title: A new model of progressive visceral leishmaniasis in hamsters by natural transmission via bites of vector sand flies.
abstract: BACKGROUND
  Visceral leishmaniasis (VL) is transmitted by sand flies. Protection of needle-challenged vaccinated mice was abrogated in vector-initiated cutaneous leishmaniasis, highlighting the importance of developing natural transmission models for VL.
  
  
  METHODS
  We used Lutzomyia longipalpis to transmit Leishmania infantum or Leishmania donovani to hamsters. Vector-initiated infections were monitored and compared with intracardiac infections. Body weights were recorded weekly. Organ parasite loads and parasite pick-up by flies were assessed in sick hamsters.
  
  
  RESULTS
  Vector-transmitted L. infantum and L. donovani caused ≥5-fold increase in spleen weight compared with uninfected organs and had geometric mean parasite loads (GMPL) comparable to intracardiac inoculation of 10(7)-10(8) parasites, although vector-initiated disease progression was slower and weight loss was greater. Only vector-initiated L. infantum infections caused cutaneous lesions at transmission and distal sites. Importantly, 45.6%, 50.0%, and 33.3% of sand flies feeding on ear, mouth, and testicular lesions, respectively, were parasite-positive. Successful transmission was associated with a high mean percent of metacyclics (66%-82%) rather than total GMPL (2.0 × 10(4)-8.0 × 10(4)) per midgut.
  
  
  CONCLUSIONS
  This model provides an improved platform to study initial immune events at the bite site, parasite tropism, and pathogenesis and to test drugs and vaccines against naturally acquired VL.
authors.affiliation: Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
authors.forename: Hamide
authors.initials: H
authors.lastname: Aslan
authors.forename: Ranadhir
authors.initials: R
authors.lastname: Dey
authors.forename: Claudio
authors.initials: C
authors.lastname: Meneses
authors.forename: Philip
authors.initials: P
authors.lastname: Castrovinci
authors.forename: Selma Maria Bezerra
authors.initials: SM
authors.lastname: Jeronimo
authors.forename: Gætano
authors.initials: G
authors.lastname: Oliva
authors.forename: Laurent
authors.initials: L
authors.lastname: Fischer
authors.forename: Robert C
authors.initials: RC
authors.lastname: Duncan
authors.forename: Hira L
authors.initials: HL
authors.lastname: Nakhasi
authors.forename: Jesus G
authors.initials: JG
authors.lastname: Valenzuela
authors.forename: Shaden
authors.initials: S
authors.lastname: Kamhawi
mesh_terms: D000818:Animals; D001835:Body Weight; D006224:Cricetinae; D004195:Disease Models, Animal; D018450:Disease Progression; D007299:Insect Bites and Stings / Q000469:parasitology*; D007303:Insect Vectors / Q000469:parasitology*; D007893:Leishmania donovani / Q000472:pathogenicity; D018314:Leishmania infantum / Q000472:pathogenicity; D016773:Leishmaniasis, Cutaneous / Q000469:parasitology / Q000473:pathology / Q000635:transmission; D007898:Leishmaniasis, Visceral / Q000469:parasitology / Q000473:pathology* / Q000635:transmission; D008297:Male; D009929:Organ Size; D059208:Parasite Load; D011576:Psychodidae / Q000469:parasitology*; D013154:Spleen / Q000469:parasitology / Q000473:pathology