Severe adenovirus infection outbreak in Colombia: Experience from a tertiary pediatric hospital in 2022. / Brote de adenovirus grave en Colombia: experiencia de un hospital pediátrico de tercer nivel en 2022

Introduction. During the SARS-CoV-2 pandemic, many countries experienced decreased respiratory virus circulation, followed by an out-of-season outbreak. In a pediatric hospital in Colombia, we observed a surge in severe adenovirus infections, leading to concerns about the impact of eased public health restrictions and immune debt in children under five years old. Objective. To describe the clinical characteristics of patients with severe adenovirus infection in a pediatric hospital in Colombia. Materials and methods. We reviewed the data of 227 patients with severe adenovirus infection at the Fundación Hospital Pediátrico La Misericordia. Results. A total of 196 patients were included in this study. The median age was two years, and 62% were male. Adenoviruses were isolated from all patients' samples. Ninetyseven percent were admitted to the pediatric intensive care unit, 94% required respiratory support, and the in-hospital lethality rate was 11%. Conclusion. In 2022, there was an outbreak of severe adenovirus infections, affecting mainly children under five years of age, with higher-than-usual mortality.

Introducción. Durante la pandemia por SARS-CoV-2, muchos países evidenciaron una disminución en la circulación de virus respiratorios, seguida por un brote fuera de la temporada esperada. En un hospital de Colombia, se observó un aumento en los casos de infección grave por adenovirus, lo cual generó preocupación sobre el impacto que tuvo la disminución de los cuidados establecidos durante pandemia y la posible deuda inmunológica en niños menores de cinco años. Objetivo. Describir las características clínicas de los pacientes con infección grave por adenovirus en un hospital pediátrico de Colombia. Materiales y métodos. Se revisaron 227 pacientes con infección grave por adenovirus en la Fundación Hospital Pediátrico La Misericordia, desde el 1° de enero hasta el 31 de diciembre de 2022. Resultados. El estudio incluyó 196 casos. La edad media de los pacientes fue de dos años y el 62 % eran de sexo masculino. Los adenovirus se aislaron a partir de las muestras de todos los pacientes. El 97 % de los pacientes ingresó a la unidad de cuidados intensivos, el 94 % requirió soporte ventilatorio y la tasa de mortalidad fue del 11 %. Conclusiones. En el 2022 hubo un brote de adenovirus que afectó principalmente a los niños menores de cinco años, con una mortalidad mayor a lo reportado con anterioridad en Colombia.

Evaluation of the safety profile of the quadrivalent vaccine against human papillomavirus in the risk of developing autoimmune, neurological, and hematological diseases in adolescent women in Colombia.

BACKGROUND: Cervical cancer eradication is one of the main goals for 2030 by the World Health Organization, which can only be achieved with high vaccination rates against Human Papilloma Virus. In Colombia, more and better scientific evidence is required to increase confidence in vaccination. The objective of this study is to evaluate the safety profile of the quadrivalent vaccine against HPV in the risk of developing autoimmune, neurological, and hematological diseases in adolescent women in Colombia. METHODS: We designed a cohort study based on national HPV vaccination records and incident diagnostic data for the diseases of special interest during 2012 and 2021. We included adolescent women between 9 and 19 years old and compared vaccinated and non-vaccinated cohorts using an Inverse Probability of Treatment Weighting (IPWT) method for each scenario disease and follow-up period (180 and 360 days). FINDINGS: The Odds Ratio (OR) of developing diseases of interest was estimated during two follow up periods, 180 and 360 days after the follow-up index date (Vaccination Day). The OR for developing rheumatoid arthritis was 4·4; CI95% (1·74 - 11·14), juvenile idiopathic arthritis was 2·76 IC95% (1·50 - 5·11), idiopathic thrombocytopenic purpura was 2·54 IC95% (1·28 - 5·02) and thyrotoxicosis was 2·86 IC95% (1·03 - 7·95), when comparing the vaccinated versus unvaccinated population. However, the temporal distribution of cases incident did not reveal a clear difference between the cohorts, since the rate of appearance of new cases has a constant linear behavior for the two groups. INTERPRETATION: For rheumatoid arthritis, juvenile idiopathic arthritis, idiopathic thrombocytopenic purpura, and thyrotoxicosis; the application of the vaccine had an effect on the development of the disease. Nevertheless, our results should be interpreted with caution and be further studied, considering that the biological plausibility of the events occurred without a clear temporal pattern in relation to the exposure to the vaccine.

Polymorphisms in Human IL4, IL10, and TNF Genes Are Associated with an Increased Risk of Developing NSAID-Exacerbated Respiratory Disease.

BACKGROUND: The role of genetics in non-steroidal anti-inflammatory drugs (NSAID) exacerbated respiratory disease (NERD) is unclear, with different candidates involved, such as HLA genes, genes related to leukotriene synthesis, and cytokine genes. This study aimed to determine possible associations between 22 polymorphisms in 13 cytokine genes. METHODS: We included 195 patients (85 with NERD and 110 with respiratory disease who tolerate NSAIDs) and 156 controls (non-atopic individuals without a history of asthma, nasal polyposis (NP), or NSAID hypersensitivity). Genotyping was performed by sequence-specific primer polymerase chain reaction (PCR-SSP). Amplicons were analyzed by horizontal gel electrophoresis in 2% agarose. RESULTS: Significant differences in allele and genotype frequency distributions were found in TNF (rs1800629), IL4 (rs2243248 and rs2243250), and IL10 (rs1800896, rs1800871, and rs1800872) genes in patients with NSAID hypersensitivity. In all cases, the minor allele and the heterozygous genotype were more prevalent in NERD. An association of TNF rs1800629 SNP with respiratory disease in NSAID-tolerant patients was also found. CONCLUSIONS: Retrospectively recorded, we found strong associations of NERD with polymorphisms in IL4, IL10, and TNF genes, suggesting that these genes could be involved in the inflammatory mechanisms underlying NERD.

Association Between Unbalanced Solutions and Acute Kidney Injury During Fluid Resuscitation in Children With Sepsis.

OBJECTIVE: To evaluate the outcomes of patients with sepsis-associated organ dysfunction and septic shock who receive fluid resuscitation with balanced and unbalanced solutions in a middle-income country. DESIGN: An observational, analytical cohort study with propensity score matching (PSM) in children admitted to a pediatric intensive care unit (PICU). Patients from one month to 17 years old who required fluid boluses due to hemodynamic instability were included. The primary outcome was the presence of acute kidney injury and the secondary outcomes were the need to begin continuous renal replacement therapy (CRRT), metabolic acidosis, PICU length of stay and mortality. MEASUREMENTS AND MAIN RESULTS: Out of the 1,074 admissions to the PICU during the study period, 99 patients had sepsis-associated organ dysfunction and septic shock. Propensity score matching was performed including each patient´s baseline characteristics. The median age was 9.9 months (IQR 4.9-22.2) with 55.5% of the patients being male. Acute kidney injury was seen less frequently in children who received a balanced solution than in those who received an unbalanced solution (20.3% vs 25.7% P = 0.006 ORa, 0.75; 95% CI, 0.65-0.87), adjusted for disease severity. In addition, the group that received balanced solutions had less need for CRRT (3.3 % vs 6.5%; P = 0.02 ORa 0.48; 95% CI, 0.36-0.64) and a shorter PICU stay (6 days IQR 4.4-20.2 vs 10.2 days IQR 4.7-26; P < 0.001) than the group with unbalanced solutions. We found no difference in the frequency of metabolic acidosis (P = 0.37), hyperchloremia (P = 0.11) and mortality (P = 0.25) between the 2 groups. CONCLUSION: In children with sepsis-associated organ dysfunction and septic shock, the use of unbalanced solutions for fluid resuscitation is associated with a higher frequency of acute kidney injury, a greater need for continuous renal support and a longer PICU stay compared to the use of balanced solutions, in a middle-income country.

Applications of Molecular Genetics to the Study of Asthma.

Asthma is a multifactorial disease. This fact, associated to the diversity of asthma phenotypes, has made difficult to obtain a clear pattern of inheritance. With the huge development of molecular genetics technologies, candidate gene studies are giving way to different types of studies from the genomic point of view.These approaches are allowing the identification of several genes associated with asthma. However, in these studies, there are some conflicting results between different populations and there is still a lack of knowledge about the actual influence of the gene variants. Some confounding factors are, among others, the inappropriate sample size, population stratification, differences in the classification of the phenotypes, or inadequate coverage of the genes.To confirm the real effect of the reported associations, it is necessary to consider both the genetic and environmental factors and perform functional studies that explain the molecular mechanisms mediating between the emergence of gene variants and the development of the disease.The development of experimental techniques opens a new horizon that allows the identification of major genetic factors of susceptibility to asthma. The resulting classification of the population groups based on their genetic characteristics, will allow the application of specific and highly efficient treatments.

Introduction to the Gene Expression Analysis.

In 1941, Beadle and Tatum published experiments that would explain the basis of the central dogma of molecular biology, whereby the DNA through an intermediate molecule, called RNA, results proteins that perform the functions in cells. Currently, biomedical research attempts to explain the mechanisms by which develops a particular disease, for this reason, gene expression studies have proven to be a great resource. Strictly, the term "gene expression" comprises from the gene activation until the mature protein is located in its corresponding compartment to perform its function and contribute to the expression of the phenotype of cell.The expression studies are directed to detect and quantify messenger RNA (mRNA) levels of a specific gene. The development of the RNA-based gene expression studies began with the Northern Blot by Alwine et al. in 1977. In 1969, Gall and Pardue and John et al. independently developed the in situ hybridization, but this technique was not employed to detect mRNA until 1986 by Coghlan. Today, many of the techniques for quantification of RNA are deprecated because other new techniques provide more information. Currently the most widely used techniques are qPCR, expression microarrays, and RNAseq for the transcriptome analysis. In this chapter, these techniques will be reviewed.

Validation of Reference Genes in mRNA Expression Analysis Applied to the Study of Asthma.

The quantitative Polymerase Chain Reaction is the most used technique for the study of gene expression. To correct putative experimental errors of this technique is necessary normalizing the expression results of the gene of interest with the obtained for reference genes. Here, we describe an example of the process to select reference genes. In this particular case, we select reference genes for expression studies in the peripheral blood mononuclear cells of asthmatic patients.

Interactions of DNA and Proteins: Electrophoretic Mobility Shift Assay in Asthma.

Electrophoretic mobility shift assays (EMSA) are used to characterize interactions between nucleic acids and proteins in native conditions. This is based on the fact that the electrophoretic mobility of a nucleic acid becomes slower when it forms complexes with proteins. There are many different variants and applications of this methodology. In this chapter we describe a detailed EMSA protocol applied to the study of asthma.

Notes from the Field: Health Care-Associated Hepatitis A Outbreak - Texas, 2015.

On August 27-28, 2015, the Texas Department of State Health Services received calls from Fort Bend County and Harris County health departments requesting postexposure prophylaxis (PEP) recommendations for contacts of two nurses (patients A and B) with confirmed hepatitis A virus (HAV) infection. Both nurses had symptom onset during August 15-19 and worked for the same pediatric home health care agency in another jurisdiction. Because of the proximity of the onset dates, a common source exposure was suspected. The state and local health departments began an investigation to identify potentially exposed patients, their families, and other agency personnel; offer PEP; and identify the source of exposure.