Phenotypic prevalence and targeted genotyping of glucose-6- phosphate dehydrogenase deficiency among patients attending malaria diagnostic posts in Quibdó, Colombia, with exploratory multisite data from Chocó
This study in Quibdó, Colombia, reveals a 10.4% phenotypic prevalence of G6PD deficiency among malaria patients, with a higher burden in women and Afro-descendant populations, and identifies the A− variant as the predominant molecular cause while highlighting the need for broader genetic screening and routine quantitative testing before administering radical-cure malaria treatments.
Original paper licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). This is an AI-generated explanation of a preprint that has not been peer-reviewed. It is not medical advice. Do not make health decisions based on this content. Read full disclaimer
In the human body, red blood cells act as tireless couriers, ferrying oxygen to every tissue. To survive their journey, these cells rely on a specific chemical shield called an enzyme, known as glucose-6-phosphate dehydrogenase, or G6PD for short. This enzyme is the cell's primary defense against oxidative stress, a type of chemical wear and tear that can damage the cell's structure. Without enough of this enzyme, red blood cells become fragile and can burst open when the body encounters certain triggers, such as specific infections, foods like fava beans, or common medications used to treat malaria. This condition, known as G6PD deficiency, is one of the most common inherited enzyme disorders in the world. It has a complex relationship with malaria; while the deficiency can offer some protection against the disease, it creates a dangerous dilemma for doctors. The most effective drugs for curing a specific type of malaria, Plasmodium vivax, can trigger a life-threatening collapse of red blood cells in people with this deficiency. Therefore, before a doctor can safely prescribe these life-saving treatments, they must know if a patient carries this hidden vulnerability.
In the Chocó region of Colombia, a tropical area on the Pacific coast known for its high rates of malaria and its diverse population of Afro-descendant, Indigenous, and mixed-ancestry communities, this medical puzzle has remained largely unsolved. For years, doctors in this region have administered the necessary malaria cures without routinely checking for the enzyme deficiency, relying instead on broad assumptions about who might be at risk. A new study conducted in the city of Quibdó and surrounding towns has changed that picture by bringing a precise, on-the-ground look at the reality of the situation. Researchers set out to measure the actual levels of this protective enzyme in hundreds of people seeking care for fever and suspected malaria, and to identify the specific genetic variations causing the deficiency in this unique population.
The team gathered a large group of 914 individuals who had come to local diagnostic posts with symptoms of malaria between late 2025 and mid-2026. Using a portable device that measures enzyme activity directly from a drop of blood, they screened every participant. The results revealed that the condition is far more common than previously realized in this specific context. Approximately one in ten people in the study had lower-than-normal levels of the enzyme. When the researchers looked closer, they found that about 5.5% of the group had levels so low that they were classified as deficient, meaning they were at high risk of a severe reaction if given the standard malaria cure. The study also highlighted that this risk is not evenly distributed across the population. Women were more likely to show reduced enzyme levels than men, a pattern consistent with how the gene is inherited. Furthermore, the prevalence varied significantly by ethnicity; nearly 13% of participants who identified as Afro-descendant showed reduced activity, compared to only about 6% of those identifying as mestizo and less than 1% of those identifying as Indigenous.
To understand the genetic roots of these findings, the researchers took blood samples from those with low enzyme levels and analyzed their DNA. They specifically looked for three known genetic variants that are common in the Americas: two of African origin and one of Mediterranean origin. The genetic analysis confirmed that the vast majority of the cases in the primary group were linked to the African variants, which aligns with the demographic history of the region. However, the study uncovered a significant gap in current medical knowledge. Even after testing for these three specific genetic causes, the researchers could not explain the genetic basis for the low enzyme levels in nearly 17% of the people they tested. This means that a simple genetic test looking only for these three known variants would miss a substantial number of people who are actually at risk.
The study also included a smaller, separate group of patients recruited in 2023 from four different towns, a group chosen specifically because they were already known to have the deficiency or a history of malaria. In this group, the genetic landscape looked slightly different, with a higher frequency of one specific variant, but the researchers noted that this group was not a random sample of the general population and was used only to broaden the genetic picture. Across all the data, the Mediterranean genetic variant was not found in any of the samples, confirming that it is likely absent in this part of Colombia. The most critical takeaway from the work is that relying solely on genetic testing for a few known variants is insufficient. Because so many cases of low enzyme activity could not be explained by the three variants the team looked for, the researchers concluded that the only safe way to determine who can take the malaria cure is to measure the enzyme activity directly in every patient, regardless of their ethnicity or family history.
This approach ensures that no one is left behind by a genetic test that might miss a rare or unknown variation. The findings support a shift in how malaria is treated in this region, moving away from assumptions based on ancestry and toward a system where every patient is screened with a quantitative test before receiving the radical cure. By identifying the true scope of the deficiency and acknowledging the limits of current genetic panels, the study provides a clear path forward for protecting patients while allowing doctors to safely eliminate the malaria parasite from the body. The work underscores that in a region as genetically diverse as Chocó, the only reliable guide to safety is a direct measurement of the body's own defenses.
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