A long-standing belief in malaria science is being challenged. People with the Duffy-negative blood type once considered to be naturally protected from Plasmodium vivax Malaria may no longer be fully resistant, according to a new systematic review and meta analysis from Sudan. Published in Malaria Journal in 2026, the study found measurable Plasmodium vivax infections among Duffy-negative individuals, suggesting the parasite may be evolving alternative pathways to invade red blood cells.
Traditionally, Plasmodium vivax one of the major malaria causing parasites, was believed to require the Duffy antigen receptor on red blood cells to enter and cause infection. People lacking this receptor commonly known as Duffy-negative individuals were considered naturally protected, particularly across many African populations.
What the new study found?
Researchers reviewed 16 studies conducted between 2005 and 2025 involving 5753 participants across different regions of Sudan. They found that P. vivax infections were present in both Duffy-positive and Diffy-negative populations. A meta-analysis of 5 studies specifically examining Duffy antigen status showed a pooled prevalence of 11.7% of P. vivax infection among Duffy-negative individuals (95% CI:7.2-17.3%). Researchers reported moderate heterogeneity across studies and found no major publication bias,, although the smaller number of studies limits interpretation. The authors concluded that these findings challenge the long-standing assumptions of complete Duffy-mediated protection.
How Is The Parasite Doing This?
Scientists believe the answer may lie in parasite adaptation. The study found substantial genetic diversity in the Plasmodium vivax Duffy Binding Protein (PvDBP) including multiple haplotypes and gene duplications such as Malagasy-type and Cambodian-type duplications. These genetic changes may help the parasite bypass the traditional Duffy receptor pathway and infect Duffy-negative hosts. Earlier genomic studies from Sudan have also suggested that p. vivax may be using alternative invasion pathways in Duffy-negative individuals, while a 2022 systematic review confirmed infections in Duffy-negative populations across multiple geographies.
Why This Matters For India?
While Duffy-negative is more common in Africa than in India, the findings are still important for Indian malaria surveillance. India Continues to report a significant burden of Plasmodium vivax malaria, which is known for its ability to hide in the liver as hypnozoites-dormant forms that can reactivate later and cause repeated relapses without a new mosquito bite. This makes P. vivax harder to eliminate that many people assume. If the parasite is evolving new invasion strategies globally, malaria control programmes may need stronger molecular surveillance and updated diagnostic approaches rather than relying on older biological assumptions.
Understanding Duffy-positive vs Duffy-negative
The Duffy antigens works like a ‘door’ on the surface of red blood cells. if a person has this receptor, they are called as Duffy-positive which means P.vivax can easily use that route to enter the cell. If a person does not have this receptor, they are Duffy-negative. For decades, scientists believed the parasite could not infect them because the ‘door’ was missing. This new research suggests the parasite may have found another way in.
The Bigger Public Health Warning
Experts say these findings could have implications for malaria elimination strategies across Africa and beyond. If Duffy-negative individuals can carry infections even at lower parasite levels they may become an under-recognized reservoir of transmission, making malaria harder to detect track and eliminate. For countries targeting malaria elimination, including India, the message is clear- Plasmodium vivax should not be underestimated.