Expert Reviewed By: Dr. Brandon Colby MD
Malaria is a life-threatening disease caused by Plasmodium parasites transmitted through the bites of infected Anopheles mosquitoes. Despite significant global efforts to combat malaria, it remains a major public health concern, with an estimated 229 million cases and 409,000 deaths in 2019. The development of resistance to malaria in certain populations has been a topic of intense research, as understanding the genetic factors that contribute to this resistance could lead to new therapeutic strategies and improved disease management.
Understanding Genetic Factors in Malaria Resistance
Various genetic factors have been identified that influence an individual's susceptibility or resistance to malaria. These factors can be broadly classified into those related to red blood cell (RBC) variants, pathogen receptors, cyto-adherence, inflammation, and immunity (1). For example, some RBC variants, such as sickle cell trait and glucose-6-phosphate dehydrogenase deficiency, have been known to confer resistance to malaria. Additionally, variations in genes encoding pathogen receptors and cyto-adherence molecules can affect the ability of Plasmodium parasites to invade and multiply within host cells, thereby influencing disease outcome.
Diagnosing Malaria Resistance
Traditionally, diagnosing malaria resistance has relied on clinical observation and laboratory testing, such as blood smears and rapid diagnostic tests. However, these methods do not provide information on the underlying genetic factors contributing to resistance. Recent advances in genetic testing have enabled the identification of specific gene mutations and variations associated with malaria resistance.
Adenosine Monophosphate Deaminase 3 (AMPD3) Activation and Malaria Resistance
A recent study in mice reported a mutation in the AMPD3 gene that led to rapid RBC turnover, increased erythropoiesis (production of new RBCs), shortened RBC lifespan, and resistance to the rodent malaria Plasmodium chabaudi (2). This finding suggests that genetic testing for AMPD3 activation could potentially identify individuals with increased resistance to malaria.
Genetic Resistance to Drug Treatment in Plasmodium falciparum
Another area of concern in malaria management is the development of resistance to antimalarial drugs. A study investigating drug resistance in the P. falciparum parasite revealed increased gene copy number, protein expression, and point mutations at catalytic site residues, which contributed to resistance against purine nucleoside phosphorylase inhibitors (3). Genetic testing for these specific mutations could help identify drug-resistant strains of the parasite and inform treatment decisions.
Using Genetic Testing to Combat Malaria
Genetic testing offers several potential benefits in the management of malaria, including:
Identification of At-Risk Populations
By identifying individuals with genetic factors that confer susceptibility to malaria, public health officials can target interventions, such as insecticide-treated bed nets and prophylactic medications, to those most in need.
Personalized Treatment Strategies
Genetic testing can help identify drug-resistant strains of the parasite, enabling healthcare providers to select the most effective treatment options for individual patients.
Development of New Therapeutics
Understanding the genetic factors that contribute to malaria resistance can inform the development of new drugs and therapies. For example, a recent study used a novel genomics strategy to rapidly identify mutations associated with drug resistance in the rodent parasite Plasmodium chabaudi (4).
In conclusion, genetic testing holds significant promise in the ongoing battle against malaria. By unraveling the genetic factors that contribute to resistance and susceptibility, researchers and healthcare providers can develop more targeted and effective strategies to combat this devastating disease.
About The Expert Reviewer
Dr. Brandon Colby MD is a US physician specializing in the personalized prevention of disease through the use of genomic technologies. He’s an expert in genetic testing, genetic analysis, and precision medicine. Dr. Colby is also the Founder of and the author of Outsmart Your Genes.
Dr. Colby holds an MD from the Mount Sinai School of Medicine, an MBA from Stanford University’s Graduate School of Business, and a degree in Genetics with Honors from the University of Michigan. He is an Affiliate Specialist of the American College of Medical Genetics and Genomics (ACMG), an Associate of the American College of Preventive Medicine (ACPM), and a member of the National Society of Genetic Counselors (NSGC)