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.)

• Authors: Yaya I Coulibaly, Benoit Dembele, Abdallah A Diallo, Ettie M Lipner, Salif S Doumbia, Siaka Y Coulibaly, Siaka Konate, Dapa A Diallo, Daniel Yalcouye, Joseph Kubofcik, Ogobara K Doumbo, Abdel K Traore, Adama D Keita, Michael P Fay, Sekou F Traore, Thomas B Nutman, Amy D Klion
• Journal: The New England journal of medicine (N Engl J Med) Vol. 361 Issue 15 Pg. 1448-58 (Oct 08 2009) ISSN: 1533-4406 [Electronic] United States
• PMID: 19812401 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Intramural)
• Copyright: 2009 Massachusetts Medical Society

Chemical References

• Anti-Bacterial Agents
• Filaricides
• Ivermectin
• Albendazole
• Doxycycline

Topics

• Adolescent
• Adult
• Aged
• Albendazole (therapeutic use)
• Animals
• Anti-Bacterial Agents (administration & dosage, adverse effects, therapeutic use)
• Doxycycline (administration & dosage, adverse effects, therapeutic use)
• Drug Therapy, Combination
• Elephantiasis, Filarial (complications, drug therapy)
• Female
• Filaricides (therapeutic use)
• Humans
• Ivermectin (therapeutic use)
• Male
• Mansonella (isolation & purification)
• Mansonelliasis (complications, drug therapy)
• Middle Aged
• Rickettsiaceae Infections (complications, drug therapy)
• Symbiosis
• Treatment Outcome
• Wolbachia
• Wuchereria bancrofti (isolation & purification)
• Young Adult