Randomised community-based trial of annual single-dose diethylcarbamazine with or without ivermectin against Wuchereria bancrofti infection in human beings and mosquitoes

doi:10.1016/S0140-6736(97)07081-5

The Lancet

Volume 351, Issue 9097, 17 January 1998, Pages 162-168

https://doi.org/10.1016/S0140-6736(97)07081-5 Get rights and content

Summary

Background

WHO has targeted lymphatic filariasis for elimination. Studies of vector-parasite relations of Wuchereria bancrofti suggest that a reduction in the microfilarial reservoir by mass chemotherapy may interrupt transmission and thereby eliminate infection. However, no field data exist on the impact of chemotherapy alone on vector efficiency and transmission intensity of W bancrofti. We compared the impact of an annual community-wide single-dose treatment with diethylcarbamazine alone or with ivermectin on rate and intensity of microfilaraemia, and transmission intensity in an area of Papua New Guinea endemic for intense W bancrofti transmission.

Methods

We carried out clinical and parasitological surveys in 14 communities in matched pairs. People aged 5 years or older in seven communities received randomly assigned diethylcarbamazine 6 mg/kg and people in the other seven communities received diethylcarbamazine 6 mg/kg plus ivermectin 400 μg/kg. We made physical examinations for hydroceles and leg oedema and investigated microfilarial densities by membrane filtration before and after treatment. We selected five communities for monthly entomological surveys between September, 1993, and September, 1995. Mosquitoes were collected in these communities by the all-night landing catch method and were individually dissected to identify rates of infection and infectiveness.

Findings

2219 (87·6%) of 2534 eligible people received treatment. Microfilarial rate and density had decreased 1 year after treatment in all 14 communities; this decrease was significantly higher in communities given combined therapy than in those given diethylcarbamazine alone (mean decreases 57·5% and 30·6%, respectively; p=0·0013). Greater decreases were also seen in community-specific microfilarial intensity with combined therapy (mean reductions 91·1% and 69·8%, respectively; p=0·0047). The rate of leg oedema was not altered, but the frequency of advanced hydroceles decreased by 47% with combined therapy and 56% with diethylcarbamazine alone. 26 641 Anopheles punctulatus mosquitoes were caught during 499 person-nights of landing catches. Exposure to infective third-stage larvae decreased in all monitored five communities. Annual transmission potential decreased by between 75·7% and 98·8% in combined-therapy communities and between 75·6% and 79·4% in communities given diethylcarbamazine alone. Transmission was almost interrupted in two communities treated with combined therapy.

Interpretation

Annual single-dose community-wide treatment with diethylcarbamazine alone or with ivermectin is effective for the control of lymphatic filariasis in highly endemic areas, but combination therapy brings about greater decreases in rates and intensity of microfilaraemia.

Introduction

Lymphatic filariasis has been identified by WHO as a public-health problem and targeted for elimination.1, 2 The disease is a major cause of morbidity, primarily lymphoedema of the legs and hydroceles, and impedes socioeconomic development in 73 endemic countries, in which 1·1 billion people are at risk and 120 million are infected.³ Filariasis-control programmes aimed at interrupting transmission of Wuchereria bancrofti have relied wholly or mainly on community-level drug administration. For nearly 50 years, diethylcarbamazine has been the drug of choice because it significantly decreases the intensity of microfilaraemia. However, many people remain microfilaraemic after taking full courses of the drug, and where culicine mosquitoes are vectors, these individuals may serve as reservoirs for continued transmission.⁴ Studies have shown that treatment with ivermectin leads to more substantial and sustained reductions in microfilaraemia than diethylcarbamazine.5, 6 Limited clinical trials on selected individuals suggest that combined ivermectin and diethylcarbamazine is more effective than ivermectin alone, possibly because diethylcarbamazine is active against the adult stage of W bancrofti7, 8, 9 or the combination has greater microfilaricidal activity than either drug alone. Community-wide treatment with combined ivermectin and diethylcarbamazine has, therefore, been identified as a possibly means for elimination of lymphatic filariasis.¹⁰

Analyses of the relation between W bancrofti and its mosquito vector suggest that reductions in vector density and intensity of microfilaraemia below certain thresholds could lead to breaks in transmission and, ultimately, eradicate anopheline-transmitted filariasis.11, 12 In areas where anopheline mosquitoes are the main vectors of W bancrofti, such as the Solomon Islands and Togo, transmission was completely interrupted through a reduction in vector density by the spraying of residual insecticides aimed at controlling malaria.13, 14 Since vector control alone is impractical or ineffective in many areas of the world endemic for filariasis, reduction of the microfilarial reservoir through community-wide chemotherapy has been proposed as a cost-effective alternative to limit or break transmission of W bancrofti.¹⁰ Chemotherapy without vector control or a natural decline in vector density has not yet been shown to lead to breaks in transmission of W bancrofti.¹¹

We compared, in a randomised study, the impact of community-wide treatment with annual single dose of diethylcarbamazine or combined diethylcarbamazine and ivermectin on bancroftian filariasis in a highly endemic area of East Sepik Province, Papua New Guinea. We studied the effects of treatment on infection, disease, and transmission and the prospects of achieving WHO's goal of elimination.

Section snippets

Study population

In 1994 we carried out parasitological and clinical surveys of people in 14 communities in the East Sepik Province, Papua New Guinea, located within 20 km of the Dreikikir government station (figure 1). The average annual rainfall in East Sepik Province is 1600 mm, and relative humidity varies between 80% and 100%. Rainfall is seasonal and most abundant between December and June (wet season). Lymphatic filariasis is highly endemic in these conditions, and anopheline mosquitoes are the main

Results

The first round of parasitological and physical examinations and treatment occurred between June and October, 1994. Randomisation by transmission zone ensured that communities receiving different treatments were comparable for rate of microfilaria and mean intensity of microfilaraemia before treatment. Parasitological variables were generally greater in the higher than the lower transmission zones before treatment (table). 1 year after drug administration, microfilarial rate and intensity were

Discussion

WHO has stated that elimination of lymphatic filariasis is achievable within 10 years.1, 2 In this trial, our main objective was to find out the efficacy of annual single-dose diethylcarbamazine alone compared with combined treatment with ivermectin in limiting the transmission of W bancrofti in a highly endemic area of Papua New Guinea. By monitoring entomological indices of transmission and the rate and intensity of microfilaraemia before and after treatment, we were also able to gain new

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ArticlesRandomised community-based trial of annual single-dose diethylcarbamazine with or without ivermectin against Wuchereria bancrofti infection in human beings and mosquitoes

Summary

Background

Methods

Findings

Interpretation

Introduction

Section snippets

Study population

Results

Discussion

Lancet

Trans R Soc Trop Med Hyg

Parasitol Today

Trans R Soc Trop Med Hyg

Trans R Soc Trop Med Hyg

Trans R Soc Trop Med Hyg

Trans R Soc Trop Med Hyg

Trans R Soc Trop Med Hyg

Trop Dis Res News

Re-assessing the global prevalence and distribution of lymphatic filariasis

Parasitology

The significance of low density microfilaraemia in the transmission of lymphatic filarial parasites

J Trop Med Hyg

Comparative efficacy of clearing dose and single high dose ivermectin and diethylcarabamazine against Wuchereria bancrofti microfilaremia

Am J Trop Med Hyg

Comparison of single-dose diethylcarbamzine and ivermectin for treatment of bancroftian filarisis in Papua New Guinea

Am J Trop Med Hyg

Single dose of ivermectin 400 μg/kg: the most effective dosage in bancroftian filariasis

Southeast Asian J Trop Med Public Health

Combination ivermectin plus diethylcarabamzine, a new effective tool for control of lymphatic filarisiasis

Ann Trop Med Parasitol

Can anopheline-transmitted filariasis be eradicated?

J Trop Med Hyg

Etude parasitologique, cliniue et entomologique sur la filariose de Bancroft dans le sud du Dahomey et du Togo

Cah ORSTOM Serie Entomol Med Parasitol

Articles
Randomised community-based trial of annual single-dose diethylcarbamazine with or without ivermectin against Wuchereria bancrofti infection in human beings and mosquitoes