Resistance phenotype and virulence potential of Leclercia adecarboxylata strains isolated from different sources.

Introduction. Leclercia adecarboxylata is a member of Enterobacterales, often considered an opportunistic pathogen. Recent reports have highlighted L. adecarboxylata as an emerging pathogen harbouring virulence and resistance determinants.Gap statement. Little information exists on virulence and resistance determinants in L. adecarboxylata strains isolated from environmental, food, and clinical samples.Aim. To determine the presence of resistance and virulence determinants and plasmid features in L. adecarboxylata strains isolated from environmental, food, and clinical samples, as well as their phylogenetic relationship.Results. All strains tested showed resistance to ß-lactams and quinolones but were sensitive to aminoglycosides and nitrofurans. However, even though fosfomycin resistance is considered a characteristic trait of L. adecarboxylata, the resistance phenotype was only observed in 50 % of the strains; bla TEM was the most prevalent BLEE gene (70 %), while the quinolone qnrB gene was observed in 60 % of the strains. Virulence genes were differentially observed in the strains, with adhesion-related genes being the most abundant, followed by toxin genes. Finally, all strains carried one to seven plasmid bands ranging from 7 to 125 kbps and harboured several plasmid addiction systems, such as ParDE, VagCD, and CcdAB in 80 % of the strains.Conclusions. L. adecarboxylata is an important emerging pathogen that may harbour resistance and virulence genes. Additionally, it has mobilizable genetic elements that may contribute to the dissemination of genetic determinants to other bacterial genera.

Genomic Analysis of Early SARS-CoV-2 Variants Introduced in Mexico.

The coronavirus disease 2019 (COVID-19) pandemic has affected most countries in the world. Studying the evolution and transmission patterns in different countries is crucial to enabling implementation of effective strategies for disease control and prevention. In this work, we present the full genome sequence for 17 SARS-CoV-2 isolates corresponding to the earliest sampled cases in Mexico. Global and local phylogenomics, coupled with mutational analysis, consistently revealed that these viral sequences are distributed within 2 known lineages, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage A/G, containing mostly sequences from North America, and lineage B/S, containing mainly sequences from Europe. Based on the exposure history of the cases and on the phylogenomic analysis, we characterized 14 independent introduction events. Additionally, three cases with no travel history were identified. We found evidence that two of these cases represented local transmission cases occurring in Mexico during mid-March 2020, denoting the earliest events described for the country. Within this local transmission cluster, we also identified an H49Y amino acid change in the Spike protein. This mutation represents a homoplasy occurring independently through time and space and may function as a molecular marker to follow any further spread of these viral variants throughout the country. Our results provide a general picture of the SARS-CoV-2 variants introduced at the beginning of the outbreak in Mexico, setting the foundation for future surveillance efforts.IMPORTANCE Understanding the introduction, spread, and establishment of SARS-CoV-2 within distinct human populations as well as the evolution of the pandemics is crucial to implement effective control strategies. In this work, we report that the initial virus strains introduced in Mexico came from Europe and the United States and that the virus was circulating locally in the country as early as mid-March. We also found evidence for early local transmission of strains with a H49Y mutation in the Spike protein, which could be further used as a molecular marker to follow viral spread within the country and the region.

Modification of HIF-1α, NF-aκB, IGFBP-3, VEGF and adiponectin in diabetic foot ulcers treated with hyperbaric oxygen.

Introduction: Diabetic foot ulcers are a frequent complication of diabetes and the first cause of non-traumatic lower limb amputation. They affect quality of life, restrict social productivity and generate a high economic burden for health care systems. Hyperbaric oxygen (HBO2) therapy is an adjunctive treatment option because it improves wound healing in the short term. However, its ability to modulate the pro- and anti-inflammatory balance and the hypoxic cell response in the clinical setting has not been fully described. Objective: To determine modifications in HIF-1α, NF-κB, IGFBP-3, and VEGF expression in wounds as well as circulating inflammatory cytokines in patients with diabetic foot ulcers subjected to HBO2. Materials and methods: We studied 17 ambulatory patients and one hospitalized patient with diabetic foot ulcers classified as Grade 3 or 4 according to the Wagner scale. All underwent HBO2 therapy. Tissue expression of HIF-1α, NF-κB, IGFBP-3, and VEGF was determined by immunohistochemistry. Plasma levels of adiponectin, IL-6, IFN-γ, IL-10 and IL-4 were measured by ELISA and chemiluminescence. Fibrosis and angiogenesis were determined by Masson's trichrome staining. Results: Ulcers in all patients healed after one month of HBO2, and none presented relapses at the one-year follow-up. At the beginning of treatment, HIF-1α and NF-κB expression was observed mainly in the nucleus, whereas these proteins were localized in the cytoplasm at the end of HBO2. There were significant modifications in VEGF expression after therapy, an increase in the plasma level of proinflammatory IL-6, and a decrease in that of IFN-γ. IGFBP-3 expression and plasma levels of adiponectin were increased at the end of HBO2. Increases in fibrosis and angiogenesis were also observed. Conclusion: These results suggest that adjuvant HBO2 modifies the proinflammatory balance related to the cellular response to hypoxia.

Differential Detection of Enterovirus and Herpes Simplex Virus in Cerebrospinal Fluid by Real-Time RT-PCR.

BACKGROUND: Enterovirus (EV) and herpes simplex virus 1 and 2 (HSV1 and HSV2) are the main etiologic agents of central nervous system infections. Early laboratory confirmation of these infections is performed by viral culture of the cerebrospinal fluid (CSF), or the detection of specific antibodies in serum (e.g., HSV). The sensitivity of viral culture ranges from 65 to 75%, with a recovery time varying from 3 to 10 days. Serological tests are faster and easy to carry out, but they exhibit cross-reactivity between HSV1 and HSV2. Although molecular techniques are more sensitive (sensitivity >95%), they are more expensive and highly susceptible to cross-contamination. METHODS: A real-time RT-PCR for the detection of EV, HSV1, and HSV2 was compared with end-point nested PCR. RESULTS: We tested 87 CSF samples of patients with a clinical diagnosis of viral meningitis or encephalitis. Fourteen samples were found to be positive by RT-PCR, but only 8 were positive by end-point PCR. The RT-PCR showed a specificity range of 94-100%, the negative predictive value was 100%, and the positive predictive value was 62, 100, and 28% for HSV1, HSV2, and EV, respectively. CONCLUSION: Real-time RT-PCR detected EV, HSV1, and HSV2 with a higher sensitivity and specificity than end-point nested RT-PCR.

[Descriptive epidemiology of children with acute myeloid leukemia residing in Mexico City: a report from the Mexican Inter-Institutional Group for Identifying Childhood Leukemia Causes]. / Epidemiología descriptiva de la leucemia mieloide aguda (LMA) en niños residentes de la Ciudad de México: reporte del Grupo Mexicano Interinstitucional para la Identificación de las Causas de la Leucemia en Niños.

INTRODUCTION: Acute myeloid leukemias represent the second most common childhood leukemia subtype. In Mexico, there are few studies on descriptive epidemiology for this disease. AIMS: To report acute myeloid leukemia incidence for children less than 15 years of age in the Metropolitan Area of the Valley of Mexico for a period of five years (2010-2014) and to analyze whether there are differences in the incidence of acute myeloid leukemia by regions. MATERIAL AND METHODS: A descriptive study was conducted in nine public hospitals in Mexico City. The crude annual average incidence rate and adjusted average annual incidence rate were calculated. RESULTS: A total of 190 patients with diagnosis of de novo acute myeloid leukemia were analyzed. Male sex (57.2%) and acute myeloid leukemia-M3 subtype (25.3%) were more frequent. The adjusted average annual incidence rates for Mexico City and for the Metropolitan Area of the Valley of Mexico were 8.18 and 7.74 per million children under 15 years old, respectively. CONCLUSIONS: It seems that childhood acute myeloid leukemia incidence is increasing in Mexico City, which makes the identification of associated risk factors imperative.

Genetic polymorphisms of the tumor necrosis factor and lymphotoxin alpha in type 2 diabetes.

OBJECTIVE: To investigate the frequency of the single-base change polymorphic variants identified in tumor necrosis factor (TNF) gene (-308 G/A) and lymphotoxin alpha (LTA) (+252 G/A) in patients with type 2 diabetes (T2D). METHODS: A prospective study in a Mexican-mestizo population of 51 patients with T2D and 48 healthy subjects was carried out. We took a peripheral blood sample from each individual for identification of the polymorphic genotypes by polymerase chain reaction. RESULTS: The genotype distribution in T2D was: TNF alpha homozygous 0%; TNFG/A heterozygous 20%; TNFG homozygous 80%. CONCLUSIONS: In regards to the TNF -308 G/A genotype, we found a significant difference (p = 0.012) with a bigger frequency in the group of patients. The health controls showed a higher frequency of TNF -308 G/G genotype (p = 0.034).

[Mixed analysis of the satisfaction survey of the Primary Health Care course of the Institute of Health for Well-being]. / Análisis mixto de la encuesta de satisfacción del curso de Atención Primaria de Salud del Instituto de Salud para el Bienestar.

Background: Describing the perception towards the online course on Primary Health Care (PHC) of the Institute of Health for Well-being (INSABI) will allow to establish improvement actions. Objective: Describe the factors that contribute to satisfaction with the PHC course offered online by INSABI. Material and methods: 620 records of the Health Education System for Well-being were studied. Satisfaction was determined using a Likert-type questionnaire with three dimensions: virtual environment, cognitive area, and measurement of learning. A deductive analysis of the open opinions was carried out. Results: 70% of the health personnel approved the course in less than a week, with an initial score of 5.41 ±1.9 points and final score of 7.8 ± 1.2. More than 65% had scores above the average in the three dimensions. Satisfaction with the virtual environment was 15.57 ± 3.4 points, and 15.73 ± 3.3 with the cognitive dimension. Age and gender were associated with dissatisfaction with the virtual environment and in the cognitive dimension, age was associated with dissatisfaction; 27.7% expressed negative comments, 28.5% related to course extension; 15.5% about the didactic techniques, 10.9% about the speakers and 10.4% about the final exam. Conclusions: The course generates significant learning, 62.4% of the students have a positive or neutral opinion. However, 27.8% expressed dissatisfaction, the majority related to the extension of the course.

Introducción: describir la percepción hacia el curso en línea de Atención Primaria de Salud (APS) del Instituto de Salud para el Bienestar (INSABI) permitirá establecer acciones de mejora. Objetivo: conocer el grado de satisfacción con el curso sobre APS que el INSABI ofrece en línea mediante un análisis mixto. Material y métodos: se estudiaron 620 registros del Sistema Educativo de Salud para el Bienestar. La satisfacción se determinó mediante un cuestionario tipo Likert con tres dimensiones: ambiente virtual, área cognitiva y medición del aprendizaje. Se realizó un análisis deductivo de las opiniones abiertas. Resultados: el 70% de los trabajadores de la salud aprobaron el curso en menos de una semana con una calificación inicial de 5.41 ± 1.9 puntos y la final de 7.8 ± 1.2. Más del 65% tuvieron puntuaciones por arriba de la media en las tres dimensiones. La satisfacción con el ambiente virtual fue de 15.57 ± 3.4 puntos, y de 15.73 ± 3.3 con la dimensión cognitiva. La edad y el sexo se asociaron a insatisfacción con el ambiente virtual y en la dimensión cognitiva, la edad se asoció con insatisfacción; el análisis cualitativo mostró que 27.7% expresaron comentarios negativos, 28.5% relacionadas con la extensión del curso; 15.5% sobre las técnicas didácticas, 10.9% acerca de los ponentes y 10.4% sobre el examen final. Conclusiones: el curso genera aprendizaje significativo, el 62.4% de los educandos tienen una opinión positiva o neutra. Sin embargo, 27.8% manifestaron insatisfacción, la mayoría relacionada con la extensión del curso.

[Development of the INSABI educational strategy: a lesson learned from the COVID-19 epidemic]. / Desarrollo de la estrategia educativa del INSABI: una lección aprendida a partir de la epidemia de COVID-19.

The Institute for Health for Well-being (INSABI according to its initials in Spanish), in collaboration with the National Institute of Medical Sciences and Nutrition Salvador Zubirán (INCMNSZ), instituted the Continuous Training on clinical management "Mexico against COVID-19" in 2020, with the purpose of training the frontline health personnel in the care for patients with COVID-19 in the context of hospital reconversion through the COVIDUTI platform. Virtual conferences were held for medical personnel from all over the country with the possibility of interacting with various specialists. In 2020, 215 sessions were held and 158 in 2021. That year educational content was expanded and included topics for other health categories, such as nursing and social work. In October 2021, it was established the Health Educational System for Well-being (SIESABI), with the aim of promoting continuous and permanent education for health workers. It currently offers face-to-face and virtual courses, permanent seminars, and telementoring, with the possibility of providing academic follow-up to its subscribers and linking priority courses that are on other platforms. The educational platform is an opportunity to unify the efforts of the health system in Mexico in the continuous and permanent education of professionals who care for people without social security and thereby contribute to the implementation of a model of care based on primary health care (PHC).

El Instituto de Salud para el Bienestar (INSABI), en colaboración con el Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), instituyó el entrenamiento continuo sobre manejo clínico "México contra COVID-19" en 2020, con el propósito de capacitar al personal de salud de primera línea en la atención de pacientes con COVID-19 en el contexto de la reconversión hospitalaria mediante la plataforma COVIDUTI. Se realizaron conferencias virtuales dirigidas a personal médico de todo el país con la posibilidad de interactuar con diversos especialistas. En 2020 se realizaron 215 sesiones y 158 en 2021. Ese año se ampliaron contenidos educativos y se incluyeron temas para otras categorías de salud, como enfermería y trabajo social. En octubre de 2021 se estableció el Sistema Educativo de Salud para el Bienestar (SIESABI), con el objetivo de promover la educación continua y permanente para los trabajadores de la salud. Actualmente ofrece cursos presenciales, virtuales, seminarios permanentes y telementorías, con la posibilidad de dar seguimiento académico a sus suscriptores y vincular cursos prioritarios que están en otras plataformas. La plataforma educativa es una oportunidad para unificar los esfuerzos del sistema de salud en México en la educación continua y permanente de los profesionales que atienden a personas sin seguridad social y, con ello, contribuir en la implementación de un modelo de atención basado en Atención Primaria de Salud (APS).

Genomic insights of Leclercia adecarboxylata strains linked to an outbreak in public hospitals in Mexico.

BACKGROUND: Leclercia adecarboxylata is a bacteria closely related to Escherichia coli according to its biochemical characteristics and is commonly considered non-pathogenic although a growing number of publications classify it as an emerging pathogen. Fosfomycin resistance is a common trait for L. adecarboxylata encoded by fosALA gene. OBJECTIVE: To analyze genomic traits of sixteen L. adecarboxylata strains isolated from blood culture and a bottle of total parenteral nutrition. METHODS: Twenty-eight L. adecarboxylata strains isolated from blood culture and a bottle of total parenteral nutrition were identified biochemically with a Vitek ® automated system. The strains were phenotyped by their growth on Eosin Methylene Blue agar or MacConkey agar plates. Additionally, Pulsed field gel electrophoresis (PFGE) was performed to establish the clonal relationship. The genomic DNA of sixteen strains was obtained using a Qubit ® dsDNA HS Assay Kit and sequenced on an Illumina ® MiSeq instrument. Draft genomes were assembled using PROKKA and Rast. Assemblies were submitted to Resfinder and PathogenFinder from the Center for Genomic Epidemiology in order to find resistance genes and pathogenic potential. IslandViewer4 was also used to find Pathogenicity and Phage Islands. For identification of the fosA gene, manual curation and Clustal analysis was performed. A novel FosA variant was identified. Finally, phylogenetic analysis was performed using VAMPhyRE software and Mega X. RESULTS: In this paper, we report the genomes of sixteen strains of Leclercia adecarboxylata causing an outbreak associated with parenteral nutrition in public hospitals in Mexico. The genomes were analyzed for genetic determinants of virulence and resistance. A high pathogenic potential (pathogenicity index 0.82) as well as multiple resistance genes including carbapenemics, colistin and efflux pumps were determined. Based on sequence analysis, a new variant of the fosALA gene was described. Finally, the outbreak was confirmed by establishing the clonal relationship among the sixteen genomes obtained. CONCLUSIONS: Commensal strains of L. adecarboxylata may acquire genetic determinants that provide mechanisms of host damage and go unnoticed in clinical diagnosis. L. adecarboxylata can evolve in a variety of ways including the acquisition of resistance and virulence genes representing a therapeutic challenge in patient care.

Pandemic influenza A/H1N1 virus infection and TNF, LTA, IL1B, IL6, IL8, and CCL polymorphisms in Mexican population: a case-control study.

BACKGROUND: Some patients have a greater response to viral infection than do others having a similar level of viral replication. Hypercytokinemia is the principal immunopathological mechanism that contributes to a severer clinical course in cases of influenza A/H1N1. The benefit produced, or damage caused, by these cytokines in severe disease is not known. The genes that code for these molecules are polymorphic and certain alleles have been associated with susceptibility to various diseases. The objective of the present study was to determine whether there was an association between polymorphisms of TNF, LTA, IL1B, IL6, IL8, and CCL1 and the infection and severity of the illness caused by the pandemic A/H1N1 in Mexico in 2009. METHODS: Case-control study. The cases were patients confirmed with real time PCR with infection by the A/H1N1 pandemic virus. The controls were patients with infection like to influenza and non-familial healthy contacts of the patients with influenza. Medical history and outcome of the disease was registered. The DNA samples were genotyped for polymorphisms TNF rs361525, rs1800629, and rs1800750; LTA rs909253; IL1B rs16944; IL6 rs1818879; IL8 rs4073; and CCL1 rs2282691. Odds ratio (OR) and the 95% confidence interval (95% CI) were calculated. The logistic regression model was adjusted by age and severity of the illness in cases. RESULTS: Infection with the pandemic A/H1N1 virus was associated with the following genotypes: TNF rs361525 AA, OR = 27.00; 95% CI = 3.07-1248.77); LTA rs909253 AG (OR = 4.33, 95% CI = 1.82-10.32); TNF rs1800750 AA (OR = 4.33, 95% CI = 1.48-12.64); additionally, LTA rs909253 AG showed a limited statistically significant association with mortality (p = 0.06, OR = 3.13). Carriers of the TNF rs1800629 GA genotype were associated with high levels of blood urea nitrogen (p = 0.05); those of the TNF rs1800750 AA genotype, with high levels of creatine phosphokinase (p=0.05). The IL1B rs16944 AA genotype was associated with an elevated number of leukocytes (p <0.001) and the IL8 rs4073 AA genotype, with a higher value for PaO2 mm Hg. CONCLUSION: The polymorphisms of genes involved in the inflammatory process contributed to the severity of the clinical behavior of infection by the pandemic influenza A/H1N1 virus.

Functional state analysis of phagocytic cells of patients with type 2 diabetes and pulmonary tuberculosis.

BACKGROUND: The phagocytic function in pulmonary tuberculosis (PTB) and Type 2 diabetes (T2D) has been explored mainly in macrophages but not in polymorphonuclears (PMN). The purpose of this study was to determine the functional status of PMN leukocytes in patients with pulmonary tuberculosis (PTB), Type 2 diabetes (T2D), and in patients with both diseases. METHODS: An observational, prospective, and comparative study was carried out. 30 ambulatory patients with T2D, 10 with PTB undergoing treatment and 10 patients with PTB and T2D, and 44 healthy subjects were studied. PMN leukocytes were separated, the capacity of these cells to produce hydrogen peroxide and to reduce nitroblue tetrazolium (NBT) in response to stimulus with the phorbolic ester of myristic acid (PMA) was measured; and the capacity of PMN leukocytes to adhere to surfaces was determined. RESULTS: Concerning the test for adherence, on comparing healthy subjects with patients with T2D+PTB, we observed a clear decrease in cellular adherence in the group of patients with both diseases; it was statistically significant (p = 0.007).With regard to phagocytic function, we observed that in NBT reduction as well as in hydrogen peroxide production, statistically significant differences were not obtained on comparing healthy subjects with any of the three groups of patients. CONCLUSIONS: We observed a clear decrease in cellular adherence when both diseases co-exist. These results could indicate the need for the co-existence of T2D and TB to cause deterioration in the cells' adherence activity. The microtechniques employed permit the evaluation in a practical manner of certain phagocytic-activity expressions.

[CSF RT-PCR standardization in pediatric patients with enteroviral central nervous system infection]. / Estandarización de RT-PCR en LCR de pacientes pediátricos con infección del sistema nervioso central por enterovirus.

OBJECTIVE: We standardized the RT-PCR panviral CSF and determined its applicability in detecting acute enterovirus infection in the central nervous system in children under 15 years. MATERIAL AND METHODS: RT-PCR was performed directly in CSF samples of 10 pediatric patients with suspected CNS infection and 9, with different conditions of the central nervous system. RESULTS: 80% (8/10) of RT-PCR samples were positive for enterovirus in patients with suspected CNS infection and no sample was positive in patients with different ailments. CONCLUSIONS: Since enteroviruses are among the main etiologies of pediatric encephalitis, RT-PCR could be particularly useful for rapid detection in CSF.

[Pro-inflammatory cytokines related to severity and mortality in type 2 diabetes patients with soft tissue infection]. / Citocinas, diabetes e infección de tejidos blandos. Su relación con la severidad y mortalidad.

OBJECTIVE: to determine the relation between IL6, IL10 and TNFa serum levels in a cohort of patients with type 2 diabetes (T2D) and severe soft tissue infections (STI), with severity and mortality factors. METHODS: A. comparative and transversal, study with 15 adult patients, any gender, with T2D and STI were done. A T2D control group of 20 patients without STI was included. Apache II Score, glycemia and by ELISA, IL6, IL10 and TNFa, were determined. RESULTS: in all patients, it was a correlation at beginning between glycemia and IL6 (r = 0.67, IC 95 % 0.24-0.88), as soon as glycemia and Apache II, (r = 0.59, IC 95 % 0.11-0.83). CONCLUSIONS: although IL6 was very usefulness, it is not a routine test in clinical laboratory and it is expensive, but in medical practice, it could be possible to evaluate these patients with Apache II Score and glycemia. However, in STI, the values of IL6 and IL10 were highly significant. It is likely that IL6 is a marker of poor outcome.

Genetic diversity and spatiotemporal dynamics of DENV-1 and DENV-2 infections during the 2012-2013 outbreak in Mexico.

Dengue fever is caused by four related dengue virus serotypes, DENV-1 to DENV-4, where each serotype comprises distinct genotypes and lineages. The last major outbreak in Mexico occurred during 2012 and 2013, when 112,698 confirmed cases were reported (DENV-1 and DENV-2 were predominant). Following partial E, NS2A and NS5 gene sequencing, based on the virus genome variability, we analyzed 396 DENV-1 and 248 DENV-2 gene sequences from serum samples from dengue acute clinical cases from 13 Mexican states, Mutations were identified, and their genetic variability estimated, along with their evolutionary relationship with DENV sequences sampled globally. DENV-1 genotype V and DENV-2 Asian-American genotype V were the only genotypes circulating during the outbreak. Mutations in NS2A and NS5 proteins were widely disseminated and suggested local emergence of new lineages. Phylogeographic analysis suggested viral spread occurred from coastal regions, and tourist destinations, such as Yucatan and Quintana Roo, which played important roles in disseminating these lineages.

A Multimodal Strategy to Reduce the Risk of Hospitalization/death in Ambulatory Patients with COVID-19.

BACKGROUND: Different interventions have been implemented worldwide for the house-hold monitoring of patients with mild COVID-19 to reduce the burden of healthcare systems and guarantee quality of care. Telephone follow up and treatment kits have not been evaluated in the context of a national-wide primary care program. AIM OF THE STUDY: To compare the risk of hospitalization and death for COVID-19 between ambulatory patients who received and those who did not receive a treatment kit and telephone follow-up in a developing country METHODS: A two-group comparative analysis was conducted using data from the medical information systems of the Mexican Institute of Social Security. We included a total of 28,048 laboratory-confirmed SARS-CoV-2 patients: 7,898 (28.2%) received a medical kit and 20,150 (71.8%) did not. The incidence rates of hospitalization and death combined were calculated. To identify significant associations between hospitalization or death and treatment medical kits, we calculated the risk ratios using a multivariate logistic model. RESULTS: The incidence of hospitalization was 6.14% in patients who received a kit and 11.71% in those who did not. Male sex, age, and a medical history of obesity, hypertension, diabetes, immunosuppression, or kidney disease were associated with increased risk of hospitalization or death. The risk rates were reduced in patients who received a medical kit or telephone follow-up. In the multivariate model, receiving a medical kit was associated with a lower risk of hospitalization or death from COVID-19: adjusted risk ratio 0.41 (95% confidence interval 0.36-0.47). CONCLUSION: Use of a multimodal strategy may reduce the risk of hospitalization and death in adult outpatients with mild COVID-19.

Low Prevalence of ETV6::RUNX1 Fusion Gene in a Hispanic Population.

ETV6::RUNX1 is a genetic rearrangement of good prognosis in children with acute lymphoblastic leukemia (ALL). In Mexico, its prevalence is low in comparison with Caucasian populations. We developed a novel TaqMan one-step RT-qPCR approach to assess the prevalence of four genetic rearrangements in a cohort of Hispanic children with ALL from Mexico City. The prevalence of common fusion gene transcripts was as follows: TCF3::PBX1 7.7%; BCR::ABL1p 190 3.3%; and KMT2A::AFF1 2.8%, and ETV6::RUNX1was observed with low prevalence (10.5%) in comparison to that reported for developed countries. This is consistent with previous findings on Mexican children with ALL and similar to those reported on children from Hispanic populations. The confirmation of a low prevalence of ETV6::RUNX1 in children of a Hispanic origin represents an advancement in the description of genetic factors of ALL in these populations.

Genetic Diversity and Spatiotemporal Dynamics of Chikungunya Infections in Mexico during the Outbreak of 2014-2016.

Chikungunya virus (CHIKV) is an alphavirus transmitted by Aedes mosquitoes, which causes Chikungunya fever. Three CHIKV genotypes have been identified: West African, East-Central-South African and Asian. In 2014, CHIKV was detected for the first time in Mexico, accumulating 13,569 confirmed cases in the following three years. Studies on the molecular diversification of CHIKV in Mexico focused on limited geographic regions or investigated only one structural gene of the virus. To describe the dynamics of this outbreak, we analyzed 309 serum samples from CHIKV acute clinical cases from 15 Mexican states. Partial NSP3, E1, and E2 genes were sequenced, mutations were identified, and their genetic variability was estimated. The evolutionary relationship with CHIKV sequences sampled globally were analyzed. Our sequences grouped with the Asian genotype within the Caribbean lineage, suggesting that the Asian was the only circulating genotype during the outbreak. Three non-synonymous mutations (E2 S248F and NSP3 A437T and L451F) were present in our sequences, which were also identified in sequences of the Caribbean lineage and in one Philippine sequence. Based on the phylogeographic analysis, the viral spread was reconstructed, suggesting that after the introduction through the Mexican southern border (Chiapas), CHIKV dispersed to neighboring states before reaching the center and north of the country through the Pacific Ocean states and Quintana Roo. This is the first viral phylogeographic reconstruction in Mexico characterizing the CHIKV outbreak across the country.

Pregnant Women Infected with Zika Virus Show Higher Viral Load and Immunoregulatory Cytokines Profile with CXCL10 Increase.

BACKGROUND: Zika virus (ZIKV) infection during pregnancy usually shows only mild symptoms and is frequently subclinical. However, it can be vertically transmitted to the fetus, causing microcephaly and other congenital defects. During pregnancy, the immune environment modifications can alter the response to viruses in general and ZIKV in particular. OBJECTIVE: To describe the role of pregnancy in the systemic pro- and anti-inflammatory response during symptomatic ZIKV infection. MATERIALS AND METHODS: A multiplex assay was used to measure 25 cytokines, chemokines, and receptors in 110 serum samples from pregnant and nonpregnant women with and without ZIKV infection with and without symptoms. Samples were collected through an epidemiological surveillance system. RESULTS: Samples from pregnant women with ZIKV infection showed a higher viral load but had similar profiles of inflammatory markers as compared with nonpregnant infected women, except for CXCL10 that was higher in infected pregnant women. Notably, the presence of ZIKV in pregnancy favored a regulatory profile by significantly increasing anti-inflammatory cytokines such as interleukin (IL)-10, receptors IL-1RA, and IL-2R, but only those pro-inflammatory cytokines such as IL-6, interferon (IFN)-α, IFN-γ and IL-17 that are essential for the antiviral response. Interestingly, there were no differences between symptomatic and weakly symptomatic ZIKV-infected groups. CONCLUSION: Our results revealed a systemic anti-inflammatory cytokine and chemokine profile that could participate in the control of the virus. The anti-inflammatory response in pregnant women infected with ZIKA was characterized by high CXCL10, a cytokine that has been correlated with congenital malformations.

Structural Characterization of Haemophilus influenzae Enolase and Its Interaction with Human Plasminogen by In Silico and In Vitro Assays.

Haemophilus influenzae is the causal agent of invasive pediatric diseases, such as meningitis, epiglottitis, pneumonia, septic arthritis, pericarditis, cellulitis, and bacteremia (serotype b). Non-typeable H. influenzae (NTHi) strains are associated with localized infections, such as otitis media, conjunctivitis, sinusitis, bronchitis, and pneumonia, and can cause invasive diseases, such as as meningitis and sepsis in immunocompromised hosts. Enolase is a multifunctional protein and can act as a receptor for plasminogen, promoting its activation to plasmin, which leads to the degradation of components of the extracellular matrix, favoring host tissue invasion. In this study, using molecular docking, three important residues involved in plasminogen interaction through the plasminogen-binding motif (251EFYNKENGMYE262) were identified in non-typeable H. influenzae enolase (NTHiENO). Interaction with the human plasminogen kringle domains is conformationally stable due to the formation of four hydrogen bonds corresponding to enoTYR253-plgGLU1 (K2), enoTYR253-plgGLY310 (K3), and enoLYS255-plgARG471/enoGLU251-plgLYS468 (K5). On the other hand, in vitro assays, such as ELISA and far-western blot, showed that NTHiENO is a plasminogen-binding protein. The inhibition of this interaction using polyclonal anti-NTHiENO antibodies was significant. With these results, we can propose that NTHiENO-plasminogen interaction could be one of the mechanisms used by H. influenzae to adhere to and invade host cells.