Beyond Ancestry: Unraveling the Hispanic Predominance in Balamuthia Encephalitis

To the Editors: Balamuthia mandrillaris is an opportunistic, free-living ameba that causes a rare but fatal infection of the central nervous system.1 Fewer than 300 cases have been reported worldwide, yet the majority have occurred in the Americas, particularly among individuals of Hispanic origin.1,2 This striking concentration has prompted speculation about genetic predisposition. The idea seemed plausible since infections often arise in healthy people, recur within specific clusters and resemble other granulomatous diseases where host genetics influence outcome. However, as evidence has accumulated, this explanation may appear insufficient. Environmental exposure, occupational contact and social inequity together provide a far more compelling framework for understanding risk. In regions such as California, Texas and Arizona, up to 3 quarters of reported cases have been among Hispanic patients. The infection frequently affects immunocompetent hosts, suggesting that host factors might shape disease course. By analogy to infections such as leishmaniasis and tuberculosis, it was reasonable to suspect that variation in cytokine or human leukocyte antigens genes could influence macrophage activation and granulomatous containment.3 Yet no consistent genetic association has been demonstrated, and the overlap between the geography of infection and the ecology of the organism is striking. Balamuthia is a thermotolerant ameba that thrives in warm, arid soils rich in organic matter.2 Its cysts can survive for long periods in dust and sediment. The regions of highest environmental suitability including semidesert zones of the southwestern United States, northern Mexico, and coastal Peru, are home to dense Hispanic populations engaged in agriculture, construction and landscaping. Frequent soil contact, minor abrasions and limited access to protective gear or healthcare increase the likelihood of inoculation or inhalation.1 The so-called Hispanic predominance may therefore reflect coincidence of occupation, environment and exposure. The infection occurs where the pathogen lives and where people are most likely to encounter it. Clinically, infection may affect both healthy and immunocompromised individuals. Entry occurs through the skin or respiratory tract, followed by spread to the brain, where trophozoites cause necrosis and granulomatous inflammation.1 Effective defense depends on rapid Th1-type responses, but malnutrition, immunosuppression, or coinfection favors dissemination. Such vulnerabilities align with social determinants of health that disproportionately affect marginalized groups.3 Even if immunogenetic variation modulates severity, exposure and inequity remain the critical determinants of susceptibility. Recent genomic investigations have identified Balamuthia genes linked to virulence and environmental adaptation.4 Climate change may further expand its ecological range, while surveillance and awareness remain limited.5 In summary, the hypothesis of genetic predisposition arose logically but fails to explain the clear ecological and occupational clustering of cases. To frame Balamuthia encephalitis as a Hispanic disease may risk interpreting an ecological and structural phenomenon as biological. Consideration of environmental factors, such as inequality, will direct attention to modifiable factors such as soil contact, occupational protection, early diagnosis, and equitable healthcare. The true question is not whether Hispanic populations are genetically predisposed, but why they are disproportionately exposed/underserved, and unprotected in environments where Balamuthia thrives. Only by addressing those inequities can we hope to prevent future cases of a disease that remains fatal, neglected, and preventable. ACKNOWLEDGMENTS Ruqaiyyah Siddiqui and Naveed Ahmed Khan are supported by the Air Force Office of Scientific Research (AFOSR), USA.