Luz Stella Giraldo Cardona

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.

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.

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.

Introduction: The use of psychoactive substances in homeless individuals prolongs their time on the streets and increases the risk of acquiring chronic and infectious diseases. Objective: To identify substances use profiles in homeless individuals. Method: A cross-sectional study was conducted with 368 homeless individuals who attended the Centro Día Program in Itagüí, Antioquia, Colombia. Information related to psychoactive substance use was extracted from clinical records, with prior approval for its use. Profiles of stimulants, depressant, and hallucinogenic or psychoactive substance use affecting the Central Nervous System were created. Prevalence, prevalence ratios, and a multiple correspondence analysis were estimated. Results: A total of 88.3 % of participants were men, with an average age of 41.1 years (SD = 14.8). The prevalence of substance use was identified as 73.9 %, with hallucinogenic or psychoactive (marijuana) and depressants (alcohol) being the most common. The profile analysis showed that single men who had been on the streets for more than 3 months were more likely to consume stimulant and depressant drugs. Conclusions: The persistence of psychoactive substance use, as well as inadequate addiction management, increases social vulnerability, which can exacerbate issues such as begging and criminal behavior.

Background: Early detection of severe dengue (SD) is crucial in preventing life-threatening complications. Despite its importance, comprehensive knowledge about these early indicators is still limited. This study aimed to identify predictors of SD in a hyperendemic region of Colombia. Methods: A cross-sectional analysis was conducted using data from 2018 to 2022, encompassing 233 patients. By utilizing the 2009 World Health Organization dengue classifications, cases were differentiated between severe dengue (SD) and non-severe dengue (non-SD). Among these, 47 were confirmed as SD. Associations between clinical, demographic, and laboratory data and disease severity were examined using Fisher’s exact tests or the Mann–Whitney U test (p < 0.05). Profiles for SD and non-SD cases were established through multiple correspondence analysis, and a logistic regression-based predictive model was validated using training and test sets. The model’s performance was evaluated using the area under the receiver operating characteristic curve (AUC-ROC), accuracy, sensitivity, F1-score, and precision. Results: Differences in place of residence, comorbidities, type of infection, and signs and symptoms were observed between the severe dengue (SD) and non-severe dengue (non-SD) groups. Median levels of platelets, white blood cells (WBC), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were found to be higher in the SD group compared to the non-SD group. Neutrophils, leukocytes, platelets, AST, and primary infection were significant predictors of SD. The model demonstrated an area under the receiver operating characteristic curve (AUC) of 0.91 (95% CI, 0.85–0.96). Conclusions: The developed predictive model provides significant assistance to clinicians in assessing SD risk and optimizing triage, which is particularly crucial during dengue outbreaks.

Introducción: La bronquiolitis es una enfermedad del tracto respiratorio que se caracteriza por la inflamación de los bronquiolos, afecta principalmente a niños menores de 2 años. Aunque el tratamiento con antibióticos no está indicado, el uso de estos medicamentos se ha reportado como un hallazgo frecuente. Objetivo: Determinar la frecuencia y las características del uso inadecuado de antibióticos para el tratamiento de bronquiolitis en pacientes menores de 2 años en un hospital de baja complejidad en Antioquia, Colombia. Métodos: Estudio descriptivo de tipo transversal con 48 registros de fuente secundaria. Se estimó la proporción de uso de antibióticos y las frecuencias por tipo de antibiótico, además de caracterizar el tipo de antibiótico. Se estimaron pruebas de hipótesis Fisher para evaluar la relación considerando un valor p < 0,05 como significativo. Resultados: Se estudiaron 48 pacientes con diagnóstico de bronquiolitis, la mayoría con edades entre 0 y 6 meses (56,3%). El 45,8% de los menores fue tratado con antibióticos, siendo ampicilina-sulbactam el antibiótico más usado (59,1%). Se encontró asociación entre el uso de antibióticos, la hospitalización y tener leucocitosis (p<0,05). No se reportó ningún efecto adverso asociado al uso de antibióticos. Conclusiones: El uso de antibióticos para el manejo de bronquiolitis en infantes es una práctica frecuente en la institución de estudio. En ninguno de los pacientes que recibieron terapia antibiótica se encontraron hallazgos clínicos que soportaran la presencia de una infección bacteriana, por lo que se evidencia falta de adherencia a las guías de práctica clínica.

: Dengue is the most common arboviral disease in the world. Traditionally, it has affected more adults, but the incidence in children has increased in recent years. Colombia is no stranger to this change; therefore, we aimed to find the differences in signs, symptoms, and clinical, hematological, and hemogram characteristics between children under 12 years old and individuals aged 12 years and older in an endemic region of Colombia in 2020–2022. The analyses were conducted with baseline data, corresponding to a cross-sectional design. Multiple correspondence analysis was used for general, dermatological, and clinical symptom profiles. Discriminant analysis was used for laboratory profiles. Multiple correspondence analysis was applied to nominal categorical data, employing Euclidean distances to analyze age groups. Discriminant analysis was applied to a training sample and validated on a test sample. The overall agreement of the model’s discrimination, sensitivity, specificity, and fit indicators was calculated. The results indicated that individuals under 12 years exhibited distinct dermatological and clinical features, including rash, pruritus, hypotension, lymphocyte count, and platelet count, compared with those aged 12 years and older. In contrast, those 12 years and older were profiled for general and clinical symptoms such as pain (back pain, retro-orbital pain, headache), dizziness, chills, hematuria, tachypnea, and elevated/high hematocrit, hemoglobin, and basophil values. These findings are crucial to understanding the high incidence in children; they also facilitate rapid understanding of the disease in clinical care settings and differentiate it from other febrile outbreaks. This will affect disease control, particularly in severe cases, and reduce mortality.

La caracterización del conflicto armado es un tema de interés mundial por el alto costo humano y material que implica. Para determinar el nivel de exposición a eventos de conflicto, se ha reconocido una limitación de herramientas psicométricamente válidas. En los conflictos armados de larga duración y baja intensidad, como el colombiano, se aplican criterios espacio-temporales para generar tipologías o medias ecológicas de los niveles de exposición al conflicto sin estudiar a priori la exposición de cada individuo. El Cuestionario de Exposición al Conflicto Armado (CECA) fue desarrollado para caracterizar la exposición a eventos directos e indirectos del conflicto y sus efectos, desde la experiencia de sus actores. El instrumento CECA se sometió a una evaluación de validez de contenido por parte de un panel de ocho expertos que evaluaron esta propuesta con relación a la claridad, la relevancia, la suficiencia y la coherencia, mediante un método Delphi. Se calculó el Índice de Validez de Contenido (IVC) de los ítems y el Kappa modificado para evaluar el consenso y el acuerdo de los expertos. Se estableció como punto de corte un IVC mayor a .7 y Kappa mayor a .6. De los 38 ítems propuestos, seis fueron eliminados. Se obtuvo una versión válida de 33 ítems con tres dimensiones: experiencias directas (11 ítems); experiencias indirectas (14 ítems), y desenlaces (8 ítems). En conclusión, se ha desarrollado y establecido la validez de contenido de CECA, lo que será de utilidad para los investigadores y profesionales interesados ​​en realizar investigación e intervención con población expuesta o con antecedentes de exposición a los eventos de conflicto armado.

One of the main challenges in the clinical management of dengue is the early identification of cases that could progress to severe forms of the disease. A biomarker that may enable this identification is the presence of genetic polymorphisms in genes associated with immune responses. The objective of this study was to perform a systematic review of the Latin American literature on these genes. An electronic literature search was carried out in PubMed, Scopus, Lilacs, and the Virtual Health Library, and reference lists of systematic reviews in the area. Case-control studies conducted in Latin American countries examining at least one form of genetic polymorphism related to immune responses against severe dengue were included. In total, 424 articles were identified and 26 were included in this systematic review. Of the 26 selected articles, 16 reported polymorphisms associated with the risk of developing severe dengue (Risk); Similarly, 16 articles reported polymorphisms associated with a decreased risk of severe dengue (Protective). The final analysis revealed that multiple polymorphisms in immune system genes were early markers of the progression of dengue in Latin Americans and found that polymorphisms of the TNF-alpha gene may have a critical role in dengue pathogenesis.