: Rocky Mountain spotted fever (RMSF) is an ongoing public health crisis in Mexico, particularly in states bordering the United States. The national highest incidence and mortality of RMSF occur in this region, resulting in a case-fatality rate that ranges annually between 10% and 50%, primarily affecting vulnerable groups such as children, elderly adults, and persons living in poverty. Multiple biological, environmental, and social determinants can explain its growing presence throughout the country and how it challenges the health system and society. It is necessary to integrate resources and capacities from health authorities, research centers, and society to succeed in dealing with this problem. Through a scientific symposium, a group of academicians, U.S. health officials, and Mexican health authorities met on November 8–10, 2023, in Hermosillo, Mexico, to discuss the current situation of RMSF across the country and the challenges associated with its occurrence. An urgent call for action to improve national capacity against RMSF in the aspects of epidemiological and acarological surveillance, diagnosis, medical care, case and outbreak prevention, health promotion, and research was urged by the experts. The One Health approach is a proven multidisciplinary strategy to integrate policies and interventions to mitigate and prevent the burden of cases, deaths, and suffering caused by RMSF in Mexico.

Background: Rocky Mountain spotted fever (RMSF) is a challenge for physicians because the disease can mimic other endemic febrile illnesses, such as dengue and COVID-19. The comparison of their main clinical and epidemiological manifestations in hospitalized children can help identify characteristics that improve empirical suspicion and timely therapeutic interventions. Methods: A cross-sectional study was conducted on a series of patients aged 0 to 18 years, hospitalized between 2015 and 2022, with a diagnosis of RMSF, dengue, or COVID-19. Data were retrieved from medical records. Subjects were categorized as patients with RMSF (group I) and patients with dengue and COVID-19 (group II). Descriptive statistics were used, and differences were evaluated using Student’s t-test and the chi-squared test. Results: A series of 305 subjects were studied, with 252 (82.6%) in group I. Subjects in both groups presented fever, myalgias, arthralgias, and rash, but exposure to ticks distinguished group I. The fatality rate (21.0%) in group I was higher than in group II (3.8%). Conclusions: Although fever, myalgias, arthralgias, and rash are common in all three illnesses, they are more prevalent in hospitalized patients with RMSF. In the presence of such symptoms, a history of tick exposure can guide clinical decisions in regions where all three diseases are endemic.