Genomic epidemiology of Plasmodium falciparum and Anopheles vectors in the context of malaria control on the Bijagós Archipelago of Guinea Bissau

Malaria is a disease caused by the protozoan organism Plasmodium, which kills over 400,000 people annually, with the majority of deaths occurring in children under 5 years old. The World Health Organisation is committed to help reduce malaria mortality by 90% by 2030. Despite the high coverage use of long-lasting insecticide treated bed nets (LLINs), indoor residual spraying (IRS) and artemisinin-based combination therapy (ACT) successfully reducing mortality, these tools are clearly insufficient on their own to eliminate malaria. New tools are required to address both the human and vector reservoirs of infection. Mass drug administration (MDA) with ACT has been proposed as a strategy to reduce the human reservoir of infection. The combination of an efficacious ACT and the mosquitocidal agent ivermectin (IVM) as MDA should address both the asymptomatic human reservoirs and an additional vector control approach that may interrupt transmission.

This PhD project is nested within a currently funded cluster (island) randomised placebo-controlled trial on the Bijagos Archipelago of Guinea-Bissau. The trial will evaluate the added impact of MDA with adjunctive IVM in addition to the ACT dihydroartemisinin-piperaquine (DP). The PhD project will take advantage of the trial design and geographical remoteness of the islands to investigate the population structure and drug resistance profile of P. falciparum before the MDA intervention, the impact of MDA on P. falciparum transmission and the characterisation and tracking of residual P. falciparum variants during and post-MDA using novel molecular and modelling techniques. Molecular and bioinformatics techniques will be used to determine parasite transmission, population structure and resistance profile to known anti-malarial drugs at baseline using field collected dry blood spots. P. falciparum whole genome sequencing will be used to characterise and track P. falciparum variants before and after MDA in combination with field-based metadata on human population movement during the study. The change in parasite transmission, population structure and resistance profile will be determined following intervention using dry blood spots collected after the MDA. This research is expected to support the development of innovative programmatic approaches to malaria outbreaks, elimination campaigns and epidemiological surveillance.

This research will further investigate insecticide resistance in the Anopheles mosquito vectors which transmit P. falciparum. The mainstay of malaria control on the islands is the use of Long-Lasting Insecticidal Nets, which are impregnated with insecticides. Insecticide resistance is widespread globally and threatens the use of LLINs and other vector control interventions. The insecticide resistance status of malaria vectors on the archipelago is poorly understood. This research project will investigate this using both phenotypic assays and multiplex amplicon approaches, which are a novel high-throughput genomic technique.

This project requires a wide range of quantitative and interdisciplinary skills which fit within the MRC's strategic skills priorities. Quantitative skills required include working with large datasets, bioinformatic analytics and statistical analysis, which will include excellence in R statistical package and the development of skills in bash and python. Further technological skills in parasite genome sequence technology and genomic epidemiology will be required. Interdisciplinary skills and knowledge will also be developed, including those related to genomic epidemiology, clinical trials, antimalarial resistance, public health interventions and critical thinking in disease control methods. Furthermore, this project involves developing Portuguese and Portuguese Kriol language skills in order to complete fieldwork in the Bijagós archipelago.