Diethylcarbamazine Albendazole Research Articles

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

Mass drug administration (MDA) is the cornerstone for the elimination of lymphatic filariasis (LF). The proportion of the population that is never treated (NT) is a crucial determinant of whether this goal is achieved within reasonable time frames. Using 2 individual-based stochastic LF transmission models, we assess the maximum permissible level of NT for which the 1% microfilaremia (mf) prevalence threshold can be achieved (with 90% probability) within 10 years under different scenarios of annual MDA coverage, drug combination and transmission setting. For Anopheles-transmission settings, we find that treating 80% of the eligible population annually with ivermectin + albendazole (IA) can achieve the 1% mf prevalence threshold within 10 years of annual treatment when baseline mf prevalence is 10%, as long as NT <10%. Higher proportions of NT are acceptable when more efficacious treatment regimens are used. For Culex-transmission settings with a low (5%) baseline mf prevalence and diethylcarbamazine + albendazole (DA) or ivermectin + diethylcarbamazine + albendazole (IDA) treatment, elimination can be reached if treatment coverage among eligibles is 80% or higher. For 10% baseline mf prevalence, the target can be achieved when the annual coverage is 80% and NT ≤15%. Higher infection prevalence or levels of NT would make achieving the target more difficult. The proportion of people never treated in MDA programmes for LF can strongly influence the achievement of elimination and the impact of NT is greater in high transmission areas. This study provides a starting point for further development of criteria for the evaluation of NT.

Coverage evaluation of mass drug administration with triple drug regimen in an evaluation unit in Nagpur district of Maharashtra, India.

Triple drug regimen (IDA; Ivermectin, Diethylcarbamazine, Albendazole) recommended for accelerating elimination of lymphatic filariasis was launched in India in December 2018. Nagpur district in Maharashtra was one of the first five districts where this strategy was introduced. The National Vector Borne Disease Control Programme (NVBDCP) at the district reported ~85.0% treatment coverage in the first round of mass drug administration (MDA) with IDA implemented in EU-2 in Nagpur district in January 2019. As per the national guideline, a coverage evaluation survey was carried out and both quantitative and qualitative data were collected to assess the treatment coverage, the level of community preparation and identify the gaps, if any, for improvement. A Coverage Evaluation Survey (CES) following the WHO recommended protocol was conducted in one of the two evaluation units (EU-2) in Nagpur district in March 2019. Coverage Sample Builder (CSB) V2.9 tool was used to calculate the sample size, select sites and estimate drug coverage. The CSB tool followed a two-stage cluster sampling procedure to select 30 primary sampling units (ward/village as a cluster) and a list of random numbers for selecting households (HHs) in each cluster. The results were analyzed for operational indicators. Stata ver. 14.0 software was used to construct the 95% confidence limits accounting for clustering. A total of 1601 individuals aged 5-85 years of both gender from 328 HHs were surveyed from the 30 randomly selected clusters in EU-2. The mean age was 33.8±17.6 years. Among the surveyed population, 78.0% received the drugs (programme reach) and 66.1% consumed the drugs (survey coverage). Survey coverage was significantly higher in rural (82.6%) than in urban (59.4%) and peri-urban (58.6%) areas (P<0.001). Directly observed treatment (DOT) among the surveyed population was 51.6%. Adverse events were reported among 6.9% respondents who reported to have consumed the drugs. The IDA based MDA strategy could achieve just the required level of treatment coverage (~65%) in EU-2, Nagpur district, which had previously undergone several rounds of DA-MDAs (Diethylcarbamazine, Albendazole). Having achieved an effective treatment coverage of >80% in rural areas, the coverage in urban and peri-urban areas need to be improved in order to attain the impact of IDA-MDA. It is imperative to strengthen drug delivery and community preparation activities along with improved DOT especially in urban and peri-urban areas to achieve the required level of treatment coverage. Addition of ivermectin did not have any additional perceived adverse events.

Introduction of Triple-Drug Therapy for Accelerating Lymphatic Filariasis Elimination in India: Lessons Learned.

ABSTRACT.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 made new commitments to accelerate their program to eliminate LF and initiated the new IDA protocol in five districts in the country. This article looks at the experience of India in the roll out of the new drug protocol and shares their preparations, successes, challenges, and lessons learned.

Are Alternative Strategies Required to Accelerate the Global Elimination of Lymphatic Filariasis? Insights From Mathematical Models.

BackgroundWith the 2020 target year for elimination of lymphatic filariasis (LF) approaching, there is an urgent need to assess how long mass drug administration (MDA) programs with annual ivermectin + albendazole (IA) or diethylcarbamazine + albendazole (DA) would still have to be continued, and how elimination can be accelerated. We addressed this using mathematical modeling.MethodsWe used 3 structurally different mathematical models for LF transmission (EPIFIL, LYMFASIM, TRANSFIL) to simulate trends in microfilariae (mf) prevalence for a range of endemic settings, both for the current annual MDA strategy and alternative strategies, assessing the required duration to bring mf prevalence below the critical threshold of 1%.ResultsThree annual MDA rounds with IA or DA and good coverage (≥65%) are sufficient to reach the threshold in settings that are currently at mf prevalence <4%, but the required duration increases with increasing mf prevalence. Switching to biannual MDA or employing triple-drug therapy (ivermectin, diethylcarbamazine, and albendazole [IDA]) could reduce program duration by about one-third. Optimization of coverage reduces the time to elimination and is particularly important for settings with a history of poorly implemented MDA (low coverage, high systematic noncompliance).ConclusionsModeling suggests that, in several settings, current annual MDA strategies will be insufficient to achieve the 2020 LF elimination targets, and programs could consider policy adjustment to accelerate, guided by recent monitoring and evaluation data. Biannual treatment and IDA hold promise in reducing program duration, provided that coverage is good, but their efficacy remains to be confirmed by more extensive field studies.

Children and adolescents infected withWuchereria bancroftiin Greater Recife, Brazil: a randomized, year-long clinical trial of single treatments with diethylcarbamazine or diethylcarbamazine–albendazole

In filariasis-endemic areas beyond sub-Saharan Africa, the World Health Organization's recommended strategy for interrupting transmission of the causative parasites is annual, single-dose, mass treatment with a combination of diethylcarbamazine (DEC; given at 6 mg/kg) and albendazole (ALB; given at 400 mg) for 4-6 years (the minimum estimated life-span of the adult parasites). In an open, hospital-based, randomized and controlled trial, with a blinded evaluation of outcome, 82 children and adolescents from Recife, all with Wuchereria bancrofti microfilaraemias, were given either DEC alone (6 mg/kg) or the same dose of DEC combined with ALB (at 400 mg/patient). Every 90 days for 1 year after the single treatment, each patient was checked for microfilaraemia by the filtration of up to 5 ml of venous blood collected at night. One year post-treatment, 16 (39%) of the 41 patients given DEC alone and 20 (49%) of the 41 given DEC-ALB were found microfilaraemic (relative risk=0.8, with a 95% confidence interval of 0.49-1.31) and the corresponding geometric mean levels of microfilaraemia were 2.0% and 1.8% of the levels recorded immediately pre-treatment, respectively (P>0.05). In terms of the prevalences and intensities of microfilaraemia, therefore, the addition of ALB to the DEC appeared to offer no significant benefit.

Model‐based analysis of trial data: microfilaria and worm‐productivity loss after diethylcarbamazine–albendazole or ivermectin–albendazole combination therapy against Wuchereria bancrofti

To determine the efficacies of combinations of ivermectin or diethylcarbamazine and albendazole, which are recommended for use in mass treatment programmes against lymphatic filariasis. Review of published trends in microfilarial (mf) intensities after treatment with these combination therapies. By fitting a mathematical model of treatment effects to the trial data, we quantified the efficacy of treatment, distinguishing between the killing of mf (mf loss) and a reduction in mf production by adult worms (worm-productivity loss). After diethylcarbamazine-albendazole treatment mf density dropped immediately, then slowly but steadily decreased further (four trials). After ivermectin-albendazole treatment, mf densities immediately dropped to near-zero levels, followed by a small increase (five trials). For diethylcarbamazine-albendazole treatment the average mf loss was approximately 83% (ranging from 54% to 100% in the different studies) and worm-productivity loss was 100% (in all studies). For ivermectin-albendazole treatment, average mf loss was 100% (ranging from 98% to 100%) and worm productivity loss was 96% (ranging from 83% to 100%). The effects were dose-dependent. Sensitivity analysis showed that the estimates did not depend on assumptions on worm lifespan or premature period and little on assumptions on mf lifespan. The two therapies differ with respect to their direct effect on mf, but both are highly effective against adult worms. If mass treatment with these combination therapies achieves high coverage, they can have a large impact on lymphatic filariasis transmission.

Bancroftian filariasis: effect of repeated treatment with diethylcarbamazine and albendazole on microfilaraemia, antigenaemia and antifilarial antibodies

Diethylcarbamazine/albendazole (DEC/ALB) therapy is widely used in mass drug administration (MDA) programmes aimed at eliminating lymphatic filariasis. We studied the effects of repeated annual treatments with DEC/ALB on Wuchereria bancrofti microfilaraemia, filarial antigenaemia and IgG4 antibodies to Bm14 antigen. Fifty-seven subjects with asymptomatic microfilaraemia were treated with one or seven daily doses of DEC/ALB at time zero. All subjects were re-treated with single-dose DEC/ALB 12, 24 and 36 months later. The two treatment groups had comparable pre-treatment microfilaria counts. Multidose treatment cleared microfilaraemia more effectively than single-dose treatment. Filarial antigen levels decreased equally in both treatment groups. Total antigen clearance was observed in 29.6%, 52.0%, 63.6% and 79.5% of subjects at 12, 24, 36 and 48 months. These clearance rates are much higher than those observed in prior treatment trials with DEC or ivermectin. Antibody levels increased 4 weeks after treatment and then slowly decreased in most subjects. Antibody tests turned negative in 20%, 35%, 39.4% and 52.5% of treated subjects at 12, 24, 36 and 48 months post treatment. These results show that the studied parameters decline at different rates and to differing degrees following DEC/ALB treatment. These findings have important implications regarding strategies for monitoring the effects of MDA in populations.