TY - JOUR
T1 - Efficacy and safety of intermittent preventive treatment with sulfadoxine-pyrimethamine for malaria in African infants
T2 - a pooled analysis of six randomised, placebo-controlled trials
AU - Aponte, John J.
AU - Schellenberg, David
AU - Egan, Andrea
AU - Breckenridge, Alasdair
AU - Carneiro, Ilona
AU - Critchley, Julia
AU - Danquah, Ina
AU - Dodoo, Alexander
AU - Kobbe, Robin
AU - Lell, Bertrand
AU - May, Jürgen
AU - Premji, Zul
AU - Sanz, Sergi
AU - Sevene, Esperanza
AU - Soulaymani-Becheikh, Rachida
AU - Winstanley, Peter
AU - Adjei, Samuel
AU - Anemana, Sylvester
AU - Chandramohan, Daniel
AU - Issifou, Saadou
AU - Mockenhaupt, Frank
AU - Owusu-Agyei, Seth
AU - Greenwood, Brian
AU - Grobusch, Martin P.
AU - Kremsner, Peter G.
AU - Macete, Eusebio
AU - Mshinda, Hassan
AU - Newman, Robert D.
AU - Slutsker, Laurence
AU - Tanner, Marcel
AU - Alonso, Pedro
AU - Menendez, Clara
N1 - Funding Information:
The Bill & Melinda Gates Foundation funded the pooled analyses through grants to the IPTi Consortium. We thank David Brandling-Bennett, the senior programme officer for the IPTi Consortium at the Bill & Melinda Gates Foundation; Jane Crawley, who was involved in the development and direction of the IPTi Consortium; Cornelia Bevilacqua, who monitored or audited the trials; Llorenç Quinto, who helped in the extraction of the safety data of the Manhiça trial; and Wibke Loag, who was involved in data management and extraction of data of the Kumasi trial.
PY - 2009
Y1 - 2009
N2 - Background: Intermittent preventive treatment (IPT) is a promising strategy for malaria control in infants. We undertook a pooled analysis of the safety and efficacy of IPT in infants (IPTi) with sulfadoxine-pyrimethamine in Africa. Methods: We pooled data from six double-blind, randomised, placebo-controlled trials (undertaken one each in Tanzania, Mozambique, and Gabon, and three in Ghana) that assessed the efficacy of IPTi with sulfadoxine-pyrimethamine. In all trials, IPTi or placebo was given to infants at the time of routine vaccinations delivered by WHO's Expanded Program on Immunization. Data from the trials for incidence of clinical malaria, risk of anaemia (packed-cell volume <25% or haemoglobin <80 g/L), and incidence of hospital admissions and adverse events in infants up to 12 months of age were reanalysed by use of standard outcome definitions and time periods. Analysis was by modified intention to treat, including all infants who received at least one dose of IPTi or placebo. Findings: The six trials provided data for 7930 infants (IPTi, n=3958; placebo, n=3972). IPTi had a protective efficacy of 30·3% (95% CI 19·8-39·4, p<0·0001) against clinical malaria, 21·3% (8·2-32·5, p=0·002) against the risk of anaemia, 38·1% (12·5-56·2, p=0·007) against hospital admissions associated with malaria parasitaemia, and 22·9% (10·0-34·0, p=0·001) against all-cause hospital admissions. There were 56 deaths in the IPTi group compared with 53 in the placebo group (rate ratio 1·05, 95% CI 0·72-1·54, p=0·79). One death, judged as possibly related to IPTi because it occurred 19 days after a treatment dose, was subsequently attributed to probable sepsis. Four of 676 non-fatal hospital admissions in the IPTi group were deemed related to study treatment compared with five of 860 in the placebo group. None of three serious dermatological adverse events in the IPTi group were judged related to study treatment compared with one of 13 in the placebo group. Interpretation: IPTi with sulfadoxine-pyrimethamine was safe and efficacious across a range of malaria transmission settings, suggesting that this intervention is a useful contribution to malaria control. Funding: Bill & Melinda Gates Foundation.
AB - Background: Intermittent preventive treatment (IPT) is a promising strategy for malaria control in infants. We undertook a pooled analysis of the safety and efficacy of IPT in infants (IPTi) with sulfadoxine-pyrimethamine in Africa. Methods: We pooled data from six double-blind, randomised, placebo-controlled trials (undertaken one each in Tanzania, Mozambique, and Gabon, and three in Ghana) that assessed the efficacy of IPTi with sulfadoxine-pyrimethamine. In all trials, IPTi or placebo was given to infants at the time of routine vaccinations delivered by WHO's Expanded Program on Immunization. Data from the trials for incidence of clinical malaria, risk of anaemia (packed-cell volume <25% or haemoglobin <80 g/L), and incidence of hospital admissions and adverse events in infants up to 12 months of age were reanalysed by use of standard outcome definitions and time periods. Analysis was by modified intention to treat, including all infants who received at least one dose of IPTi or placebo. Findings: The six trials provided data for 7930 infants (IPTi, n=3958; placebo, n=3972). IPTi had a protective efficacy of 30·3% (95% CI 19·8-39·4, p<0·0001) against clinical malaria, 21·3% (8·2-32·5, p=0·002) against the risk of anaemia, 38·1% (12·5-56·2, p=0·007) against hospital admissions associated with malaria parasitaemia, and 22·9% (10·0-34·0, p=0·001) against all-cause hospital admissions. There were 56 deaths in the IPTi group compared with 53 in the placebo group (rate ratio 1·05, 95% CI 0·72-1·54, p=0·79). One death, judged as possibly related to IPTi because it occurred 19 days after a treatment dose, was subsequently attributed to probable sepsis. Four of 676 non-fatal hospital admissions in the IPTi group were deemed related to study treatment compared with five of 860 in the placebo group. None of three serious dermatological adverse events in the IPTi group were judged related to study treatment compared with one of 13 in the placebo group. Interpretation: IPTi with sulfadoxine-pyrimethamine was safe and efficacious across a range of malaria transmission settings, suggesting that this intervention is a useful contribution to malaria control. Funding: Bill & Melinda Gates Foundation.
UR - http://www.scopus.com/inward/record.url?scp=70350751558&partnerID=8YFLogxK
U2 - 10.1016/S0140-6736(09)61258-7
DO - 10.1016/S0140-6736(09)61258-7
M3 - Article
C2 - 19765816
AN - SCOPUS:70350751558
SN - 0140-6736
VL - 374
SP - 1533
EP - 1542
JO - The Lancet
JF - The Lancet
IS - 9700
ER -