title: 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.
abstract: 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.
  
  
  BACKGROUND
  ISRCTN 66649839.
authors.affiliation: Faculty of Allied Health Sciences, Kwame Nkrumah University of Science and Technology Kumasi Centre for Collaborative Research in Tropical Medicine, Ghana.
authors.forename: Alexander Yaw
authors.initials: AY
authors.lastname: Debrah
authors.affiliation: Institutes for Medical Microbiology, Immunology and Parasitology.
authors.forename: Sabine
authors.initials: S
authors.lastname: Specht
authors.affiliation: Institutes for Medical Microbiology, Immunology and Parasitology Medical Biometry, Informatics and Epidemiology, University of Bonn, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Klarmann-Schulz
authors.affiliation: Kumasi Centre for Collaborative Research in Tropical Medicine, Ghana.
authors.forename: Linda
authors.initials: L
authors.lastname: Batsa
authors.affiliation: Institutes for Medical Microbiology, Immunology and Parasitology.
authors.forename: Sabine
authors.initials: S
authors.lastname: Mand
authors.affiliation: Kumasi Centre for Collaborative Research in Tropical Medicine, Ghana.
authors.forename: Yeboah
authors.initials: Y
authors.lastname: Marfo-Debrekyei
authors.affiliation: Medical Biometry, Informatics and Epidemiology, University of Bonn, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Fimmers
authors.affiliation: Institutes for Medical Microbiology, Immunology and Parasitology.
authors.forename: Bettina
authors.initials: B
authors.lastname: Dubben
authors.affiliation: Kumasi Centre for Collaborative Research in Tropical Medicine, Ghana.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kwarteng
authors.affiliation: Council for Scientific and Industrial Research, Water Research Institute.
authors.forename: Mike
authors.initials: M
authors.lastname: Osei-Atweneboana
authors.affiliation: Noguchi Memorial Institute for Medical Research, University of Ghana, Accra.
authors.forename: Daniel
authors.initials: D
authors.lastname: Boakye
authors.affiliation: Institutes for Medical Microbiology, Immunology and Parasitology Medical Biometry, Informatics and Epidemiology, University of Bonn, Germany.
authors.forename: Arcangelo
authors.initials: A
authors.lastname: Ricchiuto
authors.affiliation: Ahrensburger Stieg 17, Hamburg, Germany.
authors.forename: Marcelle
authors.initials: M
authors.lastname: Büttner
authors.affiliation: School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
authors.forename: Ohene
authors.initials: O
authors.lastname: Adjei
authors.affiliation: Centre for Neglected Tropical Diseases, Liverpool School of Tropical Medicine, United Kingdom.
authors.forename: Charles D
authors.initials: CD
authors.lastname: Mackenzie
authors.affiliation: Institutes for Medical Microbiology, Immunology and Parasitology.
authors.forename: Achim
authors.initials: A
authors.lastname: Hoerauf
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D004311:Double-Blind Method; D004318:Doxycycline / Q000008:administration & dosage*; D005260:Female; D005369:Filaricides / Q000008:administration & dosage; D005869:Ghana; D006801:Humans; D007559:Ivermectin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D017181:Onchocerca volvulus / Q000187:drug effects* / Q000382:microbiology / Q000502:physiology*; D009855:Onchocerciasis / Q000188:drug therapy*; D010919:Placebos / Q000008:administration & dosage; D016896:Treatment Outcome; D020577:Wolbachia / Q000187:drug effects*; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D005369:Filaricides; D010919:Placebos; D007559:Ivermectin; D004318:Doxycycline
keywords: Onchocerca volvulus; Wolbachia; doxycycline; ivermectin; suboptimal response