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London School of Hygiene & Tropical Medicine Malaria Centre

Malaria research in drug development, deployment and resistance

Analysis of copy number variation, drugresistant genotypes, mitochondrial haplotypes and multi-clonality in Plasmodium falciparum by direct genome sequencing from patient peripheral blood.

LSHTM investigators:
Rachel Hallett & Colin Sutherland.
External collaborators:
Dina Gamboa, Cláudia Videira, Yuri Sebastião, Susana Vaz Nery (CISA – Health Research Center, Angola).
Funding body:
Portuguese Institute for Development Assistance & Calouste Gulbenkian Foundation with the support of the Angolan Ministry of Health and the Bengo Provincial Government.

The aims of this study were:

  • to determine the prevalence of the different Plasmodium species in Northern Angola.
  • to measure the prevalences of drug-resistance associated mutations in Plasmodium falciparum genes.

Angolan collaborators carried out a large cross sectional survey of women and children in a rural area of Bengo Province, north-western Angola, approximately 60 km north of the capital Luanda. Microscopy and the molecular method PCR were compared for their ability to detect 4 different Plasmodium species infecting humans. 541 / 3316 (16.3%) of the participants were found to carry parasites by PCR and all 4 species were identified, while in comparison, the sensitivity of microscopy was only 58.23%. Plasmodium falciparum parasites were present in 97% of the infections, and we examined mutations in 2 genes (pfcrt and pfmdr1) that are known to influence parasite sensitivity to the antimalarial drugs used in Angola. The haplotypes found varied significantly from those reported in a study in Luanda 4 years previously, perhaps reflecting the heterogeneous drug pressures that can occur across a relatively small geographical area. The use of molecular methods to monitor antimalarial drug resistance provides key information to policy makers as decisions regarding the use of artemisinin combination therapies are made.