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.

Gutman, Julie R, Khairallah, Carole, Stepniewska, Kasia, Tagbor, Harry, Madanitsa, Mwayiwawo, Cairns, Matthew, L'lanziva, Anne Joan, Kalilani, Linda, Otieno, Kephas, Mwapasa, Victor, Meshnick, Steve, Kariuki, Simon, Chandramohan, Daniel, Desai, Meghna, Taylor, Steve M, Greenwood, Brian and terKuile, Feiko ORCID: https://orcid.org/0000-0003-3663-5617 (2021) '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.'. EClinicalMedicine, Vol 41, p. 101160.

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Abstract

Background
In 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.

Methods
We 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.

Findings
Five 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).

Interpretation
ISTp-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.

Funding
Centers for Disease Control and Prevention and Worldwide Antimalarial Resistance Network.

Item Type:	Article
Subjects:	WA Public Health > Health Problems of Special Population Groups > WA 310 Maternal welfare WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria WQ Obstetrics > Pregnancy > WQ 200 General works
Faculty: Department:	Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):	https://doi.org/10.1016/j.eclinm.2021.101160
Depositing User:	Tracy Seddon
Date Deposited:	10 Nov 2021 13:17
Last Modified:	10 Nov 2021 13:17
URI:	https://archive.lstmed.ac.uk/id/eprint/19395

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