A multicenter, community-based, mixed methods assessment of the acceptability of a triple drug regimen for elimination of lymphatic filariasis.

BACKGROUND: Many 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 FINDINGS: To 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/SIGNIFICANCE: IDA 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.

Safety and efficacy of co-administered diethylcarbamazine, albendazole and ivermectin during mass drug administration for lymphatic filariasis in Haiti: Results from a two-armed, open-label, cluster-randomized, community study.

In Haiti, 22 communes still require mass drug administration (MDA) to eliminate lymphatic filariasis (LF) as a public health problem. Several clinical trials have shown that a single oral dose of ivermectin (IVM), diethylcarbamazine (DEC) and albendazole (ALB) (IDA) is more effective than DEC plus ALB (DA) for clearing Wuchereria bancrofti microfilariae (Mf). We performed a cluster-randomized community study to compare the safety and efficacy of IDA and DA in an LF-endemic area in northern Haiti. Ten localities were randomized to receive either DA or IDA. Participants were monitored for adverse events (AE), parasite antigenemia, and microfilaremia. Antigen-positive participants were retested one year after MDA to assess treatment efficacy. Fewer participants (11.0%, 321/2917) experienced at least one AE after IDA compared to DA (17.3%, 491/2844, P<0.001). Most AEs were mild, and the three most common AEs reported were headaches, dizziness and abdominal pain. Serious AEs developed in three participants who received DA. Baseline prevalence for filarial antigenemia was 8.0% (239/3004) in IDA localities and 11.5% (344/2994) in DA localities (<0.001). Of those with positive antigenemia, 17.6% (42/239) in IDA localities and 20.9% (72/344, P = 0.25) in DA localities were microfilaremic. One year after treatment, 84% percent of persons with positive filarial antigen tests at baseline could be retested. Clearance rates for filarial antigenemia were 20.5% (41/200) after IDA versus 25.4% (74/289) after DA (P = 0.3). However, 94.4% (34/36) of IDA recipients and 75.9% (44/58) of DA recipients with baseline microfilaremia were Mf negative at the time of retest (P = 0.02). Thus, MDA with IDA was at least as well tolerated and significantly more effective for clearing Mf compared to the standard DA regimen in this study. Effective MDA coverage with IDA could accelerate the elimination of LF as a public health problem in the 22 communes that still require MDA in Haiti.

Translating Research into Reality: Elimination of Lymphatic Filariasis from Haiti.

Research provides the essential foundation of disease elimination programs, including the global program to eliminate lymphatic filariasis (GPELF). The development and validation of new diagnostic tools and intervention strategies, critical steps in the evolution of GPELF, required a global effort. Lymphatic filariasis research in Haiti involved many partners and was directly linked to the development of the national elimination program and to the success achieved to date. Ongoing research efforts involving many partners will continue to be important in resolving the challenges faced by the program today in its final efforts to achieve elimination.

Partnering for impact: Integrated transmission assessment surveys for lymphatic filariasis, soil transmitted helminths and malaria in Haiti.

BACKGROUND: Since 2001, Haiti's National Program for the Elimination of Lymphatic Filariasis (NPELF) has worked to reduce the transmission of lymphatic filariasis (LF) through annual mass drug administration (MDA) with diethylcarbamazine and albendazole. The NPELF reached full national coverage with MDA for LF in 2012, and by 2014, a total of 14 evaluation units (48 communes) had met WHO eligibility criteria to conduct LF transmission assessment surveys (TAS) to determine whether prevalence had been reduced to below a threshold, such that transmission is assumed to be no longer sustainable. Haiti is also endemic for malaria and many communities suffer a high burden of soil transmitted helminths (STH). Heeding the call from WHO for integration of neglected tropical diseases (NTD) activities, Haiti's NPELF worked with the national malaria control program (NMCP) and with partners to develop an integrated TAS (LF-STH-malaria) to include assessments for malaria and STH. METHODOLOGY/PRINCIPLE FINDINGS: The aim of this study was to evaluate the feasibility of using TAS surveys for LF as a platform to collect information about STH and malaria. Between November 2014 and June 2015, TAS were conducted in 14 evaluation units (EUs) including 1 TAS (LF-only), 1 TAS-STH-malaria, and 12 TAS-malaria, with a total of 16,655 children tested for LF, 14,795 tested for malaria, and 298 tested for STH. In all, 12 of the 14 EUs passed the LF TAS, allowing the program to stop MDA for LF in 44 communes. The EU where children were also tested for STH will require annual school-based treatment with albendazole to maintain reduced STH levels. Finally, only 12 of 14,795 children tested positive for malaria by RDT in 38 communes. CONCLUSIONS/SIGNIFICANCE: Haiti's 2014-2015 Integrated TAS surveys provide evidence of the feasibility of using the LF TAS as a platform for integration of assessments for STH and or malaria.

Endpoints for lymphatic filariasis programs.

In 2000, annual mass administration of diethlycarbamazine and albendazole began in Leogane Commune, Haiti, to interrupt transmission of lymphatic filariasis (LF). After 5 years of treatment, microfilaremia, antigenemia, and mosquito infection rates were significantly reduced, but LF transmission was not interrupted. These finding have implications for other LF elimination programs.

Symptoms reported after mass drug administration for lymphatic filariasis in Leogane, Haiti.

Mass drug administration (MDA) for lymphatic filariasis (LF) can cause adverse reactions from microfilarial and adult worm death. Symptoms after the fifth annual MDA in Leogane, Haiti, were studied to determine whether they resulted from parasite death. Persons reporting post-MDA systemic symptoms at 5 of 148 drug distribution posts and men reporting scrotal pain at any post were interviewed. Participants were tested with immunochromatographic tests (ICTs), and men with scrotal symptoms were examined. At the five posts, 3,781 persons took anti-filarial medication. Of these, 314 (8%) returned with symptoms; the most common were headache (36%) and gastrointestinal complaints (28%). Of the 294 (94%) who consented to ICT testing, 47 (16%) were positive. Of 69 men with scrotal symptoms who consented to ICT testing, 18 (26.1%) were positive. After Leogane's fifth MDA, most symptomatic persons had undetectable levels of filarial antigen by ICT. Free symptomatic treatment may motivate some people to report symptoms and seek care.

Participation in three consecutive mass drug administrations in Leogane, Haiti.

OBJECTIVES: In the global effort to eliminate lymphatic filariasis, mass drug administrations (MDAs) are organised annually. The success of this strategy depends on achieving high levels of drug coverage, which reduce the number of persons with circulating microfilariae and consequently transmission. Persons who consistently fail to participate in MDAs represent a potential threat to the goal of filariasis elimination. We wanted to know the drug coverage, the proportion of persons who were systematically non-compliant and factors associated with this behaviour. METHODS: We conducted three surveys following the third annual MDA of a filariasis elimination program in Leogane, Haiti: (1) a total population survey to determine coverage; (2) an adult survey to determine non-compliance and associated factors and (3) an urban survey to make a rural-urban comparison. RESULTS: During the third MDA, the overall surveyed coverage was 78.5% [95% confidence interval (CI) 74.4-82.6] A survey among adult population showed coverage estimates for persons >14 years old of 59.4% (95% CI 52.0-66.7), 61.0% (95% CI 55.0-67.4) and 67.3% (95% CI 60.5-74.0), for the first, second and third MDA respectively. The coverage in rural areas (78.3%) was significantly higher than in urban areas (68.3%, P < 0.05). Of the population > 14 years of age, 18% never took the drugs during any of three MDAs. These persons did not differ significantly from MDA participants by age, gender or other characteristics that we assessed. CONCLUSION: More research is needed to identify characteristics of systematically non-compliant persons in order to refine health education messages and improve distribution strategies to increase drug coverage.

The Leogane, Haiti demonstration project: decreased microfilaremia and program costs after three years of mass drug administration.

To support the global program to eliminate lymphatic filariasis (LF), well-monitored demonstration projects are important for defining the relationship between coverage and reductions in microfilaremia. We are using mass treatment with diethylcarbamazine (DEC) and albendazole in an effort to eliminate LF from Leogane, Haiti. Wuchereria bancrofti microfilaremia prevalence at baseline ranged from 0.8% to 15.9% in four sentinel sites. After three rounds of DEC-albendazole mass drug administration (MDA), both microfilaremia prevalence and intensity decreased dramatically. Mild and moderate adverse reactions after treatment were common, especially after the first MDA, but decreased after subsequent MDAs. Drug coverage for the first year was estimated to be 72%, but concerns about adverse reactions appeared to decrease drug coverage in the second MDA. As a result of community education efforts that focused on providing a greater understanding of adverse reactions, coverage increased dramatically for the third round. Program efficiency increased substantially; the costs per person treated for three rounds of MDA were 2.23 US dollars, 1.96 US dollars, and 1.30 US dollars per person, respectively. The Leogane experience highlights the importance of adapting community education and mobilization campaigns to achieve and maintain good coverage.

Community-wide reduction in prevalence and intensity of intestinal helminths as a collateral benefit of lymphatic filariasis elimination programs.

Annual mass treatment with antifilarial drugs is the cornerstone of the global program to eliminate lymphatic filariasis (LF). Although the primary goal of the program is to interrupt transmission of LF, additional public health benefits also are expected because of the known anthelminthic properties of these drugs. Since rapid re-infection with intestinal helminths occurs following treatment, annual de-worming may not be sufficient to produce a lasting reduction in the prevalence and intensity of these infections. We conducted stool examinations in four sentinel communities before and approximately nine months after each of two rounds of mass drug administration (MDA) with diethylcarbamazine and albendazole in the context of an LF elimination program in Leogane, Haiti. At baseline, overall Ascaris, Trichuris, and hookworm infection prevalences were 20.9%, 34.0%, and 11.2%, respectively (n = 2,716 stools). Nine months after the second MDA, Ascaris, Trichuris and hookworm prevalences had decreased significantly, to 14.1%, 14.6%, and 2.0%, respectively (n = 814 stools). Infection intensity decreased significantly for all three parasites as well. These results demonstrate that substantial reductions in intestinal helminth infections are associated with mass treatment of filariasis in Haiti and are consistent with the conclusion that high levels of coverage for the LF program can decrease transmission of geohelminths.