Primer to malaria genomic surveillance
Why is it important?
Malaria, a vector-borne parasitic disease, is a major health and economic burden in several developing countries. Genomic surveillance has played an important role in the control of malaria parasites and their mosquito vectors. At present, there are five species commonly known to infect humans namely, Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, Plasmodium ovale and Plasmodium knowlesi. The first two species cause health problems on a population scale.
What is the challenge?
Even though malaria elimination has been the focus of several global health initiatives for more than a decade, success is still elusive. The key challenge is the need to clear the pool of parasites from infected individuals, which is limited by drug resistance, access to health care and treatment adherence. An intensive elimination programme can significantly reduce the case number, but the pool of parasites that are capable of evading detection and treatment often returns when control measures are lacking. Hence, the genomic surveillance data is critical for the control and eventual elimination of malaria in each country. The genomic data, if collected systemically and analysed comprehensively, can track drug resistance and can determine the origin of the recalcitrant cohort.
What makes a surveillance project successful?
The genome of malaria parasites is relatively big. For example, the genome of Plasmodium falciparum is around 22 Megabases or roughly one thousand-fold the size of the SARS-CoV-2 genome. It also contains a lot of repetitive sequences. An easy yet useful approach to surveillance is targeted sequencing, which amplifies and sequences portions of the genome to track genetic markers for drug resistance and population movement. However, the genomic data can become powerful, when it is matched with the data from patients and cultivated parasites. It is equally important to have whole-genome references representing actively spreading parasites to ascertain the reliability of surveillance markers.
MalariaGEN is one of the initiatives for creating genetic resources to support the control and elimination of malaria. They curate a worldwide open database of Plasmodium falciparum genomes aiming to strengthen malaria surveillance and decision-making management.
How to maximize the benefit?
The obvious and immediate outcome of an effective surveillance strategy is the ability to determine which antimalarial drugs are still effective against circulating malaria parasites, based on mutations associated with reduced treatment effectiveness. Genomic data can help track the movements of drug-resistant parasites between regions and countries. In addition, it can reveal whether the control measure leads to elimination or the locations where different parasite populations are spreading. However, these types of analyses require appropriate experience with genomic datasets; therefore, it is important to build the local talent pool. The investment in sequencing equipment and other building initiatives could be futile without a long-term effort to train local scientists.
What is the caveat?
The presence of a drug-resistant marker does not necessarily mean that a particular drug is no longer effective. The selection of resistant markers could be an associating factor for reduced effectiveness, but its presence does not directly lead to treatment failure.
How to prepare for the future?
Malaria genomic surveillance has been ongoing in many countries producing helpful information for malaria control. The next obvious step is to integrate it with the hosts namely, humans and mosquitoes. Human genetic information can be very helpful in developing a malaria treatment regimen because there is solid evidence linking genetic variations at the human g6pd gene to the side effect of Primaquine and Tafenoquine, two vital drugs needed for malaria elimination. The genetic variation in a human drug metabolising gene was also associated with treatment effectiveness.
Genomic data from the mosquito is a powerful tool to follow resistance to insecticides used by national control programmes. Climate change and environmental deterioration have led to the movement of mosquitoes from their natural habitats or the modification of their feeding behaviour, leading to new pools of mosquitoes that can amplify existing vector-borne diseases or even bring emerging diseases with them. Considering the environmental crisis facing humanity, a comprehensive mosquito genomic surveillance programme is a matter of ‘when’, not ‘if’.
Further reading:
Plasmodium falciparum genomic surveillance reveals spatial and temporal trends, association of genetic and physical distance, and household clustering Leveraging genome editing to functionally evaluate Plasmodium diversity
Major subpopulations of Plasmodium falciparum in sub-Saharan Africa
Pathogen Genomics: A New Era in Global Health Surveillance and Strategy
Pathogen Genomics: A New Era in Global Health Surveillance and Strategy
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