Efficacy and safety of artemisinin-based antimalarial in the treatment of uncomplicated malaria in children in southern Tanzania

Kabanywanyi, Abdunoor M.; Mwita, Alex; Sumari, Deborah; Mandike, Renata; Mugittu, Kefas; Abdulla, Salim

doi:10.1186/1475-2875-6-146

Cited by 62 publications

(62 citation statements)

References 15 publications

(14 reference statements)

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“…Overall, the study showed a high efficacy of the two forms of ACTs in Nigerian children; the PCR-adjusted cure rate on day 28 was 100% in both treatment groups. These results are in agreement with earlier studies in Nigeria that have shown both combinations to be safe and well tolerated [7,8,17] and are also consistent with the high cure rates that have been reported for ACT in other malaria-endemic areas of Africa [18][19][20]. Artemisinin and related endo-peroxide antimalarials act rapidly by clearing P. falciparum in the blood, thereby providing prompt therapy for severe infections [21].…”

Section: Discussionsupporting

confidence: 91%

“…Some studies have reported a marginally higher day 28 PCR-corrected cure rate for artemether-lumefantrine over artesunate plus amodiaquine as opposed to others. Generally, studies from eastern Africa [18,24] seem to suggest that artemether-lumefantrine has more clinical benefits than artesunate plus amodiaquine, while studies from western Africa [17,20] show that artesunate plus amodiaquine tend to have marginally better efficacy rates over artemether-lumefantrine. The reason for this The figure shows the percentage reduction of parasitaemia from the recruitment day (day 0) over the follow-up period of 28 days according to the per-protocol analysis observation needs to be further investigated.…”

Section: Discussionmentioning

confidence: 99%

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Efficacy of artemisinin combination therapy for the treatment of uncomplicated falciparum malaria in Nigerian children

Ojurongbe

Lawal

Abiodun

et al. 2013

J Infect Dev Ctries

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Introduction: The development and spread of Plasmodium falciparum resistance to most commonly used antimalarials remain a major challenge in the control of malaria. Constant monitoring of drug efficacy is an important tool in establishing rational antimalarial drug policies. Methodology: A randomized comparative study was conducted at the Wesley Guild Hospital, Ilesa, Nigeria between February 2010 and September 2011 comparing the efficacy and safety of artemether-lumefantrine (Coartem) and fixed dose of artesunate plus amodiaquine (Larimal) in the treatment of uncomplicated P. falciparum malaria in children betweem 6 and 144 months of age. P. falciparum malaria parasitemia was assessed by microscopy and rapid diagnostic test. Drugs were administered according to age for three days under supervision. The primary efficacy endpoint was a day 28 PCR-corrected parasitological cure. Results: A total of 182 patients were enrolled in the two treatment groups, Coartem (n = 101) and Larimal (n = 81), and tested after 28 days. In the intention-to-treat population, Coartem (n= 101) and Larimal (n= 81) had a PCR-corrected cure rate of 98% and 100% respectively, while in the per-protocol population, Coartem (n = 89) and Larimal (n = 71) both had a PCR-corrected cure rate of 100% at day 28. Although parasite and fever clearance time was faster in the Larimal group, no significant difference was observed between the two drugs. No serious adverse effects were reported. Conclusion: Five years after being introduced in Nigeria, both Coartem and Larimal have been shown to be safe and highly effective in the treatment of uncomplicated P. falciparum malaria in children.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Efficacy of artemisinin combination therapy for the treatment of uncomplicated falciparum malaria in Nigerian children

Ojurongbe

Lawal

Abiodun

et al. 2013

J Infect Dev Ctries

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“…[37][38][39] In contrast, results from Central and East Africa show higher efficacy of AL than ASAQ, especially a higher potency in preventing reinfections. 14,40 In the present study, both treatments were equivalent regarding parasite and fever clearance rates and gametocyte carriage. As already described, 29 ACTs triggered a rapid asexual parasite clearance in the present cohort.…”

Section: Discussionmentioning

confidence: 52%

Assessment of the efficacy of first-line antimalarial drugs after 5 years of deployment by the National Malaria Control Programme in Côte d'Ivoire

Offianan¹,

Assi²,

A³

et al. 2011

OAJCT

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Background:The emergence of artemisinin resistance has raised concerns that the most potent antimalarial drug may be under threat. Artesunate + amodiaquine (ASAQ) and artemetherlumefantrine (AL) are respectively the first-and second-line treatments for uncomplicated falciparum malaria in Côte d'Ivoire. A comparison of the efficacy and safety of these two drug combinations was necessary to make evidence-based drug treatment policies. Methods:In an open-label, non inferiority, randomized, controlled clinical trial, children aged 6-59 months were randomized to receive ASAQ or AL. Both drug regimens were given for 3 days, and follow-up was for 28 days. The primary endpoint was the 28-day cure rates and was defined as proportion of patients with polymerase chain reaction (PCR)-corrected cure rate after 28 days of follow-up. Findings: A total of 251 patients who were attending the Ayame and Dabakala hospitals and presenting with symptomatic acute uncomplicated falciparum malaria were randomized to receive ASAQ (128) and AL (123). The intention-to-treat analysis showed effectiveness rates of 94.5% and 93.5% for ASAQ and AL, respectively on day 28. After adjustment for PCR results, these rates were 96.1% and 96.8%, respectively. On day 28, the per-protocol analysis showed effectiveness rates of 98.4% and 96.6% for ASAQ and AL, respectively. After adjustment by PCR for reinfection, these rates were 100% for each drug, and both regimens were well tolerated. Conclusion: ASAQ and AL remain efficacious treatments of uncomplicated falciparum malaria in Ivorian children 5 years after adoption. The efficacy of ASAQ and AL in Côte d'Ivoire requires, therefore, continuous monitoring and evaluation.

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“…In this study, we analyzed and compared malaria patients who were enrolled in Cambodia and Tanzania. Artemether-lumefantrine (AL) has been the first-line treatment for uncomplicated malaria since the end of 2006 and displays good efficacy in Tanzania (18). In Cambodia, however, its efficacy since 2002 has been reported in all but one study to be considerably and consistently lower (19,20,21).…”

mentioning

confidence: 99%

Effect of Single Nucleotide Polymorphisms in Cytochrome P450 Isoenzyme and N -Acetyltransferase 2 Genes on the Metabolism of Artemisinin-Based Combination Therapies in Malaria Patients from Cambodia and Tanzania

Hodel

Csajka

Ariey

et al. 2013

Antimicrob Agents Chemother

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The pharmacogenetics of antimalarial agents are poorly known, although the application of pharmacogenetics might be critical in optimizing treatment. This population pharmacokinetic-pharmacogenetic study aimed at assessing the effects of single nucleotide polymorphisms (SNPs) in cytochrome P450 isoenzyme genes (CYP, namely, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5) and the N-acetyltransferase 2 gene (NAT2) on the pharmacokinetics of artemisininbased combination therapies in 150 Tanzanian patients treated with artemether-lumefantrine, 64 Cambodian patients treated with artesunate-mefloquine, and 61 Cambodian patients treated with dihydroartemisinin-piperaquine. The frequency of SNPs varied with the enzyme and the population. Higher frequencies of mutant alleles were found in Cambodians than Tanzanians for CYP2C9*3, CYP2D6*10 (100C¡T), CYP3A5*3, NAT2*6, and NAT2*7. In contrast, higher frequencies of mutant alleles were found in Tanzanians for CYP2D6*17 (1023C¡T and 2850C¡T), CYP3A4*1B, NAT2*5, and NAT2*14. For 8 SNPs, no significant differences in frequencies were observed. In the genetic-based population pharmacokinetic analyses, none of the SNPs improved model fit. This suggests that pharmacogenetic data need not be included in appropriate first-line treatments with the current artemisinin derivatives and quinolines for uncomplicated malaria in specific populations. However, it cannot be ruled out that our results represent isolated findings, and therefore more studies in different populations, ideally with the same artemisininbased combination therapies, are needed to evaluate the influence of pharmacogenetic factors on the clearance of antimalarials.

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Efficacy and safety of artemisinin-based antimalarial in the treatment of uncomplicated malaria in children in southern Tanzania

Cited by 62 publications

References 15 publications

Efficacy of artemisinin combination therapy for the treatment of uncomplicated falciparum malaria in Nigerian children

Efficacy of artemisinin combination therapy for the treatment of uncomplicated falciparum malaria in Nigerian children

Assessment of the efficacy of first-line antimalarial drugs after 5 years of deployment by the National Malaria Control Programme in Côte d'Ivoire

Effect of Single Nucleotide Polymorphisms in Cytochrome P450 Isoenzyme and N -Acetyltransferase 2 Genes on the Metabolism of Artemisinin-Based Combination Therapies in Malaria Patients from Cambodia and Tanzania

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Efficacy and safety of artemisinin-based antimalarial in the treatment of uncomplicated malaria in children in southern Tanzania

Cited by 62 publications

References 15 publications

Efficacy of artemisinin combination therapy for the treatment of uncomplicated falciparum malaria in Nigerian children

Efficacy of artemisinin combination therapy for the treatment of uncomplicated falciparum malaria in Nigerian children

Assessment of the efficacy of first-line antimalarial drugs after 5 years of deployment by the National Malaria Control Programme in C&ocirc;te d'Ivoire

Effect of Single Nucleotide Polymorphisms in Cytochrome P450 Isoenzyme and N -Acetyltransferase 2 Genes on the Metabolism of Artemisinin-Based Combination Therapies in Malaria Patients from Cambodia and Tanzania

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Assessment of the efficacy of first-line antimalarial drugs after 5 years of deployment by the National Malaria Control Programme in Côte d'Ivoire