Drug and diagnostic resistance
Artemisinin and partner drug-resistant malaria parasites have emerged in Southeast Asia and more recently, in Africa. Our work uses mathematical models to better understand how antimalarial drug resistance emerges and spreads, how it affects malaria burden, how to measure resistance and how to mitigate its impact.
We have worked on estimating the potential impact of artemisinin and partner drug resistance on disease burden in Africa if it were to emerge using different scenarios about levels of treatment failure. We have developed multi-strain models which track genetic information about parasites within transmission models to understand the spread of drug resistance. We also study how resistance has spread and declined in the past.
Sulphadoxine pyrimethamine (SP) resistance has emerged and spread widely in malaria-endemic areas, meaning it is no longer widely recommended for treating clinical cases. However it is still used to protect pregnant women and children against malaria, although the efficacy is under threat given the presence of highly resistant strains in East Africa. We are using pharmacokinetic-pharmacodynamic modelling and secondary analysis of trial data to characterise the impact of resistance on preventive treatment. We are also using modelling to identify which delivery modes of chemoprevention could best slow resistance spread (timing, number of treatment courses etc).
Watson OJ, Okell LC, Hellewell J, Slater HC, Unwin HJT, Omedo I, Bejon P, Snow RW, Noor AM, Rockett K, Hubbart C, Nankabirwa JI, Greenhouse B, Chang HH, Ghani AC, Verity R. Evaluating the performance of malaria genomics for inferring changes in transmission intensity using transmission modelling. Mol Biol Evol 2020
Okell LC, Reiter LM (co-first author), Ebbe LS, Baraka V, Bisanzio D, Watson OJ, Bennett A, Verity R, Gething P, Roper C, Alifrangis M. Emerging implications of policies on malaria treatment: genetic changes in the Pfmdr-1 gene affecting susceptibility to artemether-lumefantrine and artesunate-amodiaquine in Africa. BMJ Global Health. 2018.
Slater HC, Griffin JT, Ghani AC, Okell LC. Assessing the potential impact of artemisinin and partner drug resistance in sub-Saharan Africa. Malar J. 2016 Jan 6;15:10. doi: 10.1186/s12936-015-1075-7. Publisher's link.
Jonathan B. Parr, Robert Verity, Stephanie M. Doctor, Mark Janko, Kelly Carey-Ewend, Breanna J. Turman, Corinna Keeler, Hannah C. Slater, Amy N. Whitesell, Kashamuka Mwandagalirwa, Azra C. Ghani, Joris L. Likwela, Antoinette K. Tshefu, Michael Emch, Jonathan J. Juliano, Steven R. Meshnick (2017). Pfhrp2-deleted Plasmodium falciparum parasites in the Democratic Republic of the Congo: a national cross-sectional survey. The Journal of Infectious Diseases 216(1), 36-44.
Oliver J Watson, Bo Gao, Tran Dang Nguyen, Thu Nguyen-Anh Tran, Melissa A Penny, David L Smith, Lucy Okell, Ricardo Aguas, Maciej F Boni (2021). Pre-existing partner-drug resistance facilitates the emergence and spread of artemisinin resistance: a consensus modelling study. bioRxiv 2021.04.08.437876;
Oliver J. Watson, Hannah C. Slater, Robert Verity, Jonathan B. Parr, Melchior K. Mwandagalirwa, Antoinette Tshefu, Steven R. Meshnick, Azra C. Ghani (2017). Modelling the drivers of the spread of Plasmodium falciparum hrp2 gene deletions in sub-Saharan Africa. Elife 6, e25008.
Oliver J. Watson, Robert Verity, Azra C. Ghani, Tini Garske, Jane Cunningham, Antoinette Tshefu, Melchior K. Mwandagalirwa, Steven R. Meshnick, Jonathan B. Parr, Hannah C. Slater (2019). Impact of seasonal variations in Plasmodium falciparum malaria transmission on the surveillance of pfhrp2 gene deletions. Elife 8, e40339. Publisher’s link.
Molly Deutsch-Feldman, Ozkan Aydemir, Margaret Carrel, Nicholas F. Brazeau, Samir Bhatt, Jeffrey A. Bailey, Melchior Kashamuka, Antoinette K. Tshefu, Steve M. Taylor, Jonathan J. Juliano, Steven R. Meshnick, Robert Verity (2019). The changing landscape of Plasmodium falciparum drug resistance in the Democratic Republic of Congo. BMC infectious diseases 19(1), 1-10. Publisher’s link.