Varying efficacy of intermittent preventive treatment for malaria in infants in two similar trials: public health implications.
BACKGROUND
Intermittent preventive treatment (IPTi) with sulphadoxine-pyrimethamine (SP) in infants resulted in different estimates of clinical malaria protection in two trials that used the same protocol in Ifakara, Tanzania, and Manhiça, Mozambique. Understanding the reasons for the discrepant results will help to elucidate the action mechanism of this intervention, which is essential for rational policy formulation.


METHODS
A comparative analysis of two IPTi trials that used the same study design, follow-up, intervention, procedures and assessment of outcomes, in Tanzania and Mozambique was undertaken. Children were randomised to receive either SP or placebo administered 3 times alongside routine vaccinations delivered through the Expanded Program on Immunisation (EPI). Characteristics of the two areas and efficacy on clinical malaria after each dose were compared.


RESULTS
The most relevant difference was in ITN's use ; 68% in Ifakara and zero in Manhiça. In Ifakara, IPTi was associated with a 53% (95% CI 14.0; 74.1) reduction in the risk of clinical malaria between the second and the third dose; during the same period there was no significant effect in Manhiça. Similarly, protection against malaria episodes was maintained in Ifakara during 6 months after dose 3, but no effect of IPTi was observed in Manhiça.


CONCLUSIONS
The high ITN coverage in Ifakara is the most likely explanation for the difference in IPTi efficacy on clinical malaria. Combination of IPTi and ITNs may be the most cost-effective tool for malaria control currently available, and needs to be explored in current and future studies.


BACKGROUND
Manhiça study registration number: NCT00209795Ifakara study registration number: NCT88523834.
Menendez
Clara
C
Barcelona Center for International Health Research (CRESIB), Hospital Clinic, Institut d'Investigacions Biomedicas August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Spain. menendez@clinic.ub.es
Schellenberg
David
D
Macete
Eusebio
E
Aide
Pedro
P
Kahigwa
Elizeus
E
Sanz
Sergi
S
Aponte
John J
JJ
Sacarlal
Jahit
J
Mshinda
Hassan
H
Tanner
Marcel
M
Alonso
Pedro L
PL
D000962:Antimalarials / Q000008:administration & dosage*; D001512:Bedding and Linens; D004334:Drug Administration Schedule; D004338:Drug Combinations; D006801:Humans; D007223:Infant; D007306:Insecticides; D008288:Malaria / Q000517:prevention & control*; D009032:Mosquito Control; D009073:Mozambique / Q000453:epidemiology; D011634:Public Health; D011739:Pyrimethamine / Q000008:administration & dosage*; D016032:Randomized Controlled Trials as Topic; D013413:Sulfadoxine / Q000008:administration & dosage*; D013607:Tablets; D013636:Tanzania / Q000453:epidemiology
D000962:Antimalarials; D004338:Drug Combinations; D007306:Insecticides; D013607:Tablets; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D011739:Pyrimethamine