Impact of intermittent preventive treatment with dihydroartemisinin-piperaquine on malaria in Ugandan schoolchildren: a randomized, placebo-controlled trial

Joaniter I Nankabirwa, Bonnie Wandera, Pauline Amuge, Noah Kiwanuka, Grant Dorsey, Philip J Rosenthal, Simon J Brooker, Sarah G Staedke, Moses R Kamya, Joaniter I Nankabirwa, Bonnie Wandera, Pauline Amuge, Noah Kiwanuka, Grant Dorsey, Philip J Rosenthal, Simon J Brooker, Sarah G Staedke, Moses R Kamya

Abstract

Background: Intermittent preventive treatment (IPT) in schoolchildren offers a promising option for malaria control. However, the optimal drug and dosing regimens for IPT remain to be determined.

Methods: We conducted a randomized, double-blind, placebo-controlled trial in 740 schoolchildren aged 6-14 years living in a setting of high malaria transmission in Uganda. Enrolled children were randomized to dihydroartemisinin-piperaquine (DP) given once a month (IPTm), DP given once a school term (4 treatments over 12 months, IPTst), or placebo and followed for 12 months. The primary outcome was the incidence of malaria over 12 months. Secondary outcomes included parasite prevalence and anemia over 12 months. Analyses were conducted on an intention-to-treat basis.

Results: In the placebo arm, the incidence of malaria was 0.34 episodes per person-year and the prevalence of parasitemia and anemia was 38% and 20%, respectively. IPTm reduced the incidence of malaria by 96% (95% confidence interval [CI], 88%-99%, P < .0001), the prevalence of asymptomatic parasitemia by 94% (95% CI, 92%-96%, P < .0001), and the prevalence of anemia by 40% (95% CI, 19%-56%, P < .0001). IPTst had no significant effect on the incidence of symptomatic malaria or the prevalence of anemia, but reduced the prevalence of asymptomatic parasitemia by 54% (95% CI, 47%-60%, P < .0001).

Conclusions: Monthly IPT with DP offered remarkable protection against clinical malaria, parasitemia, and anemia in schoolchildren living in a high-malaria-transmission setting.

Clinical trials registration: NCT01231880.

Keywords: intermittent preventive treatment; malaria; schoolchildren.

Figures

Figure 1.
Figure 1.
Trial profile. Abbreviations: F/up, follow-up; IPTm, intermittent preventive treatment once a month; IPTst, intermittent preventive treatment once a school term.
Figure 2.
Figure 2.
Cumulative risk of malaria over 1 year of follow-up by treatment group. Abbreviations: IPTm, intermittent preventive treatment once a month; IPTst, intermittent preventive treatment once a school term.

References

    1. Noor AM, Kirui VC, Brooker SJ, Snow RW. The use of insecticide treated nets by age: implications for universal coverage in Africa. BMC Public Health. 2009;9:369.
    1. Pullan RL, Bukirwa H, Staedke SG, Snow RW, Brooker S. Plasmodium infection and its risk factors in eastern Uganda. Malar J. 2010;9:2.
    1. Clarke SE, Brooker S, Njagi JK, et al. Malaria morbidity among school children living in two areas of contrasting transmission in western Kenya. Am J Trop Med Hyg. 2004;71:732–8.
    1. Brooker S, Guyatt H, Omumbo J, Shretta R, Drake L, Ouma J. Situation analysis of malaria in school-aged children in Kenya—what can be done? Parasitol Today. 2000;16:183–6.
    1. Fernando SD, Rodrigo C, Rajapakse S. The ‘hidden’ burden of malaria: cognitive impairment following infection. Malar J. 2010;9:366.
    1. Brooker S, Akhwale W, Pullan R, et al. Epidemiology of plasmodium-helminth co-infection in Africa: populations at risk, potential impact on anemia, and prospects for combining control. Am J Trop Med Hyg. 2007;77(6 suppl):88–98.
    1. Al Serouri AW, Grantham-McGregor SM, Greenwood B, Costello A. Impact of asymptomatic malaria parasitaemia on cognitive function and school achievement of schoolchildren in the Yemen Republic. Parasitology. 2000;121(pt 4):337–45.
    1. Nankabirwa J, Wandera B, Kiwanuka N, Staedke SG, Kamya MR, Brooker SJ. Asymptomatic Plasmodium infection and cognition among primary schoolchildren in a high malaria transmission setting in Uganda. Am J Trop Med Hyg. 2013;88:1102–8.
    1. Clarke SE, Jukes MC, Njagi JK, et al. Effect of intermittent preventive treatment of malaria on health and education in schoolchildren: a cluster-randomised, double-blind, placebo-controlled trial. Lancet. 2008;372:127–38.
    1. Dicko A, Sagara I, Sissoko MS, et al. Impact of intermittent preventive treatment with sulphadoxine-pyrimethamine targeting the transmission season on the incidence of clinical malaria in children in Mali. Malar J. 2008;7:123.
    1. Kweku M, Liu D, Adjuik M, et al. Seasonal intermittent preventive treatment for the prevention of anaemia and malaria in Ghanaian children: a randomized, placebo controlled trial. PLoS One. 2008;3
    1. Cisse B, Cairns M, Faye E, et al. Randomized trial of piperaquine with sulfadoxine-pyrimethamine or dihydroartemisinin for malaria intermittent preventive treatment in children. PLoS One. 2009;4
    1. Barger B, Maiga H, Traore OB, et al. Intermittent preventive treatment using artemisinin-based combination therapy reduces malaria morbidity among school-aged children in Mali. Trop Med Int Health. 2009;14:784–91.
    1. Nankabirwa J, Cundill B, Clarke S, et al. Efficacy, safety, and tolerability of three regimens for prevention of malaria: a randomized, placebo-controlled trial in Ugandan schoolchildren. PLoS One. 2010;5:e13438.
    1. Okello PE, Van Bortel W, Byaruhanga AM, et al. Variation in malaria transmission intensity in seven sites throughout Uganda. Am J Trop Med Hyg. 2006;75:219–25.
    1. World Health Organization. Iron deficiency anaemia: assessment, prevention and control. A guide for programme managers. Geneva, Switzerland: WHO; 2001.
    1. Staedke SG, Jagannathan P, Yeka A, et al. Monitoring antimalarial safety and tolerability in clinical trials: a case study from Uganda. Malar J. 2008;7:107.
    1. Tarning J, Ashley EA, Lindegardh N, et al. Population pharmacokinetics of piperaquine after two different treatment regimens with dihydroartemisinin-piperaquine in patients with Plasmodium falciparum malaria in Thailand. Antimicrob Agents Chemother. 2008;52:1052–61.
    1. Kamya MR, Yeka A, Bukirwa H, et al. Artemether-lumefantrine versus dihydroartemisinin-piperaquine for treatment of malaria: a randomized trial. PLoS Clin Trials. 2007;2:e20
    1. Yeka A, Dorsey G, Kamya MR, et al. Artemether-lumefantrine versus dihydroartemisinin-piperaquine for treating uncomplicated malaria: a randomized trial to guide policy in Uganda. PLoS One. 2008;3:e2390
    1. Smithuis F, Kyaw MK, Phe O, et al. Effectiveness of five artemisinin combination regimens with or without primaquine in uncomplicated falciparum malaria: an open-label randomised trial. Lancet Infect Dis. 2010;10:673–81.
    1. Lwin KM, Phyo AP, Tarning J, et al. Randomized, double-blind, placebo-controlled trial of monthly versus bimonthly dihydroartemisinin-piperaquine chemoprevention in adults at high risk of malaria. Antimicrob Agents Chemother. 2012;56:1571–7.
    1. World Health Organization. Geneva, Switzerland: WHO Global Malaria Programme; 2012. Seasonal malaria chemoprevention (SMC) for Plasmodium falciparum malaria control in highly seasonal transmission areas of the Sahel sub-regions in Africa.
    1. Gosling RD, Gesase S, Mosha JF, et al. Protective efficacy and safety of three antimalarial regimens for intermittent preventive treatment for malaria in infants: a randomised, double-blind, placebo-controlled trial. Lancet. 2009;374:1521–32.
    1. Aponte JJ, Schellenberg D, Egan A, et al. Efficacy and safety of intermittent preventive treatment with sulfadoxine-pyrimethamine for malaria in African infants: a pooled analysis of six randomised, placebo-controlled trials. Lancet. 2009;374:1533–42.
    1. Iriemenam NC, Shah M, Gatei W, et al. Temporal trends of sulphadoxine-pyrimethamine (SP) drug-resistance molecular markers in Plasmodium falciparum parasites from pregnant women in western Kenya. Malar J. 2012;11:134.
    1. Harrington WE, Mutabingwa TK, Muehlenbachs A, et al. Competitive facilitation of drug-resistant Plasmodium falciparum malaria parasites in pregnant women who receive preventive treatment. Proc Natl Acad Sci U S A. 2009;106:9027–32.
    1. Greenwood B. The use of anti-malarial drugs to prevent malaria in the population of malaria-endemic areas. Am J Trop Med Hyg. 2004;70:1–7.
    1. Davis TM, Hung TY, Sim IK, Karunajeewa HA, Ilett KF. Piperaquine: a resurgent antimalarial drug. Drugs. 2005;65:75–87.
    1. Conrad DM, LeClair N, Arinaitwe E, et al. Comparative impacts over 5 years of artemisinin-based combination therapies on P. falciparum polymorphisms that modulate drug sensitivity in Ugandan children [Epub ahead of print] J Infect Dis 2014
    1. Some AF, Sere YY, Dokomajilar C, et al. Selection of known Plasmodium falciparum resistance-mediating polymorphisms by artemether-lumefantrine and amodiaquine-sulfadoxine-pyrimethamine but not dihydroartemisinin-piperaquine in Burkina Faso. Antimicrob Agents Chemother. 2010;54:1949–54.

Source: PubMed

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