Efficacy and safety of artemether + lumefantrine, artesunate + sulphamethoxypyrazine-pyrimethamine and artesunate + amodiaquine and sulphadoxine-pyrimethamine + amodiaquine in the treatment of uncomplicated falciparum malaria in Bangui, Central African Republic: a randomized trial

Abstract

Background: The efficacy of artemisinin-based combination therapy (ACT) has been established. The objective of the present study was to compare the efficacy and safety in the Central African Republic (CAR) of three commercially available artemisinin-based combinations, artemether + lumefantrine (AL), artesunate + sulphamethoxypyrazine-pyrimethamine (AS-SMP) and artesunate + amodiaquine (AS-AQ), with those of sulphadoxine-pyrimethamine + amodiaquine (SP-AQ), which was the first-line reference treatment in the country from 2004, until it was replaced by ACT in 2006 in accordance with changes in international recommendations based on resistance identified in other regions.

Methods: Children aged six to 59 months with uncomplicated Plasmodium falciparum malaria were recruited in Bangui, the capital of the CAR. The 251 patients selected were randomly assigned to receive AL (n = 60), AS-SMP (n = 58), AS-AQ (n = 68) or SP-AQ (n = 65) and were followed up for 28 days. Clinical outcome was classified according to the standard 2003 World Health Organization protocol.

Results: At day 28, the cure rates in a per-protocol analysis were 92% (48/52) with AL, 93% (50/54) with AS-SMP, 93% (55/59) with AS-AQ and 100% (57/57) with SP-AQ, with no statistically significant difference between the four treatments. Defervescence was significantly faster with AS-AQ than with AL (p <0.035). Fatigue was reported significantly more frequently by patients receiving AQ than by those treated with AS-SMP or AL (p = 0.006). All the other adverse events reported were mild, and no significant difference was noted by treatment.

Conclusion: The three artemisinin-bsed combinations show similar, satisfactory results, comparable to that with SP-AQ. This evaluation is the first conducted in CAR since the official introduction of ACT. It should guide the National Malaria Control Programme in choosing the appropriate ACT for treatment of uncomplicated P. falciparum malaria in the future.

Figure 1

Trial design.

Figure 2

Characteristics of patients during the first three days after the start of treatment: proportion of patients with parasites, p < 0.05.

Figure 3

Characteristics of patients during the first three days after the start of treatment: median body temperature, p < 0.05.

Figure 4

Concentrations of serum liver enzymes, expressed in multiples of the upper limit of the normal range, on days 0, 1 and 3 in 81 patients given amodiaquine treatments: results of alanine aminotransferase (ALT).

Figure 5

Concentrations of serum liver enzymes, expressed in multiples of the upper limit of the normal range, on days 0, 1 and 3 in 81 patients given amodiaquine treatments: results of aspartate aminotransferase (AST).