Serum levels of IFN-ß are associated with days of evolution but not with severity of dengue.

The serum levels of beta interferon (IFN-ß) were evaluated in clinical samples taken in the acute phase of dengue fever for 107 patients during the 2011 dengue outbreak in Yucatán, México. Dengue diagnoses were confirmed by NS1 or IgM/IgG serology in all patients. Average serum IFN-ß levels in patients with dengue fever without warning signs (n = 53) were 140 pg/ml, and 105 pg/ml for patients with warning signs (n = 54). There was no statistically significant difference between IFN-ß levels for the two groups (Mann-Whitney U Test P > 0.05) and no association with warning or mild signs (OR: 0.57; 95%CI: 0.26-1.22) was indicated. Thrombocytopenia was the most prevalent warning sign (91%) in one group of patients (49) with mean 113 pg/ml IFN-ß levels. In contrast, the patients without thrombocytopenia (50) had 126 pg/ml of IFN-ß, but this level was not statistically significant (Mann-Whitney U Test P > 0.05). The average levels of IFN-ß were also found to have statistically similar results, using the 1997 WHO classification system. The amount of IFN-ß at 1-3, 4-6, and 7-9 days after onset of illness, however, did show significant differences (ANOVA P = 0.038) between patients for the 1-3 and 4-6 days pair (Scheffe post-hoc P = 0.043). These results suggest that serum levels of IFN-ß do not correlate well with the severity of dengue illness, but there is a clear association between changes in IFN-ß levels and the days of evolution during the acute phase of the disease.

Prognostic factors of COVID-19 severity and mortality in the Yucatecan ethnic of México contrast with other populations.

INTRODUCTION: Previous studies that identified the prognostic factors for the severity of the new coronavirus disease 2019 (COVID-19) in different populations have generated controversial conclusions. The lack of a standard definition of COVID-19 severity and the differences between clinical diagnoses might make it difficult to provide optimum care according to the characteristics of each population. METHODOLOGY: We investigated the factors that impacted the severe outcome or death from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients treated at the Mexican Institute of Social Security in Yucatán, México in 2020. A cross-sectional study of COVID-19 confirmed cases was done to know the prevalence and association of the demographic and clinical characteristics with a severe or fatal outcome. Information from the National Epidemiological Surveillance System (SINAVE) database was used and SPSS v 21 was used for statistical analyses. We used the World Health Organization (WHO) and the Centers for Diseases Control and Prevention (CDC) symptomatology classifications to define severe cases. RESULTS: Diabetes and pneumonia increased the risk of death and having diabetes was a prognostic factor for severe illness following SARS-CoV-2 infection. CONCLUSIONS: Our results highlight the influence of cultural and ethnic factors, the necessity to standardize the parameters for clinical diagnoses, and to use the same criteria for the definition of COVID-19 severity to establish the clinical conditions that contribute to the pathophysiology of this disease in each population.

Low Activation of CD8+ T Cells in response to Viral Peptides in Mexican Patients with Severe Dengue.

It is acknowledged that antiviral immune response contributes to dengue immunopathogenesis. To identify immunological markers that distinguish dengue fever (DF) and dengue hemorrhagic fever (DHF), 113 patients with confirmed dengue infection were analyzed at 6 or 7 days after fever onset. Peripheral blood mononuclear cells (PBMC) were isolated, lymphocyte subsets and activation biomarkers were identified by flow cytometry, and differentiation of T helper (Th) lymphocytes was achieved by the relative expression analysis of T-bet (Th1), GATA-3 (Th2), ROR-γ (Th17), and FOXP-3 (T regulatory) transcription factors quantified by real-time PCR. CD8+, CD40L+, and CD45+ cells show higher numbers in DF compared to DHF patients, whereas CD4+, CD19+, and CD25+ cells show higher numbers in DHF than DF patients. High expression of GATA-3 accompanied by low expression of T-bet indicates predominance of Th2 response. In addition, higher expression of FOXP-3 and reduced functional cytotoxic T cells (CD8+perforin+) were observed in DHF patients. In further experiments, PBMC were stimulated ex vivo with dengue virus E, NS3, NS4, and NS5 peptides, and proliferating T cell subsets were determined. Lower proliferative responses to NS3 and NS4 peptides and reduced CD8+ cytotoxic T cells were observed in DHF patients. Our results suggest that immune response to dengue is dysregulated with predominance of CD4+ T cells, low activation of Th1 cells, and downregulation of the antiviral cytotoxic activity during severe dengue, likely induced by regulatory T cells.

[Population genetics of dengue virus and transmission of dengue fever]. / Genética de las poblaciones virales y transmisión del dengue.

The endemic behavior of dengue fever in Mexico during the past five years is of major concern to every sector related with public health and the effort to control the transmission has been focused on vector control. However, regardless of the effectiveness of the intervention measures it is important to know which elements determine dengue transmission. With regard to the molecular basis for dengue transmission, a great deal of progress has been made due to the introduction of genomic and bioinformatic approaches. The goal of this review is to describe the most recent developments in this area with emphasis on the Mexican situation.

Antiviral and immunomodulatory effects of polyphenols on macrophages infected with dengue virus serotypes 2 and 3 enhanced or not with antibodies.

Background: There is a lack of specific antiviral therapy against dengue virus (DENV) in current use. Therefore, a great proportion of dengue cases progress to severe clinical forms due to a complex interplay between virus and host immune response. It has been hypothesized that heterotypic non-neutralizing antibodies enhance DENV infection in phagocytic cells, and this induces an inflammatory response that is involved in the pathogenesis of severe dengue. Purpose: To identify the antiviral and immunomodulatory effects of polyphenols on dengue virus infection. Methods: Human U937-DC-SIGN macrophages were infected with DENV serotypes 2 or 3 in the presence or not of enhancing antibody 4G2. Viral titers and the secretion of tumor necrosis factor-alpha, IL-6, IL-10 and interferon-alpha were analyzed timely. Results: DENV infection alone induced high production of IL-6 and TNF-α, but in the presence of 4G2 antibody, viral titers and TNF-α secretion were potentiated. Based on anti-inflammatory antecedents, the polyphenols curcumin, fisetin, resveratrol, apigenin, quercetin and rutin were tested for antiviral and immunomodulatory properties. Only quercetin and fisetin inhibited DENV-2 and DENV-3 infection in the absence or presence of enhancing antibody (>90%, p<0.001); they also inhibited TNF-α and IL-6 secretion (p<0.001). Conclusion: Quercetin and fisetin down-regulate the production of proinflammatory cytokines induced by DENV infection enhanced by antibodies a mechanism involved in severe dengue.

[Prevalence of neutralizing antibodies to dengue virus serotypes in university students from Tabasco, Mexico]. / Prevalencia de anticuerpos neutralizantes contra los serotipos del virus dengue en universitarios de Tabasco, México.

OBJECTIVE: Determine the seroprevalence of neutralizing antibodies to dengue virus in students from the state university of Tabasco, Mexico. MATERIAL AND METHODS: A transversal study was conducted of serum collected from students between September and November, 2005. The sera were screened for anti-dengue IgG and those that had evidence of dengue antibodies were analyzed by a plaque reduction neutralization test. RESULTS: Prevalence of anti-dengue IgG was 9.1%. The frequency of neutralizing antibodies was 100% for DENV-2, 68% for DENV-4, 20% for DENV-1, and 4 % for DENV-3. CONCLUSIONS: We found that in this population, DENV-2 circulates more than DENV-3 despite the fact that DENV-3 is more frequently isolated. Unexpectedly, neutralizing antibodies against DENV-4 were frequently found even though this serotype is almost extinct; thus, it is probable that cross-immunity could suppress DEN-4 transmission, as has been suggested.

Genética de las poblaciones virales y transmisión del dengue / Population genetics of dengue virus and transmission of dengue fever

El comportamiento endémico de la fiebre por dengue en México durante los últimos cinco años ha generado gran preocupación en todos los sectores relacionados con la salud. Los esfuerzos para interrumpir la transmisión se han concentrado en el control vectorial; sin embargo, al margen de la efectividad de las intervenciones, resulta importante establecer con claridad cuáles son los elementos determinantes de la transmisión del dengue para establecer medidas de control y vigilancia eficaces. En cuanto a los determinantes moleculares de la transmisión, mucho se ha avanzado con el desarrollo de la genómica y la bioinformática. Esta revisión pretende ofrecer un panorama de los desarrollos más recientes en ese aspecto con un énfasis en la situación de México.

The endemic behavior of dengue fever in Mexico during the past five years is of major concern to every sector related with public health and the effort to control the transmission has been focused on vector control. However, regardless of the effectiveness of the intervention measures it is important to know which elements determine dengue transmission. With regard to the molecular basis for dengue transmission, a great deal of progress has been made due to the introduction of genomic and bioinformatic approaches. The goal of this review is to describe the most recent developments in this area with emphasis on the Mexican situation.

Prevalencia de anticuerpos neutralizantes contra los serotipos del virus dengue en universitarios de Tabasco, México / Prevalence of neutralizing antibodies to dengue virus serotypes in university students from Tabasco, Mexico

OBJETIVO: Determinar la seroprevalencia de anticuerpos neutralizantes de los serotipos del virus dengue en estudiantes universitarios de Tabasco, México, durante los meses de septiembre a noviembre del año 2005. MATERIAL Y MÉTODOS: Se determinó la presencia de IgG contra el virus en el suero de estudiantes que acudieron al centro clínico de la universidad; en los sueros positivos se determinaron los anticuerpos neutralizantes mediante el ensayo de reducción de placa lítica. RESULTADOS: La prevalencia de IgG contra el dengue fue de 9.1 por ciento; de esta proporción, los anticuerpos neutralizantes fueron DENV-1 (20 por ciento), DENV-2 (100 por ciento), DENV-3 (4 por ciento) y DENV-4 (68 por ciento). CONCLUSIONES: Este estudio muestra que el serotipo transmitido con mayor frecuencia en el estado de Tabasco es el DENV-2, aunque no ha sido el aislado con más frecuencia. La elevada prevalencia de anticuerpos neutralizantes contra el DENV-4, al parecer de reacción cruzada, podría explicar la baja circulación de este serotipo en Tabasco.

OBJECTIVE: Determine the seroprevalence of neutralizing antibodies to dengue virus in students from the state university of Tabasco, Mexico. MATERIAL AND METHODS: A transversal study was conducted of serum collected from students between September and November, 2005. The sera were screened for anti-dengue IgG and those that had evidence of dengue antibodies were analyzed by a plaque reduction neutralization test. RESULTS: Prevalence of anti-dengue IgG was 9.1 percent. The frequency of neutralizing antibodies was 100 percent for DENV-2, 68 percent for DENV-4, 20 percent for DENV-1, and 4 percent for DENV-3. CONCLUSIONS: We found that in this population, DENV-2 circulates more than DENV-3 despite the fact that DENV-3 is more frequently isolated. Unexpectedly, neutralizing antibodies against DENV-4 were frequently found even though this serotype is almost extinct; thus, it is probable that cross-immunity could suppress DEN-4 transmission, as has been suggested.