Intermittent preventive treatment in infants (IPTi) has been shown in randomized trials to reduce malaria-related morbidity in African infants living in areas of high Plasmodium falciparum (Pf) transmission. It remains unclear whether IPTi is an appropriate prevention strategy in non-African settings or those co-endemic for P. vivax (Pv).
Methods and Findings
In this study, 1,121 Papua New Guinean infants were enrolled into a three-arm placebo-controlled randomized trial and assigned to sulfadoxine-pyrimethamine (SP) (25 mg/kg and 1.25 mg/kg) plus amodiaquine (AQ) (10 mg/kg, 3 d, n = 374), SP plus artesunate (AS) (4 mg/kg, 3 d, n = 374), or placebo (n = 373), given at 3, 6, 9 and 12 mo. Both participants and study teams were blinded to treatment allocation. The primary end point was protective efficacy (PE) against all episodes of clinical malaria from 3 to 15 mo of age. Analysis was by modified intention to treat. The PE (compared to placebo) against clinical malaria episodes (caused by all species) was 29% (95% CI, 10–43, p≤0.001) in children receiving SP-AQ and 12% (95% CI, −11 to 30, p = 0.12) in those receiving SP-AS. Efficacy was higher against Pf than Pv. In the SP-AQ group, Pf incidence was 35% (95% CI, 9–54, p = 0.012) and Pv incidence was 23% (95% CI, 0–41, p = 0.048) lower than in the placebo group. IPTi with SP-AS protected only against Pf episodes (PE = 31%, 95% CI, 4–51, p = 0.027), not against Pv episodes (PE = 6%, 95% CI, −24 to 26, p = 0.759). Number of observed adverse events/serious adverse events did not differ between treatment arms (p>0.55). None of the serious adverse events were thought to be treatment-related, and the vomiting rate was low in both treatment groups (1.4%–2.0%). No rebound in malaria morbidity was observed for 6 mo following the intervention.
IPTi using a long half-life drug combination is efficacious for the prevention of malaria and anemia in infants living in a region highly endemic for both Pf and Pv.
Please see later full article for the Editors’ Summary (link below).
Citation: Senn N, Rarau P, Stanisic DI, Robinson L, Barnadas C, et al. (2012) Intermittent Preventive Treatment for Malaria in Papua New Guinean Infants Exposed to Plasmodium falciparum and P. vivax: A Randomized Controlled Trial. PLoS Med 9(3): e1001195. doi:10.1371/journal.pmed.1001195
Academic Editor: Sanjeev Krishna, St George’s Hospital Medical School, United Kingdom
Received: July 5, 2011; Accepted: February 9, 2012; Published: March 27, 2012
Funding: This work was supported by a grant to the PNG Institute of Medical Research from the Bill & Melinda Gates Foundation’s Global Health Program (Grand ID# 34678). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS.
Competing interests: SJR is a member of the PLoS Medicine Editorial Board. The authors have declared that no competing interests exist.
Abbreviations: AE, adverse event; AQ, amodiaquine; AS, artesunate; ATP, according to protocol; EPI, Expanded Programme on Immunization; Hb, hemoglobin; IPT, intermittent preventive treatment; IPTi, intermittent preventive treatment in infants; IRR, incidence rate ratio; LDR-FMA, ligase detection reaction/fluorescent microsphere assay; mITT, modified intention to treat; PE, protective efficacy; Pf, Plasmodium falciparum ; PNG, Papua New Guinea; Pv, Plasmodium vivax ; PYAR, person-year at risk; SAE, serious adverse event; SP, sulfadoxine-pyrimethamine
Authors: Nicolas Senn1,2,3,4#, Patricia Rarau1#, Danielle I. Stanisic1,5, Leanne Robinson1,5, Céline Barnadas1,5, Doris Manong1, Mary Salib1, Jonah Iga1, Nandao Tarongka1, Serej Ley1, Anna Rosanas-Urgell1, John J. Aponte6, Peter A. Zimmerman7, James G. Beeson5,8, Louis Schofield5, Peter Siba1, Stephen J. Rogerson2, John C. Reeder8, Ivo Mueller1,5,6*
1 Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea, 2 Department of Medicine, University of Melbourne, Melbourne Australia, 3 Swiss Tropical and Public Health Institute, Basel, Switzerland, 4 University of Basel, Basel, Switzerland, 5 Infection and Immunity Division, Walter and Eliza Hall Institute, Melbourne, Australia, 6 Barcelona Centre for International Health Research (CRESIB), Barcelona, Spain, 7 Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio, United States of America, 8 Burnet Institute, Melbourne, Australia
Source: PLOS Medicine
Copyright: © 2012 Senn et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.