A Randomized, Double-Blind Clinical Trial of a 3-Week Course of Doxycycline plus Albendazole and Ivermectin for the Treatment of Wuchereria bancrofti Infection

• Published in: Clinical infectious diseases Vol. 42; no. 8; pp. 1081 - 1089
• Main Authors: Turner, Joseph D., Mand, Sabine, Debrah, Alexander Yaw, Muehlfeld, Johannes, Pfarr, Kenneth, McGarry, Helen F., Adjei, Ohene, Taylor, Mark J., Hoerauf, Achim
• Format: Journal Article
• Language: English
• Published: United States The University of Chicago Press 15-04-2006; University of Chicago Press; Oxford University Press
• Subjects: Adolescent; Adult; Adults; Adverse drug reactions; Aged; Albendazole - therapeutic use; Albs; Animals; Anthelmintics - therapeutic use; Antibiotics; Articles and Commentaries; Bacteria; Blood; Blood plasma; Clinical trials; Cytokines; Disease transmission; Double-Blind Method; Doxycycline - therapeutic use; Drug therapy; Drug Therapy, Combination; Filariasis; Filariasis - drug therapy; Ghana; Humans; Infectious diseases; Ivermectin - therapeutic use; Microfilariae; Middle Aged; Patient Dropouts; Placebos; Plasma; Sample size; Wolbachia; Worms; Wuchereria bancrofti; Ghana
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1086/501351

Background. Eight- and 6-week courses of doxycycline are superior to standard treatment of bancroftian filariasis. Standard treatment (albendazole plus ivermectin) is associated with adverse reactions. We assessed whether a shorter (i.e, 3-week) course of doxycycline with standard treatment would show superior efficacy to standard treatment alone and reduce the incidence of adverse reactions. Methods. A total of 44 adults from Ghana were recruited in January 2003: 20 received doxycycline (200 mg/day) for 3 weeks, and 24 received matching placebo. Participants received albendazole (400 mg) and ivermectin (150 µg/kg) at month 4, and adverse reactions were assessed 48 h later. Treatment efficacy was evaluated at months 4, 12, and 24. Results. The microfilariae level was significantly reduced after receipt of doxycycline treatment at months 4 (P = .017), 12 (P = .001), and 24 (P = .005). The microfilariae level was only significantly reduced at month 12 in the placebo group (P = .041). At all follow-up points, the microfilariae level was significantly lower in the doxycycline group. Adverse reactions to standard antifilarial treatment were similar in frequency between the doxycycline group (in 7 of 11 subjects) and the placebo group (in 13 of 17 subjects). Moderate reactions only occurred in the placebo group (in 3 of 17 subjects). Severity of adverse reaction was associated with microfilaremia (P = .037), Wolbachia bacteria in plasma (P = .048), and proinflammatory cytokines in plasma (P = .019). Adult parasite viability was not significantly different between doxycycline and placebo groups at months 12 or 24. Conclusions. Treatment with doxycycline for 3 weeks is more effective in inducing a long-term amicrofilaremia than is standard treatment alone, but it is ineffective at inducing curative effects. Inflammatory reactions to antifilarial treatment are associated with levels of microfilariae and Wolbachia endosymbionts released into plasma.