title: Therapeutic efficacy and macrofilaricidal activity of doxycycline for the treatment of river blindness.
abstract: BACKGROUND
  Onchocerca volvulus and lymphatic filariae, causing river blindness and elephantiasis, depend on endosymbiotic Wolbachia bacteria for growth, development, fertility, and survival. Clinical trials have shown that doxycycline treatment eliminates Wolbachia, causing long-term sterilization of adult female filariae and effecting potent macrofilaricidal activity. The continual reinfection by drug-naive worms that occurs in these trial settings dilutes observable anti-Wolbachia and antifilarial effects, making it difficult to estimate therapeutic efficacy and compare different doxycycline regimens, evaluated at different times after treatment.
  
  
  METHODS
  A meta-analytical modeling framework is developed to link all usable data collected from clinical trials measuring the Wolbachia status and viability of individual female adult worms collected at various times after treatment with 4, 5, or 6 weeks of daily 100 or 200 mg oral doxycycline. The framework is used to estimate efficacy parameters that are not directly measurable as trial outcomes.
  
  
  RESULTS
  The estimated efficacy of doxycycline (the maximum proportional reduction in the percentage of adult female O. volvulus positive for Wolbachia) is 91%-94% on average, irrespective of the treatment regimen. Efficacy is >95% in the majority of trial participants. The life span of Wolbachia-depleted worms is reduced by 70%-80%, from approximately 10 years to 2-3 years.
  
  
  CONCLUSIONS
  The efficacy parameters are pertinent to the prospects of using doxycycline on a "test and treat" basis for onchocerciasis control and confirm doxycycline as a potent macrofilaricidal therapy. The modeling approach is more generally relevant to the design and evaluation of clinical trials for antifilarial drugs conducted in endemic settings.
authors.affiliation: Department of Infectious Disease Epidemiology, Imperial College London, United Kingdom.
authors.forename: Martin
authors.initials: M
authors.lastname: Walker
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Specht
authors.affiliation: Department of Infectious Disease Epidemiology, Imperial College London, United Kingdom.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Churcher
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Hoerauf
authors.affiliation: Department of Parasitology, Liverpool School of Tropical Medicine, United Kingdom.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Taylor
authors.affiliation: Department of Infectious Disease Epidemiology, Imperial College London, United Kingdom.
authors.forename: María-Gloria
authors.initials: MG
authors.lastname: Basáñez
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology* / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004318:Doxycycline / Q000494:pharmacology* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015233:Models, Statistical; D017181:Onchocerca volvulus / Q000382:microbiology*; D015827:Onchocerciasis, Ocular / Q000188:drug therapy*; D016896:Treatment Outcome; D020577:Wolbachia / Q000187:drug effects*
chemical_list: D000871:Anthelmintics; D004318:Doxycycline
keywords: clinical trials; doxycycline; efficacy; macrofilaricide; onchocerciasis