EDCTP Alumni Network

Title

Validation of New Biomarkers for Monitoring Plasmodium falciparum Reduced susceptibility/Tolerance or Resistance to Artemisinin Derivatives and Partner Drugs in Nigeria

Objectives

1. Evaluate clinical treatment response parameters, in vitro and in vivo efficacy and drug blood levels of artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ) combinations in patients’ infected with P. falciparum in Ibadan, Southwest Nigeria 2. Use the PCR, DNA sequencing approaches to identify new biomarkers/ molecular determinants of P. falciparum response to ARTs and Partner drugs in vitro and in vivo 3. Validate the role of new biomarkers/molecular determinants of P. falciparum response to ARTs and partner drugs by collating SNPs/SNPs patterns in parasite genes with clinical treatment response parameters, patients’ treatment outcome, blood drug levels and in vitro quantitative responses (phenotypes).

Host Organisation

Institution	Country
University of Ibadan	Nigeria

Study Design

In vitro and in vivo bio-markers studies

Results & Outcomes

Five major sub-studies were completed. The capacity building programme at the grantee’s laboratory at the College of Medicine, University of Ibadan, in Nigeria has been improved and has been used to train several students.

Publications

Sowunmi A, Adewoye EO, Gbotosho GO, Happi CT, Sijuade A, Folarin OA, Okuboyejo TM, Michael OS. Factors contributing to delay in parasite clearance in uncomplicated falciparum malaria in children. Malaria Journal. 2010;9(1):53

Gbotosho GO, Happi C, Folarin O, Keyamo O, Sowunmi A, Oduola AMJ. Rapid Detection of Lactate Dehydrogenase and Genotyping of Plasmodium falciparum in Saliva of Children with Acute Uncomplicated Malaria. American Journal of Tropical Medicine and Hygiene. 2010;83(3):496-501

Michael OS, Gbotosho GO, Folarin OA, Okuboyejo T, Sowunmi A, Oduola, AMJ, Happi CT. Early variations in Plasmodium falciparum dynamics in Nigerian children after treatment with two artemisinin-based combinations: implications on delayed parasite clearance. Malaria Journal. 2010;9:335.

Van Tyne D, Park DJ, Schaffner SF, Neafsey DE, Angelino E, Cortese JF, Barnes KG, Rosen DM, Lukens AK, Daniels RF, Milner, Jr DA, Johnson, Shlyakhter I, Grossman SR, Becker JS, Yamins D, Karlsson EK, Ndiaye D, Sarr O, Mboup S, Happi C, Furlotte NA, Eskin E, Kang HM, Hartl DL, Birren BW, Wiegand RC, Lander ES, Wirth DF, Volkman SK, Sabeti PC. Identification and Functional Validation of the Novel Antimalarial Resistance Locus PF10_0355 Project Porftolio Page 375 of 622 in Plasmodium falciparum. PLoS Genetics. 2011; 7(4): e1001383. doi:10.1371/journal.pgen.1001383.