A randomized trial of doxycycline for Mansonella perstans infection.
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.)
Coulibaly
Yaya I
YI
Faculty of Medicine, Pharmacy and Odontostomatology, University of Bamako, Bamako, Mali.
Dembele
Benoit
B
Diallo
Abdallah A
AA
Lipner
Ettie M
EM
Doumbia
Salif S
SS
Coulibaly
Siaka Y
SY
Konate
Siaka
S
Diallo
Dapa A
DA
Yalcouye
Daniel
D
Kubofcik
Joseph
J
Doumbo
Ogobara K
OK
Traore
Abdel K
AK
Keita
Adama D
AD
Fay
Michael P
MP
Traore
Sekou F
SF
Nutman
Thomas B
TB
Klion
Amy D
AD
D000293:Adolescent; D000328:Adult; D000368:Aged; D015766:Albendazole / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004318:Doxycycline / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004605:Elephantiasis, Filarial / Q000150:complications / Q000188:drug therapy; D005260:Female; D005369:Filaricides / Q000627:therapeutic use*; D006801:Humans; D007559:Ivermectin / Q000627:therapeutic use; D008297:Male; D008366:Mansonella / Q000302:isolation & purification; D008368:Mansonelliasis / Q000150:complications / Q000188:drug therapy*; D008875:Middle Aged; D012288:Rickettsiaceae Infections / Q000150:complications / Q000188:drug therapy*; D013559:Symbiosis; D016896:Treatment Outcome; D020577:Wolbachia; D014958:Wuchereria bancrofti / Q000302:isolation & purification; D055815:Young Adult
D000900:Anti-Bacterial Agents; D005369:Filaricides; D007559:Ivermectin; D015766:Albendazole; D004318:Doxycycline