PMID- 20838642
OWN - NLM
STAT- MEDLINE
DCOM- 20110218
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 5
IP  - 9
DP  - 2010 Sep 7
TI  - Protective efficacy of intermittent preventive treatment of malaria in infants 
      (IPTi) using sulfadoxine-pyrimethamine and parasite resistance.
PG  - e12618
LID - 10.1371/journal.pone.0012618 [doi]
LID - e12618
AB  - BACKGROUND: Intermittent Preventive Treatment of malaria in infants using 
      sulfadoxine-pyrimethamine (SP-IPTi) is recommended by WHO for implementation in 
      settings where resistance to SP is not high. Here we examine the relationship 
      between the protective efficacy of SP-IPTi and measures of SP resistance. METHODS 
      AND RESULTS: We analysed the relationship between protective efficacy reported in 
      the 7 SP-IPTi trials and contemporaneous data from 6 in vivo efficacy studies 
      using SP and 7 molecular studies reporting frequency of dhfr triple and dhps 
      double mutations within 50 km of the trial sites. We found a borderline 
      significant association between frequency of the dhfr triple mutation and 
      protective efficacy to 12 months of age of SP-IPTi. This association is 
      significantly biased due to differences between studies, namely number of doses 
      of SP given and follow up times. However, fitting a simple probabilistic model to 
      determine the relationship between the frequency of the dhfr triple, dhps double 
      and dhfr/dhps quintuple mutations associated with resistance to SP and protective 
      efficacy, we found a significant inverse relationship between the dhfr triple 
      mutation frequency alone and the dhfr/dhps quintuple mutations and efficacy at 35 
      days post the 9 month dose and up to 12 months of age respectively. CONCLUSIONS: 
      A significant relationship was found between the frequency of the dhfr triple 
      mutation and SP-IPTi protective efficacy at 35 days post the 9 month dose. An 
      association between the protective efficacy to 12 months of age and dhfr triple 
      and dhfr/dhps quintuple mutations was found but should be viewed with caution due 
      to bias. It was not possible to define a more definite relationship based on the 
      data available from these trials.
FAU - Griffin, Jamie T
AU  - Griffin JT
AD  - MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease 
      Epidemiology, Imperial College, London, United Kingdom.
FAU - Cairns, Matthew
AU  - Cairns M
FAU - Ghani, Azra C
AU  - Ghani AC
FAU - Roper, Cally
AU  - Roper C
FAU - Schellenberg, David
AU  - Schellenberg D
FAU - Carneiro, Ilona
AU  - Carneiro I
FAU - Newman, Robert D
AU  - Newman RD
FAU - Grobusch, Martin P
AU  - Grobusch MP
FAU - Greenwood, Brian
AU  - Greenwood B
FAU - Chandramohan, Daniel
AU  - Chandramohan D
FAU - Gosling, Roly D
AU  - Gosling RD
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20100907
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antimalarials)
RN  - 0 (Drug Combinations)
RN  - 0 (Protozoan Proteins)
RN  - 37338-39-9 (fanasil, pyrimethamine drug combination)
RN  - 88463U4SM5 (Sulfadoxine)
RN  - EC 1.1.1.1 (Alcohol Dehydrogenase)
RN  - EC 1.5.1.3 (Tetrahydrofolate Dehydrogenase)
RN  - Z3614QOX8W (Pyrimethamine)
SB  - IM
MH  - Alcohol Dehydrogenase/genetics/metabolism
MH  - Antimalarials/*therapeutic use
MH  - Drug Combinations
MH  - *Drug Resistance
MH  - Female
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - Infant, Newborn, Diseases/*drug therapy/parasitology/*prevention & control
MH  - Malaria, Falciparum/*drug therapy/parasitology/*prevention & control
MH  - Male
MH  - Mutation
MH  - Plasmodium falciparum/*drug effects/enzymology/genetics
MH  - Protozoan Proteins/genetics/metabolism
MH  - Pyrimethamine/*therapeutic use
MH  - Sulfadoxine/*therapeutic use
MH  - Tetrahydrofolate Dehydrogenase/genetics/metabolism
PMC - PMC2935388
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2010/09/15 06:00
MHDA- 2011/02/22 06:00
PMCR- 2010/09/07
CRDT- 2010/09/15 06:00
PHST- 2009/12/11 00:00 [received]
PHST- 2010/08/06 00:00 [accepted]
PHST- 2010/09/15 06:00 [entrez]
PHST- 2010/09/15 06:00 [pubmed]
PHST- 2011/02/22 06:00 [medline]
PHST- 2010/09/07 00:00 [pmc-release]
AID - 09-PONE-RA-14849R2 [pii]
AID - 10.1371/journal.pone.0012618 [doi]
PST - epublish
SO  - PLoS One. 2010 Sep 7;5(9):e12618. doi: 10.1371/journal.pone.0012618.