Increasing antimalarial drug resistance in Uganda and revision of the national drug policy.

Chloroquine (CQ) resistance was first documented in Uganda in 1988. Subsequent surveillance of antimalarial drug resistance, conducted by the Ugandan Ministry of Health and several research organizations, suggests that resistance to CQ is now widespread, reaching critical levels in many areas of the country. In June 2000, the Ministry of Health held a National Consensus Meeting to evaluate the available drug efficacy data and review the national antimalarial drug policy. After extensive debate, the combination of CQ + sulfadoxine-pyrimethamine (SP) was chosen to replace CQ as the first-line treatment of uncomplicated malaria as an interim policy. This review evaluates the in vivo drug efficacy studies conducted in Uganda since 1988 and issues confronted in revision of the drug policy. The Ugandan experience illustrates the challenges faced by sub-Saharan African countries confronted with rising CQ resistance but limited data on potential alternative options. The choice of CQ + SP as a provisional policy in the absence of prerequisite efficacy, safety and cost-effectiveness data reflects the urgency of the malaria treatment problem, and growing pressure to adopt combination therapies. Surveillance of CQ + SP treatment efficacy, collection of additional data on alternative regimens and active consensus building among key partners in the malaria community will be necessary to develop a rational long-term antimalarial treatment policy in Uganda.

Amodiaquine, sulfadoxine/pyrimethamine, and combination therapy for treatment of uncomplicated falciparum malaria in Kampala, Uganda: a randomised trial.

BACKGROUND: Increasing Plasmodium falciparum resistance to chloroquine in sub-Saharan Africa necessitates use of alternative antimalarial agents. Affordable alternative treatments include sulfadoxine/pyrimethamine and amodiaquine. Combination of antimalarial agents can increase therapeutic efficacy and delay emergence of drug resistance. We compared the efficacy of sulfadoxine/pyrimethamine, amodiaquine, and an amodiaquine/sulfadoxine/pyrimethamine combination for treatment of uncomplicated malaria in a region of high chloroquine resistance. METHODS: Patients with symptoms of uncomplicated falciparum malaria and confirmed disease in Kampala, Uganda, were randomly assigned to receive sulfadoxine/pyrimethamine (25 mg/kg sulfadoxine, and 1.25 mg/kg pyrimethamine) plus placebo; amodiaquine (25 mg/kg) plus placebo; or amodiaquine plus sulfadoxine/pyrimethamine. Patients were followed up for 14 days, and clinical and parasitological outcomes were assessed. FINDINGS: 90% (400/445) of patients enrolled in the study successfully completed 14 days of follow-up. Treatment failure based on clinical criteria occurred in 13 of 131 (10%) patients on sulfadoxine/ pyrimethamine, nine of 131 (7%) on amodiaquine, and four of 138 (3%) on amodiaquine/sulfadoxine/pyrimethamine. Based on parasitological criteria, treatment failed in 26%, 16%, and 10% of these patients, respectively. Amodiaquine/sulfadoxine/pyrimethamine was significantly more effective than sulfadoxine/pyrimethamine alone in children aged younger than 5 years (clinical failure in 3.5% vs 13.9%, respectively, risk difference 10.4% [95% CI, 1.6-19.3] p=0.021; parasitological failure in 12.8% vs 26.4%, risk difference 13.6% [1.2-26.0] p=0.041). INTERPRETATION: Sulfadoxine/pyrimethamine, amodiaquine, and amodiaquine/sulfadoxine/pyrimethamine were all effective for treatment of uncomplicated falciparum malaria in Uganda. The amodiaquine/sulfadoxine/pyrimethamine combination was the most effective, and could be the optimum low-cost alternative to chloroquine in Africa.

The comparative efficacy of chloroquine and sulfadoxine-pyrimethamine for the treatment of uncomplicated falciparum malaria in Kampala, Uganda.

Chloroquine (CQ) remains the first-line treatment for uncomplicated malaria in much of Africa despite the growing problem of resistance to this drug. Sulfadoxine-pyrimethamine (SP) is often used after CQ treatment failure and has replaced CQ as the first-line treatment in parts of Africa. To compare the efficacy of these 2 regimens, we evaluated, in March-August 1999, clinical and parasitological responses over 28 days in 214 children and adults from Kampala, Uganda, with uncomplicated falciparum malaria. Compared to SP, significantly more patients treated with CQ developed early or late clinical failure (54% vs 11%, P < 0.001) and parasitological failure (72% vs 30%, P < 0.001) during 14 days of follow-up. The risk of treatment failure occurring after day 14 was similar between the 2 treatment groups. Among those treated with CQ, children aged < 5 years were at higher risk of clinical failure than older individuals (76% vs 28%, P < 0.001), an association not seen with SP (11% vs 10%, P = 0.91). Although early parasite clearance was significantly better in the SP group (P = 0.001), fever clearance at day 3 was the same (CQ 85%, SP 86%). These and other recent findings suggest that consideration be given to replacing CQ as the first-line therapy for uncomplicated malaria in Uganda, particularly in young children.

Amodiaquine; sulfadoxine/pyrimethamine; and combination therapy for treatment of uncomplicated falciparum malaria in Kampala; Uganda:a randomised trial

Increasing Plasmodium falciparum resistance to chloroquine in sub-Saharan Africa necessitates use of alternative antimalarial agents. Affordable alternative treatments inlude sulfadoxine/pyrimethamine and amodiaquine. Combination of antimalarial agents can increase thepeutic resistance. We compared the efficacy of sulfadoxine/pryrimethamine; amodiaquine; and an amodiaquine/sulfadoxine/pyrimethamine combination for treatment of uncomplicated malaria in a region of high chloroquine resistance. Methods: Patients with symptoms of uncomplicated falciparum malaria and confirmed disease in Kampala; Uganda; were randomly assigned to receive sulfadoxine/pyrimethamine) plus placebo; amodiaquine (25mg/kg) sulfadoxine and 1.25mg/kg prymethamine) plus placebo; or amodiaquine plus sulfadoxine/pyrimethamine. Patients were followed up for 14 days; and clinical and parasitological outcomes were assessed. Findings: 90(400/445) of patients enrolled in the study successfully completed 14 days of follow-up. Treatment failure based on clinical criteria occurred in 13 of 131 (10) patients on sulfadoxine/pyrimethamine. Based on parasitological criteria; treatment failed in 26; 16; and 10of these patients; respectively. Amodiaquine/sulfadoxine/pyrimethamine was significantly more effective than sulfadoxine/pyrimethamine alone in children aged younger than 5 years (clinical failure in 3.5vs 13.9; respectively; risk difference 10.4[95CI; 1.6-19.3] p=0.021; parasitological failure in 12.8vs 26.4; risk difference 13.61.2-26.0] p=0.041) Interpretation Sulfadoxine/pyrimethamine; amodiaquine; and amodiaquine/sulfadoxine/pyrimethamine were all effective for treatment of uncomplicated falciparum malaria in Uganda. The amodiaquine/sulfadoxine/pyrimethamine combination was the most effective; and could be the optimum low-cost alternative to chloroquine in Africa