Amodiaquine for treating malaria

Olliaro, Piero; Mussano, Paola

doi:10.1002/14651858.cd000016

Cited by 81 publications

(80 citation statements)

References 31 publications

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“…22 It is, therefore, surprising that, in patients treated with AL where the lumefantrine component has little or no antipyretic property, fever clearance was similar to that of the children treated with AA. This would suggest that, in this cohort of children, fever clearance paralleled parasite clearance.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Efficacy and Effects of Artemether-Lumefantrine and Artesunate-Amodiaquine Coformulated or Copackaged on Malaria-Associated Anemia in Children with Uncomplicated Plasmodium falciparum Malaria in Southwest Nigeria

Gbotosho¹,

Sowunmi²,

Dokunmu³

et al. 2011

The American Society of Tropical Medicine and Hygiene

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The therapeutic efficacy and effects of artemether-lumefantrine (AL) and artesunate-amodiaquine co-formulated (AAcf) or co-packaged (AAcp) on malaria-associated anemia (MAA) were evaluated in 285 children < 12 years of age with uncomplicated Plasmodium falciparum malaria randomized to receive one of the three drug combinations. Fever and parasite clearance times were similar in all treatment groups. Mean drug-attributable fall in hematocrit (DAFH), defined as difference between hematocrit values pre- and 3 d post- initiation of treatment, was low (< 4.5%) and rates of recovery from MAA were similar with all treatments. Mean areas under curve (AUCs) of the plot of deficit in hematocrit levels from 30% versus time in anemic children were similar in all groups. All regimens were well tolerated. AL, AAcf and AAcp cleared fever and parasitemia rapidly and had similar rates of resolution of MAA after treatment in malarious Nigerian children.

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Section: Discussionmentioning

confidence: 99%

Therapeutic Efficacy and Effects of Artemether-Lumefantrine and Artesunate-Amodiaquine Coformulated or Copackaged on Malaria-Associated Anemia in Children with Uncomplicated Plasmodium falciparum Malaria in Southwest Nigeria

Gbotosho¹,

Sowunmi²,

Dokunmu³

et al. 2011

The American Society of Tropical Medicine and Hygiene

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“…The former was expected, because the amodiaquine component of AA has a potent antipyretic effect. 31 This antipyretic effect may be dose-dependent: a recent study from the area showed that children who received higher doses cleared parasitemia or fever significantly faster than children receiving the standard doses of AA. 32 Rapid asexual parasite clearance is characteristic of all ACTs 33 and the ACTs evaluated in the present cohort of children.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Efficacies of Artemisinin-Based Combination Therapies in Nigerian Children with Uncomplicated Falciparum Malaria during Five Years of Adoption as First-Line Treatments

Gbotosho

Sowunmi²,

Happi³

et al. 2011

The American Society of Tropical Medicine and Hygiene

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Abstract. The therapeutic efficacies of 3-day regimens of artesunate-amodiaquine and artemether-lumefantrine during 5 years of adoption as first-line treatments were evaluated in 811 ≤ 12-year-old malarious children. Compared with artemether-lumefantrine, amodiaquine-artesunate significantly reduced the proportion of children with fever and parasitemia 1 day after treatment (day 1; P < 0.008 for both). The proportion of parasitemic children on day 2 and gametocytemia on presentation and carriage reduced significantly over the years ( P < 0.000001 and P < 0.03, respectively; test for trend). Overall efficacy was 96.5% (95% confidence interval [CI] = 94.5-98.6) and remained unchanged over the years ( P = 0.87; test for trend). Kinetics of parasitemias after treatments were estimated by a non-compartmental model. Declines of parasitemias were monoexponential, with a mean elimination half-life of 1.09 hours (95% CI = 1.0-1.16). Parasitemia half-lives and efficacy were similar for both regimens and in all ages. Artesunate-amodiaquine and artemether-lumefantrine remain efficacious treatments of uncomplicated falciparum malaria in Nigerian children 5 years after adoption.

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“…Against the backdrop of this figure, we endorse earlier recommendations (10) for using adequate protocols and to report study results stratified or adjusted by age and, ideally, pretreatment parasite density. This is especially important for large meta-analyses of antimalarial trials, which have mainly reported averaged treatment outcomes (29). For proof-of-principle studies, e.g., in phase II, trials with semi-immune populations (older children, adults) may be desirable due to safety and ethical considerationswith the important limitation that the results may tell only about 25% of the "truth" of the performance of a drug in particularly susceptible high-risk populations.…”

Section: Vol 52 2008mentioning

confidence: 99%

Effects of Plasmodium falciparum Parasite Population Size and Patient Age on Early and Late Parasitological Outcomes of Antimalarial Treatment in Children

Borrmann

Matsiégui

Missinou

et al. 2008

Antimicrob Agents Chemother

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The design and interpretation of trials assessing the chemotherapeutic effects of antimalarial drugs depend on our understanding of how different selection criteria affect treatment outcomes. In this study, we analyzed the effects of baseline parameters on the initial parasite elimination rate and the risk of subsequent recrudescence as a marker for incompletely eliminated asexual blood-stage parasites in pediatric patients with uncomplicated Plasmodium falciparum infection treated with amodiaquine in a high-transmission area. We found that (i) parasite population size and patient age independently determine early and late parasitological treatment outcome measurements; (ii) the rate of recrudescence is higher in patients 1 to 3 years of age than in patients aged <1 or >3 years; (iii) patients aged >5 years with parasite densities between 2,000 and 10,000/l have a lower recrudescence rate (13%; 95% confidence interval [CI], 8% to 21%) than patients aged <5 years with parasite densities of >10,000/l (40%; 95% CI, 30% to 50%); and (iv) the sensitivity of detecting recrudescences outside this high-risk group, i.e., in patients of >5 years of age or with parasite densities of <10,000/l, is as low as 27% or 22%, respectively. In conclusion, these findings highlight the need to use adequate selection criteria and to report parasitological outcome results adjusted for the readily available determinants of chemotherapeutic failure, i.e., patient age and baseline parasitemia. The thresholds may vary by transmission intensity and drug regimen. A better understanding of the limitations of antimalarial regimens in high-risk subgroups of patients has important implications for setting policy recommendations.Antimalarial treatment trials provide the empirical evidence base for antimalarial treatment policies in countries where malaria is endemic (44). These trials use variable endpoints to address a range of public health questions. For instance, trials conducted to monitor the emergence or the spread of in vivo resistance or to determine the chemotherapeutic efficacy of a new regimen are designed to measure the ability of the treatment to completely eliminate asexual blood-stage parasites and, thus, to prevent recrudescent infections. On the other hand, the delay of reinfection caused by the effects of slowly eliminated drugs on the erythrocytic and, in some cases, hepatic stages of Plasmodium falciparum infection (14) can be an important additional clinical benefit of antimalarial treatment. This has been investigated in studies that use a combined measurement of the chemotherapeutic and the "posttreatment prophylactic" effects ("recurrence rate") or that simply determine the requirement for retreatment (12). Regardless of the objectives in these trials, the characterization of the limitations of an antimalarial regimen in important subgroups of patients at high risk of failure, who may also be disproportionately susceptible to adverse clinical outcomes, will provide critical information for setting policy recommendations. ...

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Amodiaquine for treating malaria

Cited by 81 publications

References 31 publications

Therapeutic Efficacy and Effects of Artemether-Lumefantrine and Artesunate-Amodiaquine Coformulated or Copackaged on Malaria-Associated Anemia in Children with Uncomplicated Plasmodium falciparum Malaria in Southwest Nigeria

Therapeutic Efficacy and Effects of Artemether-Lumefantrine and Artesunate-Amodiaquine Coformulated or Copackaged on Malaria-Associated Anemia in Children with Uncomplicated Plasmodium falciparum Malaria in Southwest Nigeria

Therapeutic Efficacies of Artemisinin-Based Combination Therapies in Nigerian Children with Uncomplicated Falciparum Malaria during Five Years of Adoption as First-Line Treatments

Effects of Plasmodium falciparum Parasite Population Size and Patient Age on Early and Late Parasitological Outcomes of Antimalarial Treatment in Children

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