Failure of artesunate-mefloquine combination therapy for uncomplicated Plasmodium falciparum malaria in southern Cambodia

Rogers, William O.; Sem, Rithy; Tero, Thong; Chim, Pheaktra; Lim, Pharath; Muth, Sinuon; Socheat, Duong; Ariey, Frédéric; Wongsrichanalai, Chansuda

doi:10.1186/1475-2875-8-10

Cited by 196 publications

(198 citation statements)

References 21 publications

Supporting

Mentioning

188

Contrasting

Unclassified

Order By: Relevance

“…The multiplication extent at the baseline of 13% was a clear cause of concern as reported earlier, 41 because pfmdr1 multicopy occurrence seems to be associated with longer parasite clearance time and higher initial parasitaemias. 42 Luckily, no significant difference in multiplication extent could be detected in a 5-year time span. A telltale for the increased copy number in the isolates from Suriname could be the absence of the pfmdr1 N86Y mutation, which has been reported as a negative marker for increased copy number.…”

Section: Discussionmentioning

confidence: 93%

Molecular Surveillance as Monitoring Tool for Drug-Resistant Plasmodium falciparum in Suriname

Adhin

Labadie-Bracho²,

Bretas³

2013

The American Society of Tropical Medicine and Hygiene

View full text Add to dashboard Cite

Abstract. The aim of this translational study was to show the use of molecular surveillance for polymorphisms and copy number as a monitoring tool to track the emergence and dynamics of Plasmodium falciparum drug resistance. A molecular baseline for Suriname was established in 2005, with P. falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance (pfmdr1) markers and copy number in 40 samples. The baseline results revealed the existence of a uniformly distributed mutated genotype corresponding with the fully mefloquine-sensitive 7G8-like genotype (Y184F, S1034C, N1042D, and D1246Y) and a fixed pfmdr1 N86 haplotype. All samples harbored the pivotal pfcrtK76T mutation, showing that chloroquine reintroduction should not yet be contemplated in Suriname. After 5 years, 40 samples were assessed to trace temporal changes in the status of pfmdr1 polymorphisms and copy number and showed minor genetic alterations in the pfmdr1 gene and no significant changes in copy number, thus providing scientific support for prolongation of the current drug policy in Suriname.

show abstract

Section: Discussionmentioning

confidence: 93%

Molecular Surveillance as Monitoring Tool for Drug-Resistant Plasmodium falciparum in Suriname

Adhin

Labadie-Bracho²,

Bretas³

2013

The American Society of Tropical Medicine and Hygiene

View full text Add to dashboard Cite

show abstract

“…Earlier studies showed that mefloquine was effective against P. falciparum in vitro, and showed low IC 50 values of 28.7-130 nM. 27,34,35 Mefloquine showed high IC 50 values (272 μM) for mammalian cells (dog neurons). 36 Doses of pepstatin A and mefloquine for bovine babesiosis most effectively suppressed parasite growth compared with other drugs that have been tested for the treatment of babesiosis.…”

Section: Discussionmentioning

confidence: 99%

“…The in vivo growth inhibition assay for pepstatin A, mefloquine, and pepstatin A/ mefloquine combinations (2.5 mg/kg/2.5 mg/kg and 5 mg/kg/ 5 mg/kg) was performed in BALB/c mice as described. 8,34 Twenty-eight week-old female BALB/c mice were divided into five groups of four mice and intraperitoneally inoculated with 1 + 10 6 B. microti-infected erythrocytes. In the first group, mefloquine dissolved in DMSO was administered at a dose rate of 5 mg/kg.…”

Section: Methodsmentioning

confidence: 99%

Inhibitory Effects of Pepstatin A and Mefloquine on the Growth of Babesia Parasites

Munkhjargal¹,

AbouLaila²,

Terkawi³

et al. 2012

The American Society of Tropical Medicine and Hygiene

View full text Add to dashboard Cite

Abstract. We evaluated the inhibitory effects of pepstatin A and mefloquine on the in vitro and in vivo growths of Babesia parasites. The in vitro growth of Babesia bovis, B. bigemina, B. caballi, and B. equi was significantly inhibited (P 0.05) by micromolar concentrations of pepstatin A (50% inhibitory concentrations = 38.5, 36.5, 17.6, and 18.1 μM, respectively) and mefloquine (50% inhibitory concentrations = 59.7, 56.7, 20.7, and 4 μM, respectively). Furthermore, both reagents either alone at a concentration of 5 mg/kg or in combinations (2.5/2.5 and 5/5 mg/kg) for 10 days significantly inhibited the in vivo growth of B. microti in mice. Mefloquine treatment was highly effective and the combination treatments were less effective than other treatments. Therefore, mefloquine may antagonize the actions of pepstatin A against babesiosis and aspartic proteases may play an important role in the asexual growth cycle of Babesia parasites.

show abstract

“…Cambodian samples were collected between August 2006 and December 2007 as part of a chloroquine treatment trial at the Chumkiri health center in Kampot Province. 27 Details of the study have previously been published. Antirelapse therapy with primaquine was not given.…”

Section: Methodsmentioning

confidence: 99%

Plasmodium vivax Isolates from Cambodia and Thailand Show High Genetic Complexity and Distinct Patterns of P. vivax Multidrug Resistance Gene 1 (pvmdr1) Polymorphisms

Lin¹,

Patel²,

Kharabora³

et al. 2013

The American Society of Tropical Medicine and Hygiene

Self Cite

View full text Add to dashboard Cite

Abstract. Plasmodium vivax accounts for an increasing fraction of malaria infections in Thailand and Cambodia. We compared P. vivax genetic complexity and antimalarial resistance patterns in the two countries. Use of a heteroduplex tracking assay targeting the merozoite surface protein 1 gene revealed that vivax infections in both countries are frequently polyclonal (84%), with parasites that are highly diverse (H E = 0.86) but closely related (G ST = 0.18). Following a history of different drug policies in Thailand and Cambodia, distinct patterns of antimalarial resistance have emerged: most Cambodian isolates harbor the P. vivax multidrug resistance gene 1 ( pvmdr1) 976F mutation associated with chloroquine resistance (89% versus 8%, P 0.001), whereas Thai isolates more often display increased pvmdr1 copy number (39% versus 4%, P 0.001). Finally, genotyping of paired isolates from individuals suspected of suffering relapse supports a complex scheme of relapse whereby recurrence of multiple identical variants is sometimes accompanied by the appearance of novel variants.

show abstract

Failure of artesunate-mefloquine combination therapy for uncomplicated Plasmodium falciparum malaria in southern Cambodia

Abstract: Background: Resistance to anti-malarial drugs hampers control efforts and increases the risk of morbidity and mortality from malaria. The efficacy of standard therapies for uncomplicated Plasmodium falciparum and Plasmodium vivax malaria was assessed in Chumkiri, Kampot Province, Cambodia.

Cited by 196 publications

References 21 publications

Molecular Surveillance as Monitoring Tool for Drug-Resistant Plasmodium falciparum in Suriname

Molecular Surveillance as Monitoring Tool for Drug-Resistant Plasmodium falciparum in Suriname

Inhibitory Effects of Pepstatin A and Mefloquine on the Growth of Babesia Parasites

Plasmodium vivax Isolates from Cambodia and Thailand Show High Genetic Complexity and Distinct Patterns of P. vivax Multidrug Resistance Gene 1 (pvmdr1) Polymorphisms

Contact Info

Product

Resources

About