<i>In vivo</i> drug resistance of falciparum malaria in mining areas of Venezuela

Aché, Alberto; Escorihuela, Marta; Vivas, Esther; Páez, E.; Miranda, Leandro S. M.; Matos, António P.; Perez, Winder B.; Díaz, Ómar Huertas; Izarra, E.

doi:10.1046/j.1365-3156.2002.00936.x

Cited by 16 publications

(12 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This efficiency is much higher than that estimated for P. vivax in Western Venezuela, where only 0.32% of infective bites infected a person (RubioPalis et al 1992). On the other hand, the high incidence reported for the study area might also be due to failure to complete treatment and/or multiple drug resistance (Caraballo & Rodríguez-Acosta 1999, Aché et al 2002.…”

Section: Discussionmentioning

confidence: 99%

“…The biting rate, sporozoite rate and EIR are so low that these parameters would not be a practical indicator of the efficacy of control campaigns in this area. The control of malaria in the municipality of Sifontes is complex due to its highly mobile population (Aché et al 2002, Moreno et al 2007), the circulation of P. falciparum strains with multidrug resistance (Caraballo & Rodríguez-Acosta 1999, Aché et al 2002), houses with incomplete or no walls in miners' camps and Amerindian villages and the outdoor biting and resting behavior of the principal vectors (Moreno et al 2007). New approaches should be developed that take into consideration legislation on illegal mining, education, community participation and rapid diagnosis and effective treatment where monitoring of drug resistance is essential.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Malaria entomological inoculation rates in gold mining areas of Southern Venezuela

Moreno

Rubio-Palis

Páez³

et al. 2009

Mem. Inst. Oswaldo Cruz

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Malaria entomological inoculation rates in gold mining areas of Southern Venezuela

Moreno

Rubio-Palis

Páez³

et al. 2009

Mem. Inst. Oswaldo Cruz

View full text Add to dashboard Cite

show abstract

“…In Uganda, the 28-day genotype-corrected failure rate was 23%; some failures may have been due to poor treatment compliance, but no association between measures of compliance and treatment efficacy was identified (1). On the other hand, some studies have shown excellent efficacy for quinine, including over 95% success after 14 to 28 days for the treatment of falciparum malaria in Equatorial Guinea (45), in Venezuela (2), and in returned travelers in France (32). Second, quinine is poorly tolerated, especially later in the course of 7 days of treatment, suggesting that noncompliance with full treatment courses is common (19,50).…”

mentioning

confidence: 99%

Limited Ability of Plasmodium falciparum pfcrt , pfmdr1 , and pfnhe1 Polymorphisms To Predict Quinine In Vitro Sensitivity or Clinical Effectiveness in Uganda

Baliraine¹,

Nsobya²,

Achan³

et al. 2011

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Quinine is a standard drug for treating severe malaria in Africa, and it is also increasingly used to treat uncomplicated disease. However, failures of quinine therapy are common, and it is unknown if failures in Africa are due to drug resistance. Recent studies have identified associations between in vitro quinine sensitivity and polymorphisms in genes encoding putative transporters, including well-described polymorphisms in pfcrt and pfmdr1 and varied numbers of DNNND or DDNHNDNHNND repeats in microsatellite 4760 (ms4760) of the predicted sodium-hydrogen exchanger, pfnhe1. To better characterize mediators of quinine response, we assessed associations between genetic polymorphisms, in vitro quinine sensitivity, and quinine treatment responses in Kampala, Uganda. Among 172 fresh clinical isolates tested in vitro, decreasing sensitivity to quinine was associated with accumulation of pfmdr1 mutations at codons 86, 184, and 1246. Nearly all parasites had pfcrt 76T, preventing analysis of associations with this mutation. pfnhe1 ms4760 was highly polymorphic. Parasites with 2 copies of either ms4760 repeat showed modest decreases in quinine sensitivity compared to those with 1 or >3 repeats, but the differences were not statistically significant. None of the above polymorphisms predicted treatment failure among 66 subjects treated with quinine for uncomplicated malaria. Our data suggest that quinine sensitivity is a complex trait and that known polymorphisms in pfcrt, pfmdr1, and pfnhe1, while associated with quinine sensitivity, are not robust markers for quinine resistance.

show abstract

“…A mutation of the CQ resistance gene pfcrt at codon 76 (pfcrt-76) has been associated with reduced susceptibility to QN in vitro, although transfection studies have shown conflicting results (16,37). A seminal study on the association of polymorphisms in pfnhe, a sodium hydrogen exchanger gene, and the in vitro activity of QN indicated that an increase in the number of DNNND repeats (1)(2)(3)(4)(5) in an ms4760 microsatellite was associated with reduced susceptibility to QN (10), and this finding was confirmed recently (13). Variations in the copy number of this repeat in isolates from areas where QN efficacy is known to be reduced in vivo have also been reported (41).…”

mentioning

confidence: 99%

In Vitro Activities of Quinine and Other Antimalarials and pfnhe Polymorphisms in Plasmodium Isolates from Kenya

Okombo

Kiara

Rono

et al. 2010

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Resistance to the amino alcohol quinine has been associated with polymorphisms in pfnhe, a sodium hydrogen exchanger. We investigated the role of this gene in quinine resistance in vitro in isolates from Kenya. We analyzed pfnhe whole-gene polymorphisms, using capillary sequencing, and pfcrt at codon 76 (pfcrt-76) and pfmdr1 at codon 86 (pfmdr1-86), using PCR-enzyme restriction methodology, in 29 isolates from Kilifi, Kenya, for association with the in vitro activities of quinine and 2 amino alcohols, mefloquine and halofantrine. In vitro activity was assessed as the drug concentration that inhibits 50% of parasite growth (IC 50 ). The median IC 50 s of quinine, halofantrine, and mefloquine were 92, 22, and 18 nM, respectively. The presence of 2 DNNND repeats in microsatellite ms4760 of pfnhe was associated with reduced susceptibility to quinine (60 versus 227 nM for 1 and 2 repeats, respectively; P < 0.05), while 3 repeats were associated with restoration of susceptibility. The decrease in susceptibility conferred by the 2 DNNND repeats was more pronounced in parasites harboring the pfmdr1-86 mutation. No association was found between susceptibility to quinine and the pfcrt-76 mutation or between susceptibility to mefloquine or halofantrine and the pfnhe gene and the pfcrt-76 and pfmdr1-86 mutations. Using previously published data on the in vitro activities of chloroquine, lumefantrine, piperaquine, and dihydroartemisinin, we investigated the association of their activities with pfnhe polymorphism. With the exception of a modulation of the activity of lumefantrine by a mutation at position 1437, pfnhe did not modulate their activities. Two DNNND repeats combined with the pfmdr1-86 mutation could be used as an indicator of reduced susceptibility to quinine.The amino alcohol quinine (QN) remains one of the important drugs against malaria. It is the drug of choice for the treatment of severe malaria, and in most African countries, including Kenya, where artemisinin-based combinations (lumefantrine-artemether, amodiaquine-artesunate) are now first-line treatments, 7-day quinine monotherapy has become the second-line treatment for uncomplicated malaria (44). However, there is evidence of selection and spread of QN-resistant parasites or those with reduced susceptibility to 8,30,34). This observation led to the investigation of artesunate (an artemisinin derivative) as an alternative to QN for the treatment of severe malaria (14). However, this option could now be compromised by the emergence of artemisinin resistance (9).Several studies have been dedicated to understanding the mechanisms of quinine resistance. Polymorphisms in pfmdr, a gene associated with chloroquine (CQ) resistance, modulate QN susceptibility (27,33,36). A mutation of the CQ resistance gene pfcrt at codon 76 (pfcrt-76) has been associated with reduced susceptibility to QN in vitro, although transfection studies have shown conflicting results (16,37). A seminal study on the association of polymorphisms in pfnhe, a sodium hydrogen exchanger gene, a...

show abstract

In vivo drug resistance of falciparum malaria in mining areas of Venezuela

Cited by 16 publications

References 3 publications

Malaria entomological inoculation rates in gold mining areas of Southern Venezuela

Malaria entomological inoculation rates in gold mining areas of Southern Venezuela

Limited Ability of Plasmodium falciparum pfcrt , pfmdr1 , and pfnhe1 Polymorphisms To Predict Quinine In Vitro Sensitivity or Clinical Effectiveness in Uganda

In Vitro Activities of Quinine and Other Antimalarials and pfnhe Polymorphisms in Plasmodium Isolates from Kenya

Contact Info

Product

Resources

About