TY - JOUR
T1 - Intermittent screening and treatment with artemisinin-combination therapy versus intermittent preventive treatment with sulphadoxine-pyrimethamine for malaria in pregnancy: a systematic review and individual participant data meta-analysis of randomised clinical trials
AU - Gutman, Julie R.
AU - Khairallah, Carole
AU - Stepniewska, Kasia
AU - Tagbor, Harry
AU - Madanitsa, Mwayiwawo
AU - Cairns, Matthew
AU - L'lanziva, Anne Joan
AU - Kalilani, Linda
AU - Otieno, Kephas
AU - Mwapasa, Victor
AU - Meshnick, Steve
AU - Kariuki, Simon
AU - Chandramohan, Daniel
AU - Desai, Meghna
AU - Taylor, Steve M.
AU - Greenwood, Brian
AU - Ter Kuile, Feiko
PY - 2021/10/25
Y1 - 2021/10/25
N2 - BackgroundIn sub-Saharan Africa, the efficacy of intermittent preventive therapy in pregnancy with sulphadoxine-pyrimethamine (IPTp-SP) for malaria in pregnancy is threatened by parasite resistance. We conducted an individual-participant data (IPD) meta-analysis to assess the efficacy of intermittent screening with malaria rapid diagnostic tests (RDTs) and treatment of RDT-positive women with artemisinin-based combination therapy (ISTp-ACT) compared to IPTp-SP, and understand the importance of subpatent infections.MethodsWe searched MEDLINE and the Malaria-in-Pregnancy Library on May 6, 2021 for trials comparing ISTp-ACT and IPTp-SP. Generalised linear regression was used to compare adverse pregnancy outcomes (composite of small-for-gestational-age, low birthweight (LBW), or preterm delivery) and peripheral or placental at delivery. The effects of subpatent (PCR-positive, RDT/microscopy-negative) infections were assessed in both arms pooled using multi-variable fixed-effect models adjusting for the number of patent infections. PROSPERO registration: CRD42016043789.FindingsFive trials conducted between 2007 and 2014 contributed (10,821 pregnancies), two from high SP-resistance areas where quintuple mutant parasites are saturated, but sextuple mutants are still rare (Kenya and Malawi), and three from low-resistance areas (West-Africa). Four trials contributed IPD data (N=10,362). At delivery, the prevalence of any malaria infection (relative risk [RR]=1.08, 95% CI 1.00-1.16, I=67.0 %) and patent infection (RR=1.02, 0.61-1.16, I=0.0%) were similar. Subpatent infections were more common in ISTp recipients (RR=1.31, 1.05-1.62, I=0.0%). There was no difference in adverse pregnancy outcome (RR=1.00, 0.96-1.05; studies=4, N=9,191, I=54.5%). Subpatent infections were associated with LBW (adjusted RR=1.13, 1.07-1.19), lower mean birthweight (adjusted mean difference=32g, 15-49), and preterm delivery (aRR=1.35, 1.15-1.57).InterpretationISTp-ACT was not superior to IPTp-SP and may result in more subpatent infections than the existing IPTp-SP policy. Subpatent infections were associated with increased LBW and preterm delivery. More sensitive diagnostic tests are needed to detect and treat low-grade infections.FundingCenters for Disease Control and Prevention and Worldwide Antimalarial Resistance Network.
AB - BackgroundIn sub-Saharan Africa, the efficacy of intermittent preventive therapy in pregnancy with sulphadoxine-pyrimethamine (IPTp-SP) for malaria in pregnancy is threatened by parasite resistance. We conducted an individual-participant data (IPD) meta-analysis to assess the efficacy of intermittent screening with malaria rapid diagnostic tests (RDTs) and treatment of RDT-positive women with artemisinin-based combination therapy (ISTp-ACT) compared to IPTp-SP, and understand the importance of subpatent infections.MethodsWe searched MEDLINE and the Malaria-in-Pregnancy Library on May 6, 2021 for trials comparing ISTp-ACT and IPTp-SP. Generalised linear regression was used to compare adverse pregnancy outcomes (composite of small-for-gestational-age, low birthweight (LBW), or preterm delivery) and peripheral or placental at delivery. The effects of subpatent (PCR-positive, RDT/microscopy-negative) infections were assessed in both arms pooled using multi-variable fixed-effect models adjusting for the number of patent infections. PROSPERO registration: CRD42016043789.FindingsFive trials conducted between 2007 and 2014 contributed (10,821 pregnancies), two from high SP-resistance areas where quintuple mutant parasites are saturated, but sextuple mutants are still rare (Kenya and Malawi), and three from low-resistance areas (West-Africa). Four trials contributed IPD data (N=10,362). At delivery, the prevalence of any malaria infection (relative risk [RR]=1.08, 95% CI 1.00-1.16, I=67.0 %) and patent infection (RR=1.02, 0.61-1.16, I=0.0%) were similar. Subpatent infections were more common in ISTp recipients (RR=1.31, 1.05-1.62, I=0.0%). There was no difference in adverse pregnancy outcome (RR=1.00, 0.96-1.05; studies=4, N=9,191, I=54.5%). Subpatent infections were associated with LBW (adjusted RR=1.13, 1.07-1.19), lower mean birthweight (adjusted mean difference=32g, 15-49), and preterm delivery (aRR=1.35, 1.15-1.57).InterpretationISTp-ACT was not superior to IPTp-SP and may result in more subpatent infections than the existing IPTp-SP policy. Subpatent infections were associated with increased LBW and preterm delivery. More sensitive diagnostic tests are needed to detect and treat low-grade infections.FundingCenters for Disease Control and Prevention and Worldwide Antimalarial Resistance Network.
KW - artemisinin combination therapy
KW - intermittent preventive treatment
KW - intermittent screening
KW - Malaria
KW - pregnancy
KW - sulphadoxine-pyrimethamine
U2 - 10.1016/j.eclinm.2021.101160
DO - 10.1016/j.eclinm.2021.101160
M3 - Article
SN - 2589-5370
VL - 41
SP - 101160
JO - eClinicalMedicine
JF - eClinicalMedicine
M1 - 101160
ER -
