TRANSACTIONSOFTHEROYAL SOCIE~OFTROPICALMEDICINEANDHYGIENE(2002)96,325-326

Efficacy of repeated doses of ivermectin against MansoneNa persfans

J. Gardo&*, J. Kamgno*, N. Gardon-Wendel*, Demanga-Ngangue3, B. 0. L. Duke4 and M. Boussinesq’* ‘Institut Pasteur de la Guyane, B. I? 6010, 97306 Cayenne Cedex, French Guiana; ‘Laboratoire mixte IRD-CM: d’Epid&niologie et de Sand publique, Centre Pasteur du Cameroun, B.P. 1274, Yaoundi, Cameroon; 3D&gation provinciale de la Sante! publique, B.P. 106, Douala, Cameroon; 4River Blindness Foundation, 2 Hillside, Lancaster LA 1 1 YH, UK

Abstract Treatment of Mansonella perstans infection, although seldom necessary, is difficult. In a 3 year’s trial of normal and high-dose annual and 3-monthly ivermectin treatment against Oncho- cerca volvulus, the effects on M. perstans were recorded and related to the cumulative dose received. The World Health Organization’s Afri- can Programme for Onchocerciasis Control may thus reduce the endemicity of M. perstans.

Keywords: mansonellosis, Mansonella perstam, chemo- therapy, ivermectin, Cameroon

Although often regarded as non-pathogenic, Manso- nella perstans may cause fever, itching, cutaneous swel- lings, arthralgia, and fatigue, and can also produce pericarditis, hepatitis, or encephalitis ( JANSSENS, 1964; HOLMES et al., 1969). However, this filaria is one of the most difficult to treat. Diethylcarbamazine has little effect on it (HOLMES et al., 1969); mebenda- zole, when given at doses a200 mg daily, reduces the number of microfilariae (mf) but treatment has to be given daily for 3-4 weeks to be effective (MAERTENS & WBRY,~~~~;WAHLGREN&FROLOV,~~~~;RICHARD- LENOBLE et al., 1985; VAN HOEGAERDEN et al., 1987); albendazole has to be given at doses 2400 mg per day for at least 10 d (VANDEN ENDEN et al., 1992; LIPANI et al., 1997; DUONG et al., 1998); and a single dose of ivermectin has, at the most, a limited effect on the parasite (SCHULZ-KEY et al., 1990; VAN DEN ENDEN et al., 1993).

We recently performed a trial of the effect of high and/or 3-monthly doses of ivermectin on Onchocerca volvulus. As some of the patients were also infected with M. perstans, we also studied the effect of the various regimens on the mf of this fllaria.

The patients were adult males from the Central Province of Cameroon, infected with 0. volvulus but otherwise in a good state of health, who had not received any filaricidal treatment during the previous 5 years. They were randomly divided into 4 groups, which were treated with ivermectin for 3 years at (a) annual doses of 150 pg/kg, (b) annual high doses (400 pg kg 150 pg /

once, then 2 doses of 800 pg/kg), (c) kg every 3 months, and (d) high doses (2 doses

of 400 pgLg/kg, then 10 doses of 800 pg/kg) every 3 months. Just before the first dose, a calibrated thick blood film (30 @) was prepared from each patient, and the M. perstans mf were counted. Three years after the first treatment, the remaining patients were re- examined similarly, but the volume of the blood films

*Author for correspondence: fax +‘237 231564, e-mail boussinesq@pasteur.cm

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was increased to 50 p.L. At this time, the patients treated annually had received their last dose one year previously, whereas the others had received their last treatment only 3 months before.

Among the patients present at both examinations, 65 harboured n/r. perstuns mf initially; all the patients with mf at the second examination were already microfilar- aemic at the outset of the trial. The Table shows the percentage of patients who were still microfilaraemic after 3 years of treatment, and the mean mf load found in each of the 4 groups at each examination. When considering the arithmetic means, the loads were re- duced by two-thirds in the group treated with the standard dose (150 ug/kg annually), by 97% in the group treated with high doses 3-monthly, and by 85% in the other 2 groups. Although the group treated with high doses 3-monthly included only 7 patients, and despite the fact that the latter had, initially, significantly higher mf loads than those of the other groups, it seems that the efficacy of ivermectin on M. perstans is related to the cumulative dose received. Whether this is the result of a macrofilaricidal or a purely microfilaricidal action is unknown. However, despite the fact that the relationship between the microfilaraemia, the number of mf ingested by the Culicoides vectors, and the num- ber of larvae reaching the infective stage is poorly documented (HOPKINS & NICHOLAS, 1952), the Afri- can Programme for Onchocerciasis Control (APOC), which is based upon large-scale repeated ivermectin treatments, is likely to have a marked impact on the level of endemicity of M. perstuns.

Acknowledgements We thank the staff of the Laboratoire mixte IRl-CPC

d’Epidemiologie et de Sante publique du Centre Pasteur du Cameroun for their help, and the patients who participated in the trial. The study was supported by the River Blindness Foundation.

References Duong, T. H., Kombila, M., Ferrer, A., Nguiri, C. & Richard-

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Received 8 November 2001; revised 27 November 2001; accepted for publication 30 November 2001

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