Sustained clinical benefit of malaria chemoprevention with sulfadoxine-pyrimethamine (SP) in pregnant women in a region with high SP resistance markers

J Infect. 2024 May;88(5):106144. doi: 10.1016/j.jinf.2024.106144. Epub 2024 Apr 2.

Abstract

Objective: The effectiveness of intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) is threatened by increasing SP-resistance in Africa. We assessed the level of SP-resistance markers, and the clinical and parasitological effectiveness of IPTp-SP in southern Mozambique.

Methods: P. falciparum infection, antimalarial antibodies and dhfr/dhps SP-resistance mutants were detected by quantitative polymerase chain reaction (qPCR), suspension array technology and targeted deep sequencing, respectively, among 4016 HIV-negative women in Maputo province (2016-2019). Univariate and multivariate regression models were used to assess the association between taking the recommended three or more IPTp-SP doses (IPTp3+) and parasitological and clinical outcomes.

Results: 84.3% (3385/4016) women received three or more IPTp-SP doses. The prevalence of quintuple mutants at first antenatal care (ANC) visit was 94.2%. IPTp3+ was associated with a higher clearance rate of qPCR-detected infections from first ANC visit to delivery (adjusted odds ratio [aOR]=5.9, 95% CI: 1.5-33.3; p = 0.012), lower seroprevalence at delivery of antibodies against the pregnancy-specific antigen VAR2CSADBL34 (aOR=0.72, 95% CI: 0.54-0.95; p = 0.022), and lower prevalence of low birth weight deliveries (aOR: 0.61, 95% CI: 0.41-0.90; p = 0.013).

Conclusion: A sustained parasitological effect of IPTp-SP contributes to the clinical effectiveness of IPTp3+ in areas with high prevalence of SP-resistance markers.

Keywords: Antimalarial resistance; Chemoprevention; Intermittent preventive treatment; Malaria; Pregnancy; Sulfadoxine-pyrimethamine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antimalarials* / therapeutic use
  • Chemoprevention / methods
  • Drug Combinations*
  • Drug Resistance*
  • Female
  • Humans
  • Malaria, Falciparum* / epidemiology
  • Malaria, Falciparum* / prevention & control
  • Mozambique / epidemiology
  • Plasmodium falciparum* / drug effects
  • Plasmodium falciparum* / genetics
  • Pregnancy
  • Pregnancy Complications, Parasitic / drug therapy
  • Pregnancy Complications, Parasitic / prevention & control
  • Pyrimethamine* / administration & dosage
  • Pyrimethamine* / therapeutic use
  • Sulfadoxine* / administration & dosage
  • Sulfadoxine* / therapeutic use
  • Young Adult

Substances

  • Sulfadoxine
  • Pyrimethamine
  • fanasil, pyrimethamine drug combination
  • Drug Combinations
  • Antimalarials