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Efficacy and safety of artesunate plus amodiaquine in routine use for the treatment of uncomplicated malaria in Casamance, southern Sénégal.

Brasseur P, Agnamey P, Gaye O, Vaillant M, Taylor WR, Olliaro PL - Malar. J. (2007)

Bottom Line: Efficacy, by Kaplan Meier survival analysis (n = 966), and safety (adverse event rates, n = 752) were determined over 28 days.By Day 28, the mean total bilirubin (n = 72), AST (n = 94) and ALT (n = 95) values decreased.Long-term monitoring of safety and efficacy should continue.

View Article: PubMed Central - HTML - PubMed

Affiliation: UR 077, IRD, Dakar, Sénégal. brasseur@ird.sn

ABSTRACT

Background: There are no data on the long term use of an artemisinin combination treatment in moderate or high transmission areas of Africa.

Methods and findings: Artesunate plus amodiaquine (AS+AQ) was used to treat slide-proven Plasmodium falciparum-infected patients of all ages in the Oussouye district, Casamance, Senegal, over a period of six years (2000 to 2005). Efficacy, by Kaplan Meier survival analysis (n = 966), and safety (adverse event rates, n = 752) were determined over 28 days. A weight-based dosing regimen was used for the loose tablets during 2000-2003 (n = 731) and a commercially available co-blister was used during 2004-2005 (n = 235). Annual crude (non PCR corrected) rates remained stable over the study period [range 88.5-96.7%; overall 94.6 (95% CI 92.9-95.9)]. Nine co-blister treated patients (0.9%) withdrew because of drug-related adverse events; seven had gastrointestinal complaints of whom two were hospitalized for vomiting. By Day 28, the mean total bilirubin (n = 72), AST (n = 94) and ALT (n = 95) values decreased. Three patients had Day 28 AST/ALT values > 40 < 200 IU/L. Changes in white cell counts were unremarkable (n = 87).

Conclusion: AS+AQ in combination was highly efficacious and well-tolerated in this area and justifies the decision to use it as first line treatment. Long-term monitoring of safety and efficacy should continue.

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Related in: MedlinePlus

Kaplan-Meier of one minus survival curves to show cumulative parasitological failure rates overall (2000–05) and by year of treatment (all ages combined).
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Figure 3: Kaplan-Meier of one minus survival curves to show cumulative parasitological failure rates overall (2000–05) and by year of treatment (all ages combined).

Mentions: The Kaplan-Meier estimates of the crude cure efficacy rate was 94.6% (95% CI 93.0; 95.9) for all years combined. By individual years cure rates were 96.7% [93.2; 98.4] in 2000, 94.0% [90.6; 96.2] in 2001, 95.7% [90.0; 98.2] in 2002, 94.9% [88.2; 97.8] in 2003, 88.5% [79.0; 93.8] in 2004 and 95.9% [91.1; 98.1] in 2005. There were no differences (p = 0.12) in cure rates between years by the log rank test for homogeneity over time (Figure 3) All patients cleared their parasites by Day 3 (no early treatment failure, ETF); 36 patients returned with parasites during follow-up (late treatment failures, LTF) and nine were withdrawn due to an adverse event (considered as failures in our analysis – see below); 32 were lost to follow-up (censored) (Table 2). All treatment failures were retreated successfully with injectable quinine. All 36 LTFs occurred in patients under 16 years of age (20 in the age range 6–10). Efficacy was 95% in 0–10 years and 97% in 11 and above (log rank test, p = 0.03). In 2005 the losses to follow up amounted to 15%, while they were ≤3% in the other years.


Efficacy and safety of artesunate plus amodiaquine in routine use for the treatment of uncomplicated malaria in Casamance, southern Sénégal.

Brasseur P, Agnamey P, Gaye O, Vaillant M, Taylor WR, Olliaro PL - Malar. J. (2007)

Kaplan-Meier of one minus survival curves to show cumulative parasitological failure rates overall (2000–05) and by year of treatment (all ages combined).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2211754&req=5

Figure 3: Kaplan-Meier of one minus survival curves to show cumulative parasitological failure rates overall (2000–05) and by year of treatment (all ages combined).
Mentions: The Kaplan-Meier estimates of the crude cure efficacy rate was 94.6% (95% CI 93.0; 95.9) for all years combined. By individual years cure rates were 96.7% [93.2; 98.4] in 2000, 94.0% [90.6; 96.2] in 2001, 95.7% [90.0; 98.2] in 2002, 94.9% [88.2; 97.8] in 2003, 88.5% [79.0; 93.8] in 2004 and 95.9% [91.1; 98.1] in 2005. There were no differences (p = 0.12) in cure rates between years by the log rank test for homogeneity over time (Figure 3) All patients cleared their parasites by Day 3 (no early treatment failure, ETF); 36 patients returned with parasites during follow-up (late treatment failures, LTF) and nine were withdrawn due to an adverse event (considered as failures in our analysis – see below); 32 were lost to follow-up (censored) (Table 2). All treatment failures were retreated successfully with injectable quinine. All 36 LTFs occurred in patients under 16 years of age (20 in the age range 6–10). Efficacy was 95% in 0–10 years and 97% in 11 and above (log rank test, p = 0.03). In 2005 the losses to follow up amounted to 15%, while they were ≤3% in the other years.

Bottom Line: Efficacy, by Kaplan Meier survival analysis (n = 966), and safety (adverse event rates, n = 752) were determined over 28 days.By Day 28, the mean total bilirubin (n = 72), AST (n = 94) and ALT (n = 95) values decreased.Long-term monitoring of safety and efficacy should continue.

View Article: PubMed Central - HTML - PubMed

Affiliation: UR 077, IRD, Dakar, Sénégal. brasseur@ird.sn

ABSTRACT

Background: There are no data on the long term use of an artemisinin combination treatment in moderate or high transmission areas of Africa.

Methods and findings: Artesunate plus amodiaquine (AS+AQ) was used to treat slide-proven Plasmodium falciparum-infected patients of all ages in the Oussouye district, Casamance, Senegal, over a period of six years (2000 to 2005). Efficacy, by Kaplan Meier survival analysis (n = 966), and safety (adverse event rates, n = 752) were determined over 28 days. A weight-based dosing regimen was used for the loose tablets during 2000-2003 (n = 731) and a commercially available co-blister was used during 2004-2005 (n = 235). Annual crude (non PCR corrected) rates remained stable over the study period [range 88.5-96.7%; overall 94.6 (95% CI 92.9-95.9)]. Nine co-blister treated patients (0.9%) withdrew because of drug-related adverse events; seven had gastrointestinal complaints of whom two were hospitalized for vomiting. By Day 28, the mean total bilirubin (n = 72), AST (n = 94) and ALT (n = 95) values decreased. Three patients had Day 28 AST/ALT values > 40 < 200 IU/L. Changes in white cell counts were unremarkable (n = 87).

Conclusion: AS+AQ in combination was highly efficacious and well-tolerated in this area and justifies the decision to use it as first line treatment. Long-term monitoring of safety and efficacy should continue.

Show MeSH
Related in: MedlinePlus