Efficacy of amodiaquine against chloroquine-resistant malaria in Cameroon

Fadat, G.; Bras, J. Le; Hengy, C.; Louis, Jean‐Paul; Gimou, Marie-Madeleine; Verdier, F.

doi:10.1016/0140-6736(91)91959-x

Cited by 13 publications

(6 citation statements)

References 4 publications

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“…Consequently, both pyrimethaminesulfadoxine and amodiaquine may still be used for treatment of malaria in certain situations (Fadat et al 1991;Hall et al 1977). …”

Section: Risk-benefit Considerationsmentioning

confidence: 98%

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Adverse Effects of Antimalarials

Luzzi

Peto

1993

Drug Safety

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Various drugs are widely used in the prophylaxis and treatment of malaria. In the prevention of malaria in travellers, a careful risk-benefit analysis is required to balance the risk of acquiring potentially serious malaria against the risk of harm from the prophylactic agent. Unfortunately, the information needed to perform accurate analyses of this type is not available for most antimalarials. In the prophylaxis of malaria, chloroquine and proguanil have an excellent safety record, being very rarely associated with severe adverse reactions in the recommended dosages. However, in many parts of the world they are no longer effective prophylactic agents. Pyrimethamine-dapsone (Maloprim) is associated with agranulocytosis, especially if the recommended dose is exceeded, and should be reserved as a second-line agent for travellers to high risk areas. Pyrimethamine-sulfadoxine (Fansidar) and amodiaquine are associated with a relatively high incidence of potentially fatal reactions, and are no longer recommended for prophylaxis. Mefloquine, a relative newcomer, may provoke severe neuropsychiatric reactions with a frequency of 1 in 15,000 to 20,000 users at the prophylactic dosage. In the treatment of Plasmodium falciparum malaria, which has a high mortality if untreated, a greater risk of adverse reactions to antimalarial drugs is acceptable. As chloroquine resistance has become widespread, alternative agents including quinine, mefloquine, pyrimethamine-sulfadoxine, tetracyclines, halofantrine and artemisinin (qinghaosu) and its derivatives may be used in treatment regimens. The therapeutic ratios for chloroquine, quinine and mefloquine are narrow and toxicity is frequent when recommended treatment dosages are exceeded; parenteral administration above the recommended dose range is especially associated with the hazards of cardiac and neurological toxicity.

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“…Consequently, both pyrimethaminesulfadoxine and amodiaquine may still be used for treatment of malaria in certain situations (Fadat et al 1991;Hall et al 1977). …”

Section: Risk-benefit Considerationsmentioning

confidence: 98%

“…Serious hepatic disorders also occurred, with a frequency of I in 15 000 users (Phillips-Howard & West 1990). Recently, workers have suggested that the value of amodiaquine in the treatment of chloroquine-resistant malaria in areas of troublesome multiple drug resistance should be reassessed (Fadat et al 1991). …”

Section: Amodiaquinementioning

confidence: 98%

Adverse Effects of Antimalarials

Luzzi

Peto

1993

Drug Safety

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“…The interest in amodiaquine, especially in combination with sulfadoxine-pyrimethamine or artesunate, as a replacement drug in areas of chloroquine resistance continues to grow (7,13,38) despite the important limitation of geographically heterogeneous response rates (1) and the potential for high degrees of amodiaquine cross-resistance with chloroquine (2). An overall parasitological failure rate of 35% clearly neither warrants the use of amodiaquine as monotherapy nor encourages its use in combination with other drugs.…”

Section: Discussionmentioning

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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“…Twenty-six percent (17/66) of tested pretreatment P. falciparum field isolates had 50% in vitro growth inhibition at concentrations of N-desethyl-amodiaquine (DEAQ)-the major biologically active metabolite of amodiaquine-above the proposed resistance threshold of 60 nmol/L, but baseline median DEAQ 50% inhibitory concentration values were not associated with subsequent risk of asexual parasite recrudescence ( Because of rare but serious hematological and hepatic toxicity when used for malaria prophylaxis [1,2], amodiaquine is recommended only for treatment of falciparum malaria [3,4]. There was a renewed interest in amodiaquine monotherapy in the face of high chloroquine resistance in the 1990s, because it was shown to retain higher efficacy than chloroquine against chloroquineresistant parasites [5,6]. Since then, amodiaquine has been used widely in Africa as an alternative to chloroquine or as second-line treatment.…”

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confidence: 98%

In Vivo and In Vitro Efficacy of Amodiaquine againstPlasmodium falciparumin an Area of Continued Use of 4‐Aminoquinolines in East Africa

et al. 2009

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In light of reports of increasing resistance of parasites to amodiaquine in African countries in which Plasmodium falciparum is endemic as well as the paucity of recent in vitro sensitivity data, we assessed the in vivo and in vitro sensitivity to amodiaquine of P. falciparum isolates from 128 pediatric outpatients (0.5-10 years old) in Pingilikani, Kilifi District, Kenya, who were treated with amodiaquine (10 mg/kg/day for 3 days). The polymerase chain reaction-corrected parasitological cure rate on day 28 (by Kaplan-Meier analysis) was 82% (95% confidence interval [CI], 74%-88%). Twenty-six percent (17/66) of tested pretreatment P. falciparum field isolates had 50% in vitro growth inhibition at concentrations of N-desethyl-amodiaquine (DEAQ)-the major biologically active metabolite of amodiaquine-above the proposed resistance threshold of 60 nmol/L, but baseline median DEAQ 50% inhibitory concentration values were not associated with subsequent risk of asexual parasite recrudescence (29 nmol/L [95% CI, 23-170 nmol/L] and 34 nmol/L [95% CI, 30-46 nmol/L] for patients with and those without recrudescences, respectively). The median absolute neutrophil count dropped by 1.3 X 10(3) cells/microL (95% CI, -1.7 X 10(3) to -0.7 X 10(3) cells/microL) between days 0 and 28. The high prevalence of in vitro and in vivo resistance precludes the use of amodiaquine on its own as second-line treatment. These findings also suggest that the value of amodiaquine combinations as first- or second-line treatment in areas with similar patterns of 4-aminoquinoline resistance should be reassessed.

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Efficacy of amodiaquine against chloroquine-resistant malaria in Cameroon

Cited by 13 publications

References 4 publications

Adverse Effects of Antimalarials

Adverse Effects of Antimalarials

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

In Vivo and In Vitro Efficacy of Amodiaquine againstPlasmodium falciparumin an Area of Continued Use of 4‐Aminoquinolines in East Africa

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