Introduction of Triple-Drug Therapy for Accelerating Lymphatic Filariasis Elimination in India: Lessons Learned.
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SUBMITTER: Tripathi B
PROVIDER: S-EPMC9154644 | biostudies-literature | 2022 Mar
REPOSITORIES: biostudies-literature
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Introduction of Triple-Drug Therapy for Accelerating Lymphatic Filariasis Elimination in India: Lessons Learned.
Tripathi Bhupendra B Roy Nupur N Dhingra Neeraj N
The American journal of tropical medicine and hygiene 20220315 5_Suppl
There are 670 million people at risk of contracting lymphatic filariasis (LF) in India, which bears 40% of the global burden of the disease. The National Program to Eliminate LF was launched in 2004 first with a single-drug therapy-diethylcarbamazine (DEC), followed by a two-drug therapy-DEC + albendazole (DA). In 2017, following successful drug trials, World Health Organization endorsed a new triple-drug therapy to fight LF using ivermectin with DEC and albendazole (IDA). 1 In June 2018, India ...[more]
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Project description:BackgroundThe Global Programme to Eliminate Lymphatic Filariasis (GPELF) was launched in response to the call proposed at the 50th World Health Assembly. The goal of the GPELF is to ensure that all the countries where the disease is endemic would have been transmission-free or would have entered post-intervention mass drug administration (MDA) surveillance by 2020. However, several countries are still not on track to discontinue MDA as planned. Thus, issues remain regarding the achievement of stated goals and how to effectively monitor the disease in the post-control and post-elimination phases.Main textChina was once a lymphatic filariasis (LF) endemic country with heavy disease burden. There were three milestones in the LF control phase of China, including: the proposal that the major focus of the control strategy should be on infectious sources; the three regimens of diethylcarbamazine (DEC) administration according to LF endemic extent; and the establishment of the threshold for LF transmission interruption. It has been ten years since China entered the post-elimination stage (declaration of LF elimination in China was in 2007). Two schemes and a diagnostic criterion were issued to guide all levels of disease control and prevention workers that conduct LF surveillance, as well as those caring for chronic filariasis patients. Regular training courses are held to maintain LF control skills in grass-root institutions. The Notifiable Diseases Reporting System, which included LF in 2004, plays an important role in LF post-elimination surveillance. Until now, no resurgence of LF cases has been detected, except for LF residue foci being found in Fuchuan County of the Guangxi Zhuang Autonomous Region. To confirm that transmission is no longer achievable after a decade since the declaration of LF elimination in China, it is expected within the next two years a transmission assessment survey, conducted in previous LF-endemic areas.ConclusionsDEC-fortified salt can help accelerate the progress of GPELF before the sprite phase. Sophisticated diagnostic criteria, systematic surveillance regimes, the Direct Network Report system, and regular trainings can effectively prevent the recrudescence of LF during surveillance phases.
| S-EPMC6685173 | biostudies-literature
Project description:BackgroundFollowing the World Health Assembly resolution on Elimination of lymphatic filariasis (ELF) as a public health problem by the year 2020, a Global Program (GPELF) was launched in 1997 to help endemic countries to initiate national programs. The current strategy to interrupt transmission of LF, is administration of once-yearly, single-dose, two-drug regimen (Albendazole with Diethylcarbamazine (DEC) to be used in endemic areas with the goal of reaching 65% epidemiological coverage for 4-6 years. We report findings of independent assessment from year 2010 to 2015 for last six rounds, after initial five rounds of Mass Drug Administration (MDA) since 2005 for ELF in endemic area of Gujarat.MethodsIndependent assessment of MDA was performed to find coverage and compliance indicators, reasons for non-coverage and non-compliance in five Implementation Units (IUs). Pre, during and post MDA evaluations were done in three phases. The impact of MDA was measured by microfilaraemia survey. A total of eight sites, four random and four fixed sentinel sites were selected to calculate microfilaria rate (MF) per IUs per year. In years 2010 to 2015, we report results from 125,936 nocturnal blood smears and 17551 population in 120 selected clusters. Four clusters were selected per year in each of the five IUs for assessment of MDA round.ResultPost MDA survey showed drug coverage between 81%-88% and epidemiological coverage 77%-89% across years. Main reasons for non-coverage were drug administrator related (the team did not visit or missed people) while non-compliance was population related (fear of side effects, sickness, people forgot or absent). During MDA findings show that the directly observed consumption is considerably improved from 58% in 2010 to 82% in 2015. The knowledge about benefits of drug provided also increased from 59% to 90% over the years. The current MF rate is less than one in all IUs with an overall 68% percent decrease from baseline year 2005 to year 2015. The average MF rate of Gujarat is 0.44 for year 2015.ConclusionsThe findings show that achieving adequate epidemiological and drug coverage is possible by actual field level operation of the program in large endemic areas. The results and feedback from independent assessment, performed regularly, could guide the policymakers and program managers for mid-term corrections and to frame strategies to enhance program. Monitoring of coverage and impact indicator together informs decisions for reaching end-point of MDA. The impact indicator- microfilaria rate in all IUs of South Gujarat Region has reached and remained less than one percent signaling end-points of MDA. Post MDA stringent monitoring in form of TAS is recommended to keep vigil on maintenance of elimination achieved.
| S-EPMC5391126 | biostudies-literature
Project description:BackgroundThe World Health Organization has targeted lymphatic filariasis for global elimination by 2020 with a strategy of mass drug administration. This trial tested whether a single dose of a three-drug regimen of ivermectin plus diethylcarbamazine plus albendazole results in a greater sustained clearance of microfilariae than a single dose of a two-drug regimen of diethylcarbamazine plus albendazole and is noninferior to the two-drug regimen administered once a year for 3 years.MethodsIn a randomized, controlled trial involving adults from Papua New Guinea with Wuchereria bancrofti microfilaremia, we assigned 182 participants to receive a single dose of the three-drug regimen (60 participants), a single dose of the two-drug regimen (61 participants), or the two-drug regimen once a year for 3 years (61 participants). Clearance of microfilariae from the blood was measured at 12, 24, and 36 months after trial initiation.ResultsThe three-drug regimen cleared microfilaremia in 55 of 57 participants (96%) at 12 months, in 52 of 54 participants (96%) at 24 months, and in 55 of 57 participants (96%) at 36 months. A single dose of the two-drug regimen cleared microfilaremia in 18 of 56 participants (32%) at 12 months, in 31 of 55 participants (56%) at 24 months, and in 43 of 52 participants (83%) at 36 months (P=0.02 for the three-drug regimen vs. a single dose of the two-drug regimen at 36 months). The two-drug regimen administered once a year for 3 years cleared microfilaremia in 20 of 59 participants (34%) at 12 months, in 42 of 56 participants (75%) at 24 months, and in 51 of 52 participants (98%) at 36 months (P=0.004 for noninferiority of the three-drug regimen vs. the two-drug regimen administered once a year for 3 years at 36 months). Moderate adverse events were more common in the group that received the three-drug regimen than in the combined two-drug-regimen groups (27% vs. 5%, P<0.001). There were no serious adverse events.ConclusionsThe three-drug regimen induced clearance of microfilariae from the blood for 3 years in almost all participants who received the treatment and was superior to the two-drug regimen administered once and noninferior to the two-drug regimen administered once a year for 3 years. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT01975441 .).
| S-EPMC6194477 | biostudies-literature
Project description:Lymphatic filariasis (LF) is a neglected tropical disease transmitted by mosquitoes. Nepal has implemented a national effort to eliminate LF by 2020 through mass drug administration (MDA) using diethylcarbamazine (DEC) and albendazole (ALB). We assessed the impact of MDAs on LF in selected districts of Nepal after the recommended six MDA rounds had been completed.Baseline surveys were conducted in seven districts and mapping data were used as baseline in the other three districts before starting MDA in 2009. LF antigen (Ag) prevalence ranged from 1.06% to 20% among districts included in the baseline and mapping study. The number of people who received DEC and ALB were recorded during each MDA round and population-based cluster surveys were conducted at least once in each district during the life of the program. The reported MDA coverage in five districts was consistently at least 65%. Two districts achieved the targeted coverage in four out of five rounds and the rest three districts achieved the target only in the first round. A pre-transmission assessment survey (pre-TAS) was conducted in one sentinel site and at least one spot check site in each of the districts after five MDA rounds. In pre-TAS, all the sites of five districts (Pyuthan, Arghakhanchi, Kaski, Bhaktapur, and Kathmandu) and all but one spot check site of Lalitpur district had LF Ag < 2% (ranging from 0.0% to 1.99%). Transmission assessment survey (TAS) was conducted in six evaluation units (EUs) consisting of six districts qualified on pre-TAS. Though MDA coverage of 65% was not achieved in three districts (Kathmandu, Lalitpur and Bhaktapur), Nepal government in consultation with World Health Organization (WHO) decided to conduct TAS. All six EUs achieved the LF Ag threshold required to stop MDA in TAS, despite the low reported MDA coverage in those three districts.Although Nepal has achieved significant progress towards LF elimination, five rounds of MDA were not sufficient to disrupt the transmission cycle in all districts, probably because of high baseline prevalence.
| S-EPMC5536438 | biostudies-other
Project description: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.
| S-EPMC7728255 | biostudies-literature
Project description:BackgroundMany countries will not reach elimination targets for lymphatic filariasis in 2020 using the two-drug treatment regimen (diethylcarbamazine citrate [DEC] and albendazole [DA]). A cluster-randomized, community-based safety study performed in Fiji, Haiti, India, Indonesia and Papua New Guinea tested the safety and efficacy of a new regimen of ivermectin, DEC and albendazole (IDA).Methodology/principal findingsTo assess acceptability of IDA and DA, a mixed methods study was embedded within this community-based safety study. The study objective was to assess the acceptability of IDA versus DA. Community surveys were performed in each country with randomly selected participants (>14 years) from the safety study participant list in both DA and IDA arms. In depth interviews (IDI) and focus group discussions (FGD) assessed acceptability-related themes. In 1919 individuals, distribution of sex, microfilariae (Mf) presence and circulating filarial antigenemia (CFA), adverse events (AE) and age were similar across arms. A composite acceptability score summed the values from nine indicators (range 9-36). The median (22.5) score indicated threshold of acceptability. There was no difference in scores for IDA and DA regimens. Mean acceptability scores across both treatment arms were: Fiji 33.7 (95% CI: 33.1-34.3); Papua New Guinea 32.9 (95% CI: 31.9-33.8); Indonesia 30.6 (95% CI: 29.8-31.3); Haiti 28.6 (95% CI: 27.8-29.4); India 26.8 (95% CI: 25.6-28) (P<0.001). AE, Mf or CFA were not associated with acceptability. Qualitative research (27 FGD; 42 IDI) highlighted professionalism and appreciation for AE support. No major concerns were detected about number of tablets. Increased uptake of LF treatment by individuals who had never complied with MDA was observed.Conclusions/significanceIDA and DA regimens for LF elimination were highly and equally acceptable in individuals participating in the community-based safety study in Fiji, Haiti, India, Indonesia, and Papua New Guinea. Country variation in acceptability was significant. Acceptability of the professionalism of the treatment delivery was highlighted.
| S-EPMC7928496 | biostudies-literature
Project description:In the global drive for elimination of lymphatic filariasis (LF), 15 countries have achieved validation of elimination as a public health problem (EPHP). Recent empirical evidence has demonstrated that EPHP does not always lead to elimination of transmission (EOT). Here we show how the probability of elimination explicitly depends on key biological parameters, many of which have been poorly characterized, leading to a poor evidence base for the elimination threshold. As more countries progress towards EPHP it is essential that this process is well-informed, as prematurely halting treatment and surveillance programs could pose a serious threat to global progress. We highlight that refinement of the weak empirical evidence base is vital to understand drivers of elimination and inform long-term policy.
| S-EPMC7413036 | biostudies-literature
Project description:BackgroundThe 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 findingWe 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.ConclusionsWe 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.
| S-EPMC4364952 | biostudies-literature
Project description: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.
| S-EPMC5441634 | biostudies-literature
Project description:BackgroundLymphatic filariasis is targeted for elimination in India through mass drug administration (MDA) with diethylcarbamazine (DEC) combined with albendazole (ABZ). For the strategy to be effective, >65% of those living in endemic areas must be covered by and compliant to MDA. Post the MDA 2011 campaign in the endemic district of Odisha, we conducted a survey to assess: (i) the filariasis knowledge in the community, (ii) the coverage and compliance of MDA from the community perspective, and (iii) factors affecting compliance, as well as the operational issues involved in carrying out MDA activities from the drug distributor's perspective.MethodsA sample of 691 participants - both male and female, aged two years or above - were selected through multistage stratified sampling and interviewed using a semi-structured questionnaire. Additionally, drug distributors and the medical officers in charge of the MDA were also interviewed to understand some of the operational issues encountered during MDA.ResultsNinety-nine percent of the study participants received DEC and ABZ tablets during MDA, of which only just above a quarter actually consumed the drugs. The cause of non-compliance was mostly due to fear of side effects, lack of awareness of the benefits of MDA, and non-attendance of health staff in the villages. Lack of adequate training of drug distributors and poor health communication activities before the MDA campaign commenced and the absence of follow-up by health workers following MDA were a few of the operational difficulties encountered during the MDA campaign.ConclusionCurrently MDA is restricted to the distribution of drugs only and the key issues of implementation in compliance, health education, managing side effects, and logistics are not given enough attention. It is therefore essential to address the issues linked to low compliance to make the program more efficient and achieve the goal of filariasis elimination.
| S-EPMC4166397 | biostudies-literature