Multinormal in vitro distribution model suitable for the distribution of Plasmodium falciparum chemosusceptibility to doxycycline.
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.
Briolant
Sébastien
S
Unité de Recherche en Biologie et Epidémiologie Parasitaires, Institut de Médecine Tropicale du Service de Santé des Armées, Le Pharo, Marseille, France.
Baragatti
Meili
M
Parola
Philippe
P
Simon
Fabrice
F
Tall
Adama
A
Sokhna
Cheikh
C
Hovette
Philippe
P
Mamfoumbi
Modeste Mabika
MM
Koeck
Jean-Louis
JL
Delmont
Jean
J
Spiegel
André
A
Castello
Jacky
J
Gardair
Jean Pierre
JP
Trape
Jean Francois
JF
Kombila
Maryvonne
M
Minodier
Philippe
P
Fusai
Thierry
T
Rogier
Christophe
C
Pradines
Bruno
B
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*
D000900:Anti-Bacterial Agents; D000962:Antimalarials; D004318:Doxycycline