Chloroquine versus Sulfadoxine-Pyrimethamine for Treatment of Plasmodium falciparum Malaria in Savannakhet Province, Lao People's Democratic Republic: An Assessment of National Antimalarial Drug Recommendations

Mayxay, Mayfong; Newton, Paul N.; Khanthavong, Maniphono; Pongvongsa, Tiengkham; Phetsouvanh, Rattanaxay; Phompida, Samlane; Brockman, Alan; White, Nicholas J.

doi:10.1086/377734

Cited by 33 publications

(47 citation statements)

References 15 publications

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“…Phalanxay and Xepon districts (Savannakhet Province) are located 605 km and 665 km, respectively, southeast of Vientiane, the capital of Laos. Phalanxay (78 villages, population = 24,730) and Xepon (88 villages, population = 48,000) are inhabited predominantly by rice farmers of the Lao Theung ethnic group 2,11,13,14. A sample size calculation was performed for the whole multi-center study.…”

Section: Methodsmentioning

confidence: 99%

“…At presentation, venous blood samples were obtained for parasite count, hematologic tests, and biochemical tests; three blood spots were collected on 3MM filter paper (Whatman, Maidstone, United Kingdom) for genotyping by polymerase chain reaction (PCR) in the event of reappearance of P. falciparum during follow-up 13. A 12-lead electrocardiogram (ECG) (CarTouch; Cardionics S.A., Belgium) was obtained.…”

Section: Methodsmentioning

confidence: 99%

“…Parasite counts in thick and thin blood films stained with Field's stain were obtained daily until parasite clearance and then weekly from day 7 13. Polymerase chain reaction amplification was performed on paired samples for parasite genotyping to distinguish between reinfection and recrudescence 15…”

Section: Methodsmentioning

confidence: 99%

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A Phase III, Randomized, Non-Inferiority Trial to Assess the Efficacy and Safety of Dihydroartemisinin-Piperaquine in Comparison with Artesunate-Mefloquine in Patients with Uncomplicated Plasmodium falciparum Malaria in Southern Laos

Mayxay¹,

Keomany²,

Khanthavong³

et al. 2010

The American Society of Tropical Medicine and Hygiene

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We conducted an open, randomized clinical trial of oral dihydroartemisinin-piperaquine (DP) versus artesunate-mefloquine (AM) in 300 patients in Laos with uncomplicated Plasmodium falciparum malaria as part of a multicentre study in Asia. Survival analysis and adjustment for re-infection showed that the 63-day cure rates (95% confidence interval [CI]) were 100% for AM and 99.5% (96.4–99.8%) for DP. The 63-day cure rates per protocol were 99% (97 of 98) for AM and 99.5% (196 of 197) for DP (P = 0.55). The difference (AM minus DP) in cure rates (95% CI) was −0.5% (−5.1 to 2.0%), which is within the 5% non-inferiority margin. The median fever and parasite clearance times were also similar for AM and DP. The proportion of patients with at least one recorded potential adverse event was significantly higher in the AM group (38 of 87, 44%) than in the DP group (57 of 182, 31%) (relative risk = 0.6, 95% CI = 0.4–0.9; P = 0.04). Dihydroartemisinin-piperaquine is not inferior to AM in the treatment of uncomplicated P. falciparum malaria in Laos and is associated with fewer adverse effects. The results of this study were similar to those of the larger multicentre study.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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A Phase III, Randomized, Non-Inferiority Trial to Assess the Efficacy and Safety of Dihydroartemisinin-Piperaquine in Comparison with Artesunate-Mefloquine in Patients with Uncomplicated Plasmodium falciparum Malaria in Southern Laos

Mayxay¹,

Keomany²,

Khanthavong³

et al. 2010

The American Society of Tropical Medicine and Hygiene

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“…12 Among 80 Lao patients, the level of humoral immunity to P. falciparum and the risk of therapeutic failure were correlated with the parasite count on admission to the hospital and the length of time to the resolution of fever. 29 Djimde et al 30 showed that the clearance of P. falciparum organisms carrying a mutant transporter gene, pfcrt K76T, that was linked with resistance to chloroquine correlated with acquired immunity in subjects in sub-Saharan Africa.…”

Section: Safety and Tolerabilitymentioning

confidence: 99%

Effectiveness of Antimalarial Drugs

Smego¹

2005

N Engl J Med

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“…In these areas, it has recently been observed that the reappearance of chloroquinesensitive P. falciparum strains has followed chloroquine withdrawal (15,21). This phenomenon, if confirmed in the future, could make reusing chloroquine as the first line treatment of malaria possible (18,21), e.g., in combination with artemisinin derivatives. However, such a therapeutic option would imply public health surveillance based upon sensitive techniques.…”

mentioning

confidence: 93%

Use of a Locked-Nucleic-Acid Oligomer in the Clamped-Probe Assay for Detection of a Minority Pfcrt K76T Mutant Population of Plasmodium falciparum

et al. 2005

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Given the emergence of drug resistance and the high rate of polyclonal microorganism infections, the availability of a fast and sensitive test to detect minority mutant populations would be an improvement in the diagnosis of infectious diseases. A clamped-probe real-time PCR assay to diagnose the Plasmodium falciparum K76T mutation in clone populations was developed, using a wild-type-specific locked-nucleic-acid-containing oligomer to suppress wild-type PCR amplification and to enhance melting analysis with a mutation-specific detection probe.In the last few decades, the emergence of drug resistance has become a major problem for the treatment of various infectious diseases. Bacterial, viral, or parasitic infections are often polyclonal (4,10,12,25,27). Drug-resistant individuals may hide among a sensitive population and the identification of a resistant clone may have implications for epidemiology and treatment. Molecular diagnosis of resistant microorganisms by mutation detection is a routine examination in virology (17,20) and has started to be used in bacteriology (5,19,23) and parasitology (24). Recent virology studies have indicated that the presence of minority drug-resistant variants may be an independent predictor of treatment failure (8, 9). The emergence of nosocomial infections caused by drug-resistant bacteria also represents a significant threat for debilitated patients (22). As a consequence, a need exists to have a fast and sensitive diagnostic test to identify minority populations of resistant organisms. In order to improve the efficacy of such a genotype-assisted diagnosis, methods have been developed to lower the detection threshold of minority populations among a wild-type one. This trend was demonstrated by two recent studies. First, a rapid and accurate method of duplex real-time PCR used to detect ampicillin-resistant Enterococcus faecium, a major cause of nosocomial infections, was recently published (19). Second, an RNA heteroduplex generator tracking assay elicited a decrease in the detection threshold of type 1 human immunodeficiency virus mutant populations from 20 to 0.5% (12). Concerning the diagnosis of Plasmodium falciparum malaria, the detection of a minority population has become important with the discovery of Pfcrt K76T mutation, which has been correlated with in vitro chloroquine resistance (1,7,26).Chloroquine has proved to be one of the most successful drugs ever deployed against P. falciparum malaria, mainly because it is well tolerated and available at a very low cost. Over the last three decades, P. falciparum chloroquine resistance has significantly increased, and many countries have discarded this drug from the antimalarial weaponry. In these areas, it has recently been observed that the reappearance of chloroquinesensitive P. falciparum strains has followed chloroquine withdrawal (15, 21). This phenomenon, if confirmed in the future, could make reusing chloroquine as the first line treatment of malaria possible (18, 21), e.g., in combination with artemisinin derivati...

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Chloroquine versus Sulfadoxine-Pyrimethamine for Treatment of Plasmodium falciparum Malaria in Savannakhet Province, Lao People's Democratic Republic: An Assessment of National Antimalarial Drug Recommendations

Cited by 33 publications

References 15 publications

A Phase III, Randomized, Non-Inferiority Trial to Assess the Efficacy and Safety of Dihydroartemisinin-Piperaquine in Comparison with Artesunate-Mefloquine in Patients with Uncomplicated Plasmodium falciparum Malaria in Southern Laos

A Phase III, Randomized, Non-Inferiority Trial to Assess the Efficacy and Safety of Dihydroartemisinin-Piperaquine in Comparison with Artesunate-Mefloquine in Patients with Uncomplicated Plasmodium falciparum Malaria in Southern Laos

Effectiveness of Antimalarial Drugs

Use of a Locked-Nucleic-Acid Oligomer in the Clamped-Probe Assay for Detection of a Minority Pfcrt K76T Mutant Population of Plasmodium falciparum

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