Optimization of Mass Drug Administration With Existing Drug Regimens for Lymphatic Filariasis and Onchocerciasis (DOLF-Indo)

Approximately 3,500 people will participate per year. The study population will include females and males over 5 years of age who live in filariasis endemic areas. The study will be performed in Indonesia in B. timori and W. bancrofti endemic areas over a period of 4 years. Participants will be studied only once in cross-sectional surveys. Some subjects may be included in more than one annual population survey, but this is not a longitudinal study. Purpose of the study is to evaluate different mass drug administration (MDA) regimens for lymphatic filariasis and also to study the impact of MDA on soil transmitted helminth infections (STH). MDA will administered by others (e.g., Ministry of Health). Results of this study may enhance efforts to control and eliminate these important neglected tropical diseases.

The investigators will test the hypothesis that accelerated mass drug administration will be superior to annual MDA for elimination of lymphatic filariasis and for control of soil transmitted helminth infections (STH):

1. Compare the relative impact and cost effectiveness of annual vs. twice yearly mass drug administration (MDA) for elimination of lymphatic filariasis (LF).
2. Study the impact of annual vs. semiannual MDA on soil transmitted helminth (STH) infection in these populations.

Study Overview

• Status: Completed
• Conditions: Lymphatic Filariasis; Soil Transmitted Helminth Infections
• Intervention / Treatment: Drug: Albendazole (annual); Drug: Diethylcarbamazine (annual); Drug: Albendazole (semiannual); Drug: Diethylcarbamazine (semiannual)

Detailed Description

Lymphatic filariasis (LF) is a deforming and disabling infectious disease that causes elephantiasis and genital deformity (especially hydroceles). The infection affects some 120 million people in 81 countries in tropical and subtropical regions with well over 1 billion people at risk of acquiring the disease. LF is caused by Wuchereria bancrofti and Brugia spp. (B. malayi and B.timori), nematode parasites that are transmitted by mosquitoes. This study is based on the assumption that currently used mass drug administration (MDA) regimens and schedules are not optimal for achieving elimination of LF. These regimens (either annual Albendazole (Alb) 400 mg plus diethylcarbamazine (DEC) 6 mg/kg or Alb 400 mg plus ivermectin (Iver) 200 µg/kg for LF) were developed more than 10 years ago.

Drugs used for LF MDA are also active against soil transmitted helminth infections (STH, e.g., Ascaris, Hookworm, and Trichuris). De-worming campaigns using anthelminthics usually target special groups of the population, such as schoolchildren, and have limited impact on the transmission. Treatment of the total population and semiannual treatments may reduce re-infection considerably and will most likely lead to reduced infection densities and infection prevalences. Suppression of STH is an important ancillary benefit of MDA programs for filarial infections.

Purpose: The study aims to compare the effectiveness once yearly (1X) versus twice yearly (2X) mass drug administration (MDA) for the elimination of lymphatic filariasis and for control of soil-transmitted helminths (intestinal parasites) in large populations. Mass drug administration will be provided by the Indonesia Ministry of Health. This project will assess the impact of the public health program.

Procedures: Study procedures include collection of finger prick blood that will be tested for microfilaremia and for serology testing (antigenemia and antibody testing). Stool samples will be collected to detect STH infections. All assays will be performed in Indonesia (filarial serology tests, blood smears for detection of microfilariae (MF), and stool examinations for detection of worm eggs).

Washington University researchers developed the protocol, will provide training and guidance to Indonesian researchers, and work with them to analyze the data. Indonesian researchers will consent the participants, obtain stool and blood specimens, perform laboratory tests on the specimens, and enter data on participants and lab results.

• Study Type: Observational
• Enrollment (Actual): 17108

Contacts and Locations

Study Locations

• Indonesia
  • Java
    • Jakarta, Java, Indonesia, 10430
      • University of Indonesia, Department of Parasitology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study populations are people who live in areas of Indonesia that are endemic for lymphatic filariasis.

Description

Inclusion Criteria:

• Areas should be endemic for filariasis and have limited or no prior experience with MDA. Males and Females greater than or equal to 5 years of age.

Exclusion Criteria:

• Children less than 5 years of age.

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Paga (annual MDA); This group includes eligible residents of the village of Paga. This cohort will receive once yearly MDA (Albendazole 400 mg plus diethylcarbamazine 6 mg/kg) which will be administered by the Indonesian Ministry of Health as part of their national filariasis elimination program. Paga received a total of three rounds of MDA over a period of 24 months (once every 12 months).	Drug: Albendazole (annual); Albendazole 400 mg pnce annually; Other Names: Albenza (Albendazole, also known as ALB); Drug: Diethylcarbamazine (annual); Diethylcarbamazine 6 mg/kg once annually; Other Names: Diethylcarbamazine, Also known as DEC, (N, N-diethyl-4-methyl-1-piperazine carboxamide dihydrogen citrate). ATC Code: P02CB02 QP52AH02
Lewomada (annual MDA); This group includes eligible residents of the village of Lewomada. This cohort will receive once yearly MDA (Albendazole 400 mg plus diethylcarbamazine 6 mg/kg) which will be administered by the Indonesian Ministry of Health as part of their national filariasis elimination program. Lewomada received a total of three rounds of MDA over a period of 24 months (once every 12 months).	Drug: Albendazole (annual); Albendazole 400 mg pnce annually; Other Names: Albenza (Albendazole, also known as ALB); Drug: Diethylcarbamazine (annual); Diethylcarbamazine 6 mg/kg once annually; Other Names: Diethylcarbamazine, Also known as DEC, (N, N-diethyl-4-methyl-1-piperazine carboxamide dihydrogen citrate). ATC Code: P02CB02 QP52AH02
Pruda (semiannual MDA); This group includes eligible residents of the village of Pruda. This cohort will receive twice yearly MDA (Albendazole 400 mg plus diethylcarbamazine 6 mg/kg) which will also be administered by the Indonesian Ministry of Health. Pruda received a total of five rounds of MDA over a period of 24 months (once every 6 months).	Drug: Albendazole (semiannual); Albendazole 400 mg twice annually; Other Names: Albenza (Albendazole, also known as ALB); Drug: Diethylcarbamazine (semiannual); Diethylcarbamazine 6 mg/kg twice annually; Other Names: Diethylcarbamazine, Also known as DEC, (N, N-diethyl-4-methyl-1-piperazine carboxamide dihydrogen citrate). ATC Code: P02CB02 QP52AH02
Pekalongan (annual MDA); This group includes the villages of Banyurip Ageng and Jenggot. This cohort will receive once yearly MDA (Albendazole 400 mg plus diethylcarbamazine 6 mg/kg) which will be administered by the Indonesian Ministry of Health as part of their national filariasis elimination program. Pekalongan study sites were dropped after the first year follow-up due to lower than expected rates of lymphatic filariasis.	Drug: Albendazole (annual); Albendazole 400 mg pnce annually; Other Names: Albenza (Albendazole, also known as ALB); Drug: Diethylcarbamazine (annual); Diethylcarbamazine 6 mg/kg once annually; Other Names: Diethylcarbamazine, Also known as DEC, (N, N-diethyl-4-methyl-1-piperazine carboxamide dihydrogen citrate). ATC Code: P02CB02 QP52AH02
Pekalongan (semiannual MDA); This group includes the villages of Kertoharjo and Pabean. This cohort will receive twice yearly MDA (Albendazole 400 mg plus diethylcarbamazine 6 mg/kg) which will also be administered by the Indonesian Ministry of Health. Pekalongan study sites were dropped after the first year follow-up due to lower than expected rates of lymphatic filariasis.	Drug: Albendazole (semiannual); Albendazole 400 mg twice annually; Other Names: Albenza (Albendazole, also known as ALB); Drug: Diethylcarbamazine (semiannual); Diethylcarbamazine 6 mg/kg twice annually; Other Names: Diethylcarbamazine, Also known as DEC, (N, N-diethyl-4-methyl-1-piperazine carboxamide dihydrogen citrate). ATC Code: P02CB02 QP52AH02

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of Microfilaria in Blood as Determined by Microscopy of Participant Blood	Microfilariae (filarial parasites) will be detected in blood smears by microscopy. Samples will be collected in annual and semiannual community surveys. Prevalence rates (a measure of the disease rates in the population sampled) are expressed as % positive for microfilaremia (having microfilaria in the blood).	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of Positive Brugia Rapid Antifilarial Antibody Tests	This outcome is reported as the frequency of participants with positive Brugia Rapid antifilarial antibody tests. Data was only collected at baseline and at year 3 for this outcome measure and no antibody data was collected for the Pekalongan study sites.	3 years
Prevalence of Circulating Filarial Antigen in Blood as Determined by ICT Card Test	Prevalence of filarial antigenemia (detected with the Binax Filariasis Now card test "ICT" card test) among the population surveyed. Prevalence data are expressed as %.	3 years
Prevalence of Ascaris Infection	Prevalence of Ascaris infection is defined by the number of participants with any Ascaris worm eggs present in their stool sample as analyzed with microscopy.	2 Years
Prevalence of Hookworm Infection	Prevalence of hookworm infection is defined by the number of participants with any hookworm eggs present in their stool sample as analyzed with microscopy.	2 years
Prevalence of Trichuris Infection	Prevalence of trichuris infection is defined by the number of participants with any trichuris worm eggs present in their stool sample as analyzed with microscopy.	2 years

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Peter U Fischer, Ph.D., Washington University School of Medicine; Study Director: Taniawati Supali, Ph.D., Indonesia University

Publications and helpful links

Helpful Links

• Death to Onchocerciasis and Lymphatic Filariasis (DOLF)

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 1, 2011
• Primary Completion (ACTUAL): March 1, 2015
• Study Completion (ACTUAL): December 1, 2015

Study Registration Dates

• First Submitted: April 11, 2012
• First Submitted That Met QC Criteria: July 18, 2013
• First Posted (ESTIMATE): July 23, 2013

Study Record Updates

• Last Update Posted (ACTUAL): November 17, 2020
• Last Update Submitted That Met QC Criteria: October 26, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Albendazole; Diethylcarbamazine; Filariasis; MDA Mass Drug Administration; STH Soil Transmitted Helminths
• Additional Relevant MeSH Terms: Skin Diseases; Infections; Lymphatic Diseases; Vector Borne Diseases; Parasitic Diseases; Skin Diseases, Parasitic; Skin Diseases, Infectious; Spirurida Infections; Secernentea Infections; Nematode Infections; Lymphedema; Filariasis; Elephantiasis, Filarial; Elephantiasis; Onchocerciasis; Helminthiasis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Anticoagulants; Antiprotozoal Agents; Antiparasitic Agents; Chelating Agents; Sequestering Agents; Filaricides; Antinematodal Agents; Anthelmintics; Antiplatyhelmintic Agents; Calcium Chelating Agents; Lipoxygenase Inhibitors; Anticestodal Agents; Mebendazole; Piperazine; Piperazine citrate; DMP 777; Citric Acid; Sodium Citrate; Albendazole; Diethylcarbamazine
• Other Study ID Numbers: 201103313

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No