Berta Nelly Restrepo

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.

Background: Chikungunya, and Zika emerged in the 2010s in the Americas, causing simultaneous epidemics with dengue. However, little is known of these Aedes -borne diseases (ABDs) joint patterns and contributors at the population-level. Methods: We applied a novel Poisson-multinomial spatial model to the registered cases of dengue (n=291,820), chikungunya (n=75,913), and Zika (n=72,031) by municipality in Colombia, 2014-2016. This model estimates the relative risk of total ABDs cases and associated factors, and, simultaneously, the odds of presence and contributors of each disease using dengue as a baseline category. This approach allows us to identify combined characteristics of ABDs, since they are transmitted by the same mosquitoes, while also identifying differences between them. Findings: We found an increased ABDs risk in valleys and south of the Andes, the Caribbean coast, and borders, with temperature as the main contributor (Relative Risk 2.32, 95% Credible Interval, CrI, 2.05-2.64). Generally, dengue presence was the most probable among the ABDs, although that of Zika was greater on Caribbean islands. Chikungunya and Zika were more likely present than dengue in municipalities with less vegetation (Odds Ratio, OR, 0.75, 95%CrI 0.65-0.86, and 0.85, 95%CrI 0.74-0.99, respectively). Chikungunya tended to be present in more socially vulnerable areas than dengue (OR 1.20, 95%CrI 0.99-1.44) and Zika (OR 1.19, 95%CrI 0.95-1.48). Interpretation: Important differences between the ABDs were identified and can help guide local and context-specific interventions, such as those aimed at preventing cases importation in border and tourism locations and reducing chikungunya burden in socially vulnerable regions.

: 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.

BACKGROUND Involvement of the central nervous system during infection with dengue virus (DENV) is recognized. However, ischemic stroke is rarely reported. Herein are described 2 cases of patients with ischemic stroke in which DENV infection was demonstrated. CASE REPORT The first patient was a 51-year-old woman that presented altered consciousness, monoparesis, facial palsy, dysarthria, Babinski sign, and syncope 7 days from the onset of fever. She had a history of carotid artery atherothrombosis and previous stroke. Magnetic resonance imaging (MRI) showed an acute infarction of the right middle cerebral artery. DENV was confirmed by the presence of NS1 and IgM in serum. The patient was treated with intravenous fluids and recovered well, with only right facial paresis still present at discharge. The second patient was a 50-year-old man who presented with headache, altered consciousness, and mutism after a febrile episode 1 week prior. This patient had a previous history of stroke, glioblastoma resection, epilepsy, hypothyroidism, and diabetes. MRI demonstrated a subacute ischemic event. The diagnosis of dengue was confirmed by serum NS1 and IgM and by RT-PCR in serum and cerebrospinal fluid. DENV-1 serotype was observed in serum and cerebrospinal fluid. The patient was treated with intravenous fluids and was discharged in good condition. In both patients, thrombocytopenia and leukopenia was demonstrated, and hemoconcentration was demonstrated in the second patient. CONCLUSIONS In tropical and subtropical countries, DENV infection can represent a potential cause of ischemic stroke in patients with a history of comorbidities, including stroke.

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.

The pathogenesis of the severity of chikungunya infection is not yet fully understood. Objective: To assess the role of the cytokines/chemokines and system of complement in the evolution of chikungunya infection. Methods: In both acute and chronic phases, we measured the serum levels of 12 cytokines/chemokines and two complement mediators: mannose-binding lectin (MBL) and C3a, in 83 patients with chikungunya infection and ten healthy controls. Results: During the acute phase, 75.9% of the patients developed musculoskeletal disorders, and in 37.7% of them, these disorders persisted until the chronic phase. In general, patients had higher levels of cytokines than healthy controls, with significant differences for IFN-gamma, IL-6, IL-8, IL-10, and MIP-1. Most cytokines exhibited a downward trend during the chronic phase. However, only IL-10, and MIP-1 levels were significantly lower in the chronic phase. Additionally, these levels never decreased to concentrations found in healthy controls. Moreover, MBL levels were significantly higher in the acute phase compared with the chronic phase. C3a levels were significantly higher in patients with musculoskeletal disorder compared with patients without it, in both acute-phase 118.2 (66.5-252.9), and chronic phase 68.5 (64.4-71.3), P < 0.001. Interestingly, C3a levels were significantly higher when patients had a severe disease version. Besides, in the acute phase, C3a levels were higher in patients that suffer arthritis as opposed to when they suffer arthralgia, 194.3 (69.5-282.2), and 70.9 (62.4-198.8), P = 0.013, respectively. Conclusions: Our results showed an immunological response that persisted until the chronic phase and the role of the complement system in the severity of the disease.

Background: Chikungunya, dengue, and Zika are three different arboviruses which have similar symptoms and are a major public health issue in Colombia. Despite the mandatory reporting of these arboviruses to the National Surveillance System in Colombia (SIVIGILA), it has been reported that the system captures less than 10% of diagnosed cases in some cities. Methodology/Principal findings: To assess the scope and degree of arboviruses reporting in Colombia between 2014–2017, we conducted an observational study of surveillance data using the capture-recapture approach in three Colombian cities. Using healthcare facility registries (capture data) and surveillance-notified cases (recapture data), we estimated the degree of reporting by clinical diagnosis. We fit robust Poisson regressions to identify predictors of reporting and estimated the predicted probability of reporting by disease and year. To account for the potential misclassification of the clinical diagnosis, we used the simulation extrapolation for misclassification (MC-SIMEX) method. A total of 266,549 registries were examined. Overall arboviruses’ reporting ranged from 5.3% to 14.7% and varied in magnitude according to age and year of diagnosis. Dengue was the most notified disease (21–70%) followed by Zika (6–45%). The highest reporting rate was seen in 2016, an epidemic year. The MC-SIMEX corrected rates indicated underestimation of the reporting due to the potential misclassification bias. Conclusions: These findings reflect challenges on arboviruses’ reporting, and therefore, potential challenges on the estimation of arboviral burden in Colombia and other endemic settings with similar surveillance systems.

This report presents the case of a 38-year-old woman who initially consulted for an undifferentiated fever and that despite the fact that her clinical condition evolved with signs/symptoms compatibles with dengue with alarm signs and the detection of anti-dengue IgM in a single sample indicates that it is a probable case that could have happened during the last three months. However, the patient keeps consulting, repeatedly, for little improvement. On the tenth day of the onset of symptoms, polyarticular symmetric edema accompanied by pain was observed, as well as hyperpigmented lesions in the nasolabial fold. The diagnosis of chikungunya was confirmed by the presence of IgM antibodies. In endemic countries for dengue and chikungunya the possibility of co-infection exists, but its diagnosis may go unnoticed. On the other hand, this co-infection may worsen the clinical course of these diseases. Therefore, it is necessary that the physician to orient his evaluation in the search of the clinical and laboratory characteristics of both diseases, which allow him to make the diagnosis of coinfection, in order to guarantee a patient adequate management and minimize complications.

Summary: Although dengue can progress to severe stages, the exact causes of this phenomenon are unknown; however, the possibility of monocyte participation is acknowledged. It has been suggested that monocyte subsets (classical, intermediate and non‐classical) play differential roles in dengue immunopathology. Therefore, we determined the count of monocyte subsets and obtained the clinical information of patients with dengue. We noted a significant decrease in the count of non‐classical monocytes in patients compared with controls. With this finding, we focused on studying the phenotype of non‐classical monocytes in the present study. An increase in activation and differentiation markers, such as CD64, CD86, the percentage of tumor necrosis factor‐ α ⁺ cells and exposure of phosphatidylserine, were recorded in the non‐classical monocytes of patients compared with controls. Moreover, a significant decrease in the expression of CX3CR1 with a corresponding increase in the expressions of CCR2, CCR5, CD11b and CD54 was detected in the non‐classical monocytes of patients in comparison with that of the controls. Significant increases in the frequency of microparticles from endothelium and in the concentrations of interleukin‐6 (IL‐6), IL‐8 and IL‐10 were noted in the plasma of patients. These findings demonstrate that in patients with dengue, non‐classical monocytes are activated, exhibiting a phenotype associated with more differentiation, produces tumor necrosis factor‐ α and has a profile of less endothelial surveillance closer to the cellular migration. These changes were associated with hepatic compromise, endothelial alteration and high concentration of circulating cytokines. Hence, alterations of non‐classical monocytes seem to be associated with the immunopathology of dengue infection.