Effectiveness of intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine: An in silico pharmacological model

Objective: To explore the efficacy of intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine and pyrimethamine (SP) against sensitive parasites. Methods: A pharmacological model was used to investigate the effectiveness of the previous recommended at least two-dose regimen, currently recommended three-dose regimen and 4, 6, 8-weekly regimens with specific focus on the impact of various non-adherence patterns in multiple transmission settings. Results: The effectiveness of the recommended three-dose regimen is high in all the transmission intensities, i.e. >99%, 98% and 92% in low, moderate and high transmission intensities respectively. The simulated 4 and 6 weekly IPTp-SP regimens were able to prevent new infections with sensitive parasites in almost all women (>99%) regardless of transmission intensity. However, 8 weekly interval dose schedules were found to have 71% and 86% protective efficacies in high and moderate transmission areas, respectively. It highlights that patients are particularly vulnerable to acquiring new infections if IPTp-SP doses are missed. Conclusions: The pharmacological model predicts that full adherence to the currently recommended three-dose regimen should provide almost complete protection from malaria infection in moderate and high transmission regions. However, it also highlights that patients are particularly vulnerable to acquiring new infections if IPTp doses are spaced too widely or if doses are missed. Adherence to the recommended IPTp-SP schedules is recommended.