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In vitro response to chloroquine, monodesethylamodiaquine, mefloquine, lumefantrine, and dihydroartemisinin was assessed by the radioisotopic microtest in Yaoundé, Cameroon, during 2000–2004 and compared with our previous data obtained during 1996–1999. Based on the cut-off value of 100 nmol/L, 36.3% of isolates were chloroquine-susceptible (N = 175; geometric mean IC50, 40.3 nmol/L) and 63.7% were chloroquine-resistant (N = 307; geometric mean IC50, 211 nmol/L). There was no significant difference (P > 0.05) in the mean IC50s from 1996 to 2004, but a significant linear trend (P < 0.05) toward an increased proportion of chloroquine-resistant isolates was observed from 1996 (49%) to 2004 (69%). All chloroquine-susceptible isolates and most chloroquine-resistant isolates were susceptible to monodesethylamodiaquine (i.e., IC50 < 60 nmol/L). Despite the positive correlation between chloroquine and monodesethylamodiaquine (r = 0.739, P < 0.05), the IC50s for monodesethylamodiaquine remained stable during 1997–2004, with no increase in the proportion of monodesethylamodiaquine-resistant isolates. Mefloquine, lumefantrine, and dihydroartemisinin were equally active against the chloroquine-susceptible and chloroquine-resistant parasites. The responses to these three drugs were positively correlated, and a significant decrease (P < 0.05) in the mean IC50s was observed during the study period compared with our earlier data in 1997–1999, probably because of their inverse relationship with chloroquine response. The in vitro results were in general agreement with the in vivo response to chloroquine and amodiaquine. In vitro drug susceptibility assay is a useful, complementary laboratory tool for determining the trend of response to drugs for which there is still no established molecular marker and may serve as an early warning system for emerging drug resistance.
Received March 23, 2006. Accepted for publication September 4, 2006.
Acknowledgment: The authors thank the staff of Nlongkak Catholic missionary dispensary for recruitment of patients.
Financial support: This study was supported by the French Ministry of Research (Programme PAL+) and the World Health Organization, Geneva, Switzerland (contract C8/181/32).
* Address correspondence to Leonardo Basco, Unité de Recherche Paludologie Afro-tropicale, Institut de Recherche pour le Développement (IRD) and Laboratoire de Recherche sur le Paludisme, Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale (OCEAC), BP 288, Yaoundé, Cameroon. E-mail: lkbasco{at}yahoo.fr
Authors’ addresses: Leonardo K. Basco, Unité de Recherche Paludologie Afro-tropicale, Institut de Recherche pour le Développement (IRD) and Laboratoire de Recherche sur le Paludisme, Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale (OCEAC), BP 288, Yaoundé, Cameroon, Telephone: 237-223-22-32, Fax: 237-223-00-61, E-mail: lkbasco{at}yahoo.fr. Pascal Ringwald, Global Malaria Programme, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland, Telephone: 41-22-7913469, Fax: 41-22-7914824, E-mail: ringwaldp{at}who.int.
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