PMID- 20209126
OWN - NLM
STAT- MEDLINE
DCOM- 20110111
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 5
IP  - 3
DP  - 2010 Mar 1
TI  - Duration of protection against clinical malaria provided by three regimens of 
      intermittent preventive treatment in Tanzanian infants.
PG  - e9467
LID - 10.1371/journal.pone.0009467 [doi]
LID - e9467
AB  - BACKGROUND: Intermittent preventive treatment in infants (IPTi) is a new malaria 
      control tool. However, it is uncertain whether IPTi works mainly through 
      chemoprophylaxis or treatment of existing infections. Understanding the mechanism 
      is essential for development of replacements for sulfadoxine-pyrimethamine (SP) 
      where it is no longer effective. This study investigated how protection against 
      malaria given by SP, chlorproguanil-dapsone (CD) and mefloquine (MQ), varied with 
      time since administration of IPTi. METHODS AND FINDINGS: A secondary analysis of 
      data from a randomised, placebo-controlled trial in an area of high antifolate 
      resistance in Tanzania was conducted. IPTi using SP, CD, MQ or placebo was given 
      to 1280 infants at 2, 3 and 9 months of age. Poisson regression with random 
      effects to adjust for potential clustering of malaria episodes within children 
      was used to calculate incidence rate ratios for clinical malaria in defined time 
      strata following IPTi. The short-acting antimalarial CD gave no protection 
      against clinical malaria, whereas long-acting MQ gave two months of substantial 
      protection (protective efficacy (PE) 73.1% (95% CI: 23.9, 90.5) and 73.3% (95% 
      CI: 0, 92.9) in the first and second month respectively). SP gave some protection 
      in the first month after treatment (PE 64.5% (95% CI: 10.6, 85.9)) although it 
      did not reduce the incidence of malaria up to 12 months of age. There was no 
      evidence of either long-term protection or increased risk of malaria for any of 
      the regimens. CONCLUSION: Post-treatment chemoprophylaxis appears to be the main 
      mechanism by which IPTi protects children against malaria. Long-acting 
      antimalarials are therefore likely to be the most effective drugs for IPTi, but 
      as monotherapies could be vulnerable to development of drug resistance. Due to 
      concerns about tolerability, the mefloquine formulation used in this study is not 
      suitable for IPTi. Further investigation of combinations of long-acting 
      antimalarials for IPTi is needed. TRIAL REGISTRATION: Clinicaltrials.gov 
      NCT00158574.
FAU - Cairns, Matthew
AU  - Cairns M
AD  - Department of Epidemiology and Population Health, London School of Hygiene & 
      Tropical Medicine, London, United Kingdom. matthew.cairns@lshtm.ac.uk
FAU - Gosling, Roly
AU  - Gosling R
FAU - Carneiro, Ilona
AU  - Carneiro I
FAU - Gesase, Samwel
AU  - Gesase S
FAU - Mosha, Jacklin F
AU  - Mosha JF
FAU - Hashim, Ramadhan
AU  - Hashim R
FAU - Kaur, Harparkash
AU  - Kaur H
FAU - Lemnge, Martha
AU  - Lemnge M
FAU - Mosha, Frank W
AU  - Mosha FW
FAU - Greenwood, Brian
AU  - Greenwood B
FAU - Chandramohan, Daniel
AU  - Chandramohan D
LA  - eng
SI  - ClinicalTrials.gov/NCT00158574
GR  - Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20100301
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antimalarials)
RN  - 0 (Drug Combinations)
RN  - 0 (Placebos)
RN  - 0 (chloroguanil, dapsone drug combination)
RN  - 37338-39-9 (fanasil, pyrimethamine drug combination)
RN  - 88463U4SM5 (Sulfadoxine)
RN  - 8W5C518302 (Dapsone)
RN  - S61K3P7B2V (Proguanil)
RN  - TML814419R (Mefloquine)
RN  - Z3614QOX8W (Pyrimethamine)
SB  - IM
MH  - Antimalarials/pharmacology
MH  - Dapsone/therapeutic use
MH  - Drug Administration Schedule
MH  - Drug Combinations
MH  - Drug Resistance
MH  - Humans
MH  - Immunization Schedule
MH  - Infant
MH  - Infant, Newborn
MH  - Malaria/*prevention & control
MH  - Mefloquine/therapeutic use
MH  - Pediatrics/*methods
MH  - Placebos
MH  - Proguanil/analogs & derivatives/therapeutic use
MH  - Pyrimethamine/therapeutic use
MH  - Research Design
MH  - Sulfadoxine/therapeutic use
MH  - Tanzania
MH  - Time Factors
MH  - Treatment Outcome
PMC - PMC2830887
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2010/03/09 06:00
MHDA- 2011/01/12 06:00
PMCR- 2010/03/01
CRDT- 2010/03/09 06:00
PHST- 2009/05/23 00:00 [received]
PHST- 2010/01/29 00:00 [accepted]
PHST- 2010/03/09 06:00 [entrez]
PHST- 2010/03/09 06:00 [pubmed]
PHST- 2011/01/12 06:00 [medline]
PHST- 2010/03/01 00:00 [pmc-release]
AID - 09-PONE-RA-10557R2 [pii]
AID - 10.1371/journal.pone.0009467 [doi]
PST - epublish
SO  - PLoS One. 2010 Mar 1;5(3):e9467. doi: 10.1371/journal.pone.0009467.