PMID- 23225897
OWN - NLM
STAT- MEDLINE
DCOM- 20130404
LR  - 20131121
IS  - 1537-6613 (Electronic)
IS  - 0022-1899 (Linking)
VI  - 207
IP  - 5
DP  - 2013 Mar 1
TI  - A community-randomized evaluation of the effect of intermittent preventive 
      treatment in infants on antimalarial drug resistance in southern Tanzania.
PG  - 848-59
LID - 10.1093/infdis/jis742 [doi]
AB  - BACKGROUND: Intermittent preventive treatment in infants (IPTi) is the 
      administration of sulfadoxine-pyrimethamine (SP) at 2, 3, and 9 months of age to 
      prevent malaria. We investigated the influence of IPTi on drug resistance. 
      METHODS: Twenty-four areas were randomly assigned to receive or not receive IPTi. 
      Blood collected during representative household surveys at baseline and 15 and 27 
      months after implementation was tested for SP and resistance markers. RESULTS: 
      The frequency of SP in blood was similar in the IPTi and comparison areas at 
      baseline and at 15 months. dhfr and dhps mutations were also similar at baseline 
      and then increased similarly in both arms after 15 months of SP-IPTi. First-line 
      treatment was switched from SP to artemether-lumefantrine before the final 
      survey, when SP positivity fell among infants in comparison areas but increased 
      in IPTi areas. This was accompanied by an increase in dhfr but not dhps mutations 
      in IPTi areas (P = .004 and P = .18, respectively). CONCLUSIONS: IPTi did not 
      increase drug pressure or the selection on dhfr and dhps mutants, when SP was the 
      first-line malaria treatment. Introduction of artemether-lumefantrine was 
      followed by an increase in dhfr mutations, consistent with weak selection 
      attributable to SP-IPTi, but not by an increase in dhps mutations, suggesting a 
      fitness cost of this mutation.
FAU - Pearce, Richard J
AU  - Pearce RJ
AD  - London School of Hygiene and Tropical Medicine, London, United Kingdom.
FAU - Ord, Rosalynn
AU  - Ord R
FAU - Kaur, Haprarksh
AU  - Kaur H
FAU - Lupala, Cecylia
AU  - Lupala C
FAU - Schellenberg, Joanna
AU  - Schellenberg J
FAU - Shirima, Kitzito
AU  - Shirima K
FAU - Manzi, Fatuma
AU  - Manzi F
FAU - Alonso, Pedro
AU  - Alonso P
FAU - Tanner, Marcel
AU  - Tanner M
FAU - Mshinda, Hassan
AU  - Mshinda H
FAU - Roper, Cally
AU  - Roper C
FAU - Schellenberg, David
AU  - Schellenberg D
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20121205
PL  - United States
TA  - J Infect Dis
JT  - The Journal of infectious diseases
JID - 0413675
RN  - 0 (Antimalarials)
RN  - 0 (Drug Combinations)
RN  - 37338-39-9 (fanasil, pyrimethamine drug combination)
RN  - 88463U4SM5 (Sulfadoxine)
RN  - EC 1.5.1.3 (Tetrahydrofolate Dehydrogenase)
RN  - EC 6.3.2.- (Peptide Synthases)
RN  - EC 6.3.2.12 (dihydrofolate synthetase)
RN  - Z3614QOX8W (Pyrimethamine)
SB  - IM
MH  - Antimalarials/*administration & dosage/blood/pharmacology
MH  - *Drug Administration Schedule
MH  - Drug Combinations
MH  - *Drug Resistance
MH  - Female
MH  - Humans
MH  - Infant
MH  - Malaria/*parasitology/*prevention & control
MH  - Male
MH  - Mutation
MH  - Peptide Synthases/genetics
MH  - Plasmodium/*drug effects
MH  - Pyrimethamine/*administration & dosage/blood/pharmacology
MH  - Selection, Genetic
MH  - Sulfadoxine/*administration & dosage/blood/pharmacology
MH  - Tanzania
MH  - Tetrahydrofolate Dehydrogenase/genetics
EDAT- 2012/12/12 06:00
MHDA- 2013/04/05 06:00
CRDT- 2012/12/11 06:00
PHST- 2012/12/11 06:00 [entrez]
PHST- 2012/12/12 06:00 [pubmed]
PHST- 2013/04/05 06:00 [medline]
AID - jis742 [pii]
AID - 10.1093/infdis/jis742 [doi]
PST - ppublish
SO  - J Infect Dis. 2013 Mar 1;207(5):848-59. doi: 10.1093/infdis/jis742. Epub 2012 Dec 
      5.