Epidemiology and Clinical Outcomes of HTLV-1: A Comprehensive Narrative Review of Endemic and Nonendemic Regions.

Human T-lymphotropic virus Type 1 (HTLV-1) is a globally distributed, oncogenic retrovirus endemic in specific regions, including southwestern Japan, sub-Saharan Africa, the Caribbean, parts of South America (notably Brazil), Iran, and Indigenous communities in Australia. Although most infections are asymptomatic, a minority of carriers develop severe, life-altering conditions: adult T-cell leukemia/lymphoma (ATL) or HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). This narrative review presents a comprehensive analysis of epidemiological studies, clinical reports, and public health surveillance data. Data on HTLV-1 prevalence, incidence, clinical outcomes, proviral load associations, and public health measures were extracted and compared across major endemic and nonendemic regions. HTLV-1 exhibits extreme geographic heterogeneity. Hyperendemic foci include southwestern Japan (carrier population ∼534,000 in 2020), parts of Brazil (estimated 800,000 carriers), the Caribbean (e.g., Jamaica, general population prevalence ∼6.1%), and sub-Saharan Africa (estimated 2-5 million infections, the largest global burden). In Central Australia, prevalence among Indigenous adults over 45 reaches 49.3%, the highest recorded regional rate globally. Prevalence varies significantly within populations: In Brazil, it is highest in the north/northeast. In Gabon, rural prevalence is 8.7%, rising to 12.5% in rainforest provinces, with Pygmy ethnicity identified as an independent risk factor. In Iran, prevalence is concentrated in the northeast (2%-7%), whereas the rest of the country shows rates below 1%. In contrast, prevalence is very low in nonendemic areas such as the United States and most of Europe (< 0.01% in Spain and Italy), except for Romania (5.3 per 10,000 donors) and areas with migrant populations. Incidence data are sparse but informative: In Japan, the annual incidence among blood donors is 6.88 per 100,000 person-years for women and 2.29 per 100,000 person-years for men. In the United Kingdom, the incidence of HAM/TSP among HTLV-1 carriers is 1.98 per 1000 person-years. A Brazilian cohort reported an HAM/TSP incidence of 1.47% over 3 years, substantially higher than Japan's lifetime risk of 0.25%. HTLV-1 remains a significant yet profoundly neglected global pathogen, exhibiting extreme geographic heterogeneity in prevalence, clinical outcomes, and transmission dynamics, driven by complex interactions of viral genetics, host factors, and disparities in public health infrastructure. Although proven cost-effective interventions such as universal antenatal screening in Japan have demonstrably reduced transmission, the persistent "silent" spread in endemic, low-resource regions particularly sub-Saharan Africa and Indigenous Australia demonstrates a critical global health inequity demanding urgent, region-specific strategies for screening, prevention, and patient care to mitigate its substantial burden of morbidity and mortality.