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.

Killer-cell immunoglobulin-like receptors and cytomegalovirus reactivation during late pregnancy.

Human cytomegalovirus (CMV) represents an important public health concern as it is associated with severe morbidity and mortality in transplant recipients, HIV-infected individuals and pregnant women given the risk of congenital infection. Congenital CMV is a leading cause of neurological sequelae, developmental delay and birth defects worldwide. Cytomegalovirus can be transmitted to the foetus following maternal infection or reactivation. NK cells expressing killer-cell immunoglobulin-like receptors (KIR) are part of the innate immune system and the first line of defence against viral incursions. Previous reports have shown that KIR genes are associated with CMV infections in the post-transplant setting. In this study, we set out to determine whether a protective effect of KIR genes over CMV infection is seen in Mexican pregnant women. Cytomegalovirus infection was assessed through nucleic acid testing in 200 pregnant women and 600 healthy blood donors comprising the Mexican mestizo reference population. Killer-cell immunoglobulin-like receptors and HLA-C genotypes were obtained from 200 pregnant women and 300 reference samples using a comprehensive PCR-SSP approach. We observed statistically lower carrier frequencies of cB03|tA01 gene-content haplotype, of cB03 haplotype motif, of the KIR2DL5 + 2DS3/2DS5 gene pair and of KIR2DL5 amongst CMV-positive pregnant women in comparison with those CMV negative. None of these were associated with CMV status in the reference population. Logistic regression analysis revealed that the most important factor determining CMV status during third-trimester pregnancies was the KIR2DL5 + 2DS3/2DS5 gene pair (OR 0.376 (95%CI 0.174, 0.811, P = 0.013). Our results indicate that CMV-protective KIR gene associations described in Caucasoid populations are also present in the genetically distinct Mexican mestizo population. Our results suggest that certain KIR gene combinations provide protection against CMV infections occurring during late-term pregnancies, a finding of utmost epidemiological importance given its implication with congenital CMV infections.

Effects of cytomegalovirus infection in human neural precursor cells depend on their differentiation state.

Cytomegalovirus (CMV) is the most common cause of congenital infection in developed countries and a major cause of neurological disability in children. Although CMV can affect multiple organs, the most important sequelae of intrauterine infection are related to lesions of the central nervous system. However, little is known about the pathogenesis and the cellular events responsible for neuronal damage in infants with congenital infection. Some studies have demonstrated that neural precursor cells (NPCs) show the greatest susceptibility to CMV infection in the developing brain. We sought to establish an in vitro model of CMV infection of the developing brain in order to analyze the cellular events associated with invasion by this virus. To this end, we employed two cell lines as a permanent source of NPC, avoiding the continuous use of human fetal tissue, the human SK-N-MC neuroblastoma cell line, and an immortalized cell line of human fetal neural origin, hNS-1. We also investigated the effect of the differentiation stage in relation to the susceptibility of these cell lines by comparing the neuroblastoma cell line with the multipotent cell line hNS-1. We found that the effects of the virus were more severe in the neuroblastoma cell line. Additionally, we induced hNS-1 to differentiate and evaluated the effect of CMV in these differentiated cells. Like SK-N-MC cells, hNS-1-differentiated cells were also susceptible to infection. Viability of differentiated hNS-1 cells decreased after CMV infection in contrast to undifferentiated cells. In addition, differentiated hNS-1 cells showed an extensive cytopathic effect whereas the effect was scarce in undifferentiated cells. We describe some of the effects of CMV in neural stem cells, and our observations suggest that the degree of differentiation is important in the acquisition of susceptibility.

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.

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.

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.

Effect of rapid diagnosis on management of influenza A infections.

BACKGROUND: Few studies have examined the impact of rapid viral diagnostic tests on patient management. OBJECTIVE: To assess the effect of rapid diagnosis of influenza A infections on patient management. METHODS: The medical records of children with respiratory infections who were evaluated at a children's hospital between July 1, 1995, and June 30, 1997, were reviewed. Children (n = 56) evaluated in the Emergency Department (ED) who had a positive influenza A enzyme immunoassay (EIA) were compared with two control groups for the likelihood of admission, antibiotic use and duration of hospitalization and antibiotic administration. RESULTS: Patients discharged from the ED with a positive EIA test were less likely to receive antibiotics than those with a negative EIA test (20% vs. 53%; P = 0.04). Patients admitted to the hospital with a positive EIA test were as likely to receive antibiotics as those without a rapid diagnosis, but the duration of antibiotic administration was significantly shorter in the group with a positive EIA test (3.5 vs. 5.4 days; P = 0.03). Patients with a positive EIA test also were more likely to receive antiviral therapy than either control group (25% vs. 0 and 1.8%; P < 0.001). CONCLUSIONS: The detection of influenza A by EIA has a positive impact on medical management by decreasing antibiotic use in pediatric patients evaluated in an ED, by decreasing the duration of antibiotic use in hospitalized patients and by encouraging antiviral therapy.

Reevaluation of antipyretics in children with enteric fever.

BACKGROUND: The Committee on Infectious Diseases of the American Academy of Pediatrics recommends withholding antipyretic administration to patients with enteric fever because of the risk of shock developing as a consequence. OBJECTIVE: To evaluate the effects of antipyretics on blood pressure in children with enteric fever. METHODS: A retrospective review of medical records of patients admitted to Texas Children's Hospital from January, 1977, to October, 1997, with a diagnosis of enteric fever. All febrile episodes were evaluated for the use of antipyretics and evidence of hypotension or cardiovascular decompensation associated with them. RESULTS: Twenty-nine patients with enteric fever were identified. Salmonella typhi caused 23 of these infections. Antipyretics were used in all but one patient. We did not find any association between the use of antipyretics and the development of hypotension. One patient developed shock and adult respiratory distress syndrome >36 h after start of antibiotic therapy and unrelated to fever or antipyretic use. Two patients had evidence of dehydration. No other complications occurred. CONCLUSIONS: We did not find any complications associated with the use of acetaminophen or ibuprofen in children with enteric fever. The effects of antipyretics in enteric fever should be further studied.

Cytomegalovirus urinary excretion and long term outcome in children with congenital cytomegalovirus infection. Congenital CMV Longitudinal Study Group.

BACKGROUND: Cytomegalovirus (CMV) is the most frequent cause of congenital infection, and both symptomatic and asymptomatic infants may have long term sequelae. Children with congenital CMV infection are chronically infected and excrete CMV in the urine for prolonged periods. However, the effect of prolonged viral replication on the long term outcome of these children is unknown. OBJECTIVE: To determine whether duration of CMV excretion is associated with outcome at 6 years of life in symptomatic and asymptomatic congenitally infected children. METHODS: Longitudinal cohort study. Children congenitally infected with CMV were identified at birth and followed prospectively in a study of long term effects of congenital CMV infection. The relationship between duration of CMV urinary excretion and growth, neurodevelopment and presence and progression of sensorineural hearing loss (SNHL) at 6 years of age was determined. RESULTS: There was no significant difference in the duration of viral urinary excretion between children born with asymptomatic (median, 4.55 years) and symptomatic (median, 2.97 years) congenital CMV infection (P = 0.11). Furthermore there was no association between long term growth or cognitive outcome and duration of viral excretion. However, a significantly greater proportion of children who excreted CMV for <4 years had SNHL and progressive SNHL compared with children with CMV excretion >4 years (P = 0.019, P = 0.009, respectively). CONCLUSIONS: Children congenitally infected with CMV are chronically infected for years, but the duration of CMV urinary excretion is not associated with abnormalities of growth, or neurodevelopmental deficits. However, SNHL and progressive SNHL were associated with a shorter duration of CMV excretion.

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.

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.

Candidal meningitis in neonates: a 10-year review.

Candidal meningitis may complicate systemic candidiasis in the premature neonate. We conducted a 10-year retrospective review of 106 cases of systemic candidiasis in neonates to define the incidence, clinical features, laboratory findings, treatment, and outcome of candidal meningitis. Twenty-three of the 106 neonates had candidal meningitis (0.4% of admissions to the neonatal intensive care unit). The median gestational age was 26.2 weeks, the median birth weight was 820 g, and the median age at the onset of illness was 8 days. Clinical disease was severe and commonly was manifested by respiratory decompensation. Findings of cerebrospinal fluid (CSF) analyses varied: pleocytosis was inconsistent, hypoglycorrhachia was common, gram staining was uniformly negative, and Candida was isolated from 17 neonates (74%). Each infant was treated with amphotericin B (median cumulative dose, 30 mg/kg); 5 also received flucytosine therapy. In conclusion, initial clinical features of candidal meningitis are indistinguishable from those of other causes of systemic infection in premature neonates, and normal CSF parameters do not exclude meningitis. Timely initiation of amphotericin B monotherapy was associated with an excellent outcome.

Evaluation of a neuraminidase detection assay for the rapid detection of influenza A and B virus in children.

A prototype version of a new diagnostic assay for influenza A and B (Zstat Flutrade mark) based on detection of viral neuraminidase was evaluated and compared to culture in 196 clinical samples. Children with respiratory illnesses were prospectively evaluated at a pediatrician's office and at a large children's hospital using the neuraminidase assay and viral culture performed on respiratory secretions. Influenza virus was isolated from 51 samples and 83 were positive by the neuraminidase assay. When compared to culture the sensitivity of the assay was 96%, specificity was 77%, positive predictive value was 59%, and negative predictive value was 98%. Testing in the laboratory of pure cultures of bacteria and non-influenza viruses frequently found in the respiratory tract showed 0% cross-reactivity with the neuraminidase assay and 100% specificity for influenza virus in vitro. This new assay provided useful information for the preliminary diagnosis of influenza A and B infections and appears to be suitable for both point-of-care use in the physician's office and rapid diagnosis in a virology laboratory. The high sensitivity makes it particularly useful as a screening test for exclusion of influenza A and B infections. To confirm the diagnosis and exclude a false-positive result, as well as to determine the influenza virus type, a viral culture may be considered.