Pathogenesis and Immunity

Project Coordinator:    Prof Stephen Rogerson (University of Melbourne, Australia)

Co-investigators:         

Prof Steve Meshnick and Dr Steve Taylor (University of North Caroline, USA), Alfredo Mayor (IS Global, Spain)

Objectives

To augment understanding of the impact of malaria in pregnancy on maternal health, and the impact of our interventions on the burden of disease and how malaria prevention affects the development of immunity to malaria in pregnancy.

Activities

Activities tool place in Cameroon, Gambia, Mali, Burkina Faso, DRC, Kenya, Uganda, Tanzania, Malawi and Barcelona.

The project undertook three main activities:

  1. The Molecular Support Centre worked closely with all the trial coordinators to ensure the integrity of study-specific molecular protocols, developed and validated new protocols for parasite detection and drug-resistance genotyping, and directly measured parasite genotypes in support of the multi-country IPTp-mon study. These activities varied by project.
  2. The Histopathology Support Centre provided a training workshop for over 30 delegates with seven international faculties in Cameroon in 2009 and subsequently QC was provided to sites undertaking histological studies of placental malaria.
  3. Training awards in laboratory studies supported junior scientists in Malawi, Mali, The Gambia and PNG to preform adjunct studies to the clinical trials.
Results and Conclusions

There are multiple results to these activities (full details in the studies below), for example:

An estimated 1million births annually in the DR Congo are affected by P. falciparum, and full adherence to preventive measures could prevent 47,000 LBW babies.

Parasites bearing triple-mutant dhps haplotypes are emerging de novo in East African parasite populations without requiring geographic spread.

The efficacy of IPTp-SP to prevent low birth weight is correlated with the prevalence of markers of resistance to SP.

The drug-resistance genotyping methods and findings were presented at WHO Evidence Review Group meetings in July 2013 and 2015, contributing to the WHO’s Technical Expert Group on Drug Efficacy and Response in December 2015 (WHO Minutes of the Technical Expert Group (TEG) on Drug Efficacy and Response, Geneva, 10-11 December 2015).

Publications

Rogerson, S. J., et al. (2018). "Burden, pathology, and costs of malaria in pregnancy: new developments for an old problem." Lancet Infect Dis 18(4): e107-e118.

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.

Mayor, A., et al. (2015). "Changing Trends in P. falciparum Burden, Immunity, and Disease in Pregnancy." N Engl J Med 373(17): 1607-1617.

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.

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.

Taylor, S. M., et al. (2014). "A quality control program within a clinical trial Consortium for PCR protocols to detect Plasmodium species." J Clin Microbiol 52(6): 2144-2149.

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. (2012). "Antenatal receipt of sulfadoxine-pyrimethamine does not exacerbate pregnancy-associated malaria despite the expansion of drug-resistant Plasmodium falciparum: clinical outcomes from the QuEERPAM study." Clin Infect Dis 55(1): 42-50.

Mayor, A., et al. (2012). "Placental infection with Plasmodium vivax: a histopathological and molecular study." J Infect Dis 206(12): 1904-1910.

Taylor, S. M., et al. (2012). "Adaptive evolution and fixation of drug-resistant Plasmodium falciparum genotypes in pregnancy-associated malaria: 9-year results from the QuEERPAM study." Infect Genet Evol 12(2): 282-290.

Taylor, S. M., et al. (2011). "Quantification of the burden and consequences of pregnancy-associated malaria in the Democratic Republic of the Congo." J Infect Dis 204(11): 1762-1771.

Taylor, S. M., et al. (2010). "High-throughput pooling and real-time PCR-based strategy for malaria detection." J Clin Microbiol 48(2): 512-519.

Rogerson, S. J., et al. (2007). "Malaria in pregnancy: pathogenesis and immunity." Lancet Infect Dis 7(2): 105-117.