In Vitro Monitoring of Plasmodium falciparum Drug Resistance in French Guiana: a Synopsis of Continuous Assessment from 1994 to 2005

Abstract

Implemented as one arm of the malaria control program in French Guiana in the early 1990s, our laboratory has since established in vitro profiles for parasite drug susceptibility to a panel of eight antimalarials for more than 1,000 Plasmodium falciparum isolates from infected patients. The quinine-doxycycline combination was introduced in 1995 as the first-line drug treatment against uncomplicated P. falciparum malaria, replacing chloroquine, and the first-line drug combination was changed to the artemether-lumefantrine combination in 2002. Resistance to chloroquine declined 5 years after it was dropped in 1995 as the first-line drug, but unlike similar situations in Africa, there was a rapid halt to this decline. Doxycycline susceptibility substantially decreased from 2002 to 2005, suggesting parasite selection under quinine-doxycycline drug pressure. Susceptibility to mefloquine decreased from 1997 onward. Throughout the period from 1994 to 2005, most isolates were sensitive in vitro to quinine, amodiaquine, and atovaquone. Susceptibility to amodiaquine was strongly correlated with that to chloroquine and to a lesser extent with that to mefloquine and halofantrine. Susceptibilities to mefloquine and to halofantrine were also strongly correlated. The Guyana Shield currently has the highest malaria rates in South America and is the only geographical area in the Americas where Plasmodium falciparum infection is diagnosed more frequently than P. vivax infection. In French Guiana, P. falciparum accounts for 60 to 70% of the 3,000 to 5,000 malaria cases reported every year (3). Malaria occurs in isolated geographical foci situated along the rivers in the Amazonian forest, and the population has little specific immunity. Malarial control involves spraying insecticides over the coastal region, where approximately 80% of the population resides, and using bed nets, an evidence-based drug policy, and deploying health services in remote endemic areas to provide prompt treatment by public primary health centers and/or private practitioners.As in the neighboring countries of the Amazon basin (36), P. falciparum is multidrug resistant, with failures documented for chloroquine (18), the amodiaquine/sulfadoxine-pyrimethamine combination (22), halofantrine (9, 19), chloroquine-proguanil (19), and even quinine (6). In the last decade, the drug policy in French Guiana has been based on both an in vivo assessment of therapeutic efficacy and longitudinal monitoring of in vitro drug susceptibility. In 1995, the quinine-doxycycline combination was recommended as the first-line treatment. It was replaced by the artemether-lumefantrine combination in 2002.Monitoring drug resistance is particularly important in this region, where illegal gold-mining activities in the malaria endemicity areas are associated with erratic consumption of antimalarials and frequently with self-medication, unclear compliance to recommended regimens, and the formulation and use of illegally imported molecules of unknown quality, which contribute to the select...

Discordant Temporal Evolution of Pfcrt and Pfmdr1 Genotypes and Plasmodium falciparum In Vitro Drug Susceptibility to 4-Aminoquinolines after Drug Policy Change in French Guiana

“…The in vitro susceptibility to a panel of antimalarials of 513 P. falciparum isolates collected longitudinally during the years 2000 to 2005 by our reference center has been reported (28). Similar procedures were used for 187 isolates collected in the years 2006 to…”

“…Sensitivity to mefloquine decreased progressively after its introduction. Susceptibility to amodiaquine was correlated positively with susceptibility to chloroquine and more moderately with susceptibility to mefloquine or halofantrine (28).…”

“…Mefloquine or halofantrine was used as a second-line treatment from 1990 to 2002, when it was replaced with atovaquone-proguanil (28). We reported that these changes impacted on in vitro drug sensitivity profiles.…”

Investigation of a Sudden Malaria Outbreak in the Isolated Amazonian Village of Saül, French Guiana, January–April 2009

“…The "Centre National de Référence de la Chimiorésistance du Paludisme" (CNRCP) at IPG regularly collects P. falciparum isolates and determines their in vitro susceptibility profiles for a panel of antimalarials using the isotopic method. 9 Entomological investigation. Two entomological surveys were organized in the village of Saü l and its surroundings from January 12-14, 2009 and from April 6-10, 2009.…”

Fusion of field studies and the laboratory solves a puzzle in antimalarial resistance

“…Comparing these data to results measured from isolates collected between 1983 and 1987 (11) revealed that highly resistant parasites prevailed until about 1999. However, when chloroquine treatment was no longer recommended for P. falciparum malaria the level of resistance fell sharply, and plummeted after introduction of artemisinin combination therapies in 2002 (12,13). Pelleau et al (1) assessed the genotypes of more than 1,000 of these chloroquine-susceptible isolates: all parasites still retained the ancestral SVMNT "chloroquine-resistant" genotype!…”