Parasitology


Supplement
Research Article

An analysis of the safety of the single dose, two drug regimens used in programmes to eliminate lymphatic filariasis


J.  HORTON  a1 c1, C.  WITT  a2, E.A.  OTTESEN  a2, J.K.  LAZDINS  a3, D.G.  ADDISS  a4, K.  AWADZI  a5, M.J.  BEACH  a4, V.Y.  BELIZARIO  a6, S.K.  DUNYO  a7, M.  ESPINEL  a8, J.O.  GYAPONG  a9, M.  HOSSAIN  a10, M.M.  ISMAIL  a11, R.L.  JAYAKODY  a11, P.J.  LAMMIE  a4, W.  MAKUNDE  a12, D.  RICHARD-LENOBLE  a13, B.  SELVE  a14, R.K.  SHENOY  a15, P.E.  SIMONSEN  a16, C.N.  WAMAE  a17 and M.V.  WEERASOORIYA  a18
a1 Department of Therapeutics (Tropical Medicine), SmithKline Beecham International, Brentford, Middlesex, UK TW8 9BD
a2 Lymphatic Filariasis Elimination (CPE/CEE/FIL), Department of Control, Prevention and Eradication, World Health Organization, 1211 Geneva 27, Switzerland
a3 Special Programme for Research and Training in Tropical Diseases (TDR), World Health Organization, 1211 Geneva 27, Switzerland
a4 Division of Parasitic Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, GA 30341 USA
a5 Onchocerciasis Chemotherapy Research Centre, Hohoe Hospital, Hohoe, Ghana
a6 College of Public Health, University of the Philippines, Manila, Philippines
a7 Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana
a8 Instituto Juan Cesar Garcia, P.O. Box 17-11-6292, Quito, Ecuador
a9 Health Research Unit, Ministry of Health, P. O. Box 184, Accra, Ghana
a10 Institute of Epidemiology, Disease Control and Research (IEDCR), Mohakhali, Dhaka-1212, Bangladesh
a11 Faculty of Medicine, University of Colombo, Kynsey Rd., Colombo 8, Sri Lanka
a12 Bombo Research Station, Tanga, Tanzania
a13 Parasitologie-Médicine Tropicale, Faculté de Médicine, Tours, France
a14 Misima Mines Pty, Ltd, Bwagoia, Misima Island, Papua New Guinea
a15 Filariasis Chemotherapy Unit, T. D. Medical College Hospital, Alleppey 688011, Kerala, India
a16 Danish Bilharziasis Laboratory, Jaegersborg Alle 1 D, 2920 Charlottenlund, Denmark
a17 Kenya Medical Research Institute (KEMRI), Nairobi, Kenya
a18 Filariasis Research Laboratory, Faculty of Medicine, University of Ruhuna, Galle, Sri Lanka

Abstract

This review of the safety of the co-administration regimens to be used in programmes to eliminate lymphatic filariasis (albendazole+ivermectin or albendazole+diethylcarbamazine [DEC]) is based on 17 studies conducted in Sri Lanka, India, Haiti, Ghana, Tanzania, Kenya, Ecuador, the Philippines, Gabon, Papua New Guinea, and Bangladesh. The total data set comprises 90635 subject exposures and includes individuals of all ages and both genders. Results are presented for hospital-based studies, laboratory studies, active surveillance of microfilaria-positive and microfilaria-negative individuals, and passive monitoring in both community-based studies and mass treatment programmes of individuals treated with albendazole (n=1538), ivermectin (9822), DEC (576), albendazole+ivermectin (7470), albendazole+DEC (69020), or placebo (1144). The most rigorous monitoring, which includes haematological and biochemical laboratory parameters pre- and post-treatment, provides no evidence that consistent changes are induced by any treatment; the majority of abnormalities appear to be sporadic, and the addition of albendazole to either ivermectin or DEC does not increase the frequency of abnormalities. Both DEC and ivermectin show, as expected, an adverse event profile compatible with the destruction of microfilariae. The addition of albendazole to either single-drug treatment regimen does not appear to increase the frequency or intensity of events seen with these microfilaricidal drugs when used alone. Direct observations indicated that the level of adverse events, both frequency and intensity, was correlated with the level of microfilaraemia. In non microfilaraemic individuals, who form 80–90% of the ‘at risk’ populations to be treated in most national public health programmes to eliminate lymphatic filariasis (LF), the event profile with the compounds alone or in combination does not differ significantly from that of placebo. Data on the use of ivermectin+albendazole in areas either of double infection (onchocerciasis and LF), or of loiais (with or without concurrent LF) are still inadequate and further studies are needed. Additional data are also recommended for populations infected with Brugia malayi, since most data thus far derive from populations infected with Wuchereria bancrofti.


Key Words: Lymphatic filariasis; albendazole; ivermectin; diethylcarbamazine; DEC; drug regimens for LF; drug safety; adverse events; Wuchereria bancrofti; Brugia malayi; Programme to Eliminate Lymphatic Filariasis (PELF); tropical disease control.

Correspondence:
c1 Corresponding author: Tel: 44-181-975-3638. Fax: 44-181-975-3514. E-mail: John.HORTON@sb.com


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