title: Treatment of visceral leishmaniasis: model-based analyses on the spread of antimony-resistant L. donovani in Bihar, India.
abstract: BACKGROUND
  Pentavalent antimonials have been the mainstay of antileishmanial therapy for decades, but increasing failure rates under antimonial treatment have challenged further use of these drugs in the Indian subcontinent. Experimental evidence has suggested that parasites which are resistant against antimonials have superior survival skills than sensitive ones even in the absence of antimonial treatment.
  
  
  RESULTS
  We use simulation studies based on a mathematical L. donovani transmission model to identify parameters which can explain why treatment failure rates under antimonial treatment increased up to 65% in Bihar between 1980 and 1997. Model analyses suggest that resistance to treatment alone cannot explain the observed treatment failure rates. We explore two hypotheses referring to an increased fitness of antimony-resistant parasites: the additional fitness is (i) disease-related, by causing more clinical cases (higher pathogenicity) or more severe disease (higher virulence), or (ii) is transmission-related, by increasing the transmissibility from sand flies to humans or vice versa.
  
  
  CONCLUSIONS
  Both hypotheses can potentially explain the Bihar observations. However, increased transmissibility as an explanation appears more plausible because it can occur in the background of asymptomatically transmitted infection whereas disease-related factors would most probably be observable. Irrespective of the cause of fitness, parasites with a higher fitness will finally replace sensitive parasites, even if antimonials are replaced by another drug.
authors.affiliation: Department of Medical Biometry, University of Tuebingen, Tuebingen, Germany. anette.stauch@medizin.uni-tuebingen.de
authors.forename: Anette
authors.initials: A
authors.lastname: Stauch
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Duerr
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Dujardin
authors.forename: Manu
authors.initials: M
authors.lastname: Vanaerschot
authors.forename: Shyam
authors.initials: S
authors.lastname: Sundar
authors.forename: Martin
authors.initials: M
authors.lastname: Eichner
mesh_terms: D000818:Animals; D000965:Antimony / Q000008:administration & dosage* / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000008:administration & dosage* / Q000494:pharmacology; D004351:Drug Resistance; D006801:Humans; D007194:India; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000635:transmission; D008962:Models, Theoretical; D011576:Psychodidae; D017211:Treatment Failure
chemical_list: D000981:Antiprotozoal Agents; D000965:Antimony