The Experts below are selected from a list of 213 Experts worldwide ranked by ideXlab platform
David B A Hutchinson - One of the best experts on this subject based on the ideXlab platform.
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atovaquone proguanil compared with Chloroquine and Chloroquine sulfadoxine pyrimethamine for treatment of acute plasmodium falciparum malaria in the philippines
The Journal of Infectious Diseases, 1999Co-Authors: Dorina G Bustos, Craig J Canfield, Editha Canetemiguel, David B A HutchinsonAbstract:This randomized, open-label clinical trial compared a fixed-dose combination of atovaquone and proguanil (n = 55) with Chloroquine (n = 23) or a combination of Chloroquine, sulfadoxine, and pyrimethamine (n = 32) for treatment of acute falciparum malaria in the Philippines. Patients were hospitalized for 28 days to ensure medication compliance and prevent reinfection. Atovaquone-proguanil produced a significantly higher cure rate (100%) compared with that for Chloroquine (30.4%; P<.0001) or Chloroquine-sulfadoxine-pyrimethamine (87.5%; P<.05). Treatments did not differ significantly with respect to parasite clearance time (mean: 46.7 h for atovaquone-proguanil, 60.0 h for Chloroquine, and 42.8 h for Chloroquine-sulfadoxine-pyrimethamine) or fever clearance time (mean, 38.8, 46.8, and 34.5 h, respectively). Adverse events were typical of malaria symptoms; the most frequently reported events were vomiting (18% for atovaquone-proguanil, 17% for Chloroquine, and 9% for Chloroquine-sulfadoxine-pyrimethamine), abdominal pain (15%, 17%, and 3%, respectively), anorexia (11%, 13%, and 0%, respectively), and headache (6%, 17%, and 3%, respectively). Atovaquone-proguanil was well tolerated and more effective than Chloroquine or Chloroquine-sulfadoxine-pyrimethamine for treatment of multidrug-resistant falciparum malaria in the Philippines.
Christopher V Plowe - One of the best experts on this subject based on the ideXlab platform.
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return of Chloroquine antimalarial efficacy in malawi
The New England Journal of Medicine, 2006Co-Authors: Miriam K Laufer, Terrie E Taylor, Phillip C Thesing, Nicole D Eddington, Rhoda Masonga, Fraction K Dzinjalamala, Shannon L Takala, Christopher V PloweAbstract:BACKGROUND In 1993, Malawi became the first country in Africa to replace Chloroquine with the combination of sulfadoxine and pyrimethamine for the treatment of malaria. At that time, the clinical efficacy of Chloroquine was less than 50%. The molecular marker of Chloroquine-resistant falciparum malaria subsequently declined in prevalence and was undetectable by 2001, suggesting that Chloroquine might once again be effective in Malawi. METHODS We conducted a randomized clinical trial involving 210 children with uncomplicated Plasmodium falciparum malaria in Blantyre, Malawi. The children were treated with either Chloroquine or sulfadoxine–pyrimethamine and followed for 28 days to assess the antimalarial efficacy of the drug. RESULTS In analyses conducted according to the study protocol, treatment failure occurred in 1 of 80 participants assigned to Chloroquine, as compared with 71 of 87 participants assigned to sulfadoxine–pyrimethamine. The cumulative efficacy of Chloroquine was 99% (95% confidence interval [CI], 93 to 100), and the efficacy of sulfadoxine–pyrimethamine was 21% (95% CI, 13 to 30). Among children treated with Chloroquine, the mean time to parasite clearance was 2.6 days (95% CI, 2.5 to 2.8) and the mean time to the resolution of fever was 10.3 hours (95% CI, 8.1 to 12.6). No unexpected adverse events related to the study drugs occurred. CONCLUSIONS Chloroquine is again an efficacious treatment for malaria, 12 years after it was withdrawn from use in Malawi. (ClinicalTrials.gov number, NCT00125489.)
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Chloroquine resistant malaria
The Journal of Infectious Diseases, 2001Co-Authors: Thomas E. Wellems, Christopher V PloweAbstract:: The development of Chloroquine as an antimalarial drug and the subsequent evolution of drug-resistant Plasmodium strains had major impacts on global public health in the 20th century. In P. falciparum, the cause of the most lethal human malaria, Chloroquine resistance is linked to multiple mutations in PfCRT, a protein that likely functions as a transporter in the parasite's digestive vacuole membrane. Rapid diagnostic assays for PfCRT mutations are already employed as surveillance tools for drug resistance. Here, we review recent field studies that support the central role of PfCRT mutations in Chloroquine resistance. These studies suggest Chloroquine resistance arose in > or = 4 distinct geographic foci and substantiate an important role of immunity in the outcomes of resistant infections after Chloroquine treatment. P. vivax, which also causes human malaria, appears to differ from P. falciparum in its mechanism of Chloroquine resistance. Investigation of the resistance mechanisms and of the role of immunity in therapeutic outcomes will support new approaches to drugs that can take the place of Chloroquine or augment its efficiency.
Dorina G Bustos - One of the best experts on this subject based on the ideXlab platform.
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atovaquone proguanil compared with Chloroquine and Chloroquine sulfadoxine pyrimethamine for treatment of acute plasmodium falciparum malaria in the philippines
The Journal of Infectious Diseases, 1999Co-Authors: Dorina G Bustos, Craig J Canfield, Editha Canetemiguel, David B A HutchinsonAbstract:This randomized, open-label clinical trial compared a fixed-dose combination of atovaquone and proguanil (n = 55) with Chloroquine (n = 23) or a combination of Chloroquine, sulfadoxine, and pyrimethamine (n = 32) for treatment of acute falciparum malaria in the Philippines. Patients were hospitalized for 28 days to ensure medication compliance and prevent reinfection. Atovaquone-proguanil produced a significantly higher cure rate (100%) compared with that for Chloroquine (30.4%; P<.0001) or Chloroquine-sulfadoxine-pyrimethamine (87.5%; P<.05). Treatments did not differ significantly with respect to parasite clearance time (mean: 46.7 h for atovaquone-proguanil, 60.0 h for Chloroquine, and 42.8 h for Chloroquine-sulfadoxine-pyrimethamine) or fever clearance time (mean, 38.8, 46.8, and 34.5 h, respectively). Adverse events were typical of malaria symptoms; the most frequently reported events were vomiting (18% for atovaquone-proguanil, 17% for Chloroquine, and 9% for Chloroquine-sulfadoxine-pyrimethamine), abdominal pain (15%, 17%, and 3%, respectively), anorexia (11%, 13%, and 0%, respectively), and headache (6%, 17%, and 3%, respectively). Atovaquone-proguanil was well tolerated and more effective than Chloroquine or Chloroquine-sulfadoxine-pyrimethamine for treatment of multidrug-resistant falciparum malaria in the Philippines.
Terrie E Taylor - One of the best experts on this subject based on the ideXlab platform.
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return of Chloroquine antimalarial efficacy in malawi
The New England Journal of Medicine, 2006Co-Authors: Miriam K Laufer, Terrie E Taylor, Phillip C Thesing, Nicole D Eddington, Rhoda Masonga, Fraction K Dzinjalamala, Shannon L Takala, Christopher V PloweAbstract:BACKGROUND In 1993, Malawi became the first country in Africa to replace Chloroquine with the combination of sulfadoxine and pyrimethamine for the treatment of malaria. At that time, the clinical efficacy of Chloroquine was less than 50%. The molecular marker of Chloroquine-resistant falciparum malaria subsequently declined in prevalence and was undetectable by 2001, suggesting that Chloroquine might once again be effective in Malawi. METHODS We conducted a randomized clinical trial involving 210 children with uncomplicated Plasmodium falciparum malaria in Blantyre, Malawi. The children were treated with either Chloroquine or sulfadoxine–pyrimethamine and followed for 28 days to assess the antimalarial efficacy of the drug. RESULTS In analyses conducted according to the study protocol, treatment failure occurred in 1 of 80 participants assigned to Chloroquine, as compared with 71 of 87 participants assigned to sulfadoxine–pyrimethamine. The cumulative efficacy of Chloroquine was 99% (95% confidence interval [CI], 93 to 100), and the efficacy of sulfadoxine–pyrimethamine was 21% (95% CI, 13 to 30). Among children treated with Chloroquine, the mean time to parasite clearance was 2.6 days (95% CI, 2.5 to 2.8) and the mean time to the resolution of fever was 10.3 hours (95% CI, 8.1 to 12.6). No unexpected adverse events related to the study drugs occurred. CONCLUSIONS Chloroquine is again an efficacious treatment for malaria, 12 years after it was withdrawn from use in Malawi. (ClinicalTrials.gov number, NCT00125489.)
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reemergence of Chloroquine sensitive plasmodium falciparum malaria after cessation of Chloroquine use in malawi
The Journal of Infectious Diseases, 2003Co-Authors: James G Kublin, Joseph F Cortese, Eric Mbindo Njunju, Rabia A G Mukadam, Jack J Wirima, Peter N Kazembe, Abdoulaye A Djimde, Bourema Kouriba, Terrie E TaylorAbstract:: In 1993, Malawi became the first African country to replace Chloroquine with sulfadoxine-pyrimethamine nationwide in response to high rates of Chloroquine-resistant falciparum malaria. To determine whether withdrawal of Chloroquine can lead to the reemergence of Chloroquine sensitivity, the prevalence of the pfcrt 76T molecular marker for Chloroquine-resistant Plasmodium falciparum malaria was retrospectively measured in Blantyre, Malawi. The prevalence of the Chloroquine-resistant pfcrt genotype decreased from 85% in 1992 to 13% in 2000. In 2001, Chloroquine cleared 100% of 63 asymptomatic P. falciparum infections, no isolates were resistant to Chloroquine in vitro, and no infections with the Chloroquine-resistant pfcrt genotype were detected. A concerted national effort to withdraw Chloroquine from use has been followed by a return of Chloroquine-sensitive falciparum malaria in Malawi. The reintroduction of Chloroquine, ideally in combination with another antimalarial drug, should be considered in areas where Chloroquine resistance has declined and safe and affordable alternatives remain unavailable.
Alan Brockman - One of the best experts on this subject based on the ideXlab platform.
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Chloroquine resistant plasmodium vivax in vitro characterisation and association with molecular polymorphisms
PLOS ONE, 2007Co-Authors: Rossarin Suwanarusk, Bruce Russell, Marina Chavchich, Ferryanto Chalfein, Enny Kenangalem, Varakorn Kosaisavee, Budi Prasetyorini, Kim A Piera, Marion Barends, Alan BrockmanAbstract:Background Treatment failure of Chloroquine for P. vivax infections has reached high levels in the eastern provinces of Indonesia, however, in vitro characterization of Chloroquine resistance and its associated molecular profile have yet to be determined. Methods Using a modified schizont maturation assay we investigated the in vitro Chloroquine susceptibility profile and molecular polymorphisms of P. vivax isolates collected from Papua, Indonesia, where high levels of clinical Chloroquine treatment failure have been reported, and from Thailand, where Chloroquine treatment is generally effective. Results The geometric mean Chloroquine IC50 for P. vivax isolates from Papua (n = 145) was 312 nM [95%CI: 237–411 nM] compared to 46.8 nM [95%CI: 34.7–63.1 nM] from Thailand (n = 81); p<0.001. Correlating with the known clinical efficacy of the area, a cut off for Chloroquine resistance was defined as 220nM, a level exceeded in 13.6% (11/81) of Thai isolates and 65% (94/145) of Papuan isolates; p<0.001. Several sequence polymorphisms in pvcrt-o and pvmdr1, and difference in pvmdr1 copy number were identified. A Y976F mutation in pvmdr1 was present in 96% (123/128) of Papuan isolates and 25% (17/69) of Thai isolates; p<0.001. Overall, the geometric mean Chloroquine IC50 in isolates with the Y976F mutation was 283 nM [95%CI: 211–379], compared to 44.5 nM [95%CI: 31.3–63.4] in isolates with the wild type; p< 0.001. Pvmdr1 amplification occurred in 23% (15/66) of Thai isolates compared to none (0/104) of Indonesian isolates (p<0.001), but was not associated with increased Chloroquine resistance after controlling for geographical location. Conclusions In vitro susceptibility testing of P. vivax discriminates between populations with differing levels of clinical efficacy of Chloroquine. The pvmdr1 polymorphism at Y976F may provide a useful tool to highlight areas of emerging Chloroquine resistance, although further studies defining its clinical correlates are needed.