been considered to be benign, only recently significant disease morbidity and mortality have been shown. Most of the knowledge about loiasis, however, stems from reports on returning travelers, while comprehensive data from patients living in endemic areas are missing. Blood microfilaremia and reported eye worm are important diagnostic manifestations of the disease, but they can occur independent of each other in affected individuals. We analyzed hematological and clinical findings according to loiasis infection states, comprising reported eye worm and microfilaremia positivity, in a large group of individuals from a highly endemic area. While we found that all loiasis infection states were significantly associated with absolute blood eosinophilia, the eosinophilia was more pronounced in microfilaremic loiasis. Further, there was an association between the extent of microfilaremia and absolute eosinophilia. Analyzing the frequency of clinical disease manifestations, we found that eye worm positive loiasis was associated with a range of symptoms, but microfilaremic loiasis was not. Summarizing, even in highly endemic populations different loiasis infection states are associated with distinct disease manifestations, underlining that loiasis is a versatile and indeed relevant disease. [ABSTRACT FROM AUTHOR]

Background: Lymphatic filariasis (LF) has been targeted for global elimination as a public health problem since 1997. The primary strategy to interrupt transmission is annual mass drug administration (MDA) for ≥5 years. The transmission assessment survey (TAS) was developed as a decision-making tool to measure LF antigenemia in children to determine when MDA in a region can be stopped. The objective of this study was to investigate potential sampling strategies for follow-up of LF-positive children identified in TAS to detect evidence of ongoing transmission. Methodology/Principle findings: Nippes Department in Haiti passed TAS 1 with 2 positive cases and stopped MDA in 2015; however, 8 positive children were found during TAS 2 in 2017, which prompted a more thorough assessment of ongoing transmission. Purposive sampling was used to select the closest 50 households to each index case household, and systematic random sampling was used to select 20 households from each index case census enumeration area. All consenting household members aged ≥2 years were surveyed and tested for circulating filarial antigen (CFA) using the rapid filarial test strip and for Wb123-specific antibodies using the Filaria Detect IgG4 ELISA. Among 1,927 participants, 1.5% were CFA-positive and 4.5% were seropositive. CFA-positive individuals were identified for 6 of 8 index cases. Positivity ranged from 0.4–2.4%, with highest positivity in the urban commune Miragoane. Purposive sampling found the highest number of CFA-positives (17 vs. 9), and random sampling found a higher percent positive (2.4% vs. 1.4%). Conclusions/Significance: Overall, both purposive and random sampling methods were reasonable and achievable methods of TAS follow-up in resource-limited settings. Both methods identified additional CFA-positives in close geographic proximity to LF-positive children found by TAS, and both identified strong signs of ongoing transmission in the large urban commune of Miragoane. These findings will help inform standardized guidelines for post-TAS surveillance. Author summary: Lymphatic filariasis (LF) is a debilitating parasitic disease that has been targeted for global elimination. The transmission assessment survey (TAS) is a tool used to determine if LF transmission has reached low enough levels that prevention activities can be stopped. This study aimed to identify methods to investigate positive LF cases found during TAS. The investigation was conducted in Nippes Department, Haiti, where 8 positive cases were found in TAS in 2017. Participants were recruited through two methods: purposive selection of the closest 50 households to the positive case, and random selection of 20 households in the census enumeration area of the case. Participants completed a survey and were tested for LF antigen, indicative of current infection, and parasite-specific antibody, indicative of current or past infection. A total of 1,927 people participated in the study; 1.5% of these were antigen-positive, and 4.5% were antibody-positive. Purposive sampling found a higher number of antigen-positive individuals, and random sampling found a higher percent positive. Both sampling methods were feasible to use in this setting, and both methods identified signs of ongoing transmission in a large urban area. Additional research is needed to help standardize guidance for post-TAS surveillance to best identify ongoing transmission. [ABSTRACT FROM AUTHOR]

Background: Papua New Guinea (PNG) has a high burden of lymphatic filariasis (LF) caused by Wuchereria bancrofti, with an estimated 4.2 million people at risk of infection. A single co-administered dose of ivermectin, diethylcarbamazine and albendazole (IDA) has been shown to have superior efficacy in sustained clearance of microfilariae compared to diethylcarbamazine and albendazole (DA) in small clinical trials. A community-based cluster-randomised trial of DA versus IDA was conducted to compare the safety and efficacy of IDA and DA for LF in a moderately endemic, treatment-naive area in PNG. Methodology: All consenting, eligible residents of 24 villages in Bogia district, Madang Province, PNG were enrolled, screened for W. bancrofti antigenemia and microfilaria (Mf) and randomised to receive IDA (N = 2382) or DA (N = 2181) according to their village of residence. Adverse events (AE) were assessed by active follow-up for 2 days and passive follow-up for an additional 5 days. Antigen-positive participants were re-tested one year after MDA to assess treatment efficacy. Principal findings: Of the 4,563 participants enrolled, 96% were assessed for AEs within 2 days after treatment. The overall frequency of AEs were similar after either DA (18%) or IDA (20%) treatment. For those individuals with AEs, 87% were mild (Grade 1), 13% were moderate (Grade 2) and there were no Grade 3, Grade 4, or serious AEs (SAEs). The frequency of AEs was greater in Mf-positive than Mf-negative individuals receiving IDA (39% vs 20% p<0.001) and in Mf-positive participants treated with IDA (39%), compared to those treated with DA (24%, p = 0.023). One year after treatment, 64% (645/1013) of participants who were antigen-positive at baseline were re-screened and 74% of these participants (475/645) remained antigen positive. Clearance of Mf was achieved in 97% (52/54) of infected individuals in the IDA arm versus 84% (56/67) of infected individuals in the DA arm (relative risk (RR) 1.15; 95% CI, 1.02 to 1.30; p = 0.019). Participants receiving DA treatment had a 4-fold higher likelihood of failing to clear Mf (RR 4.67 (95% CI: 1.05 to 20.67; p = 0.043). In the DA arm, a significant predictor of failure to clear was baseline Mf density (RR 1.54; 95% CI, 1.09 to 2.88; p = 0.007). Conclusion: IDA was well tolerated and more effective than DA for clearing Mf. Widespread use of this regimen could accelerate LF elimination in PNG. Trial registration: Registration number NCT02899936; https://clinicaltrials.gov/ct2/show/NCT02899936. Author summary: Lymphatic filariasis (LF) is a mosquito-transmitted parasitic nematode that can live in human hosts for up to 6–8 years, disrupting the normal functions of the lymphatic system leading to the abnormal enlargement of body parts, causing pain, severe disability, and social stigma. Lymphatic filariasis can be eliminated by stopping the spread of infection through preventive chemotherapy with safe medicine combinations repeated annually. Several small-scale trials demonstrated that a single dose of a triple-drug regimen (ivermectin, diethylcarbamazine, and albendazole or IDA) was more effective at clearing infection than the standard two-drug regimen (diethylcarbamazine and albendazole or DA). This study was conducted to investigate the safety and efficacy of IDA in a large community-randomised trial in a moderate transmission setting. IDA was shown to be as safe as the standard two-drug DA treatment and more effective for clearing microfilariae compared to DA. These results show that IDA is well tolerated in PNG and has the potential to accelerate LF elimination. [ABSTRACT FROM AUTHOR]

Introduction: Lymphatic filariasis causes long term morbidity and hampers the socio-economic status. Apart from the available treatments and medication, control of vector population Culex quinquefasciatus Say through the use of chemical insecticides is a widely applied strategy. However, the unrestrained application of these insecticides over many decades has led to resistance development in the vectors. Methods: In order to determine the insecticide susceptibility/resistance status of Cx. quinquefasciatus from two filariasis endemic districts of West Bengal, India, wild mosquito populations were collected and assayed against six different insecticides and presence of L1014F; L1014S kdr mutations in the voltage-gated sodium channel gene was also screened along with the use of synergists to evaluate the role of major detoxifying enzymes in resistance development. Results: The collected mosquito populations showed severe resistance to insecticides and the two synergists used–PBO (piperonyl butoxide) and TPP (triphenyl phosphate), were unable to restore the susceptibility status of the vector thereupon pointing towards a minor role of metabolic enzymes. kdr mutations were present in the studied populations in varying percent with higher L1014F frequency indicating its association with the observed resistance to pyrethroids and DDT. This study reports L1014S mutation in Cx. quinquefasciatus for the first time. Author summary: Lymphatic filariasis is caused by a nematode worm Wuchereria bancrofti and transmitted by mosquito vector Culex quinquefasciatus. The vector Culex quinquefasciatus is a nuisance due to its biting habit and involvement in transmission of many deadly diseases in the tropics and sub tropics. Therefore, to control disease transmission by mosquito vectors, humans have been relying on the use of chemical insecticides since many decades. However, the over and unplanned application of insecticides has led to insecticide resistance in the mosquito population. As such, the insecticides have failed to produce 100 percent mortality in the mosquito vectors. This scenario is an important and urgent issue of concern because apart from medical treatment, major reliance for the control of vector-borne diseases still lies on the use of chemical insecticides targeted against the mosquito vectors. Moreover, there is a need to survey and evaluate insecticide susceptibility/resistance status of mosquito vectors along with the underlying mechanisms of resistance in national and regional level to draw an idea about the existing insecticide resistance pattern. This will further help in designing efficient vector control strategies in the near future on both national and regional basis. [ABSTRACT FROM AUTHOR]

Successful mass drug administration (MDA) campaigns have brought several countries near the point of Lymphatic Filariasis (LF) elimination. A diagnostic tool is needed to determine when the prevalence levels have decreased to a point that MDA campaigns can be discontinued without the threat of recrudescence. A six-country study was conducted assessing the performance of seven diagnostic tests, including tests for microfilariae (blood smear, PCR), parasite antigen (ICT, Og4C3) and antifilarial antibody (Bm14, PanLF, Urine SXP). One community survey and one school survey were performed in each country. A total of 8,513 people from the six countries participated in the study, 6,443 through community surveys and 2,070 through school surveys. Specimens from these participants were used to conduct 49,585 diagnostic tests. Each test was seen to have both positive and negative attributes, but overall, the ICT test was found to be 76% sensitive at detecting microfilaremia and 93% specific at identifying individuals negative for both microfilariae and antifilarial antibody; the Og4C3 test was 87% sensitive and 95% specific. We conclude, however, that the ICT should be the primary tool recommended for decision-making about stopping MDAs. As a point-of-care diagnostic, the ICT is relatively inexpensive, requires no laboratory equipment, has satisfactory sensitivity and specificity and can be processed in 10 minutes-qualities consistent with programmatic use. Og4C3 provides a satisfactory laboratory-based diagnostic alternative. [ABSTRACT FROM AUTHOR]

Globally, 40 million people live with the chronic effects of lymphatic filariasis (LF), making it the second leading cause of disability in the world. Despite this, there is limited research into the experiences of people living with the disease. This review summarises the research on the experiences of people living with LF disability. The review highlights the widespread social stigma and oppressive psychological issues that face most people living with LF-related disability. Physical manifestations of LF make daily activities and participation in community life difficult. The findings confirm the need for the Global Programme to Eliminate Lymphatic Filariasis (GPELF) to support morbidity management activities that address the complex biopsychosocial issues that people living with LF-related disability face. [ABSTRACT FROM AUTHOR]

The neglected tropical disease onchocerciasis, or river blindness, is caused by infection with the filarial nematode Onchocerca volvulus. Current estimates indicate that 17 million people are infected worldwide, the majority of them living in Africa. Today there are no non-invasive tests available that can detect ongoing infection, and that can be used for effective monitoring of elimination programs. In addition, to enable pharmacodynamic studies with novel macrofilaricide drug candidates, surrogate endpoints and efficacy biomarkers are needed but are non-existent. We describe the use of a multimodal untargeted mass spectrometry-based approach (metabolomics and lipidomics) to identify onchocerciasis-associated metabolites in urine and plasma, and of specific lipid features in plasma of infected individuals (O. volvulus infected cases: 68 individuals with palpable nodules; lymphatic filariasis cases: 8 individuals; non-endemic controls: 20 individuals). This work resulted in the identification of elevated concentrations of the plasma metabolites inosine and hypoxanthine as biomarkers for filarial infection, and of the urine metabolite cis-cinnamoylglycine (CCG) as biomarker for O. volvulus. During the targeted validation study, metabolite-specific cutoffs were determined (inosine: 34.2 ng/ml; hypoxanthine: 1380 ng/ml; CCG: 29.7 ng/ml) and sensitivity and specificity profiles were established. Subsequent evaluation of these biomarkers in a non-endemic population from a different geographical region invalidated the urine metabolite CCG as biomarker for O. volvulus. The plasma metabolites inosine and hypoxanthine were confirmed as biomarkers for filarial infection. With the availability of targeted LC-MS procedures, the full potential of these 2 biomarkers in macrofilaricide clinical trials, MDA efficacy surveys, and epidemiological transmission studies can be investigated. Author summary: Today's diagnosis of infection with the filarial parasite Onchocerca volvulus mainly depends on the microscopic analysis of skin biopsies and serological testing. The work presented here describes the use of multiple mass spectrometry-based screening methods (metabolomics and lipidomics) to search for biomarkers indicative of infection with Onchocerca volvulus. This resulted in the identification of elevated concentrations of the plasma metabolites inosine and hypoxanthine as biomarkers for filarial infection, and of the urine metabolite cis-cinnamoylglycine as biomarker for O. volvulus. Further evaluation of these biomarkers in a geographically distinct non-endemic population however invalidated the use of urine cis-cinnamoylglycine. These findings are of utmost importance as it not only opens new avenues in the development of non-invasive diagnostic tools for filarial infections, but also emphasizes the need for evaluation and validation of newly discovered biomarkers in different populations from different geographies. [ABSTRACT FROM AUTHOR]

This study presents a methodology for using tracer indicators to measure the effects of disease-specific programs on national health systems. The methodology is then used to analyze the effects of Bangladesh's Lymphatic Filariasis Elimination Program, a disease-specific program, on the health system. Using difference-in-differences models and secondary data from population-based household surveys, this study compares changes over time in the utilization rates of eight essential health services and incidences of catastrophic health expenditures between individuals and households, respectively, of lymphatic filariasis hyper-endemic districts (treatment districts) and of hypo- and non-endemic districts (control districts). Utilization of all health services increased from year 2000 to year 2014 for the entire population but more so for the population living in treatment districts. However, when the services were analyzed individually, the difference-in-differences between the two populations was insignificant. Disadvantaged populations (i.e., populations that lived in rural areas, belonged to lower wealth quintiles, or did not attend school) were less likely to access essential health services. After five years of program interventions, households in control districts had a lower incidence of catastrophic health expenditures at several thresholds measured using total household expenditures and total non-food expenditures as denominators. Using essential health service coverage rates as outcome measures, the Lymphatic Filariasis Elimination Program cannot be said to have strengthened or weakened the health system. We can also say that there is a positive association between the Lymphatic Filariasis Elimination Program's interventions and lowered incidence of catastrophic health expenditures. Author summary: Evidence to understand the interactions between disease specific programs and the health system is insufficient and largely based on opinion. This study presents a methodology for using tracer indicators to measure the effect of a disease-specific program, the Bangladesh Lymphatic Filariasis Elimination Program, on its health system. The Composite Coverage Index and incidence of catastrophic health expenditures are well-established tracer indicators for measuring the strength of a health system. In this study, they were calculated, before the program started in 2000 and after it ended in 2015, using data from Demographic and Health Surveys and Household Income and Expenditure Surveys, respectively. Using the Composite Coverage Index to measure the effects of the Lymphatic Filariasis Elimination Program revealed that it did not negatively or positively affect health service coverage rates. We can also say that there is a positive association between the program interventions and lowered incidence of catastrophic health expenditures. [ABSTRACT FROM AUTHOR]

Background: Guyana is one of four countries in the Latin American Region where lymphatic filariasis (LF) remains endemic. In preparation for the introduction of a new triple drug therapy regimen (ivermectin, diethylcarbamazine, and albendazole (IDA)) in 2019, an acceptability study was embedded within sentinel site mapping in four regions to assess mass drug administration (MDA) coverage and compliance, acceptability, and perceptions about treatment and disease. The results from this survey would inform the rollout of IDA in Guyana in 2019. Methods: Data collection for the study occurred in August 2019, using a validated questionnaire administered by trained enumerators. Across all regions, a total of 1,248 participants were sampled by the Filarial Mapping team. Four-hundred and fifty-one participants aged over 18 years were randomly selected for participation in an expanded acceptability questionnaire. All data were captured in Secure Data Kit (SDK). Results: Acceptability was measured using a mean acceptability score. Unadjusted mean scores ranged from 24.6 to 29.3, with 22.5 as the threshold of acceptability. Regional variation occurred across many indicators of interest: self-rated understanding about LF, mechanisms of LF transmission, LF drug safety and history of treatment during MDA. Region IV (Georgetown) recorded higher knowledge about LF, but lower compliance and acceptability. Number of pills was not perceived as a concern. Conclusion: Acceptability of MDA was good across all four regions under study. Results from this study set a baseline level for key indicators and acceptability, from which the acceptability of IDA can be measured. Regional variations across indicators suggest that localized approaches should be considered for social mobilization and MDA delivery to capture these contextual differences. Author summary: Guyana is one of four countries in the Latin American Region where lymphatic filariasis (LF) remains endemic in the community. In preparation for a new treatment regimen using three drugs instead of two, the research team assessed how community members in four regions of Guyana accepted the current two-drug treatment offered for LF during mass drug administration. Results from 390 participants showed that people generally accepted the treatment; however regional variation was high. Recommendations were made to the government program to inform the use of the new three-drug treatment regimen, including the need for localized approaches. [ABSTRACT FROM AUTHOR]

Improved treatments for lymphatic filariasis (LF) could accelerate the global elimination program for this disease. A triple drug combination of the anti-filarial drugs ivermectin, diethylcarbamazine (DEC) and albendazole (IDA) has been shown to be safe and effective for achieving sustained clearance of microfilariae (Mf) of the filarial parasite Wuchereria bancrofti from human blood. However, the triple drug combination has not been previously been evaluated for treatment of brugian filariasis, which accounts for about 10% of the global LF burden. This hospital-based clinical trial compared the safety and efficacy of IDA with that of the standard treatment (DEC plus albendazole, DA) in persons with Brugia timori infections on Sumba island, Indonesia. Fifty-five asymptomatic persons with B. timori Mf were treated with either a single oral dose of IDA (28 subjects) or with DEC plus albendazole (DA, 27 subjects). Participants were actively monitored for adverse events (AE) for two days after treatment by nurses and physicians who were masked regarding treatment assignments. Passive monitoring was performed by clinical teams that visited participant's home villages for an additional five days. Microfilaremia was assessed by membrane filtration of 1 ml night blood at baseline, at 24h and one year after treatment. IDA was more effective than DA for completely clearing Mf at 24 hours (25/28, 89% vs. 11/27, 41%, P < 0.001). By 12 months after treatment, only one of 28 IDA recipients had Mf in their blood (4%) vs. 10 of 27 (37%) in persons treated with DA (P = 0.002). Approximately 90% of participants had antibodies to recombinant filarial antigen BmR1 at baseline. Antibody prevalence decreased to approximately 30% in both treatment groups at 12 months. About 45% of persons in both treatment groups experienced AE such as fever, muscle aches, lower back, joint and abdominal pain. These were mostly mild and most common during the first two days after treatment. No participant experienced a severe or serious AE. This study showed that IDA was well-tolerated and significantly more effective for clearing B. timori Mf from the blood than DA. Larger studies should be performed to further assess the safety and efficacy of IDA as a mass drug administration regimen to eliminate brugian filariasis. Trial Registration:NCT02899936. Author summary: Improved treatments for lymphatic filariasis (LF) could accelerate the global elimination program for this disease. A triple drug combination of the anti-filarial drugs ivermectin, diethylcarbamazine (DEC) and albendazole (IDA) has been shown to be safe and effective for achieving sustained clearance of microfilariae (Mf) of the filarial parasite Wuchereria bancrofti from human blood. However, the triple drug combination has not been previously been evaluated for treatment of brugian filariasis, which accounts for about 10% of the global LF burden. This hospital-based clinical trial compared the safety and efficacy of IDA with that of the standard treatment (DEC plus albendazole, DA) in persons with Brugia timori infections on Sumba island, Indonesia. Fifty-five asymptomatic persons with B. timori Mf were treated with either a single oral dose of IDA (28 subjects) or with DA (27 subjects). Adverse events (AE) were assessed in the hospital for two days after treatment and for another five days in participants' home villages. IDA was much more effective than DA for clearing Mf from the blood at 24 hr. Only 1 person (4% of those treated) had Mf in their blood one year after IDA, while 10 persons (37%) treated with DA were Mf positive at that time. About 45% of persons in both treatment groups experienced mostly mild AE as fever, muscle aches, lower back, joint and abdominal pain (mostly during the first two days after treatment). This study showed that IDA was well-tolerated and significantly more effective than DA for clearing B. timori Mf from the blood. Larger studies should be performed to further assess the safety and efficacy of IDA as a mass drug administration regimen to eliminate brugian filariasis. [ABSTRACT FROM AUTHOR]

Nowadays, in most of the current active g-HAT foci ("active" here meaning there is ongoing local transmission), tsetse control campaigns do not aim at eradicating the vector, but rather at protecting people by decreasing tsetse density so that transmission is stopped (e.g., [[8]]). Detection of T. b. gambiense in the tsetse vector: Xenomonitoring Historically, the usual way of knowing if a tsetse carries trypanosomes was through dissection of the tsetse organs known to harbour trypanosome cyclical development, for I T i . Human African trypanosomiasis, also known as sleeping sickness, is a neglected tropical disease due to trypanosomes (Kinetoplastidae) transmitted to humans by a vector, the tsetse fly (Diptera: Glossinidae), that only occurs in Africa. In all areas that constitute g-HAT foci where cases have been reported in the past, there are 2 situations: either there are no longer any tsetse or there are tsetse. [Extracted from the article]

Background: Morbidity management and disability prevention (MMDP) services are essential for the management of chronic stages of lymphatic filariasis (LF) infection. However, there is limited information on health beliefs and health seeking behavior towards MMDP services for LF in endemic regions of Zambia. This study sought to document health beliefs and health seeking behavior towards MMDP services for LF in Luangwa District, Zambia. Methods: This was an exploratory qualitative study conducted with community members including LF patients, community health workers and healthcare providers. Data was collected through a series of four focus group discussions stratified by sex and 26 in-depth interviews. Data was analyzed by thematic analysis using NVivo software. Results: The perceived causes of the chronic manifestations of LF included; contact with animal feces, use of traditional herbal aphrodisiacs (mutoto), witchcraft and sexual contact with women who were menstruating or had miscarried. LF patients opted to visit traditional healers before going to health facilities. Hydrocele patients were afraid of hydrocelectomies as they were thought to cause infertility or death. Very few community members were able to identify any home and facility-based care strategies for LF patients. Health system and cultural barriers to seeking healthcare included; long distances to the health facilities, lack of awareness of existing MMDP services, perceived costs of accessing MMDP services, gender and social norms, and fear of stigmatization. Conclusion: Health seeking behavior for LF in the district is mainly driven by negative beliefs about the causes of the disease and lack of awareness of available MMDP services and homecare strategies. Lymphatic filariasis programs should promote strategies that seek to empower patients and community members with the required information to access and use the MMDP services at the health facilities, as well as adhere to self-care practices in their households. Author summary: Lymphatic filariasis (LF) infection if untreated results in fluid accumulation in the limbs or breasts (lymphedema) or genitalia (hydrocele) that is painful and causes great discomfort. Morbidity management and disability prevention (MMDP) strategies such as surgery for hydrocele, treatment of acute attacks and management of lymphedema are necessary for the management of the advanced stages of LF. However, very few countries including Zambia, have adequate information on the health beliefs and health seeking behavior of communities living in endemic areas towards MMDP services for LF. This study sought to explore community and health provider perspectives towards MMDP services for LF in a highly endemic region, Luangwa District, Zambia, between February and April 2019. Some of the perceived causes of lymphedema and hydrocele were; contact with animal feces, use of traditional herbal aphrodisiacs (mutoto), witchcraft and sexual contact with women who were menstruating or had miscarried. There was limited knowledge of home-based and facility-based care strategies for LF patients. Nevertheless, patients would often go to health facilities after visiting traditional healers and observing no improvement. Barriers to accessing healthcare included; long distances to the health facilities, lack of awareness of existing MMDP services, perceived costs of accessing healthcare services, gender and social norms and fear of stigmatization. [ABSTRACT FROM AUTHOR]