- Email: [email protected]
Efficacy of repeated doses of ivermectin against Mansonella perstans
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 Onchocerca volvulus, the effects on M. perstans were recorded and related to the cumulative dose received. The World Health Organization’s African 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, Mansonella perstans may cause fever, itching, cutaneous swellings, 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); mebendazole, 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,~~~~;RICHARDLENOBLE 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 etal., 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 once, then 2 doses of 800 pg/kg), (c) 150 pg / 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 reexamined similarly, but the volume of the blood films *Author for correspondence: [email protected]
fax +‘237 231564, e-mail
J. GARDON ETAL.
326
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 microfilaraemic 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 reduced 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 number of larvae reaching the infective stage is poorly documented (HOPKINS & NICHOLAS, 1952), the African 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. & RichardLenoble, D. (1998). Decrease in Mansonella perstuns microfilaraemia after albendazole treatment. Transactions of the Royal Society of Tropical Medicine and Hygiene, 92,459. Holmes, G. K. T., Gelfand, M., Boyt, W. & Mackenzie, I’.
(1969). A study to investigate the pathogenicity of a parasite resembling Acanthocheilonema perstans. Transactions of the Royal Society of Tropical Medicine and Hygiene, 63,479-484. Hopkins, C. A. & Nicholas, W. L. (1952). Culicoides austeni, the vector of Acanthocheilonema perstans. Annals of Tropical Medicine and Parasitology, 46,276-283. Janssens, I’. G. (1964). D. perstans est-elle pathogene pour l’homme? Annales de la Socie’te’Belge de Midecine Tropicale, 44,989-998. Lipani, F., Caramello, I’., Biglino, A. & Sacchi, C. (1997). Albendazole for the treatment of Mansonella perstans filariasis. Transactions of the Royal Sociey of Tropical Medicine and Hygiene, 91,22 1. Maertens, K. & W&y, M. (1975). Effect of mebendazole and levamisole on Onchocerca volvulus and Dipetalonema perstans. Transactions of the Royal Society of Tropical Medicine and Hygiene, 69,359-360. Richard-Lenoble, D., Kombila, M., Burnier, I. & Maganga, M. L. (1985). Filarioses au Gabon: traitement par le mebendazole des tilarioses g M. perstans et Loa loa. Bulletin de la Sock% de Pathologie Exotique, 78, 485-49 1. . Schulz-Key, H., Albrecht, W., Heuschkel, C., Wolf, H. & Awissi, D. (1990). Unterschiedliche Wirkung von Mectizana auf Mikrofilarien von Onchocerca volvt&s und Mansonella perstans in Patienten. Mitteilungen-Osterreichischen Gesellschaft fiir Tropenmedizin und Parasitologic, 12, 179-184. Van den Enden, E., Van Gompel, A., Vervoort, T., Van der Stuyft, I’. & Van den Ende, J. (1992). Mansonella perstans filariasis: failure of albendazole treatment. Annales de la &xi& Beige de M&de&e Tropicale, 72,215-218. Van den Enden, E., Van Gompel, A., Van der Smyft, I’., Vervoort, T. & Van den Ende, J. (1993). Treatment failure of a single high dose of ivermectin for Mansonella perstans filariasis. Transactions of the Royal Society of Tropical Medicine and Hygiene, 87, 90. Van Hoegaerden, M., Ivanoff, B., Flocard, F., Salle, A. & Chabaud, B. (1987). The use of mebendazole in the treatment of filariases due to Loa loa and Mansonella perstans. Annals of Tropical Medicine and Parasitology, 81, 275-282. Wahlgren, M. & Frolov, I. (1983). Treatment of Dipetalonema perstans infections with mebendazole. Transactions of the Royal Society of Tropical Medicine and Hygiene, 77,422-423. [Correspondence.]
Received 8 November accepted for publication
2001; revised 27 November 30 November 2001
2001;
Announcement ROYAL
SOCIETY OF TROPICAL MEDICINE AND Robert Cochrane Fund for Leprosy
HYGIENE
The fund, in memory of the great leprologist Robert Cochrane, is administered by the Royal Society of Tropical Medicine and Hygiene. It is used to finance up to three travel fellowships each year to a maximum value of El000 each. The fund will support travel for l Leprosy workers who need to obtain practical training in field work or in research l Experienced leprologists to provide practical clinical training in a developing country There is no restriction on the country of origin or destination providing the above requirements
are met.
Applications must be made at least six months ahead of the proposed trip, sponsored by a suitable representative of the applicant’s employer or study centre and agreed by the host organization. A short report on the travel/study should be submitted, within one month of the recipient’s return. Application forms are available from the Administrator, Royal Society of Tropical Medicine and Hygiene, Manson House, 26 Portland Place, London, WlB lEY, UK; fax +44 (0)20 7436 1389, e-mail [email protected]
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 Onchocerca volvulus, the effects on M. perstans were recorded and related to the cumulative dose received. The World Health Organization’s African 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, Mansonella perstans may cause fever, itching, cutaneous swellings, 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); mebendazole, 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,~~~~;RICHARDLENOBLE 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 etal., 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 once, then 2 doses of 800 pg/kg), (c) 150 pg / 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 reexamined similarly, but the volume of the blood films *Author for correspondence: [email protected]
fax +‘237 231564, e-mail
J. GARDON ETAL.
326
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 microfilaraemic 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 reduced 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 number of larvae reaching the infective stage is poorly documented (HOPKINS & NICHOLAS, 1952), the African 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. & RichardLenoble, D. (1998). Decrease in Mansonella perstuns microfilaraemia after albendazole treatment. Transactions of the Royal Society of Tropical Medicine and Hygiene, 92,459. Holmes, G. K. T., Gelfand, M., Boyt, W. & Mackenzie, I’.
(1969). A study to investigate the pathogenicity of a parasite resembling Acanthocheilonema perstans. Transactions of the Royal Society of Tropical Medicine and Hygiene, 63,479-484. Hopkins, C. A. & Nicholas, W. L. (1952). Culicoides austeni, the vector of Acanthocheilonema perstans. Annals of Tropical Medicine and Parasitology, 46,276-283. Janssens, I’. G. (1964). D. perstans est-elle pathogene pour l’homme? Annales de la Socie’te’Belge de Midecine Tropicale, 44,989-998. Lipani, F., Caramello, I’., Biglino, A. & Sacchi, C. (1997). Albendazole for the treatment of Mansonella perstans filariasis. Transactions of the Royal Sociey of Tropical Medicine and Hygiene, 91,22 1. Maertens, K. & W&y, M. (1975). Effect of mebendazole and levamisole on Onchocerca volvulus and Dipetalonema perstans. Transactions of the Royal Society of Tropical Medicine and Hygiene, 69,359-360. Richard-Lenoble, D., Kombila, M., Burnier, I. & Maganga, M. L. (1985). Filarioses au Gabon: traitement par le mebendazole des tilarioses g M. perstans et Loa loa. Bulletin de la Sock% de Pathologie Exotique, 78, 485-49 1. . Schulz-Key, H., Albrecht, W., Heuschkel, C., Wolf, H. & Awissi, D. (1990). Unterschiedliche Wirkung von Mectizana auf Mikrofilarien von Onchocerca volvt&s und Mansonella perstans in Patienten. Mitteilungen-Osterreichischen Gesellschaft fiir Tropenmedizin und Parasitologic, 12, 179-184. Van den Enden, E., Van Gompel, A., Vervoort, T., Van der Stuyft, I’. & Van den Ende, J. (1992). Mansonella perstans filariasis: failure of albendazole treatment. Annales de la &xi& Beige de M&de&e Tropicale, 72,215-218. Van den Enden, E., Van Gompel, A., Van der Smyft, I’., Vervoort, T. & Van den Ende, J. (1993). Treatment failure of a single high dose of ivermectin for Mansonella perstans filariasis. Transactions of the Royal Society of Tropical Medicine and Hygiene, 87, 90. Van Hoegaerden, M., Ivanoff, B., Flocard, F., Salle, A. & Chabaud, B. (1987). The use of mebendazole in the treatment of filariases due to Loa loa and Mansonella perstans. Annals of Tropical Medicine and Parasitology, 81, 275-282. Wahlgren, M. & Frolov, I. (1983). Treatment of Dipetalonema perstans infections with mebendazole. Transactions of the Royal Society of Tropical Medicine and Hygiene, 77,422-423. [Correspondence.]
Received 8 November accepted for publication
2001; revised 27 November 30 November 2001
2001;
Announcement ROYAL
SOCIETY OF TROPICAL MEDICINE AND Robert Cochrane Fund for Leprosy
HYGIENE
The fund, in memory of the great leprologist Robert Cochrane, is administered by the Royal Society of Tropical Medicine and Hygiene. It is used to finance up to three travel fellowships each year to a maximum value of El000 each. The fund will support travel for l Leprosy workers who need to obtain practical training in field work or in research l Experienced leprologists to provide practical clinical training in a developing country There is no restriction on the country of origin or destination providing the above requirements
are met.
Applications must be made at least six months ahead of the proposed trip, sponsored by a suitable representative of the applicant’s employer or study centre and agreed by the host organization. A short report on the travel/study should be submitted, within one month of the recipient’s return. Application forms are available from the Administrator, Royal Society of Tropical Medicine and Hygiene, Manson House, 26 Portland Place, London, WlB lEY, UK; fax +44 (0)20 7436 1389, e-mail [email protected]