Carbapenem-Resistant Gram-Negative Bacilli Characterization in a Tertiary Care Center from El Bajio, Mexico.

Carbapenem-resistant Gram-negative bacilli (CR-GNB) are a major public health concern. We aimed to evaluate the prevalence of CR-GNB and the frequency of carbapenemase-encoding genes in a tertiary referral center from El Bajio, Mexico. A cross-sectional study was conducted between January and October 2022; Gram-negative bacilli (GNB) were screened for in vitro resistance to at least one carbapenem. CR-GNB were further analyzed for carbapenemase-production through phenotypical methods and by real-time PCR for the following genes: blaKPC, blaGES, blaNDM, blaVIM, blaIMP, and blaOXA-48. In total, 37 out of 508 GNB were carbapenem-resistant (7.3%, 95% CI 5.2-9.9). Non-fermenters had higher rates of carbapenem resistance than Enterobacterales (32.5% vs. 2.6%; OR 18.3, 95% CI 8.5-39, p < 0.0001), and Enterobacter cloacae showed higher carbapenem resistance than other Enterobacterales (27% vs. 1.4%; OR 25.9, 95% CI 6.9-95, p < 0.0001). Only 15 (40.5%) CR-GNB had a carbapenemase-encoding gene; Enterobacterales were more likely to have a carbapenemase-encoding gene than non-fermenters (63.6% vs. 30.8%, p = 0.08); blaNDM-1 and blaNDM-5 were the main genes found in Enterobacterales; and blaIMP-75 was the most common for Pseudomonas aeruginosa. The mcr-2 gene was harbored in one polymyxin-resistant E. cloacae. In our setting, NDM was the most common carbapenemase; however, less than half of the CR-GNB showed a carbapenemase-encoding gene.

Diagnosis of bacterial meningitis caused by Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae using a multiplex real-time PCR technique.

Bacterial meningitis is one of the diseases that, despite the introduction of several vaccines, remains a serious public health concern. Streptococcus pneumoniae (Spn), Neisseria meningitidis (Nm), and Haemophilus influenzae (Hi) are responsible for most cases diagnosed in children, adolescents, and adult population. Rapid, sensitive, and specific laboratory assays are critical for effective diagnosis and treatment, particularly in countries like Mexico in which culture positivity rates are very low due to the use of antibiotics prior to sample collection and to delay in transporting samples to the laboratory. The aim of this study was to evaluate the use of real-time polymerase chain reaction (RT-PCR) of cerebrospinal fluid (CSF) as a rapid diagnostic test for bacterial meningitis and compare these results with bacterial culture in three general hospitals in Mexico. During a 5-year period (2014-2018), a total of 512 CSF samples obtained from patients in whom infectious meningitis was suspected as initial clinical diagnosis were tested with RT-PCR with species-specific targets for the three pathogens. For Spn, 5.07% samples were RT-PCR positive; 0.39% for Nm and none for Hi. Only five RT-PCR Spn positive samples had a positive culture. Sensitivity and specificity estimates for RT-PCR are 100% and 95.46%, respectively. DNA amplification methods can provide better sensitive diagnostic tests than the reference standard, which is culture, particularly when antimicrobial treatment is initiated before clinical samples can be obtained.

Neurologic adverse events among 704,003 first-dose recipients of the BNT162b2 mRNA COVID-19 vaccine in Mexico: A nationwide descriptive study.

mRNA vaccines against SARS-CoV-2 are remarkably effective. Limited information exists about the incidence of adverse events following immunization (AEFI) with their use. We conducted a prospective observational study including data from 704,003 first-doses recipients; 6536 AEFI were reported, of whom 65.1% had at least one neurologic AEFI (non-serious 99.6%). Thirty-three serious events were reported; 17 (51.5%) were neurologic (observed frequency, 2.4/100,000 doses). At the time of writing this report, 16/17 cases had been discharged without deaths. Our data suggest that the BNT162b2 mRNA COVID-19 vaccine is safe; its individual and societal benefits outweigh the low percentage of serious neurologic AEFI. This information should help to dissipate hesitancy towards this new vaccine platform.

[Prevalence of anogenital condylomas in patients with HIV infection in a center for sexually transmitted infections in Leon, Guanajuato, Mexico]. / Prevalencia de condilomas ano-genitales en pacientes con infección por VIH en un centro para infecciones de transmisión sexual en León, Guanajuato, México.

BACKGROUND: Condylomas are the most frequent sexually transmitted infection worldwide, and thus, have a close relation to HIV infection. The site and serology vary, and some pose higher risk of malignancy. AIM: To describe the prevalence, characteristics and associated factors to the presence of anogenital condylomas in patients with HIV/AIDS. METHODS: Descriptive cross-sectional study conducted in the period from June to December 2014. Adult HIV/AIDS positive patients from "CAPASITS" in Leon, Mexico, from both sexes were included. A questionnaire was performed that included: identification data, and risk factors related to anogenital condylomas. Anogenital area was examined for condylomas. Descriptive statistics were carried out according to the type and distribution of the variables, and the CD4 lymphocyte medians of patients with and without condylomas were compared using U- Mann-Whitney test. RESULTS: A total of 213 HIV/AIDS patients were included; 181 (85%) were male. The prevalence of anogenital condylomas was 30% (IC95%: 23-36%), predominating in the anal region, observed in 21% of the cases. A significant difference was found between median CD4 cell count of patients with and without condylomas (425 vs 510 CD4/mL, p= 0.034). CONCLUSION: A high prevalence of patients with anogenital condylomas was obtained. The presence of condylomas was higher in patients with lower CD4 count. Considering the high prevalence, the application of the vaccine is recommended in this patient group.

Prevalencia de condilomas ano-genitales en pacientes con infección por VIH en un centro para infecciones de transmisión sexual en León, Guanajuato, México / Prevalence of anogenital condylomas in patients with HIV infection in a center for sexually transmitted infections in Leon, Guanajuato, Mexico

INTRODUCCIÓN: Los condilomas son la infección de transmisión sexual más frecuente en el mundo y tiene estrecha relación con la infección por VIH. La topografía y la serología son variables, y algunos presentan mayor riesgo de malignización. OBJETIVO: Describir la prevalencia, características clínicas, topográficas y factores asociados a la presencia de condilomas ano-genitales en pacientes con infección por VIH/SIDA en Guanajuato. MATERIAL Y MÉTODOS: Estudio descriptivo y transversal realizado entre junio y diciembre de 2014. Se incluyeron pacientes adultos con infección por VIH/SIDA, de ambos sexos, del CAPASITS León, México. Se aplicó un cuestionario que incluyó: datos de identificación, y factores de riesgo relacionados a los condilomas ano-genitales, y se les revisó dicha región corporal en busca de condilomas. Se realizó estadística descriptiva de acuerdo al tipo y distribución de las variables y se compararon las medianas de linfocitos T CD4 (LTCD4+) de los pacientes, con y sin condilomas, con la prueba U- Mann-Whitney. RESULTADOS: Se incluyeron 213 pacientes con infección por VIH/SIDA, 181 (85%) hombres. La prevalencia de condilomas ano-genitales fue de 30% (IC95%:23-36%), con mayor frecuencia en la región anal, con 21% de los casos. Encontramos una diferencia significativa entre las medianas en el recuento de linfocitos LTCD4+ en los pacientes, con y sin condilomas, (425 vs 510 LTCD4+/mL, p = 0,034). CONCLUSIONES: Se obtuvo una prevalencia alta de pacientes con condilomas ano-genitales. La presencia de condilomas fue mayor en pacientes con menor recuento de linfocitos LTCD4+. Considerando la elevada prevalencia, se recomienda la aplicación de la vacuna en este grupo de pacientes.

BACKGROUND: Condylomas are the most frequent sexually transmitted infection worldwide, and thus, have a close relation to HIV infection. The site and serology vary, and some pose higher risk of malignancy. AIM: To describe the prevalence, characteristics and associated factors to the presence of anogenital condylomas in patients with HIV/AIDS. METHODS: Descriptive cross-sectional study conducted in the period from June to December 2014. Adult HIV/AIDS positive patients from "CAPASITS" in Leon, Mexico, from both sexes were included. A questionnaire was performed that included: identification data, and risk factors related to anogenital condylomas. Anogenital area was examined for condylomas. Descriptive statistics were carried out according to the type and distribution of the variables, and the CD4 lymphocyte medians of patients with and without condylomas were compared using U- Mann-Whitney test. RESULTS: A total of 213 HIV/AIDS patients were included; 181 (85%) were male. The prevalence of anogenital condylomas was 30% (IC95%: 23-36%), predominating in the anal region, observed in 21% of the cases. A significant difference was found between median CD4 cell count of patients with and without condylomas (425 vs 510 CD4/mL, p= 0.034). CONCLUSION: A high prevalence of patients with anogenital condylomas was obtained. The presence of condylomas was higher in patients with lower CD4 count. Considering the high prevalence, the application of the vaccine is recommended in this patient group.

Genetic variation in CCR2 and CXCL12 genes impacts on CD4 restoration in patients initiating cART with advanced immunesupression.

OBJECTIVE: We investigated the association of genetic polymorphisms in chemokine and chemokine receptor genes with poor immunological recovery in HIV patients starting combined antiretroviral therapy (cART) with low CD4 T-cell counts. METHODS: A case-control study was conducted in 412 HIV-infected patients starting cART with CD4 T-cell count <200 cells/µL and successful viral control for two years. CD4 count increase below 200 cells/µL after two years on cART was used to define INR (immunological non-responder) patients. Polymorphisms in CXCL12, CCL5 and CCR2 genes were genotyped using sequenom's MassARRAY platform. RESULTS: Thirty two percent (134/412) of patients were classified as INR. After adjusting by age, route of HIV infection, length of infection before cART and viral hepatitis coinfection, CCR2 rs1799864-AG genotype was significantly associated with INR status (OR [95% CI]: 1.80 [1.04-3.11]; p = 0.04), and CXCL12 rs1801157-TT genotype showed a trend (OR [95% CI]: 2.47 [0.96-6.35]; p = 0.06). CONCLUSIONS: CCR2 rs1799864-AG or CXCL12 rs1801157-TT genotypes influence on the probability of poor CD4 recovery in the population of HIV patients starting cART with low CD4 counts. Genotyping of these polymorphisms could be used to estimate the risk of poor CD4 restoration, mainly in patients who are diagnosed late in the course of infection.

Association of Retinal Nerve Fiber Layer Thickness With Brain Alterations in the Visual and Limbic Networks in Elderly Adults Without Dementia.

Importance: The eye is a sensory organ that is easily accessible for imaging techniques, allowing the measurement of the retinal nerve fiber layer (RNFL) thickness. The eye is part of the central nervous system, and its neurons may be susceptible to degeneration; therefore, changes in the RNFL thickness may reflect microstructural and volume alterations in the brain. Objective: To explore the association between the peripapillary RNFL thickness and brain alterations in the visual and limbic networks in elderly people without dementia. Design, Setting, and Participants: Cross-sectional analysis of the Three-City/Antioxydants, Lipides Essentiels, Nutrition et Maladies Oculaires (Alienor) Study cohort (April 2009 to December 2010). The dates of analysis were July 2017 to August 2018. The setting was a population-based study in France. The brain volume analysis included 104 participants, and the diffusion tensor imaging analysis included 79 participants. Main Outcomes and Measures: Global RNFL was assessed by spectral-domain optical coherence tomography. Brain volumes were assessed via T1-weighted magnetic resonance imaging by measurement of the global white and gray matter fractions and the hippocampal fraction. Brain microstructural alterations were assessed with diffusion tensor imaging at the level of the posterior thalamic radiations, the limbic system tracts (the fornix and cingulum bundles), and the posterior limb of the internal capsule (control region). Linear regression models adjusted for several confounders were performed. Results: Among a total of 104 participants, the mean (SD) age was 80.8 (3.9) years, and the cohort was 56.7% women (n = 59). The mean (SD) global RNFL thickness was 89.3 (12.9) µm. A thicker RNFL was associated with a greater hippocampal fraction (quantity of increase ß = 0.013; 95% CI, 0.001-0.025 per 10-µm increase in the RNFL thickness) and better diffusion tensor imaging variables in the global cingulum (mean diffusivity ß = -0.007; 95% CI, -0.015 to -0.000) and the hippocampal part of the cingulum (mean diffusivity ß = -0.009; 95% CI, -0.016 to -0.002 and radial diffusivity ß = -0.010; 95% CI, -0.018 to -0.002) and the posterior thalamic radiations (fractional anisotropy ß = 0.008; 95% CI, 0.000-0.017). No significant associations were found with other magnetic resonance imaging volumes or with other diffusion tensor imaging variables. In particular, there was no significant association with the control region of interest. Conclusions and Relevance: Results of this study suggest that in elderly individuals without dementia, a thicker RNFL was associated with better magnetic resonance imaging variables both in a region that included the visual pathways and in regions particularly involved in the neurodegenerative processes of Alzheimer disease.

Peripapillary Retinal Nerve Fiber Layer Thickness and the Evolution of Cognitive Performance in an Elderly Population.

Retinal nerve fiber layer (RNFL) thickness is reduced in Alzheimer's patients. However, whether it is associated with early evolution of cognitive function is unknown. Within 427 participants from the Three-City-Alienor longitudinal population-based cohort, we explored the relationship between peripapillary RNFL thicknesses and the evolution of cognitive performance. RNFL was assessed at baseline by spectral domain optical coherence tomography; cognitive performances were assessed at baseline and at 2 years, with the Mini-Mental State Examination, the Isaacs' set test, and the Free and Cued Selective Reminding Test (FCSRT). Multivariate linear mixed models were performed. The RNFL was not associated with initial cognitive performance. Nevertheless, a thicker RNFL was significantly associated with a better cognitive evolution over time in the free delayed recall (p = 0.0037) and free + cued delayed recall (p = 0.0043) scores of the FCSRT, particularly in the temporal, superotemporal, and inferotemporal segments. No associations were found with other cognitive tests. The RNFL was associated with changes in scores that assess episodic memory. RNFL thickness could reflect a higher risk of developing cognitive impairment over time.

Surveillance of Oseltamivir-Resistant Influenza A(H1N1)pdm09 in Guanajuato State, Mexico from 2009 to 2012.

BACKGROUND: The influenza A(H1N1)pdm09 virus was first identified in Mexico in April 2009, subsequently spreading worldwide. Soon after the WHO declared a pandemic, a series of cases involving oseltamivir-resistant viruses were described, following concerns about the spread of strains resistant to neuraminidase inhibitors that could hamper control measures. To study the prevalence of oseltamivir-resistant influenza A(H1N1)pdm09, we implemented a surveillance program across the state of Guanajuato, Mexico. METHODS: We collected respiratory samples from patients with confirmed infection with influenza A(H1N1)pdm09 virus between 2009 and 2012 in rural and urban regions in Guanajuato, Mexico. Specimens were screened for the H275Y mutation by Sanger sequencing. RESULTS: A total of 1,192 laboratory confirmed influenza A(H1N1)pdm09-positive samples were processed between 2009 and 2012. Using two endpoint real-time polymerase chain reaction, 575 samples were sequenced. Two different clusters, I and II, were identified. The H275Y substitution was found in only one sample from cluster I. CONCLUSIONS: The prevalence of oseltamivir-resistant influenza A(H1N1)pdm09 2009 viruses during the pandemic period and following years was very low in our State.

In vitro killing action of auranofin on Taenia crassiceps metacestode (cysticerci) and inactivation of thioredoxin-glutathione reductase (TGR).

Control of cellular redox homeostasis is a central issue for all living organisms. Glutathione and thioredoxin enzymatic redox systems are the usual mean used to achieve such a control. However, parasitic platyhelminths studied to date possess a nicotinamide adenine dinucleotide phosphate-dependent thioredoxin-glutathione reductase (TGR) as the sole redox control system. Thus, TGR is considered as a potential therapeutic target of parasitic platyhelminths, and based on this assumption, the gold compound auranofin is a potent inhibitor of TGR. The aim of this research was to investigate the effect of auranofin on metacestode (cysticerci) of Taenia crassiceps in culture. Accordingly, the time course for viability and respiration of cysticerci in culture was evaluated in the presence of this compound. After 4 h at 10 microM auranofin, 90% of cysticerci were alive, but respiration activity had declined by 50%. After 12 h, neither survivors nor respiration was detected; a LD(50) for auranofin of 3.8 microM was calculated. Interestingly, crude extracts of cysticerci pretreated with 3 microM auranofin nearly nil TGR activity (IC(50) = 0.6 microM). Zymography for TGR in polyacrylamide gel electrophoresis was conducted because the previously mentioned extracts clearly showed a dose-response inactivation of TGR toward auranofin. The killing of cysticerci by this gold compound is most likely related with TGR inactivation. Therefore, further research on the suitability of auranofin as a therapeutic tool in the treatment of cysticercosis in animals and humans is sustained.

The flavohemoglobin BCFHG1 is the main NO detoxification system and confers protection against nitrosative conditions but is not a virulence factor in the fungal necrotroph Botrytis cinerea.

Flavohemoglobins constitute a group of proteins involved in the metabolism of nitric oxide (NO). Botrytis cinerea was shown to have a single flavohemoglobin coding gene, Bcfhg1. Its expression was developmentally regulated, with maximum expression levels during germination of conidia, and was enhanced very quickly upon exposure to NO of germinating conidia, but not of mycelium growing and branching actively. Expression in planta paralleled the expression pattern during saprophytic growth with maximal expression occurring during the very early stages of the infection process. Bcfhg1 complemented the Saccharomyces cerevisiae yhb1 mutation, indicating that the encoded enzyme has NO dioxygenase activity. Biochemical and functional characterization of DeltaBcfhg1 mutants in comparison with the wild type strain demonstrated that, although BCFHG1 showed a high affinity for its substrate, appeared to represent the main inducible NO detoxification system and conferred protection against nitrosative stress in B. cinerea, the ability of the DeltaBcfhg1 mutant strains to infect different hosts was not affected.

Prospective, randomized, open label trial of Efavirenz vs Lopinavir/Ritonavir in HIV+ treatment-naive subjects with CD4+<200 cell/mm3 in Mexico.

OBJECTIVE: To compare the efficacy of efavirenz (EFV) vs lopinavir/ritonavir (LPV/r) in combination with azidothymidine/lamivudine in antiretroviral therapy naive, HIV+ individuals presenting for care with CD4 counts <200/mm. METHODS: Prospective, randomized, open label, multicenter trial in Mexico. HIV-infected subjects with CD4 <200/mm were randomized to receive open label EFV or LPV/r plus azidothymidine/lamivudine (fixed-dose combination) for 48 weeks. Randomization was stratified by baseline CD4 cell count (< or =100 or >100/mm). The primary endpoint was the percentage of patients with plasma HIV-1 RNA <50 copies/mL at 48 weeks by intention-to-treat analysis. RESULTS: A total of 189 patients (85% men) were randomized to receive EFV (95) or LPV/r (94). Median baseline CD4 were 64 and 52/mm, respectively (P = not significant). At week 48, by intention-to-treat analysis, 70% of EFV and 53% of LPV/r patients achieved HIV-1 RNA <50 copies/mL [estimated difference 17% (95% confidence interval 3.5 to 31), P = 0.013]. The proportion with HIV-1 RNA <400 copies/mL was 73% with EFV and 65% with LPV/r (P = 0.25). Virologic failure occurred in 7 patients on EFV and 17 on LPV/r. Mean CD4 count increases (cells/mm) were 234 for EFV and 239 for LPV/r. Mean change in total cholesterol and triglyceride levels were 50 and 48 mg/dL in EFV and 63 and 116 mg/dL in LPV/r (P = 0.24 and P < 0.01). CONCLUSIONS: In these very advanced HIV-infected ARV-naive subjects, EFV-based highly active antiretroviral therapy had superior virologic efficacy than LPV/r-based highly active antiretroviral therapy, with a more favorable lipid profile.

Mitochondrial DNA: an important female contribution to thoroughbred racehorse performance.

The mitochondrial DNA (mtDNA) molecule, carrying genes encoding for respiratory chain enzymes, is a primary candidate for demonstrating associations between genotype and athletic performance in mammalian species. In humans, variation at seven protein encoding mitochondrial loci has been implicated in influencing fitness and performance characteristics. Although thoroughbred horses are selected for racing ability, there have not been any previous reported associations between genotypes and racecourse performance. The multi-factorial nature of the inheritance of racing ability is an obvious complicating factor. However, mitochondrial gene variation may represent a measurable component contributing to performance variability. Previous population studies of thoroughbreds have shown the existence of D-loop variation. Importantly, we have observed that there is also independent and extensive functional mitochondrial gene variation in the current thoroughbred racehorse population and that significant associations exist between mtDNA haplotype, as defined by functional genes, and aspects of racing performance.

Lingual ulcer as the only sign of recurrent mycobacterial infection in an HIV/AIDS-infected patient.

The report describes an HIV/AIDS patient seen at a referral center in Mexico City, in whom a mycobacterial infection in the oral mucosa, probably tuberculosis (TB) was identified. The purpose is to describe the clinical and histological findings in an HIV-infected patient, who after being treated successfully for tuberculous lymphangitis 4 years ago, presented with a lingual ulcer as the only suggestive sign of recurrence of mycobacterial infection, probably M. tuberculosis. A 39-year-old man seen in the HIV clinic of the Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán" in Mexico City since 1991 for HIV infection. In 1999 the patient developed tuberculous lymphangitis; he was managed with a 4-drug regimen for 12 months, with improvement of local and systemic symptoms. In May of 2003, the patient presented a painful superficial lingual ulcer, 0.7 cm in diameter, well circumscribed, crateriform with slightly elevated, irregular and indurated borders, of 4 months duration. The histopathological examination showed chronic granulomatous inflammation with giant multinucleated cells, suggestive of mycobacterial infection, and recurrence of TB was considered. Rifampin, isoniazide, pyrazinamide, ethambutol and streptomycin were administered. The lingual lesion improved with partial healing at the first week and total remission at 45 days after the beginning of the antituberculous treatment. In June, 2003, the patient began highly active antiretroviral therapy (HAART) that included two NRTIs and one NNRTI. At 7 months of follow-up, the patient remains free of lingual lesions. The particularity of the present case is that the lingual ulcer was the only sign of infection by mycobacteria, suggestive of TB, in an HIV/AIDS patient that probably represented a recurrence of a previous episode.