Plasmodium Falciparum in Vivo Resistance to Quinine: Description of Two Riii Responses in French Guiana

Demar, Magalie; Carme, Bernard

doi:10.4269/ajtmh.2004.70.125

Cited by 18 publications

(11 citation statements)

References 13 publications

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“…The combination was rapidly discontinued thereafter. There was an 11% clinical failure rate for the amodiaquine/sulfadoxine-pyrimethamine combination in 1986 (22 resistance to quinine have been identified (6). From the 1980s onward, quinine was always used in association with tetracycline (similar to protocols used in Brazil and Suriname) and not with sulfadoxine-pyrimethamine, as used in Guyana.…”

Section: Methodsmentioning

confidence: 99%

“…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.…”

mentioning

confidence: 99%

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

Legrand

Volney

Meynard

et al. 2008

Antimicrob Agents Chemother

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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...

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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

Legrand

Volney

Meynard

et al. 2008

Antimicrob Agents Chemother

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“…Table II Gene inheritance, pH cyt , NHE activity (in mmol H + /L/min) and QN, CQ sensitivities (in nM [6]) for Dd2, HB3 and 13 of their progeny; N is number of cells, SEM is standard error of the mean. …”

Section: Table Imentioning

confidence: 99%

“…Due to widespread CQR, QN has reemerged as an important antimalarial drug. While the failure of QN to treat severe and complicated malaria in vivo is rare (6), evidence of reduced P. falciparum susceptibility to the drug in vivo as well as QNR concomitant with CQR in vitro are cause for concern (1,(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Plasmodium falciparum Na+/H+ exchanger activity and quinine resistance

Bennett¹,

Patel²,

Ferdig³

et al. 2007

Molecular and Biochemical Parasitology

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Mutations in the Plasmodium falciparum pfcrt gene cause resistance to the 4 -amino quinoline chloroquine (CQ) and other antimalarial drugs. Mutations and/or overexpression of a P. falciparum multidrug resistance gene homologue (pfmdr1) may further modify or tailor the degree of quinoline drug resistance. Recently (M.T. Ferdig et al., Molecular Microbiology 52: 985-997 [2004]) QTL analysis further implicated a region of P. falciparum chromosome 13 as a partner (with pfcrt) in conferring resistance to the first quinoline -based antimalarial drug, quinine (QN). Since QN resistance (QNR) and CQR are often (but not always) observed together in parasite strains, since elevated cytosolic pH is frequently (but not always) found in CQR parasites, and since the chr 13 segment linked to QNR prominently harbors a gene encoding what appears to be a P. falciparum Na + /H + exchanger (PfNHE), we have systematically measured cytosolic pH and PfNHE activity for an extended series of parasite strains used in the QTL analysis. Altered PfNHE activity does not correlate with CQR as previously proposed, but significantly elevated PfNHE activity is found for strains with high levels of QNR, regardless their CQR status. We propose that either an elevated pH cyt or a higher vacuolar pH -to -cytosolic pH gradient contributes to one common route to malarial QNR that is also characterized by recently defined chr 13 -chr 9 pairwise interactions. Based on sequence analysis we propose a model whereby observed polymorphisms in PfNHE may lead to altered Na + /H + set point regulation in QNR parasites.

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“…101 Rare reports of failure of intravenous quinine for the treatment of severe or complicated malaria have appeared sporadically. 102 Oral quinine is used to treat uncomplicated malaria, generally over a period of three to seven days in combination with another blood-stage schizonticide, typically tetracycline or doxycycline. Although one study of 86 patients in Thailand showed the superiority of a seven-day regimen combined with tetracycline (a 100 percent efficacy rate) as compared with a five-day regimen combined with tetracycline (87 percent), 103 studies performed elsewhere have shown complete efficacy with shorter regimens combining quinine, doxycycline, and primaquine.…”

Section: Mefloquinementioning

confidence: 99%