[Show abstract][Hide abstract] ABSTRACT: Annual mass treatment with albendazole and ivermectin is the mainstay of current strategies to interrupt transmission of Wuchereria bancrofti in Africa. More-effective microfilarial suppression could potentially reduce the time necessary to interrupt transmission, easing the economic burden of mass treatment programs in countries with limited resources.
To determine the effect of increased dose and frequency of albendazole-ivermectin treatment on microfilarial clearance, 51 W. bancrofti microfilaremic residents of an area of W. bancrofti endemicity in Mali were randomized to receive 2 doses of annual, standard-dose albendazole-ivermectin therapy (400 mg and 150 μg/kg; n = 26) or 4 doses of twice-yearly, increased-dose albendazole-ivermectin therapy (800 mg and 400 μg/kg; n = 25).
Although microfilarial levels decreased significantly after therapy in both groups, levels were significantly lower in the high-dose, twice-yearly group at 12, 18, and 24 months. Furthermore, there was complete clearance of detectable microfilariae at 12 months in the 19 patients in the twice-yearly therapy group with data available at 12 months, compared with 9 of 21 patients in the annual therapy group (P < .001, by Fisher's exact test). This difference between the 2 groups was sustained at 18 and 24 months, with no detectable microfilariae in the patients receiving twice-yearly treatment. Worm nests detectable by ultrasonography and W. bancrofti circulating antigen levels, as measured by enzyme-linked immunosorbent assay, were decreased to the same degree in both groups at 24 months, compared with baseline.
These findings suggest that increasing the dosage and frequency of albendazole-ivermectin treatment enhances suppression of microfilariae but that this effect may not be attributable to improved adulticidal activity.
[Show abstract][Hide abstract] ABSTRACT: Mansonella perstans infection is common in areas of Africa where Wuchereria bancrofti, a causative agent of lymphatic filariasis, is endemic. M. perstans is refractory to standard antifilarial therapies. The recent discovery of bacterial endosymbionts (e.g., wolbachia) in most filarial species, including M. perstans, provides new therapeutic options for reducing microfilaremia.
In an open-label, randomized trial, we recruited subjects with M. perstans microfilaremia, with or without concomitant W. bancrofti infection, from four villages in Mali and randomly assigned them to receive doxycycline, at a dose of 200 mg daily for 6 weeks (106 subjects), or no treatment (110). At 6 months, subjects who were coinfected with W. bancrofti underwent a second random assignment, to treatment with a single dose of albendazole (400 mg) and ivermectin (150 microg per kilogram of body weight) or no treatment. Subjects were monitored daily during the first 6-week study period for adverse events. M. perstans and W. bancrofti microfilarial levels were assessed at 6, 12, and 36 months.
At 12 months, 67 of 69 subjects who had received treatment with doxycycline only (97%) had no detectable M. perstans microfilariae per 60 microl of blood, as compared with 10 of 63 subjects who had received no treatment (16%) (relative risk, 6.18; 95% confidence interval, 3.63 to 11.89; P<0.001). At 36 months, M. perstans microfilaremia remained suppressed in 48 of 64 subjects who had received treatment with doxycycline only (75%), a finding that was consistent with a macrofilaricidal effect of doxycycline. Vomiting was more frequent in the doxycycline-treated group than in the untreated group (17% vs. 4%).
These results are consistent with previous findings that M. perstans harbors the intracellular endosymbiont, wolbachia, and suggest that doxycycline is an effective therapy for M. perstans infection. (ClinicalTrials.gov number, NCT00340691.)
New England Journal of Medicine 10/2009; 361(15):1448-58. DOI:10.1056/NEJMoa0900863 · 55.87 Impact Factor