Duration of protection against clinical malaria provided by three regimens of intermittent preventive treatment in Tanzanian infants.
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.


RESULTS
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.


CONCLUSIONS
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.


BACKGROUND
Clinicaltrials.gov NCT00158574.
Cairns
Matthew
M
Department of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, United Kingdom. matthew.cairns@lshtm.ac.uk
Gosling
Roly
R
Carneiro
Ilona
I
Gesase
Samwel
S
Mosha
Jacklin F
JF
Hashim
Ramadhan
R
Kaur
Harparkash
H
Lemnge
Martha
M
Mosha
Frank W
FW
Greenwood
Brian
B
Chandramohan
Daniel
D
D000962:Antimalarials / Q000494:pharmacology; D003622:Dapsone / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004351:Drug Resistance; D006801:Humans; D007115:Immunization Schedule; D007223:Infant; D007231:Infant, Newborn; D008288:Malaria / Q000517:prevention & control*; D015767:Mefloquine / Q000627:therapeutic use; D010372:Pediatrics / Q000379:methods*; D010919:Placebos; D002727:Proguanil / Q000031:analogs & derivatives / Q000627:therapeutic use; D011739:Pyrimethamine / Q000627:therapeutic use; D012107:Research Design; D013413:Sulfadoxine / Q000627:therapeutic use; D013636:Tanzania; D013997:Time Factors; D016896:Treatment Outcome
D000962:Antimalarials; D004338:Drug Combinations; D010919:Placebos; C519882:chloroguanil, dapsone drug combination; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D003622:Dapsone; D002727:Proguanil; D015767:Mefloquine; D011739:Pyrimethamine