Diabetes is a major cause of influenza-associated mortality in Mexico.

BACKGROUND: Influenza is a major cause of mortality worldwide. Most influenza-associated deaths are associated with cardiovascular or respiratory disorders. However, a large proportion of influenza-associated deaths do not have respiratory or cardiovascular disorders declared as the underlying cause of death. Diabetic individuals are at increased risk for influenza-mortality. In this study, we assessed the contribution of diabetes to influenza-associated mortality in Mexico. METHODS: Diabetes influenza-associated mortality was estimated for the Mexican population using National Mortality Databases from the Mexican Ministry of Health from 1998 through 2015. Diabetes influenza-associated mortality was calculated applying Serfling cyclical regression models to weekly mortality rates for persons 20-59 years, 60 and more years, and all ages, and by sex. RESULTS: There was a high correlation between weekly pneumonia and influenza mortality and diabetes-related mortality. Yearly influenza-associated diabetes mortality rates varied between 2.0 and 5.9/100,000. Up until the 2005-2006 season, diabetes-associated mortality rates were higher in females, while after that season rates were higher in males. Yearly influenza-associated diabetes mortality rates for adults 20-59 years of age ranged between 1.7 and 3.4/100,000, while estimates for adults 60 years and older ranged between 16.3 and 46.1/100,000. Approximately one third of estimated diabetes influenza-associated deaths occurred in adults 20-59 years of age. On average, diabetes deaths accounted for 19.6% of estimated influenza-associated all-cause mortality. CONCLUSION: Diabetes is a major cause of estimated influenza-associated mortality in Mexico. Health-care authorities and professionals in countries with high diabetes prevalence should be aware of the potential impact of influenza in individuals with this condition.

High prevalence of t895 and t9364 spa types of methicillin-resistant Staphylococcus aureus in a tertiary-care hospital in Mexico: different lineages of clonal complex 5.

BACKGROUND: Staphylococcus aureus is a leading cause of broad-spectrum infections both in the community and within healthcare settings. Methicillin-resistant Staphylococcus aureus (MRSA) has become a global public health issue. The aim of this study was to examine the clinical and molecular characteristics of Staphylococcus aureus isolates and to define the population structure and distribution of major MRSA clones isolated in a tertiary-care hospital in Mexico. RESULTS: From April 2017 to April 2018, 191 Staphylococcus aureus isolates were collected. The frequency of MRSA was 26.7%; these strains exhibited resistance to clindamycin (84.3%), erythromycin (86.2%), levofloxacin (80.3%), and ciprofloxacin (86.3%). The majority of MRSA strains harbored the SCCmec type II (76.4%) and t895 (56.8%) and t9364 (11.7%) were the most common spa types in both hospital-associated MRSA and community-associated MRSA isolates. ST5-MRSA-II-t895 (New York /Japan clone) and ST1011-MRSA-II-t9364 (New York /Japan-Mexican Variant clone) were the most frequently identified clones. Furthermore, different lineages of Clonal Complexes 5 (85.4%) and 8 (8.3%) were predominantly identified in this study. CONCLUSION: Our study provides valuable information about the epidemiology of MRSA in a city of the central region of Mexico, and this is the first report on the association between t895 and t9364 spa types and ST5 and ST1011 lineages, respectively. These findings support the importance of permanent surveillance of MRSA aimed to detect the evolutionary changes of the endemic clones and the emergence of new strains.

Differential expression profiles of circulating microRNAs in newborns associated to maternal pregestational overweight and obesity.

BACKGROUND: The perinatal environment has a role in the establishment of altered metabolic and inflammatory responses, and could be modulated by microRNAs regulating immune and metabolic processes. OBJECTIVE: To analyze the expression profile of four circulating microRNAs and cytokine serum concentrations in neonates born to overweight and obese women. METHODS: Pregnant women were included and grouped by pregestational body mass index (21 with normal weight, 10 overweight and 10 obese women). A peripheral blood sample was obtained from newborn infants and used to determine circulating miRNAs expression and cytokine serum concentrations. RESULTS: There were significant differences in the expression of three microRNAs between newborns of pregestational obese women and newborns from pregestational normal weight women: miR-155 (p = 0.03), miR-181a (p = 0.02) and miR-221 (p = 0.04). A significant reduction in IL-1ß (p = 0.005) expression was also found in newborns of overweight women; although this cytokine was also diminished in newborns of obese women, this was not statistically significant. An association between IL-1ß concentrations and miR-146a and miR-221 expression was also observed. CONCLUSIONS: Expression of miR-155, miR-181a and miR-221 differs in infants born to obese women compared with infants born to normal weight women. Changes in microRNA expression could participate in the epigenetic foetal programming of metabolic disorders in children born to obese women.

Complete Genome Sequence of Human Coronavirus OC43 Isolated from Mexico.

We report the complete genome sequence of the first Mexican human coronavirus (HCoV) OC43, obtained by new-generation sequencing and a metagenomic approach, isolated from a child hospitalized with pneumonia. The genome is closely related to the other OC43 genome sequences available, ranging from 99.8% to 98.2% nucleotide sequence identity.

NKG2C gene deletion in the Mexican population and lack of association to respiratory viral infections.

Expansion of a natural killer (NK) cell population that expresses NKG2C has been associated with cytomegalovirus and other viral infections. It has been suggested that this cell population may play a role in infection control. Deletion of the NKG2C gene (homozygous or heterozygous) has been reported with high prevalence in European and Asian populations. However, the effect of NKG2C genotype on NK cell responses to infection remains poorly defined. We determined the prevalence of the NKG2C deletion in a Mexican population (n = 300) and in a group of patients (n = 131) to assess whether NKG2C genotype affects the incidence of symptomatic viral infections caused by influenza or respiratory syncytial virus. The frequency of the NKG2C deletion haplotype in Mexican mestizos was significantly lower (10.3%) than that reported in other populations (17.5-21.9%). No difference in the prevalence of NKG2C deletion was observed in subjects with viral infections compared with the reference population. In addition, no differences in clinical characteristics and infection outcome were observed between patients with and without the NKG2C gene deletion. Our results indicate that copy number variation in the NKG2C gene has no impact on the severity of respiratory viral infections.

Influenza virus infection but not H1N1 influenza virus immunization is associated with changes in peripheral blood NK cell subset levels.

The innate immune system constitutes the first line of defense against viral agents, and NK cells seem to have an important protective role during the early phases of influenza virus infections. We decided to assess the levels of NK and NKT lymphocytes and the expression levels of different membrane receptors (NKp44, NKp46, NKG2A, killer cell immune-like receptor [KIR] 3DL1/DS1, KIR2DL1/DS1, and CD161) in peripheral blood samples of patients with influenza (n = 17) and healthy individuals immunized against this virus (seasonal and [H1N1]pdm2009 influenza vaccines; n = 15 and 12, respectively). Blood samples were obtained from all individuals, and NK and NKT cell subsets were analyzed by multiparametric flow cytometry. We found that the patients with severe influenza (n = 9) showed significant increases in the percentages of NKp46(+) NKp44(+) NK cells and the proportions of NK and NKT lymphocytes expressing KIR2DL1 and KIR3DL1 and reductions in the percentages of NKp46(+) NKp44(-) NK cells compared to those in the healthy controls (n = 27). In contrast, influenza immunization, against either the seasonal or the pandemic H1N1 virus, was not associated with important changes in the levels of NK and NKT lymphocytes or the expression levels of the different receptors by these cells. Our data suggest that severe influenza is associated with important and complex alterations on NK cells, which might contribute to the pathogenesis of this condition.

Human papillomavirus immunization is associated with increased expression of different innate immune regulatory receptors.

Human papillomavirus (HPV) is able to inhibit the secretion of gamma interferon (IFN-γ) and the expression of some immune innate cell receptors. Immunoglobulin-like transcript 2 (ILT2) is a regulatory receptor that seems to participate in the pathogenesis of viral infections. We have studied the expression and function of ILT2 and the expression of other NK cell receptors in 23 healthy women before and after immunization with the quadrivalent HPV (type 6/11/16/18) vaccine (Gardasil). Receptor expression was analyzed by flow cytometry in freshly isolated peripheral blood mononuclear cells as well as after in vitro stimulation with the quadrivalent HPV (type 6/11/16/18) vaccine. In addition, the regulatory function of ILT2 on cell proliferation and IFN-γ production was analyzed. We found a significant increase in the expression of ILT2 by NK and CD3(+) CD56(+) lymphocytes and monocytes after quadrivalent HPV (type 6/11/16/18) vaccine immunization. In addition, the in vitro stimulation with the quadrivalent HPV (type 6/11/16/18) vaccine also increased the proportion of CD3(-) CD56(+) ILT2(+) NK cells. Although the inhibitory function of ILT2 on cell proliferation was enhanced after HPV immunization, the in vitro engagement of this receptor did not affect the synthesis of IFN-γ induced by HPV. Finally, a significant increase in the expression of NKG2D, NKp30, and NKp46 by NK and CD3(+) CD56(+) lymphocytes was detected after quadrivalent HPV (type 6/11/16/18) vaccine immunization. Our data indicate that HPV immunization is associated with significant changes in the expression and function of different innate immune receptors, including ILT2, which may participate in the protective effect of HPV vaccines.

Population pharmacokinetics of cefepime in neonates with severe nosocomial infections.

OBJECTIVE: To define the pharmacokinetic behaviour of cefepime in neonates with severe nosocomial infections using a mixed effects model. PATIENTS AND METHODS: Thirty-one newborn infants were included in the study; 10 additional infants participated in the validation of the pharmacokinetic model. Cefepime CL and V were determined using an open monocompartmental model with first-order elimination. The influence of demographic and clinical characteristics on the model was evaluated. The non-linear mixed effect model (nonmem) program was used to determine the pharmacokinetic population model. RESULTS: The mean corrected gestational age for infants participating in the construction and validation of the model were 35 and 33 weeks, respectively. Factors included in the final pharmacokinetic model were body surface area (BSA) and calculated CL(CR). The final population model was CL (L/h) = 0.457 BSA (m(2)) + 0.243 CL(CR) (L/h) and V(L) = 4.12 BSA (m(2)). This model explains 33.3% of the interindividual variability for CL and 12.8% for V. This model was validated in ten neonates with nosocomial infections by assessing the predictive capacity of plasma cefepime concentrations using a priori and Bayesian strategies. CONCLUSIONS: The predictive performance of this population model for cefepime plasma concentrations was adequate for clinical purposes and can be used for individualizing cefepime therapy in newborn infants with severe infections. Cefepime plasma concentrations can be predicted based on BSA and calculated CL(CR). Cefepime therapy using a 250 mg/m(2) dose administered every 12 h is adequate to achieve plasma concentrations greater than 8 mug/mL during more than 60% of the dosing interval and is expected to be effective in the treatment of bloodstream infections caused by most gram negative organisms in newborn infants. A dose of 550 mg/m(2) would be required for the treatment of infections caused by Pseudomonas sp.

Effect of climatological factors on respiratory syncytial virus epidemics.

Respiratory syncytial virus (RSV) presents as yearly epidemics in temperate climates. We analysed the association of atmospheric conditions to RSV epidemics in San Luis Potosí, S.L.P., Mexico. The weekly number of RSV detections from October 2002 and May 2006 were correlated to ambient temperature, barometric pressure, relative humidity, vapour tension, dew point, precipitation, and hours of light using time-series and regression analyses. Of the variation in RSV cases, 49.8% was explained by the study variables. Of the explained variation in RSV cases, 32.5% was explained by the study week and 17.3% was explained by meteorological variables (average daily temperature, maximum daily temperature, temperature at 08:00 hours, and relative humidity at 08:00 hours). We concluded that atmospheric conditions, particularly temperature, partly explain the year to year variability in RSV activity. Identification of additional factors that affect RSV seasonality may help develop a model to predict the onset of RSV epidemics.

Early predictors of neurodevelopmental outcome in symptomatic congenital cytomegalovirus infection.

OBJECTIVE: To determine the ability of neonatal clinical, audiologic, and computed tomography (CT) findings to predict long-term neurodevelopmental outcome in children with symptomatic congenital cytomegalovirus (CMV) infection. METHODS: Longitudinal cohort study of children (n = 41) with symptomatic congenital CMV infection evaluated at birth and followed up with serial age-appropriate neurodevelopmental testing. The performance of birth characteristics as predictors of long-term outcome were determined, and clinical and CT scoring systems were developed and correlated with intellectual outcome. RESULTS: Microcephaly was the most specific predictor of mental retardation (100%; 95% CI 84.5-100) and major motor disability (92.3%; 95% CI 74.8-99). An abnormality detected by CT was the most sensitive predictor for mental retardation (100%; 95% CI 82.3-100) and motor disability (100%; 95% CI 78.2-100). A highly significant (P <.001) positive correlation was found between head size at birth and the intelligence/developmental quotient (IQ/DQ). Approximately 29% of children had an IQ/DQ >90. There was no association between sensorineural hearing loss at birth and cognitive outcome. However, children with sensorineural hearing loss on follow-up (congenital and late-onset) had a lower IQ/DQ (P =.006) than those with normal hearing. CONCLUSIONS: The presence of microcephaly at birth was the most specific predictor of poor cognitive outcome in children with symptomatic congenital CMV infection, whereas children with normal findings on head CT and head circumference proportional to weight exhibited a good cognitive outcome.