RESUMEN
OBJECTIVE: Intermittent Preventive Treatment of schoolchildren (IPTsc) is recommended by WHO as a strategy to protect against malaria; to explore whether IPTsc with dihydroartemisinin-piperaquine (DP) or artesunate-amodiaquine (ASAQ) cause a selection of molecular markers in Plasmodium falciparum genes associated with resistance in children in seven schools in Tanga region, Tanzania. METHODS: SNPs in P. falciparum genes Pfmdr1, Pfexo, Pfkelch13, and Pfcrt and copy number variations in Pfplasmepsin-2 and Pfmdr1 were assessed in samples collected at 12 months (visit 4, n=74) and 20 months (visit 6, n=364) after initiation of IPTsc and compared with the baseline prevalence (n=379). RESULTS: The prevalence of Pfmdr1 N86 and Pfexo 415G was >99% and 0%, respectively without any temporal differences observed. The prevalence of Pfmdr1 184F changed significantly from baseline (52.2%) to visit 6 (64.6%) (χ2=6.11, P=0.013), but no differences were observed between the treatment arms (χ2=0.05, P=0.98). Finally, only minor differences in the amplification of Pfmdr1 were observed; from 10.2% at baseline to 16.7% at visit 6 (χ2=0.98, P=0.32). CONCLUSIONS: The IPTsc strategy does not seem to pose a risk for the selection of markers associated with DP or ASAQ resistance. Continuously and timely surveillance of markers of antimalarial drug resistance is recommended.
Asunto(s)
Amodiaquina , Antimaláricos , Artemisininas , Combinación de Medicamentos , Resistencia a Medicamentos , Malaria Falciparum , Plasmodium falciparum , Humanos , Antimaláricos/uso terapéutico , Antimaláricos/farmacología , Tanzanía/epidemiología , Niño , Malaria Falciparum/epidemiología , Malaria Falciparum/prevención & control , Malaria Falciparum/parasitología , Malaria Falciparum/tratamiento farmacológico , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/genética , Resistencia a Medicamentos/genética , Masculino , Femenino , Amodiaquina/uso terapéutico , Artemisininas/uso terapéutico , Polimorfismo de Nucleótido Simple , Quinolinas/uso terapéutico , Preescolar , Proteínas Protozoarias/genética , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Marcadores Genéticos , Variaciones en el Número de Copia de ADN , PiperazinasRESUMEN
Previous studies have shown that a single season of intermittent preventive treatment in schoolchildren (IPTsc) targeting the transmission season has reduced the rates of clinical malaria, all-cause clinic visits, asymptomatic parasitemia, and anemia. Efficacy over the course of multiple years of IPTsc has been scantly investigated. METHODS: An open, randomized-controlled trial among schoolchildren aged 6-13 years was conducted from September 2007 to January 2010 in Kolle, Mali. Students were included in three arms: sulphadoxine-pyrimethamine+artesunate (SP+AS), amodiaquine+artesunate (AQ+AS), and control (C). All students received two full doses, given 2 months apart, and were compared with respect to the incidence of clinical malaria, all-cause clinic visits, asymptomatic parasitemia, and anemia. RESULTS: A total of 296 students were randomized. All-cause clinic visits were in the SP+AS versus control (29 (20.1%) vs. 68 (47.2%); 20 (21.7%) vs. 41 (44.6%); and 14 (21.2%) vs. 30 (44.6%); p < 0.02) in 2007, 2008, and 2009, respectively. The prevalence of asymptomatic parasitemia was lower in the SP+AS compared to control (38 (7.5%) vs. 143 (28.7%); and 47 (12.7%) vs. 75 (21.2%); p < 0.002) in 2007 and 2008, respectively. Hemoglobin concentration was significantly higher in children receiving SP+AS (11.96, 12.06, and 12.62 g/dL) than in control children (11.60, 11.64, and 12.15 g/dL; p < 0.001) in 2007, 2008, and 2009, respectively. No impact on clinical malaria was observed. CONCLUSION: IPTsc with SP+AS reduced the rates of all-cause clinic visits and anemia during a three-year implementation.