Artesunate + amodiaquine and artesunate + sulphadoxine–pyrimethamine for treatment of uncomplicated malaria in Democratic Republic of Congo: a clinical trial with determination of sulphadoxine and pyrimethamine‐resistant haplotypes

Abstract

SummaryWe undertook a trial of artesunate + amodiaquine (AS + AQ) and artesunate + sulphadoxinepyrimethamine (AS + SP) in 180 children of age 6-59 months with uncomplicated malaria in Democratic Republic of Congo. Children were randomly allocated to receive 3 days observed treatment of AS + AQ (n ¼ 90) or 3 days of AS + SP (n ¼ 90). Primary efficacy outcomes were 28-day parasite recurrence rates, and recrudescence rates were adjusted by genotyping to distinguish new infection and recrudescence. In addition, we determined the prevalence of molecular markers of resistance to sulphadoxine and pyrimethamine. Day 28 parasite recurrence rates were 16.9% (14/83; 95% CI: 9.5-26.7) in the AS + AQ group and 34.6% (28/81; 95% CI: 24.3-46.0) in the AS + SP group (P ¼ 0.009). After PCR correction, recrudescence rates were 6.7% (5/74; 95% CI: 2.2-15.1) for AS + AQ and 19.7% (13/66; 95% CI: 10.9-31.3) for AS + SP (P ¼ 0.02). There was no significant difference between the two arms in time to parasite clearance, fever clearance and gametocyte clearance. Parasite genotyping showed high frequencies of dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) molecular SPresistance markers, with 57% of the samples showing more than three mutations linked to SP resistance, and 27% with triple-dhfr/double-dhps haplotype, confirming that SP treatment failure rates are likely to be high. AS + AQ had significantly higher efficacy than AS + SP. These results contributed to the subsequent change to AS + AQ as first-line regimen in the country. Efforts to properly implement the new protocol and maintain adherence at acceptable levels should include health staff and patient sensitization. The 6.8% recrudescence rate indicates that AS + AQ should be monitored closely until a more effective artemisinin combination therapy regimen is needed and can be introduced.

Efficacy of Artesunate Plus Amodiaquine for Treatment of Uncomplicated Clinical Falciparum Malaria in Severely Malnourished Children Aged 6–59 Months, Democratic Republic of Congo

“…In 2004, a study conducted in the south of the South Kivu province presented a day 28 PCR genotyping-adjusted failure rates of 6.7% using AQ+AS [8]. Between 2003 to 2004, in Boende in north-west, the unadjusted total failures on day 28 was 41.0%; it was 8.8% in Kabalo in southeastern of DRC [29].…”

“…This prompted the National Malaria Control Program (NMCP) to change in 2005 the national antimalarial treatment policy and the first line treatment, from CQ to amodiaquine plus artesunate (AS+AQ). Nevertheless, since its implementation, few studies on AS+AQ efficacy have been carried out [8][9][10], and none of them took into account the patients' nutritional state. Nevertheless it has been often reported that both malnutrition and malaria affect antimalarial disposition [11,12].…”

Evaluation of Three Rapid Tests for Diagnosis of P. Falciparum and P. Vivax Malaria in Colombia

“…32 A total of 40% of P. falciparum infections and 38% of P. vivax infections had a parasite density below 2000 par/l, and nearly 20% and 25% were below 500 par/l. This proportion is higher than in high-endemic areas such as in Africa: in studies in DRC and Sudan (data from [33][34][35] ) we saw that only 8-11% of P. falciparum infections of clinically ill children under 5 years were below 2000 par/l. Hence, in areas of low and moderate malaria transmission, such as South America and Asia, rapid tests require a high sensitivity at lower densities of infection, to serve the non-immune populations that can suffer from clinical disease at much lower infection grades, as opposed to people in high-endemic areas in sub-Saharan Africa.…”

Development of value added tea bags and capsules of Artemisia Annua Anamed (A3) whole plant for malaria treatment

“…al. (2012);Ferreira (2010);Goulart, et al(2004);and Swarthout, et. al., (2006) indicated that flavonoids existing in the leaves and stem of Artemisia annua considerably enhance the interest of the Artemisia annua tea preparation as a treatment of malaria.…”