The safety and efficacy of sulfadoxine-pyrimethamine, amodiaquine, and their combination in the treatment of uncomplicated Plasmodium falciparum malaria.

Abstract

Abstract. The safety and efficacy of amodiaquine (AQ), sulfadoxine-pyrimethamine (SP), and coadministered AQ+SP was assessed in 351 Tanzanian children (age range, 6-59 months) with uncomplicated Plasmodium falciparum malaria. This open, randomized study followed the 28-day World Health Organization (WHO) protocol and evaluated safety using clinical and laboratory parameters. Children receiving SP were more likely to vomit during follow-up (32% vs. 17%: P ‫ס‬ 0.03), and SP alone resulted in prolonged fever clearance times. Although Day 7 and Day 14 clinical and parasitological cure rates were similar, by Day 28 45% of children treated with AQ demonstrated R1 resistance and 27.5% were clinical failures compared with 25% and 6.3%, respectively, for SP alone. Coadministered AQ+SP was safe, combined the greater clinical (96.2%) and parasitological (64.2%) efficacy of SP with the more rapid symptom resolution of AQ, and reduced the incidence of gametocytemia during follow-up (AQ+SP 12.6% vs. SP 29.9%; P ‫ס‬ 0.001). The level of R1 resistance to SP may herald a rapid decline in its efficacy as SP drug pressure increases. Coadministration of AQ+SP may delay this.

Mechanisms of Resistance of Malaria Parasites to Antifolates

“…This leads to the conclusion that if drug combinations are not potentiating, at least one of the drugs needs to be extremely effective. The combination of amiodiaquine-sulfadoxinepyrimethamine is most likely an example of this (Schellenberg et al, 2002;Gasasira et al, 2003), as is dihydroartemisinin-piperaquine (Tran et al, 2004).…”

In Vivo Assessment of Drug Efficacy against Plasmodium falciparum Malaria: Duration of Follow-Up

“…We identified a further 21 treatment arms comprising a total of 3,259 patients where both day 14 and day 28 failure rates were reported (11,12,18,19,38,40,51,55,56); 9 treatment arms were with drugs in the There were only five trials with Ͼ42 days of follow-up, and in these the day 14 assessment detected a median of 33% (0 to 62%), and the day 28 assessment was 70% (0 to 88%) of the overall failures. This is comparable with the results from the studies with genotyping: for day 14 assessment, 14% (0 to 80%) and for day 28 assessment, 82% (0 to 100%).…”

The incidence of clinical malaria detected by active case detection in children in Ifakara, southern Tanzania

“…This rolling cross-sectional survey allowed assessment of temporal variations and the age dependence of asymptomatic parasitaemia and anaemia. Children with a PCV <25% were supplied with the standard anaemia treatment (14 d of ferrous sulphate and a treatment dose of sulphadoxine-pyrimethamine [SP]) and malaria episodes were treated with SP, which remains effective in the area (Schellenberg et al, 2002).…”