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
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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 Plasmodium falciparum 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 dhfr/dhps 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 2 =67.0 %) and patent infection (RR=1.02, 0.61-1.16, I 2 =0.0%) were similar. Subpatent infections were more common in ISTp recipients (RR=1.31, 1.05-1.62, I 2 =0.0%). There was no difference in adverse pregnancy outcome (RR=1.00, 0.96-1.05; studies=4, N=9,191, I 2 =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.
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In areas of high seasonal malaria transmission, seasonal malaria chemoprevention with a combination of mefloquine, or amodiaquine and SP is being used as a strategy to reduce the incidence of malaria in pregnancy.
“To support this, in areas of high seasonal malaria transmission, seasonal malaria chemoprevention with a combination of mefloquine, or amodiaquine and SP is being used as a strategy to reduce the incidence of malaria in pregnancy [206, 211–213].”
From Current update on malaria in pregnancy: a systematic review (2025) · cites this paper as [213]
The Introduction (page unavailable) discusses amodiaquine with SP and mefloquine as alternatives for preventing malaria in pregnancy, but says poor tolerability undermines their effectiveness. It does not say these drugs are being used for seasonal malaria chemoprevention in areas of high seasonal transmission. (LLM, conf=0.84)
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New Strides in Prevention of Malaria during Pregnancy Present Multitudinous Opportunities
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Yon, J. L. T., Htet, N. H., Naing, C., Tung, W. S., Aung, H. H., & Mak, J. W. (2023) · Figshare · doi:10.6084/m9.figshare.22608463
Yon, J. L. T., Htet, N. H., Naing, C., Tung, W. S., Aung, H. H., & Mak, J. W. (2023) · Figshare · doi:10.6084/m9.figshare.22608460
Yon, J. L. T., Htet, N. H., Naing, C., Tung, W. S., Aung, H. H., & Mak, J. W. (2023) · Figshare · doi:10.6084/m9.figshare.22608466
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Yon, J. L. T., Htet, N. H., Naing, C., Tung, W. S., Aung, H. H., & Mak, J. W. (2023) · Figshare · doi:10.6084/m9.figshare.22608478
- Authors
- Gutman, J. R., Khairallah, C., Stepniewska, K., Tagbor, H., Madanitsa, M., Cairns, M., L'lanziva, A. J., Kalilani, L., Otieno, K., Mwapasa, V., Meshnick, S., Kariuki, S., Chandramohan, D., Desai, M., Taylor, S. M., Greenwood, B., & ter Kuile, F. O.
- Affiliations
- Centers for Disease Control and Prevention (US)
- Liverpool School of Tropical Medicine (GB)
- University of Oxford (GB)
- University of Health and Allied Sciences (GH)
- University of Malawi (MW)
- London School of Hygiene & Tropical Medicine (GB)
- Kenya Medical Research Institute (KE)
- University of North Carolina at Chapel Hill (US)
- Duke University (US)
- Corresponding author
- Gutman, Julie R
- ORCID
- Venue
- eClinicalMedicine
- Publisher
- Elsevier BV
- Published
- 2021-11
- Volume
- 41
- Pages
- 101160
- ISSN
- 2589-5370 (ISSN-L)
- PMC
- PMC8556518
- OpenAlex
- W3208237120
- Cited by
- 33
- References
- 54
- Citations by year
- 2025: 6 · 2024: 8 · 2023: 13 · 2022: 6
- FWCI
- 1.20
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- EClinicalMedicine (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- LSTM Online Archive (Liverpool School of Tropical Medicine) (acceptedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Greater South Information System
- Funders
- Centers for Disease Control and Prevention
- Bill and Melinda Gates Foundation (OPP1181807)
- Liverpool School of Tropical Medicine
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Global Maternal and Child Health
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Keywords
- malaria in pregnancy, intermittent screening and treatment, intermittent preventive treatment, artemisinin-based combination therapy, sulfadoxine-pyrimethamine, malaria rapid diagnostic tests, Plasmodium falciparum, parasite resistance, adverse pregnancy outcomes, low birth weight, preterm birth, small for gestational age
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