Leptospirosis is a globally distributed zoonotic disease caused by pathogenic bacteria of the Leptospira genus. Currently, 77 genomic species have been described. Leptospira interrogans is the most extensively studied species due to its high prevalence worldwide and the severity of the disease it causes in humans and animals. However, Leptospira santarosai is an important pathogenic species in the Americas, the Caribbean islands, and Taiwan. This species has a high serological diversity: it can infect domestic, wild, and agricultural production animals, causing reproductive problems and substantial economic losses. Additionally, Leptospira santarosai has been detected in water sources and wet soils. In humans, infection with this species can lead to a wide range of clinical manifestations and severe complications. Therefore, this study aimed to synthesize available information on the serological diversity, geographical distribution, natural sources of infection, and human leptospirosis caused by Leptospira santarosai to better understand their role in the leptospirosis transmission cycle. Methods: A systematic review of the literature was conducted, following the criteria established by the PRISMA-2020 guide, the search for scientific articles was conducted in five specialized and multidisciplinary databases (PubMed, Scopus, Web of Science, SciELO, and LILACS), and a search engine (Google Scholar). Two different search strategies (Leptospira santarosai OR L. santarosai) were used. Result: Once the search was carried out in the databases, 2989 scientific articles were identified. These articles underwent a process of identification, screening, eligibility, and inclusion, resulting in 84 articles that met all established inclusion criteria. These articles were included in the qualitative synthesis and elaboration of the systematic review. Conclusions: Leptospira santarosai shows a high serological diversity, with 14 serogroups and 59 serovars. The species has a wide geographic distribution, having been reported on five continents and in 26 countries, and has been described as an infectious agent in at least 24 host animals. It has also been detected in environmental sources such as water and wet soils; 24 serovars have been identified as the causative agents of human leptospirosis, causing clinical manifestations that range from mild to severe forms of the disease and clinical complications such as myocarditis, uveitis, and neuroleptospirosis. Although L. santarosai is considered native to the Americas, it shows an expansion pattern to other continents and countries. Therefore, this pathogenic species of the Leptospira genus represents an important public health problem worldwide.

Background: dengue fever is a viral infection caused by the Dengue Virus (DENV), a positive-sense RNA virus belonging to Flaviviridae family. The virus is transmitted to humans through the bite of the Aedes aegypti mosquito. Worldwide, between 100 and 400 million cases are reported annually. The infection in humans can cause three clinical forms which are related to severity: dengue without warnings signs, dengue with warnings signs, and severe dengue. Mutations in some genes that code for immune system proteins have been linked to the appearance of severe clinical forms of the disease, including TNF-α. The TNF-α plays a key role in the immunopathogenesis of the disease: mutations in this gene can increase the production of TNF-α, favoring cytokine storms and vascular damage, which is associated with severe clinical forms of the disease. Therefore, it is important to study the immunopathogenesis of the disease in the human to try to predict and control the onset of severe clinical forms and fatal cases. Methods: This study explores the link between TNF-α promoter gene polymorphism and dengue severity. We re-cruited 92 laboratory-confirmed dengue cases, including 30 dengue without warnings signs, 43 dengue with warnings signs, and 19 severe dengue. Genotyping was done using amplification by PCR (polymerase chain reaction), Sanger sequencing, and bio-informatics analysis of the TNF-α gene promoter mutations. A logistic regression assessed the association between -308 G/A TNF-α mutation and dengue severity. Results: the mutated genotype -308 G/A TNF-α was detected in 10.5% of severe cases. Interestingly, Severe cases showed higher odds of carrying the mutation than those without warnings signs. Severe cases were twice as likely to possess this mutation compared to those with warnings signs, however, no statistically significant differences were found. Genotype frequencies were consistent with Hardy-Weinberg equilibrium (p = 0.112). The estimated post hoc statistical power was 11.3%. Conclusions: Although no statistically significant association was detected, the TNF-α -308G/A polymorphism showed a trend toward increased susceptibility to severe dengue, with a higher frequency among severe cases than among patients with or without warnings signs.

Dengue fever is a viral infection caused by the dengue virus (DENV), a positive sense RNA virus belonging to Flaviviridae family. The virus is transmitted to humans through the bite of the Aedes aegypti mosquito. Worldwide, between 100 and 400 million cases are reported annually. The infection in humans can cause three clinical forms, which are related to severity: dengue without warnings signs, dengue with warnings signs, and severe dengue. Genetic variants in genes encoding immune system proteins have been associated with severe clinical forms of dengue, including variants in TNF-α. TNF-α plays a key role in dengue immunopathogenesis, and promoter polymorphisms may influence TNF-α expression and inflammatory responses associated with severe disease. Therefore, understanding host genetic variation may contribute to elucidating mechanisms involved in progression to severe clinical forms. This study explored the association between the TNF-α -308 G>A promoter polymorphism and dengue severity. We included 92 laboratory-confirmed dengue cases: 30 with dengue without warning signs, 43 with dengue with warning signs, and 19 with severe dengue. Genotyping was performed using PCR amplification, Sanger sequencing, and bioinformatic analysis of the TNF-α promoter region. Because of the low frequency of A allele carriers and sparse data, pairwise Firth penalized logistic regression models adjusted for age and primary/secondary infection status were used to evaluate the association between variant carrier status and dengue severity. The TNF-α -308 A allele was detected in a small proportion of participants, with variant carriers accounting for 10.5% of severe dengue cases. Adjusted analyses showed higher point estimates for severe dengue compared with dengue without warning signs and dengue with warning signs; however, the associations were not statistically significant, and confidence intervals were wide. Genotype frequencies showed no statistically significant deviation from Hardy–Weinberg equilibrium (p = 0.112), and the estimated post hoc statistical power was 11.3%. The TNF-α -308 G>A polymorphism was not significantly associated with dengue severity in this sample. The observed estimates were imprecise and should be considered exploratory, warranting confirmation in larger and more diverse populations.