title: Retarded Onchocerca volvulus L1 to L3 larval development in the Simulium damnosum vector after anti-wolbachial treatment of the human host.
abstract: BACKGROUND
  The human parasite Onchocerca volvulus harbours Wolbachia endosymbionts essential for worm embryogenesis, larval development and adult survival. In this study, the development of Wolbachia-depleted microfilariae (first stage larvae) to infective third stage larvae (L3) in the insect vector Simulium damnosum was analysed.
  
  
  METHODS
  Infected volunteers in Cameroon were randomly and blindly allocated into doxycycline (200 mg/day for 6 weeks) or placebo treatment groups. After treatment, blackflies were allowed to take a blood meal on the volunteers, captured and dissected for larval counting and DNA extraction for quantitative real-time PCR analysis.
  
  
  RESULTS
  PCR results showed a clear reduction in Wolbachia DNA after doxycycline treatment in microfilariae from human skin biopsies with > 50% reduction at one month post-treatment, eventually reaching a reduction of > 80%. Larval stages recovered from the insect vector had similar levels of reduction of endosymbiotic bacteria. Larval recoveries were analysed longitudinally after treatment to follow the kinetics of larval development. Beginning at three months post-treatment, significantly fewer L3 were seen in the blackflies that had fed on doxycycline treated volunteers. Concomitant with this, the proportion of second stage larvae (L2) was significantly increased in this group.
  
  
  CONCLUSIONS
  Doxycycline treatment and the resulting decline of Wolbachia endobacteria from the microfilaria resulted in retarded development of larvae in the insect vector. Thus, anti-wolbachial treatment could have an additive effect for interrupting transmission by reducing the number of L3 that can be transmitted by blackflies.
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Sigmund-Freud-Str, 25, D-53105 Bonn, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Albers
authors.forename: Mathias Eyong
authors.initials: ME
authors.lastname: Esum
authors.forename: Nicholas
authors.initials: N
authors.lastname: Tendongfor
authors.forename: Peter
authors.initials: P
authors.lastname: Enyong
authors.forename: Ute
authors.initials: U
authors.lastname: Klarmann
authors.forename: Samuel
authors.initials: S
authors.lastname: Wanji
authors.forename: Achim
authors.initials: A
authors.lastname: Hoerauf
authors.forename: Kenneth
authors.initials: K
authors.lastname: Pfarr
mesh_terms: D000328:Adult; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D002163:Cameroon; D004269:DNA, Bacterial / Q000235:genetics; D004318:Doxycycline / Q000008:administration & dosage*; D006805:Human Experimentation; D006801:Humans; D007814:Larva / Q000254:growth & development / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D017181:Onchocerca volvulus / Q000254:growth & development* / Q000382:microbiology; D016133:Polymerase Chain Reaction; D012843:Simuliidae / Q000469:parasitology*; D016896:Treatment Outcome; D020577:Wolbachia / Q000187:drug effects* / Q000302:isolation & purification; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D004318:Doxycycline