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

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

Incorporating qualitative research methods into the monitoring and evaluation of neglected tropical disease programmes: a scoping literature review.

This publication addresses the limited use of qualitative methods in neglected tropical disease (NTD) programmes. It describes a scoping literature review conducted to inform the development of a guide to inform the use of rapid qualitative assessments to strengthen NTD mass drug administration (MDA) programmes. The review assessed how qualitative methods are currently used by NTD programmes and identified qualitative approaches from other health and development programmes with the potential to strengthen the design of MDA interventions. Systematic review articles were reviewed and searched using key terms conducted on Google Scholar and PubMed. Results show that methods used by NTD programmes rely heavily on focus group discussions and in-depth interviews, often with time-consuming analysis and limited information on how results are applied. Results from other fields offered insight into a wider range of methods, including participatory approaches, and on how to increase programmatic uptake of findings. Recommendations on how to apply these findings to NTD control are made. The topic of human resources for qualitative investigations is explored and a guide to improve MDAs using qualitative methods is introduced. This guide has direct applicability across the spectrum of NTDs as well as other public health programmes.

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.

Predictors of compliance in mass drug administration for the treatment and prevention of lymphatic filariasis in Leogane, Haiti.

The global strategy for the elimination of lymphatic filariasis (LF) is based on annual mass drug administration (MDA) to interrupt transmission. Noncompliance with MDA represents a serious programmatic obstacle for the LF program because systematically noncompliant individuals may serve as a reservoir for the parasite and permit recrudescence of infection. Using a survey questionnaire concerning practices, beliefs, and attitudes towards MDA, we assessed differences between noncompliant individuals and compliant individuals in Leogane, Haiti (n = 367) after four years of treatment. A logistic regression model showed the odds of being noncompliant were significantly increased for women (odds ratio = 2.74, 95% confidence interval = 1.12-6.70), as well as for people who lacked knowledge about both LF and programs to eliminate infection. Public health programs should be designed to target people who are at risk for systematic noncompliance.

Eliminating Neglected Tropical Diseases in Urban Areas: A Review of Challenges, Strategies and Research Directions for Successful Mass Drug Administration.

Since 1950, the global urban population grew from 746 million to almost 4 billion and is expected to reach 6.4 billion by mid-century. Almost 90% of this increase will take place in Asia and Africa and disproportionately in urban slums. In this context, concerns about the amplification of several neglected tropical diseases (NTDs) are warranted and efforts towards achieving effective mass drug administration (MDA) coverage become even more important. This narrative review considers the published literature on MDA implementation for specific NTDs and in-country experiences under the ENVISION and END in Africa projects to surface features of urban settings that challenge delivery strategies known to work in rural areas. Discussed under the thematics of governance, population heterogeneity, mobility and community trust in MDA, these features include weak public health infrastructure and programs, challenges related to engaging diverse and dynamic populations and the limited accessibility of certain urban settings such as slums. Although the core components of MDA programs for NTDs in urban settings are similar to those in rural areas, their delivery may need adjustment. Effective coverage of MDA in diverse urban populations can be supported by tailored approaches informed by mapping studies, research that identifies context-specific methods to increase MDA coverage and rigorous monitoring and evaluation.

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.

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.

Controlling Neglected Tropical Diseases (NTDs) in Haiti: Implementation Strategies and Evidence of Their Success.

Lymphatic filariasis (LF) and soil-transmitted helminths (STH) have been targeted since 2000 in Haiti, with a strong mass drug administration (MDA) program led by the Ministry of Public Health and Population and its collaborating international partners. By 2012, Haiti's neglected tropical disease (NTD) program had reached full national scale, and with such consistently good epidemiological coverage that it is now able to stop treatment for LF throughout almost all of the country. Essential to this success have been in the detail of how MDAs were implemented. These key programmatic elements included ensuring strong community awareness through an evidence-based, multi-channel communication and education campaign facilitated by voluntary drug distributors; strengthening community trust of the drug distributors by ensuring that respected community members were recruited and received appropriate training, supervision, identification, and motivation; enforcing a "directly observed treatment" strategy; providing easy access to treatment though numerous distribution posts and a strong drug supply chain; and ensuring quality data collection that was used to guide and inform MDA strategies. The evidence that these strategies were effective lies in both the high treatment coverage obtained- 100% geographical coverage reached in 2012, with almost all districts consistently achieving well above the epidemiological coverage targets of 65% for LF and 75% for STH-and the significant reduction in burden of infection- 45 communes having reached the target threshold for stopping treatment for LF. By taking advantage of sustained international financial and technical support, especially during the past eight years, Haiti's very successful MDA campaign resulted in steady progress toward LF elimination and development of a strong foundation for ongoing STH control. These efforts, as described, have not only helped establish the global portfolio of "best practices" for NTD control but also are poised to help solve two of the most important future NTD challenges-how to maintain control of STH infections after the community-based LF "treatment platform" ceases and how to ensure appropriate morbidity management for patients currently suffering from lymphatic filarial disease.

Evaluation of Lymphatic Filariasis and Onchocerciasis in Three Senegalese Districts Treated for Onchocerciasis with Ivermectin.

In Africa, onchocerciasis and lymphatic filariasis (LF) are co-endemic in many areas. Current efforts to eliminate both diseases are through ivermectin-based mass drug administration (MDA). Years of ivermectin distribution for onchocerciasis may have interrupted LF transmission in certain areas. The Kédougou region, Senegal, is co-endemic for LF and onchocerciasis. Though MDA for onchocerciasis started in 1988, in 2014 albendazole had not yet been added for LF. The objective of this study was to assess in an integrated manner the LF and onchocerciasis status in the three districts of the Kédougou region after ≥10 years of ivermectin-based MDA. The study employed an African Programme for Onchocerciasis Control (APOC) onchocerciasis-related methodology. In the three districts, 14 villages close to three rivers that have Simulium damnosum breeding sites were surveyed. Convenience sampling of residents ≥5 years old was performed. Assessment for LF antigenemia by immunochromatographic testing (ICT) was added to skin snip microscopy for onchocerciasis. Participants were also tested for antibodies against Wb123 (LF) and Ov16 (onchocerciasis) antigens. In two districts, no participants were ICT or skin snip positive. In the third district, 3.5% were ICT positive and 0.7% were skin snip positive. In all the three districts, Wb123 prevalence was 0.6%. Overall, Ov16 prevalence was 6.9%. Ov16 prevalence among children 5-9 years old in the study was 2.5%. LF antigenemia prevalence was still above treatment threshold in one district despite ≥10 years of ivermectin-based MDA. The presence of Ov16 positive children suggested recent transmission of Onchocerca volvulus. This study showed the feasibility of integrated evaluation of onchocerciasis and LF but development of integrated robust methods for assessing transmission of both LF and onchocerciasis are needed to determine where MDA can be stopped safely in co-endemic areas.

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.

Costs of integrated mass drug administration for neglected tropical diseases in Haiti.

We conducted a cost analysis of Haiti's Ministry of Public Health and Population neglected tropical disease program, Projet des Maladies Tropicales Negligées and collected data for 9 of 55 communes participating in the May 2008-April 2009 mass drug administration (MDA). The Projet des Maladies Tropicales Negligées Program partnered with IMA World Health and Hôpital Ste. Croix to implement MDA for treatment of lymphatic filariasis and soil-transmitted helminthiasis by using once a year treatment with albendazole and diethylcarbamazine in a population of approximately 8 million persons. Methods included analyzing partner financial records and conducting retrospective surveys of personnel. In the nine communes, 633,261 persons were treated at a cost of U.S. $0.64 per person, which included the cost of donated drugs, and at a cost of U.S. $0.42 per person treated, when excluding donated drug costs. The MDA for lymphatic filariasis in Haiti began in 2000, with the treatment of 105,750 persons at a cost per person of U.S. $2.23. The decrease in cost per person treated is the result of cumulative implementation experience and economies of scale.

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.

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.