PMID- 18628828
OWN - NLM
STAT- MEDLINE
DCOM- 20080924
LR  - 20240326
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 3
IP  - 7
DP  - 2008 Jul 16
TI  - Modelling the epidemiological impact of intermittent preventive treatment against 
      malaria in infants.
PG  - e2661
LID - 10.1371/journal.pone.0002661 [doi]
LID - e2661
AB  - BACKGROUND: Trials of intermittent preventive treatment against malaria in 
      infants (IPTi) using sulphadoxine-pyrimethamine (SP) have shown a positive, 
      albeit variable, protective efficacy against clinical malaria episodes. The 
      impact of IPTi in different epidemiological settings and over time is unknown and 
      predictions are hampered by the lack of knowledge about how IPTi works. We 
      investigated mechanisms proposed for the action of IPTi and made predictions of 
      the likely impact on morbidity and mortality. METHODS/PRINCIPAL FINDINGS: We used 
      a comprehensive, individual-based, stochastic model of malaria epidemiology to 
      simulate recently published trials of IPTi using SP with site-specific 
      characteristics as inputs. This baseline model was then modified to represent 
      hypotheses concerning the duration of action of SP, the temporal pattern of 
      fevers caused by individual infections, potential benefits of avoiding fevers on 
      immunity and the effect of sub-therapeutic levels of SP on parasite dynamics. The 
      baseline model reproduced the pattern of results reasonably well. None of the 
      models based on alternative hypotheses improved the fit between the model 
      predictions and observed data. Predictions suggest that IPTi would have a 
      beneficial effect across a range of transmission intensities. IPTi was predicted 
      to avert a greater number of episodes where IPTi coverage was higher, the health 
      system treatment coverage lower, and for drugs which were more efficacious and 
      had longer prophylactic periods. The predicted cumulative benefits were 
      proportionately slightly greater for severe malaria episodes and 
      malaria-attributable mortality than for acute episodes in the settings modelled. 
      Modest increased susceptibility was predicted between doses and following the 
      last dose, but these were outweighed by the cumulative benefits. The impact on 
      transmission intensity was negligible. CONCLUSIONS: The pattern of trial results 
      can be accounted for by differences between the trial sites together with known 
      features of malaria epidemiology and the action of SP. Predictions suggest that 
      IPTi would have a beneficial impact across a variety of epidemiological settings.
FAU - Ross, Amanda
AU  - Ross A
AD  - Department of Public Health and Epidemiology, Swiss Tropical Institute, Basel, 
      Switzerland. amanda.ross@unibas.ch
FAU - Penny, Melissa
AU  - Penny M
FAU - Maire, Nicolas
AU  - Maire N
FAU - Studer, Alain
AU  - Studer A
FAU - Carneiro, Ilona
AU  - Carneiro I
FAU - Schellenberg, David
AU  - Schellenberg D
FAU - Greenwood, Brian
AU  - Greenwood B
FAU - Tanner, Marcel
AU  - Tanner M
FAU - Smith, Thomas
AU  - Smith T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080716
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antimalarials)
RN  - 0 (Drug Combinations)
RN  - 37338-39-9 (fanasil, pyrimethamine drug combination)
RN  - 88463U4SM5 (Sulfadoxine)
RN  - Z3614QOX8W (Pyrimethamine)
SB  - IM
EIN - PLoS ONE. 2009;4(3). doi: 10.1371/annotation/5dba0336-1efe-4387-8d9f-946b231331f3
MH  - Antimalarials/pharmacology
MH  - Child
MH  - Child, Preschool
MH  - Clinical Trials as Topic
MH  - Drug Combinations
MH  - Drug Resistance
MH  - Humans
MH  - Immune System
MH  - Infant
MH  - Malaria/*epidemiology/*prevention & control
MH  - Models, Biological
MH  - Models, Statistical
MH  - Models, Theoretical
MH  - Pyrimethamine/pharmacology
MH  - Sulfadoxine/pharmacology
MH  - Time Factors
MH  - Treatment Outcome
PMC - PMC2441827
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2008/07/17 09:00
MHDA- 2008/09/25 09:00
PMCR- 2008/07/16
CRDT- 2008/07/17 09:00
PHST- 2008/03/11 00:00 [received]
PHST- 2008/06/07 00:00 [accepted]
PHST- 2008/07/17 09:00 [pubmed]
PHST- 2008/09/25 09:00 [medline]
PHST- 2008/07/17 09:00 [entrez]
PHST- 2008/07/16 00:00 [pmc-release]
AID - 08-PONE-RA-03922R1 [pii]
AID - 10.1371/journal.pone.0002661 [doi]
PST - epublish
SO  - PLoS One. 2008 Jul 16;3(7):e2661. doi: 10.1371/journal.pone.0002661.