A Trial of Combination Antimalarial Therapies in Children from Papua New Guinea

Karunajeewa, HA; Müeller, Ivo; Senn, Michèle; Lin, Enmoore; Law, Irwin; Ps, Gomorrai; O, Oa; Griffin, Susan; Kotab, K; Suano, P; Tarongka, Nandao; A, Ura; D, Lautu; Page‐Sharp, Madhu; Wong, Rina P. M.; Salman, Sam; Siba, Peter; Kf, Ilett; Davis, Timothy M. E.

doi:10.1056/nejmoa0804915

Cited by 177 publications

(238 citation statements)

References 32 publications

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“…In a study conducted in Thailand 21 comparing the efficacy of CQ and AL combined with a 14-day course of primaquine, full treatment success was achieved in the CQ treatment group, whereas the treatment success with AL was slightly lower at 97.4%. Another study also reported greater post-treatment prophylaxis in averting P. vivax recurrences with dihydroartemisinin-piperaquine than with AL, 22 and dihydroartemisin-piperaquine has been indicated as highly efficacious as AL for the treatment of P. vivax . 23 …”

Section: Discussionmentioning

confidence: 95%

Confirmed Vivax Resistance to Chloroquine and Effectiveness of Artemether-Lumefantrine for the Treatment of Vivax Malaria in Ethiopia

Yohannes

Teklehaimanot²,

Bergqvist³

et al. 2011

The American Society of Tropical Medicine and Hygiene

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Chloroquine (CQ) is still the drug of choice for the treatment of vivax malaria in Ethiopia, whereas artemether-lumefantrine (AL) is for falciparum malaria. In this setting, clinical malaria cases are treated with AL. This necessitated the need to assess the effectiveness of AL for the treatment of Plasmodium vivax with CQ as a comparator. A total of 57 (80.3%) and 75 (85.2%) cases treated with CQ or AL, respectively, completed the study in an outpatient setting. At the end of the follow-up period of 28 days, a cumulative incidence of treatment failure of 7.5% (95% confidence interval [CI] = 2.9–18.9%) for CQ and 19% (95% CI = 11–31.6%) for AL was detected. CQ resistance was confirmed in three of five CQ treatment failures cases. The effectiveness of AL seems lower than CQ; however, the findings were not conclusive, because the AL evening doses were not supervised.

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Section: Discussionmentioning

confidence: 95%

Confirmed Vivax Resistance to Chloroquine and Effectiveness of Artemether-Lumefantrine for the Treatment of Vivax Malaria in Ethiopia

Yohannes

Teklehaimanot²,

Bergqvist³

et al. 2011

The American Society of Tropical Medicine and Hygiene

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“…[10][11][12][13] Reappearance of parasitemia after drug treatment can result from either (1) recrudescence of surviving asexual bloodstage parasites, (2) relapse from dormant liver stages known as hypnozoites, or (3) new infections with unrelated parasites. Molecular genotyping of paired parasite samples usually makes a distinction between recrudescences (with the same genotype as the initial infection) and new infections (with a different genotype), but relapses may originate from reactivation of either the same parasite clone found in the primary bloodstream infection (homologous hypnozoites) or another, genetically different clone (heterologous hypnozoites).…”

Section: Introductionmentioning

confidence: 99%

Recurrent Parasitemias and Population Dynamics of Plasmodium vivax Polymorphisms in Rural Amazonia

Orjuela-Sánchez¹,

Silva²,

Silva‐Nunes³

et al. 2009

The American Journal of Tropical Medicine and Hygiene

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Abstract. Clinical trials documented alarming post-treatment Plasmodium vivax recurrence rates caused by recrudescence of surviving asexual blood stages, relapse from hypnozoites, or new infections. Here we describe high rates of P. vivax recurrence (26-40% 180 days after treatment) in two cohorts of rural Amazonians exposed to low levels of malaria transmission after a vivax malaria episode treated with chloroquine-primaquine. Microsatellite analysis of 28 paired acute infection and recurrence parasites showed only two pairs of identical haplotypes (consistent with recrudescences or reactivation of homologous hypnozoites) and four pairs of related haplotypes (sharing alleles at 11-13 of 14 microsatellites analyzed). Local isolates of P. vivax were extraordinarily diverse and rarely shared the same haplotype, indicating that frequent recurrences did not favor the persistence or reappearance of clonal lineages of parasites in the population. This fast haplotype replacement rate may represent the typical population dynamics of neutral polymorphisms in parasites from low-endemicity areas.

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“…However, the efficacy of this treatment regimen was found to be low only 3 years after its implementation, 2 which gives a strong argument for the introduction of artemisinin-based combination therapies. A recent study conducted in PNG 3 has tested the efficacy of different artemisinin-combination therapies in children < 5 years of age with Plasmodium falciparum or Plasmodium vivax malaria. Artemether-lumefantrine was found to be the most effective combination therapy against P. falciparum with an adequate clinical and parasitological response of 97.3% at Day 28 and 95.2% at Day 42 after treatment.…”

Section: Introductionmentioning

confidence: 99%

Treatment with Coartem (Artemether-Lumefantrine) in Papua New Guinea

Schoepflin

Lin

Kiniboro

et al. 2010

The American Society of Tropical Medicine and Hygiene

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Abstract. A recent drug efficacy trial reported Coartem (artemether-lumefantrine) to be highly effective against Plasmodium falciparum in children less than 5 years of age in Papua New Guinea (PNG). In contrast, we have observed high levels of treatment failures in non-trial conditions in a longitudinal cohort study in the same age group in PNG. Recrudescences were confirmed by genotyping of three different marker genes to provide optimal discrimination power between parasite clones. After excluding genetic host factors by genotyping potentially relevant cytochrome P450 loci, the high number of treatment failures in our study is best explained by poor adherence to complex dosing regimens in combination with insufficient fat supplementation, which are both crucial parameters for the outcome of Coartem treatment. In contrast to the situation in classic drug trials with ideal treatment conditions, our field survey highlights potential problems with unsupervised usage of Coartem in routine clinical practice and under program conditions.

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A Trial of Combination Antimalarial Therapies in Children from Papua New Guinea

Cited by 177 publications

References 32 publications

Confirmed Vivax Resistance to Chloroquine and Effectiveness of Artemether-Lumefantrine for the Treatment of Vivax Malaria in Ethiopia

Confirmed Vivax Resistance to Chloroquine and Effectiveness of Artemether-Lumefantrine for the Treatment of Vivax Malaria in Ethiopia

Recurrent Parasitemias and Population Dynamics of Plasmodium vivax Polymorphisms in Rural Amazonia

Treatment with Coartem (Artemether-Lumefantrine) in Papua New Guinea

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