DOI: 10.1093/ofid/ofae143 ISSN: 2328-8957

Monthly sulfadoxine-pyrimethamine during pregnancy prevents febrile respiratory illnesses: A secondary analysis of a malaria chemoprevention trial in Uganda

Jordan John Lee, Abel Kakuru, Karen B Jacobson, Moses R Kamya, Richard Kajubi, Anju Ranjit, Stephanie L Gaw, Julie Parsonnet, Jade Benjamin-Chung, Grant Dorsey, Prasanna Jagannathan, Michelle E Roh
  • Infectious Diseases
  • Oncology
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Abstract

Background

Trials evaluating drugs for intermittent preventive treatment of malaria in pregnancy (IPTp) have shown dihydroartemisinin-piperaquine (DP) is a more efficacious antimalarial than sulfadoxine-pyrimethamine (SP), but SP is associated with higher birthweight, suggesting SP demonstrates ‘non-malarial’ effects. Chemoprevention of non-malarial febrile illnesses (NMFIs) was explored as a possible mechanism.

Methods

In this secondary analysis, we leveraged data from 654 HIV-uninfected pregnant Ugandan women enrolled in a randomized controlled trial comparing monthly IPTp-SP with IPTp-DP. Women were enrolled between 12-20 gestational weeks and followed through delivery. NMFIs were measured by active and passive surveillance and defined by absence of malaria parasitemia. We quantified associations between IPTp regimens, incident NMFIs, antibiotic prescriptions, and birthweight.

Results

Mean birthweight-for-gestational-age Z-scores (BWGAZ) were 0.189 [95% CI: 0.045-0.333] points higher in women randomized to IPTp-SP versus IPTp-DP. Women randomized to IPTp-SP had fewer incident NMFIs (IRR = 0.74 [0.58-0.95]), mainly respiratory NMFIs (IRR = 0.69 [0.48-1.00]), versus IPTp-DP. Counterintuitively, respiratory NMFI incidence was positively correlated with birthweight in multigravidae. 75% of respiratory NMFIs were treated with antibiotics. Although overall antibiotic prescriptions were similar between arms, for each antibiotic prescribed, BWGAZ increased by 0.038 [0.001-0.074] points.

Conclusions

Monthly IPTp-SP was associated with reduced respiratory NMFI incidence, revealing a potential non-malarial mechanism of SP and supporting current WHO recommendations for IPTp-SP even in areas with high-grade SP resistance. While maternal respiratory NMFIs are known risk factors of lower birthweight, most women in our study were presumptively treated with antibiotics, masking the potential benefit of SP on birthweight mediated through preventing respiratory NMFIs.

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