A randomized trial of doxycycline for Mansonella perstans infection

Abstract

Background: 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.

Methods: 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.

Results: 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%).

Conclusions: 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.)

Figure 1. Screening and Random Assignment

Wb+Mp+ refers to the group that was positive for both Mansonella perstans (Mp) and Wuchereria bancrofti (Wb); Wb−Mp+ refers to the group that was negative for W. bancrofti and positive for M. perstans. Although it was anticipated that 40 subjects would be assigned to each of the subgroups of persons who were negative for W. bancrofti and positive for M. perstans, the initial assignment was made on the basis of the results of an immunochromatographic card test (ICT). Five subjects who had been classified as positive for W. bancrofti on the basis of the ICT were found to be negative for W. bancrofti on the basis of an enzyme-linked immunosorbent assay before the initiation of doxycycline therapy and were reassigned to the corresponding subgroup within the group that was negative for W. bancrofti and positive for M. perstans.

Figure 2. Efficacy of Doxycycline in Reducing Mansonella perstans Microfilarial Levels at 6, 12, and 36 Months after Treatment

Levels of M. perstans are shown as percents of baseline levels for the groups that received no treatment, doxycycline only, a single dose of albendazole–ivermectin at 6 months, and doxycycline plus a single dose of albendazole–ivermectin at 6 months. Each circle represents the value for an individual patient. The horizontal lines represent the median values for each group at each time point. All groups received a single dose of albendazole–ivermectin between 12 and 36 months. ND denotes not detectable.

Figure 3. Efficacy of Doxycycline in Reducing Wuchereria bancrofti Microfilarial Levels at 6, 12, and 36 Months after Treatment

Levels of W. bancrofti are shown as percents of baseline levels for groups that received no treatment, doxycycline only, a single dose of albendazole–ivermectin at 6 months, and doxycycline plus a single dose of albendazole– ivermectin at 6 months. Each circle represents the value for an individual patient. The horizontal lines represent the median values for each group at each time point. All groups received a single dose of albendazole–ivermectin between 12 and 36 months. ND denotes not detectable.