Into the spotlight: A spatial study of potentially underreported leptospirosis among dengue-negative patients in São Paulo city, Brazil

Leptospirosis and dengue share similar unspecific symptoms, complicating differential diagnosis in endemic regions. This overlap is further exacerbated by the often-underrecognized nature of leptospirosis, resulting in low clinical suspicion among healthcare providers. Understanding the scale of underdiagnosed leptospirosis cases, particularly among dengue-negative patients, is critical for improving public health responses. This cross-sectional study analyzed data from 6,936 febrile patients who tested negative for dengue at public health services across São Paulo city. Serum samples from these patients were subsequently tested for anti-Leptospira IgM antibodies. Spatial analysis was conducted to identify areas at increased risk of underdiagnosed leptospirosis, and these findings were compared to cases reported in the Brazilian's Information System for Notifiable Diseases from 2009 to 2019. Our results revealed that, from the 6,936 patients tested, 786 (11.3%) were seroreactive for leptospirosis, with a higher prevalence among women (55.7%; p=0.003). Spatial analysis identified 18 high-risk clusters for potentially unrecognized leptospirosis, predominantly in peripheral regions with socioeconomic vulnerabilities. Notably, two significant high-risk areas were located in the North (RR=2.13) and South (RR=2.69) regions of the city. These findings underscore the urgent need for targeted public health interventions to improve disease surveillance and diagnostic capacity, particularly in the high-risk areas identified. Addressing underrecognition of leptospirosis is essential for reducing morbidity and mortality associated with the disease. Future research should expand on this work by integrating broader temporal, environmental, and socioeconomic data.