Limits...
Efficacy, safety, and tolerability of three regimens for prevention of malaria: a randomized, placebo-controlled trial in Ugandan schoolchildren.

Nankabirwa J, Cundill B, Clarke S, Kabatereine N, Rosenthal PJ, Dorsey G, Brooker S, Staedke SG - PLoS ONE (2010)

Bottom Line: No serious adverse events occurred, but AQ+SP was associated with increased risk of vomiting compared to placebo (13.0% [95% CI: 9.1, 18.5] vs. 4.7% [95% CI: 2.5, 8.8], respectively, p = 0.003).DP was the most efficacious and well-tolerated regimen tested, although AQ+SP appears to be a suitable alternative for IPT in schoolchildren.Use of SP for IPT may not be appropriate in areas with high-level SP resistance in Africa.

View Article: PubMed Central - PubMed

Affiliation: Uganda Malaria Surveillance Project, Kampala, Uganda.

ABSTRACT

Background: Intermittent preventive treatment (IPT) is a promising malaria control strategy; however, the optimal regimen remains unclear. We conducted a randomized, single-blinded, placebo-controlled trial to evaluate the efficacy, safety, and tolerability of a single course of sulfadoxine-pyrimethamine (SP), amodiaquine + SP (AQ+SP) or dihydroartemisinin-piperaquine (DP) among schoolchildren to inform IPT.

Methods: Asymptomatic girls aged 8 to 12 years and boys aged 8 to 14 years enrolled in two primary schools in Tororo, Uganda were randomized to receive one of the study regimens or placebo, regardless of presence of parasitemia at enrollment, and followed for 42 days. The primary outcome was risk of parasitemia at 42 days. Survival analysis was used to assess differences between regimens.

Results: Of 780 enrolled participants, 769 (98.6%) completed follow-up and were assigned a treatment outcome. The risk of parasitemia at 42 days varied significantly between DP (11.7% [95% confidence interval (CI): 7.9, 17.1]), AQ+SP (44.3% [37.6, 51.5]), and SP (79.7% [95% CI: 73.6, 85.2], p<0.001). The risk of parasitemia in SP-treated children was no different than in those receiving placebo (84.6% [95% CI: 79.1, 89.3], p = 0.22). No serious adverse events occurred, but AQ+SP was associated with increased risk of vomiting compared to placebo (13.0% [95% CI: 9.1, 18.5] vs. 4.7% [95% CI: 2.5, 8.8], respectively, p = 0.003).

Conclusions: DP was the most efficacious and well-tolerated regimen tested, although AQ+SP appears to be a suitable alternative for IPT in schoolchildren. Use of SP for IPT may not be appropriate in areas with high-level SP resistance in Africa.

Trial registration: ClinicalTrials.gov NCT00852371.

Show MeSH

Related in: MedlinePlus

Cumulative risk of recrudescence in children with malaria parasitemia at baseline over 42 days by treatment regimen.SP  =  sulfadoxine-pyrimethamine; AQ+SP  =  amodiaquine + sulfadoxine-pyrimethamine; DP  =  dihydroartemisinin-piperaquine.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2957410&req=5

pone-0013438-g002: Cumulative risk of recrudescence in children with malaria parasitemia at baseline over 42 days by treatment regimen.SP  =  sulfadoxine-pyrimethamine; AQ+SP  =  amodiaquine + sulfadoxine-pyrimethamine; DP  =  dihydroartemisinin-piperaquine.

Mentions: Of 399 children who were parasitemic at baseline, 228 were parasitemic during follow-up. The child who received rescue therapy on day 3 was classified as a recrudescence. Genotyping results were available for 221 children; genotyping was unsuccessful in 6 cases, and results were missing for one. Thus, 392 children were included in the analysis for risk of recrudescence. There were 122 recrudescences, 99 new infections, and 171 who remained free of parasites. Children treated with AQ+SP and DP were at significantly lower risk of recrudescence than those receiving SP (Figure 2, Table 3). There was no evidence that treatment with SP provided any benefit over placebo.


Efficacy, safety, and tolerability of three regimens for prevention of malaria: a randomized, placebo-controlled trial in Ugandan schoolchildren.

Nankabirwa J, Cundill B, Clarke S, Kabatereine N, Rosenthal PJ, Dorsey G, Brooker S, Staedke SG - PLoS ONE (2010)

Cumulative risk of recrudescence in children with malaria parasitemia at baseline over 42 days by treatment regimen.SP  =  sulfadoxine-pyrimethamine; AQ+SP  =  amodiaquine + sulfadoxine-pyrimethamine; DP  =  dihydroartemisinin-piperaquine.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2957410&req=5

pone-0013438-g002: Cumulative risk of recrudescence in children with malaria parasitemia at baseline over 42 days by treatment regimen.SP  =  sulfadoxine-pyrimethamine; AQ+SP  =  amodiaquine + sulfadoxine-pyrimethamine; DP  =  dihydroartemisinin-piperaquine.
Mentions: Of 399 children who were parasitemic at baseline, 228 were parasitemic during follow-up. The child who received rescue therapy on day 3 was classified as a recrudescence. Genotyping results were available for 221 children; genotyping was unsuccessful in 6 cases, and results were missing for one. Thus, 392 children were included in the analysis for risk of recrudescence. There were 122 recrudescences, 99 new infections, and 171 who remained free of parasites. Children treated with AQ+SP and DP were at significantly lower risk of recrudescence than those receiving SP (Figure 2, Table 3). There was no evidence that treatment with SP provided any benefit over placebo.

Bottom Line: No serious adverse events occurred, but AQ+SP was associated with increased risk of vomiting compared to placebo (13.0% [95% CI: 9.1, 18.5] vs. 4.7% [95% CI: 2.5, 8.8], respectively, p = 0.003).DP was the most efficacious and well-tolerated regimen tested, although AQ+SP appears to be a suitable alternative for IPT in schoolchildren.Use of SP for IPT may not be appropriate in areas with high-level SP resistance in Africa.

View Article: PubMed Central - PubMed

Affiliation: Uganda Malaria Surveillance Project, Kampala, Uganda.

ABSTRACT

Background: Intermittent preventive treatment (IPT) is a promising malaria control strategy; however, the optimal regimen remains unclear. We conducted a randomized, single-blinded, placebo-controlled trial to evaluate the efficacy, safety, and tolerability of a single course of sulfadoxine-pyrimethamine (SP), amodiaquine + SP (AQ+SP) or dihydroartemisinin-piperaquine (DP) among schoolchildren to inform IPT.

Methods: Asymptomatic girls aged 8 to 12 years and boys aged 8 to 14 years enrolled in two primary schools in Tororo, Uganda were randomized to receive one of the study regimens or placebo, regardless of presence of parasitemia at enrollment, and followed for 42 days. The primary outcome was risk of parasitemia at 42 days. Survival analysis was used to assess differences between regimens.

Results: Of 780 enrolled participants, 769 (98.6%) completed follow-up and were assigned a treatment outcome. The risk of parasitemia at 42 days varied significantly between DP (11.7% [95% confidence interval (CI): 7.9, 17.1]), AQ+SP (44.3% [37.6, 51.5]), and SP (79.7% [95% CI: 73.6, 85.2], p<0.001). The risk of parasitemia in SP-treated children was no different than in those receiving placebo (84.6% [95% CI: 79.1, 89.3], p = 0.22). No serious adverse events occurred, but AQ+SP was associated with increased risk of vomiting compared to placebo (13.0% [95% CI: 9.1, 18.5] vs. 4.7% [95% CI: 2.5, 8.8], respectively, p = 0.003).

Conclusions: DP was the most efficacious and well-tolerated regimen tested, although AQ+SP appears to be a suitable alternative for IPT in schoolchildren. Use of SP for IPT may not be appropriate in areas with high-level SP resistance in Africa.

Trial registration: ClinicalTrials.gov NCT00852371.

Show MeSH
Related in: MedlinePlus