A randomized, double-blind clinical trial of a 3-week course of doxycycline plus albendazole and ivermectin for the treatment of Wuchereria bancrofti infection.
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 microg/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.
Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
Joseph D
JD
Turner
Sabine
S
Mand
Alexander Yaw
AY
Debrah
Johannes
J
Muehlfeld
Kenneth
K
Pfarr
Helen F
HF
McGarry
Ohene
O
Adjei
Mark J
MJ
Taylor
Achim
A
Hoerauf
D000293:Adolescent; D000328:Adult; D000368:Aged; D015766:Albendazole / Q000627:therapeutic use*; D000818:Animals; D000871:Anthelmintics / Q000627:therapeutic use; D004311:Double-Blind Method; D004318:Doxycycline / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005368:Filariasis / Q000188:drug therapy*; D005869:Ghana; D006801:Humans; D007559:Ivermectin / Q000627:therapeutic use*; D008875:Middle Aged; D010352:Patient Dropouts; D014958:Wuchereria bancrofti
D000871:Anthelmintics; D007559:Ivermectin; D015766:Albendazole; D004318:Doxycycline