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Doxycycline Leads to Sterility and Enhanced Killing of Female Onchocerca volvulus Worms in an Area With Persistent Microfilaridermia After Repeated Ivermectin Treatment: A Randomized, Placebo-Controlled, Double-Blind Trial
- Source :
- Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
- Publication Year :
- 2014
-
Abstract
- Sub-optimal responses to ivermectin (IVM) have emerged. Targeting the Onchocerca volvulus Wolbachia endosymbionts with doxycycline is effective in clearing microfilariae in onchocerciasis patients with persistent microfilaridermia and in enhanced killing of adult worms after repeated standard IVM treatment.<br />Background. Ivermectin (IVM) has been the drug of choice for the treatment of onchocerciasis. However, there have been reports of persistent microfilaridermia in individuals from an endemic area in Ghana after many rounds of IVM, raising concerns of suboptimal response or even the emergence of drug resistance. Because it is considered risky to continue relying only on IVM to combat this phenomenon, we assessed the effect of targeting the Onchocerca volvulus Wolbachia endosymbionts with doxycycline for these individuals with suboptimal response. Methods. One hundred sixty-seven patients, most of them with multiple rounds of IVM, were recruited in areas with IVM suboptimal response and treated with 100 mg/day doxycycline for 6 weeks. Three and 12 months after doxycycline treatment, patients took part in standard IVM treatment. Results. At 20 months after treatment, 80% of living female worms from the placebo group were Wolbachia positive, whereas only 5.1% in the doxycycline-treated group contained bacteria. Consistent with interruption of embryogenesis, none of the nodules removed from doxycycline-treated patients contained microfilariae, and 97% of those patients were without microfilaridermia, in contrast to placebo patients who remained at pretreatment levels (P < .001). Moreover, a significantly enhanced number of dead worms were observed after doxycycline. Conclusions. Targeting the Wolbachia in O. volvulus is effective in clearing microfilariae in the skin of onchocerciasis patients with persistent microfilaridermia and in enhanced killing of adult worms after repeated standard IVM treatment. Strategies can now be developed that include doxycycline to control onchocerciasis in areas where infections persist despite the frequent use of IVM. Clinical Trials Registration. ISRCTN 66649839.
- Subjects :
- Microbiology (medical)
Adult
Male
medicine.medical_specialty
Adolescent
Helminthiasis
Placebo
Onchocerciasis
Microfilaria
Ghana
Placebos
Young Adult
Ivermectin
Double-Blind Method
Internal medicine
suboptimal response
parasitic diseases
medicine
Animals
Humans
Articles and Commentaries
Doxycycline
biology
integumentary system
doxycycline
business.industry
urogenital system
biochemical phenomena, metabolism, and nutrition
Middle Aged
medicine.disease
biology.organism_classification
Onchocerca volvulus
Anti-Bacterial Agents
Infectious Diseases
Filaricides
Treatment Outcome
Immunology
embryonic structures
Wolbachia
Female
business
medicine.drug
Subjects
Details
- ISSN :
- 15376591
- Volume :
- 61
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
- Accession number :
- edsair.doi.dedup.....84a3f3a0bf56984cee941dcacc65a00c