Longitudinal study assessing the return of chloroquine susceptibility of Plasmodium falciparum in isolates from travellers returning from West and Central Africa, 2000-2011.
BACKGROUND
Chloroquine (CQ) was the main malaria therapy worldwide from the 1940s until the 1990s. Following the emergence of CQ-resistant Plasmodium falciparum, most African countries discontinued the use of CQ, and now promote artemisinin-based combination therapy as the first-line treatment. This change was generally initiated during the last decade in West and Central Africa. The aim of this study is to describe the changes in CQ susceptibility in this African region, using travellers returning from this region as a sentinel system.


METHODS
The study was conducted by the Malaria National Reference Centre, France. The database collated the pfcrtK76T molecular marker for CQ susceptibility and the in vitro response to CQ of parasites from travellers' isolates returning from Senegal, Mali, Ivory Coast or Cameroon. As a proxy of drug pressure, data regarding CQ intake in febrile children were collated for the study period. Logistic regression models were used to detect trends in the proportions of CQ resistant isolates.


RESULTS
A total of 2874 parasite isolates were genotyped between 2000-2011. The prevalence of the pfcrt76T mutant genotype significantly decreased for Senegal (from 78% to 47%), Ivory Coast (from 63% to 37%), Cameroon (from 90% to 59%) and remained stable for Mali. The geometric mean of the 50% inhibitory concentration (IC50) of CQ in vitro susceptibility and the proportion of resistant isolates (defining resistance as an IC50 value > 100 nM) significantly decreased for Senegal (from 86 nM (59%) to 39 nM (25%)), Mali (from 84 nM (50%) to 51 nM (31%)), Ivory Coast (from 75 nM (59%) to 29 nM (16%)) and Cameroon (from 181 nM (75%) to 51 nM (37%)). Both analyses (molecular and in vitro susceptibility) were performed for the 2004-2011 period, after the four countries had officially discontinued CQ and showed an accelerated decline of the resistant isolates for the four countries. Meanwhile, CQ use among children significantly deceased in this region (fixed effects slope = -0.3, p < 10-3).


CONCLUSIONS
An increase in CQ susceptibility following official withdrawal of the drug was observed in travellers returning from West and Central African countries. The same trends were observed for molecular and in vitro analysis between 2004-2011 and they correlated to the decrease of the drug pressure.
Mère et enfant face aux infections tropicales, IRD unité mixte de recherche 216, Université Paris Descartes-Paris V, 4 avenue de l'Observatoire, Paris Cedex 06 75270, France. m.gharbi@yahoo.fr
Myriam
M
Gharbi
Jennifer A
JA
Flegg
Véronique
V
Hubert
Eric
E
Kendjo
Jessica E
JE
Metcalf
Lionel
L
Bertaux
Philippe J
PJ
Guérin
Jacques
J
Le Bras
Ahmed
A
Aboubaca
Patrice
P
Agnamey
Adela
A
Angoulvant
Patricia
P
Barbut
Didier
D
Basset
Ghania
G
Belkadi
Anne Pauline
AP
Bellanger
Dieudonné
D
Bemba
Françoise
F
Benoit-Vica
Antoine
A
Berry
Marie-Laure
ML
Bigel
Julie
J
Bonhomme
Françoise
F
Botterel
Olivier
O
Bouchaud
Marie-Elisabeth
ME
Bougnoux
Patrice
P
Bourée
Nathalie
N
Bourgeois
Catherine
C
Branger
Laurent
L
Bret
Bernadette
B
Buret
Enrique
E
Casalino
Sylviane
S
Chevrier
Frédérique
F
Conquere de Monbrison
Bernadette
B
Cuisenier
Martin
M
Danis
Marie-Laure
ML
Darde
Ludovic
L
De Gentile
Jean-Marie
JM
Delarbre
Pascal
P
Delaunay
Anne
A
Delaval
Guillaume
G
Desoubeaux
Michel
M
Develoux
Jean
J
Dunand
Rémy
R
Durand
Odile
O
Eloy
Nathalie
N
Fauchet
Bernard
B
Faugere
Alber
A
Faye
Odile
O
Fenneteau
Pierre
P
Flori
Madeleine
M
Fontrouge
Chantal
C
Garabedian
Françoise
F
Gayandrieu
Nadine
N
Godineau
Pascal
P
Houzé
Sandrine
S
Houzé
Jean-Pierre
JP
Hurst
Houria
H
Ichou
Laurence
L
Lachaud
Agathe
A
Lebuisson
Magalie
M
Lefevre
Anne-Sophie
AS
LeGuern
Gwenaë
G
Le Moal
Daniel
D
Lusina
Marie-Claude
MC
Machouart
Denis
D
Malvy
Sophie
S
Matheron
Danièle
D
Maubon
Denis
D
Mechali
Bruno
B
Megarbane
Guillaume
G
Menard
Laurence
L
Millon
Muriel Mimoun
MM
Aiach
Philippe
P
Minodier
Christelle
C
Morelle
Gilles
G
Nevez
Philippe
P
Parola
Daniel
D
Parzy
Olivier
O
Patey
Pierre
P
Patoz
Pascale
P
Penn
Alice
A
Perignon
Stéphane
S
Picot
Jean-Etienne
JE
Pilo
Isabelle
I
Poilane
Denis
D
Pons
Marie
M
Poupart
Bruno
B
Pradines
Didier
D
Raffenot
Christophe
C
Rapp
Marie-Catherine
MC
Receveur
Claudine
C
Sarfati
Yaye
Y
Senghor
Fabrice
F
Simon
Jean-Yves
JY
Siriez
Nicolas
N
Taudon
Marc
M
Thellier
Maxime
M
Thouvenin
Dominique
D
Toubas
D000293:Adolescent; D000328:Adult; D000350:Africa, Central; D000354:Africa, Western; D000368:Aged; D000369:Aged, 80 and over; D000962:Antimalarials / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000627:therapeutic use*; D004351:Drug Resistance; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D014195:Travel; D055815:Young Adult
D000962:Antimalarials; D002738:Chloroquine