London School of Hygiene & Tropical Medicine

Malaria is a major health concern in developing countries, particularly in sub-Saharan Africa (SSA), where high morbidity and mortality rates persist. In 2021, the WHO reported 247 million clinical episodes and 619,000 malaria deaths, with 95% of fatalities occurring in SSA. The region faces vulnerabilities such as local weather conditions, which favour year-round transmission, high prevalence of a very efficient vector (Anopheles gambiae complex), and a very virulent species of the malaria parasite (Plasmodium falciparum). Limited resources and socioeconomic challenges hinder effective malaria control in SSA, while emergence of resistance to front-line treatments raises concerns.

The presence of resistance to Artemisinin-based combination therapy in parts of East Africa is worrying, as the spread of this resistance threatens a dire situation for the continent. In addition, the emergence of other mutations that cause resistance to sulfadoxine-pyrimethamine could impede control programs for malaria prevention in the most vulnerable populations, which are pregnant women and young children.  

Effective vaccines are needed to enhance prevention. The introduction of the first malaria vaccine RTS,S/AS01 in 2021 marked progress, though its efficacy remains modest (~36%) even after four doses.1 Another vaccine, R21-M Matrix, shows promise with approximately 75% efficacy in an ongoing trial in Burkina Faso. 

Active surveillance is vital due to the malaria parasite's ability to evolve, aligning with the WHO strategy to combat drug resistance. Genomic sequencing is crucial for monitoring drug resistance and vaccine efficacy. The incorporation of genomic sequencing in surveillance programs faces challenges in SSA due to costs and infrastructure limitations. However, a new dawn has come with the availability of affordable technologies like Oxford Nanopore Technology (ONT) and bioinformatic workflow management software like nextflow enabling genomic surveillance in resource-constrained regions. Moreover, the availability of cloud data analysis takes away the huge costs that come with setting up and maintaining local computing clusters.

These advancements offer immense opportunities, facilitating real-time monitoring of parasite evolution, tracking drug resistance, and improving vaccine efficacy. The potential impact of these technologies on malaria control and elimination is exemplified by a recent study in Ghana, demonstrating the feasibility of monitoring genetic markers for drug resistance and vaccine targets using ONT MinION Mk1B sequencer and a custom bioinformatic pipeline deployable through nextflow.

Collaboration is key in maximising the potential of these new opportunities, as manifested in this Ghanaian study, which was carried out by scientists from the University of Ghana and the Wellcome Sanger Institute. The exchange of experiences and technical expertise among research institutions is important, particularly to support capacity building in the less technically advanced institutions in sub-Saharan Africa. Additionally, addressing persistent logistic challenges in the region is crucial to ensure easy access to reagents for continuous research. Finally, these emerging technologies mentioned above offer opportunities for surveillance of drug resistance in other pathogens of public health concern in low-income settings.

References

RTSS Clinical Trials Partnership. Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial. Lancet https://doi.org/10.1016/S0140-6736(15)60721-8 (2015).

Datoo, M. S. et al. Efficacy of a low-dose candidate malaria vaccine, R21 in adjuvant Matrix-M, with seasonal administration to children in Burkina Faso: a randomised controlled trial. Lancet 397, 1809–1818 (2021).

Datoo, M. S. et al. Efficacy and immunogenicity of R21/Matrix-M vaccine against clinical malaria after 2 years’ follow-up in children in Burkina Faso: a phase 1/2b randomised controlled trial. Lancet Infect. Dis. 22, 1728–1736 (2022).