PMID- 20368815
OWN - NLM
STAT- MEDLINE
DCOM- 20110616
LR  - 20220318
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 5
IP  - 4
DP  - 2010 Apr 2
TI  - Intermittent preventive treatment in infants for the prevention of malaria in 
      rural Western kenya: a randomized, double-blind placebo-controlled trial.
PG  - e10016
LID - 10.1371/journal.pone.0010016 [doi]
LID - e10016
AB  - BACKGROUND: Intermittent preventive treatment in infants (IPTi) with 
      sulphadoxine-pyrimethamine (SP) for the prevention of malaria has shown promising 
      results in six trials. However, resistance to SP is rising and alternative drug 
      combinations need to be evaluated to better understand the role of treatment 
      versus prophylactic effects. METHODS: Between March 2004 and March 2008, in an 
      area of western Kenya with year round malaria transmission with high seasonal 
      intensity and high usage of insecticide-treated nets, we conducted a randomized, 
      double-blind placebo-controlled trial with SP plus 3 days of artesunate (SP-AS3), 
      3 days of amodiaquine-artesunate (AQ3-AS3), or 3 days of short-acting 
      chlorproguanil-dapsone (CD3) administered at routine expanded programme of 
      immunization visits (10 weeks, 14 weeks and 9 months). PRINCIPAL FINDINGS: 1,365 
      subjects were included in the analysis. The incidence of first or only episode of 
      clinical malaria during the first year of life (primary endpoint) was 0.98 
      episodes/person-year in the placebo group, 0.74 in the SP-AS3 group, 0.76 in the 
      AQ3-AS3 group, and 0.82 in the CD3 group. The protective efficacy (PE) and 95% 
      confidence intervals against the primary endpoint were: 25.7% (6.3, 41.1); 25.9% 
      (6.8, 41.0); and 16.3% (-5.2, 33.5) in the SP-AS3, AQ3-AS3, and CD3 groups, 
      respectively. The PEs for moderate-to-severe anaemia were: 27.5% (-6.9, 50.8); 
      23.1% (-11.9, 47.2); and 11.4% (-28.6, 39.0). The duration of the protective 
      effect remained significant for up to 5 to 8 weeks for SP-AS3 and AQ3-AS3. There 
      was no evidence for a sustained beneficial or rebound effect in the second year 
      of life. All regimens were well tolerated. CONCLUSIONS: These results support the 
      view that IPTi with long-acting regimens provide protection against clinical 
      malaria for up to 8 weeks even in the presence of high ITN coverage, and that the 
      prophylactic rather than the treatment effect of IPTi appears central to its 
      protective efficacy.
FAU - Odhiambo, Frank O
AU  - Odhiambo FO
AD  - Kenya Medical Research Institute, Centre for Global Health Research, Kisumu, 
      Kenya. fodhiambo@ke.cdc.gov
FAU - Hamel, Mary J
AU  - Hamel MJ
FAU - Williamson, John
AU  - Williamson J
FAU - Lindblade, Kim
AU  - Lindblade K
FAU - ter Kuile, Feiko O
AU  - ter Kuile FO
FAU - Peterson, Elizabeth
AU  - Peterson E
FAU - Otieno, Peter
AU  - Otieno P
FAU - Kariuki, Simon
AU  - Kariuki S
FAU - Vulule, John
AU  - Vulule J
FAU - Slutsker, Laurence
AU  - Slutsker L
FAU - Newman, Robert D
AU  - Newman RD
LA  - eng
SI  - ClinicalTrials.gov/NCT00111163
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20100402
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antimalarials)
RN  - 0 (Artemisinins)
RN  - 0 (Drug Combinations)
RN  - 0 (chloroguanil, dapsone drug combination)
RN  - 37338-39-9 (fanasil, pyrimethamine drug combination)
RN  - 60W3249T9M (Artesunate)
RN  - 88463U4SM5 (Sulfadoxine)
RN  - 8W5C518302 (Dapsone)
RN  - S61K3P7B2V (Proguanil)
RN  - Z3614QOX8W (Pyrimethamine)
SB  - IM
MH  - Anemia
MH  - Antimalarials/*administration & dosage
MH  - Artemisinins/administration & dosage
MH  - Artesunate
MH  - Dapsone/administration & dosage
MH  - Double-Blind Method
MH  - Drug Combinations
MH  - Humans
MH  - Incidence
MH  - Infant
MH  - Kenya
MH  - Malaria/drug therapy/*prevention & control
MH  - Premedication/methods
MH  - Proguanil/administration & dosage/analogs & derivatives
MH  - Pyrimethamine/administration & dosage
MH  - Sulfadoxine/administration & dosage
MH  - Treatment Outcome
PMC - PMC2848869
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2010/04/07 06:00
MHDA- 2011/06/17 06:00
PMCR- 2010/04/02
CRDT- 2010/04/07 06:00
PHST- 2009/06/10 00:00 [received]
PHST- 2010/03/09 00:00 [accepted]
PHST- 2010/04/07 06:00 [entrez]
PHST- 2010/04/07 06:00 [pubmed]
PHST- 2011/06/17 06:00 [medline]
PHST- 2010/04/02 00:00 [pmc-release]
AID - 09-PONE-RA-11078R1 [pii]
AID - 10.1371/journal.pone.0010016 [doi]
PST - epublish
SO  - PLoS One. 2010 Apr 2;5(4):e10016. doi: 10.1371/journal.pone.0010016.