IPTp Effectiveness multicentre study

Project Coordinator: Prof Feiko Ter Kuile (LSTM, UK)

Project Collaborators:

Dr Linda Kalilani (College of Medicine, Malawi), Dr Sheick Coulibaly ( University of Ouagadougou,, Burkina Faso), , Dr Kassoum Kayentao (MRTC, Mali), Meghna Desai and Julie Gutman (CDC, USA), Steve Taylor (UNC, USA).

Objective

The goal was to explore the relationship between the level of sulphadoxine-pyrimethamine (SP) resistance in the population of pregnant women, the efficacy of intermittent preventive treatment in pregnancy (IPTp) with SP in clearing parasites, preventing new infections and n reducing the adverse effects of malaria at birth.

Study design

This was a multi-centre study carried out at eight sites across six countries, to monitor the effectiveness of IPTp by determining the relationship between the level of SP resistance as assessed by molecular markers, the efficacy of SP in clearing existing malaria infections (in-vivo module: 42 day follow-up of asymptomatic parasitaemic women) and the ability of IPTp-SP to reduce the adverse effect of malaria at birth (delivery module). Sites were classified as either high, medium or low resistance after measuring mutations conferring SP resistance.

Results and Conclusion

The study found that IPTp-SP was effective at reducing the risk of low birth weight, even in areas of high SP resistance. SP struggled to clear parasites in areas with over 90% of resistance and it is therefore important to look for alternatives to SP before it becomes completely redundant due to resistance.

Impact of the research

Results from the meta-analysis comparing monthly vs the standard two-dose regimen of IPTp with SP (Kayentao et al 2013) led WHO to update its policy guidelines in 2012 to monthly doses (a,b), a policy which has since been implemented throughout sub-Saharan Africa. However, increasing resistance to SP in parts of Africa has raised concern among some malaria-endemic countries. The studies on the continued effectiveness of IPTp-SP in areas of relatively high SP resistance in sub-Saharan Africa (Desai et al 2015; Desai et al 2016; Gutman et al 2015) led WHO in 2015 to recommend continued IPTp-SP implementation until a region approaches interruption of transmission (c) and to the recommendation that molecular markers could be used to track SP resistance and inform IPTp-SP policy (d).

  1. WHO Malaria Policy Advisory Committee Secretariat, 2012. Conclusions and Recommendations of September 2012 meeting. Malar J 11: 424.
  2. World Health Organization, 2013. WHO policy brief for the implementation of IPTp using sulfadoxine-pyrimethamine (IPTp-SP) April 2013.
  3. Malaria Policy Advisory Committee Meeting 11-13 September 2013, WHO Evidence Review Group on (IPT) of malaria in pregnancy: Draft Recommendations on Intermittent Preventive Treatment in Pregnancy (IPTp).
  4. WHO Minutes of the Technical Expert Group (TEG) on Drug Efficacy and Response, Geneva, 10-11 December 2015

Publications

Desai, M., et al. (2016). "Impact of Sulfadoxine-Pyrimethamine Resistance on Effectiveness of Intermittent Preventive Therapy for Malaria in Pregnancy at Clearing Infections and Preventing Low Birth Weight." Clin Infect Dis 62(3): 323-333.

Gutman, J., et al. (2016). "Reply to Harrington et al." J Infect Dis 213(3): 497-498.

Kayentao, K., et al. (2013). "Intermittent preventive therapy for malaria during pregnancy using 2 vs 3 or more doses of sulfadoxine-pyrimethamine and risk of low birth weight in Africa: systematic review and meta-analysis." JAMA 309(6): 594-604.

Coulibaly, S. O., et al. (2014). "Parasite clearance following treatment with sulphadoxine-pyrimethamine for intermittent preventive treatment in Burkina-Faso and Mali: 42-day in vivo follow-up study." Malar J 13: 41.

Taylor, S. M., et al. (2015). "Absence of putative artemisinin resistance mutations among Plasmodium falciparum in Sub-Saharan Africa: a molecular epidemiologic study." J Infect Dis 211(5): 680-688.

Taylor, S. M., et al. (2014). "Independent lineages of highly sulfadoxine-resistant Plasmodium falciparum haplotypes, eastern Africa." Emerg Infect Dis 20(7): 1140-1148.

Gutman, J., et al. (2015). "The A581G Mutation in the Gene Encoding Plasmodium falciparum Dihydropteroate Synthetase Reduces the Effectiveness of Sulfadoxine-Pyrimethamine Preventive Therapy in Malawian Pregnant Women." J Infect Dis 211(12): 1997-2005.