Efficacy and Effectiveness of Artemether-Lumefantrine after Initial and Repeated Treatment in Children &lt; 5 Years of Age with Acute Uncomplicated Plasmodium falciparum Malaria in Rural Tanzania: A Randomized Trial

Ngasala, Billy; Malmberg, Maja; Carlsson, Anja M.; Ferreira, Pedro Eduardo; Petzold, Max; Blessborn, Daniel; Bergqvist, Yngve; Gil, José Pedro; Premji, Zul; Björkman, Anders; Mårtensson, Andreas

doi:10.1093/cid/cir066

Cited by 63 publications

(71 citation statements)

References 31 publications

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“…The percentage of re-infection in this study was higher compared to the findings in the above studies. However, a more recent study, Ngasala et al, showed similar high frequencies of LPF as shown here [29]. The meeting proceedings reported by Hunt et al [12], presented evidence of parasites in East Africa being less well con- referred to as reduced efficacy of artemisinin combination therapies seen in South-east Asia [7].…”

Section: Discussionsupporting

confidence: 68%

“…There was however, a surprisingly high frequency of mutations in pfcrt and pfmdr1 in subpatent re-infections found in follow-up samples. This contrasts with most earlier studies, but a similar tendency for pfcrt is observed in Ngasala et al, where at least no significant difference in pfcrt frequencies were found in re-infections [29]. The remaining pfcrt and pfmdr1 mutations indicates that it will be very difficult to completely reverse CQ resistance once the resistance has been established and reusing CQ may lead to rapid emergence of CQ resistance.…”

Section: Totalcontrasting

confidence: 72%

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Efficacy of artemether-lumefantrine in treatment of malaria among under-fives and prevalence of drug resistance markers in Igombe-Mwanza, north-western Tanzania

Kamugisha,

Jing,

Minde

et al. 2012

Malar J

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Background: Drug resistance to anti-malarials is a major public health problem worldwide. This study aimed at establishing the efficacy of artemether-lumefantrine (ACT) in Igombe-Mwanza, north-western Tanzania after a few years of ACT use, and establish the prevalence of mutations in key targets for artemisinin, chloroquine and sulphadoxine/pyrimetamine (SP) drugs. Methods: A prospective single cohort study was conducted at Igombe health centre using artemetherlumefantrine combination therapy between February 2010 and March 2011. The follow-up period was 28 days and outcome measures were according to WHO guidelines. Blood was collected on Whatman filter paper for DNA analysis. DNA extraction was done using TRIS-EDTA method, and mutations in Pfcrt, Pfmdr1, Pfdhfr, Pfdhps and Pfatp6 were detected using PCR-RFLP methods established previously. Results: A total of 103 patients completed the 28 days follow-up. The mean haemoglobin was 8.9 g/dl (range 5.0 to 14.5 g/dl) and mean parasite density was 5,608 parasites/μl. Average parasite clearance time was 34.7 hours and all patients cleared the parasites by day 3. There was no early treatment failure in this study. Late clinical failure was seen in three (2.9%) patients and late parasitological failure (LPF) was seen in two (1.9%). PCR-corrected LPF was 1% and adequate clinical and parasitological response was 96%. The majority of parasites have wild type alleles on pfcrt 76 and pfmdr1 86 positions being 87.8% and 93.7% respectively. Mutant parasites predominated at pfdhfr gene at the main three positions 108, 51 and 59 with prevalence of 94.8%, 75.3% and 82.5% respectively. Post-treatment parasites had more wild types of pfdhps at position 437 and 540 than pre-treatment parasites. No mutation was seen in pfatp6 769 in re-infecting or recrudescing parasites.

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Section: Discussionsupporting

confidence: 68%

Section: Totalcontrasting

confidence: 72%

Efficacy of artemether-lumefantrine in treatment of malaria among under-fives and prevalence of drug resistance markers in Igombe-Mwanza, north-western Tanzania

Kamugisha,

Jing,

Minde

et al. 2012

Malar J

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“…The true efficacy of AL could be underestimated here, as we were not able to observe the three evening doses. However, previous studies comparing the efficacy of fully supervised and unsu- pervised (five out of six doses taken at home) dosing did not find significant differences in measured efficacies (28,29). Meta-analyses show that DP has higher PCR-corrected efficacies than AL, at least in the African setting (30).…”

Section: Screeningmentioning

confidence: 82%

Efficacy of Artemether-Lumefantrine and Dihydroartemisinin-Piperaquine for Treatment of Uncomplicated Malaria in Children in Zaire and Uíge Provinces, Angola

Pluciński

Talundzic

Morton

et al. 2015

Antimicrob Agents Chemother

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The development of resistance to antimalarials is a major challenge for global malaria control. Artemisinin-based combination therapies, the newest class of antimalarials, are used worldwide but there have been reports of artemisinin resistance in Southeast Asia. In February through May 2013, we conducted open-label, nonrandomized therapeutic efficacy studies of artemetherlumefantrine (AL) and dihydroartemisinin-piperaquine (DP) in Zaire and Uíge Provinces in northern Angola. The parasitological and clinical responses to treatment in children with uncomplicated Plasmodium falciparum monoinfection were measured over 28 days, and the main outcome was a PCR-corrected adequate clinical and parasitological response (ACPR) proportion on day 28. Parasites from treatment failures were analyzed for the presence of putative molecular markers of resistance to lumefantrine and artemisinins, including the recently identified mutations in the K13 propeller gene. In the 320 children finishing the study, 25 treatment failures were observed: 24 in the AL arms and 1 in the DP arm. The PCR-corrected ACPR proportions on day 28 for AL were 88% (95% confidence interval [CI], 78 to 95%) in Zaire and 97% (91 to 100%) in Uíge. For DP, the proportions were 100% (95 to 100%) in Zaire, and 100% (96 to 100%) in Uíge. None of the treatment failures had molecular evidence of artemisinin resistance. In contrast, 91% of AL late-treatment failures had markers associated with lumefantrine resistance on the day of failure. The absence of molecular markers for artemisinin resistance and the observed efficacies of both drug combinations suggest no evidence of artemisinin resistance in northern Angola. There is evidence of increased lumefantrine resistance in Zaire, which should continue to be monitored.

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“…4 Fortunately, death from malaria can be avoided with prompt diagnosis and effective therapy with artemisininbased combination therapy (ACT). 5,6 Additionally, the burden of malaria is decreasing, in large part due to enhanced government commitment and external donor funding to support the scale-up of proven interventions. 7 Although malaria prevention and treatment measures have been improved, adoption of more efficacious, but more expensive, options may be particularly burdensome to those most in need and as such treatment may be delayed or deferred.…”

Section: Introductionmentioning

confidence: 99%

Cost and Predictors of Care-Seeking Behaviors Among Caregivers of Febrile Children—Uganda, 2009

Menon

Njau

McFarland³

2016

The American Society of Tropical Medicine and Hygiene

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Abstract. Fever is a major cause of morbidity and mortality among children under 5 years of age in resource-limited countries. Although prevention and treatment of febrile illnesses have improved, the costs-both financial and nonfinancialremain barriers to care. Using data from the 2009 Uganda Malaria Indicator Survey, we describe the costs associated with the care of a febrile child and assess predictors of care-seeking behavior. Over 80% of caregivers sought care for their febrile child, however less than half did so on either the day of or the day after the development of fever. The odds of seeking care decreased with each additional month of the child's age. Caregivers living in rural areas were more likely to seek care, however were less likely to seek care promptly. Caregivers with at least a primary school education and those familiar with the protective effect of bed nets and the need to seek care promptly were more likely to seek care. Despite government assistance, the majority of caregivers did incur costs (mean 13,173 Ugandan shilling; $6.84 U.S. dollars) associated with medical care. Continued efforts targeting barriers to seeking care, including the economic burden, are necessary.

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Efficacy and Effectiveness of Artemether-Lumefantrine after Initial and Repeated Treatment in Children < 5 Years of Age with Acute Uncomplicated Plasmodium falciparum Malaria in Rural Tanzania: A Randomized Trial

Abstract: ISRCTN69189899.

Cited by 63 publications

References 31 publications

Efficacy of artemether-lumefantrine in treatment of malaria among under-fives and prevalence of drug resistance markers in Igombe-Mwanza, north-western Tanzania

Efficacy of artemether-lumefantrine in treatment of malaria among under-fives and prevalence of drug resistance markers in Igombe-Mwanza, north-western Tanzania

Efficacy of Artemether-Lumefantrine and Dihydroartemisinin-Piperaquine for Treatment of Uncomplicated Malaria in Children in Zaire and Uíge Provinces, Angola

Cost and Predictors of Care-Seeking Behaviors Among Caregivers of Febrile Children—Uganda, 2009

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