title: Multinormal in vitro distribution model suitable for the distribution of Plasmodium falciparum chemosusceptibility to doxycycline.
abstract: The distribution and range of 50% inhibitory concentrations (IC(50)s) of doxycycline were determined for 747 isolates obtained between 1997 and 2006 from patients living in Senegal, Republic of the Congo, and Gabon and patients hospitalized in France for imported malaria. The statistical analysis was designed to answer the specific question of whether Plasmodium falciparum has different phenotypes of susceptibility to doxycycline. A triple normal distribution was fitted to the data using a Bayesian mixture modeling approach. The IC(50) geometric mean ranged from 6.2 microM to 11.1 microM according to the geographical origin, with a mean of 9.3 microM for all 747 parasites. The values for all 747 isolates were classified into three components: component A, with an IC(50) mean of 4.9 microM (+/-2.1 microM [standard deviation]); component B, with an IC(50) mean of 7.7 microM (+/-1.2 microM); and component C, with an IC(50) mean of 17.9 microM (+/-1.4 microM). According to the origin of the P. falciparum isolates, the triple normal distribution was found in each subgroup. However, the proportion of isolates predicted to belong to component B was most important in isolates from Gabon and Congo and in isolates imported from Africa (from 46 to 56%). In Senegal, 55% of the P. falciparum isolates were predicted to be classified as component C. The cutoff of reduced susceptibility to doxycycline in vitro was estimated to be 35 microM.
authors.affiliation: Unité de Recherche en Biologie et Epidémiologie Parasitaires, Institut de Médecine Tropicale du Service de Santé des Armées, Le Pharo, Marseille, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Briolant
authors.forename: Meili
authors.initials: M
authors.lastname: Baragatti
authors.forename: Philippe
authors.initials: P
authors.lastname: Parola
authors.forename: Fabrice
authors.initials: F
authors.lastname: Simon
authors.forename: Adama
authors.initials: A
authors.lastname: Tall
authors.forename: Cheikh
authors.initials: C
authors.lastname: Sokhna
authors.forename: Philippe
authors.initials: P
authors.lastname: Hovette
authors.forename: Modeste Mabika
authors.initials: MM
authors.lastname: Mamfoumbi
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Koeck
authors.forename: Jean
authors.initials: J
authors.lastname: Delmont
authors.forename: André
authors.initials: A
authors.lastname: Spiegel
authors.forename: Jacky
authors.initials: J
authors.lastname: Castello
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Gardair
authors.forename: Jean Francois
authors.initials: JF
authors.lastname: Trape
authors.forename: Maryvonne
authors.initials: M
authors.lastname: Kombila
authors.forename: Philippe
authors.initials: P
authors.lastname: Minodier
authors.forename: Thierry
authors.initials: T
authors.lastname: Fusai
authors.forename: Christophe
authors.initials: C
authors.lastname: Rogier
authors.forename: Bruno
authors.initials: B
authors.lastname: Pradines
mesh_terms: D000349:Africa / Q000453:epidemiology; D000465:Algorithms; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000962:Antimalarials; D001499:Bayes Theorem; D004318:Doxycycline / Q000494:pharmacology*; D004351:Drug Resistance / Q000187:drug effects; D006801:Humans; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000469:parasitology; D015233:Models, Statistical; D010963:Plasmodium falciparum / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D000962:Antimalarials; D004318:Doxycycline