Outbreak of Fusarium solani Meningitis in Immunocompetent Persons Associated With Neuraxial Blockade in Durango, Mexico, 2022-2023.

Background: Fungal meningitis can be associated with epidural anesthesia procedures. Fusariosis is a rare infection typically affecting immunocompromised patients and rarely causes meningitis. During 2022-2023, public health officials responded to a large outbreak of Fusarium solani meningitis associated with epidural anesthesia in Durango, Mexico. Methods: The public health response and epidemiological and clinical features of patients affected by this outbreak were described. Coordinated actions were addressed to identify the etiological agent, determine its drug susceptibility, develop diagnostic tests, and implement clinical and epidemiological protocols. Retrospective analyses of clinical variables and outcomes were performed to determine association with better patient survival. Results: A total of 1801 persons exposed to epidural anesthesia were identified, of whom 80 developed meningitis. Fusarium solani was found in 3 brain biopsies and showed susceptibility to voriconazole and amphotericin B. After F solani polymerase chain reaction (PCR) implementation, 57 patients with meningitis were PCR-screened, and 31 (38.8%) had a positive result. Most patients were female (95%), and cesarean section was the most common surgical procedure (76.3%). The case fatality rate was 51.3% (41 patients) and the median hospitalization duration was 39.5 days (interquartile range, 18-86 days). Seventy-one patients (88.8%) received voriconazole/amphotericin B and 64 subjects (80%) additionally received steroids. Cox regression analysis showed an increased lethality risk in patients who received antifungal treatment after 5 days (hazard ratio, 2.1 [95% confidence interval, 1.01-4.48], P < .05). Conclusions: The F solani meningitis outbreak in Durango was an unprecedented medical challenge. Timely treatment and effective healthcare management were associated with better survival outcomes.

Fungal Infections in the ICU during the COVID-19 Pandemic in Mexico.

Background: Invasive Fungal Infections (IFI) are emergent complications of COVID-19. In this study, we aim to describe the prevalence, related factors, and outcomes of IFI in critical COVID-19 patients. Methods: We conducted a nested case-control study of all COVID-19 patients in the intensive care unit (ICU) who developed any IFI and matched age and sex controls for comparison (1:1) to evaluate IFI-related factors. Descriptive and comparative analyses were made, and the risk factors for IFI were compared versus controls. Results: We found an overall IFI prevalence of 9.3% in COVID-19 patients in the ICU, 5.6% in COVID-19-associated pulmonary aspergillosis (CAPA), and 2.5% in invasive candidiasis (IC). IFI patients had higher SOFA scores, increased frequency of vasopressor use, myocardial injury, and more empirical antibiotic use. CAPA was classified as possible in 68% and 32% as probable by ECMM/ISHAM consensus criteria, and 57.5% of mortality was found. Candidemia was more frequent for C. parapsilosis Fluconazole resistant outbreak early in the pandemic, with a mortality of 28%. Factors related to IFI in multivariable analysis were SOFA score > 2 (aOR 5.1, 95% CI 1.5-16.8, p = 0.007) and empiric antibiotics for COVID-19 (aOR 30, 95% CI 10.2-87.6, p = <0.01). Conclusions: We found a 9.3% prevalence of IFIs in critically ill patients with COVID-19 in a single center in Mexico; factors related to IFI were associated with higher SOFA scores and empiric antibiotic use for COVID-19. CAPA is the most frequent type of IFI. We did not find a mortality difference.

Bacterial incidence and drug resistance from pathogens recovered from blood, cerebrospinal and pleural fluids in 2019-2020. Results of the Invifar network.

Background: Antimicrobial resistance is a global concern. Analysis of sterile fluids is essential because microorganisms are defined as significant in most cases. Blood, cerebrospinal, and pleural fluids are frequently received in the microbiology lab because they are associated with considerable rates of morbi-mortality. Knowledge of epidemiology in these samples is needed to choose proper empirical treatments due to the importance of reducing selection pressure. Methods: We used retrospective laboratory data of blood, CSF, and pleural fluid collected from patients in Mexico between 2019 and 2020. Each laboratory identified the strains and tested susceptibility using its routine methods. For Streptococcus pneumoniae, a comparative analysis was performed with data from the broth microdilution method. Results: Forty-five centers participated in the study, with 30,746 clinical isolates from blood, 2,429 from pleural fluid, and 2,275 from CSF. For blood and CSF, Staphylococcus epidermidis was the most frequent. For blood, among gram negatives, the most frequent was Escherichia coli. Among Enterobacterales, 9.8% of K. pneumoniae were carbapenem-resistant. For S. pneumoniae, similar resistance percentages were observed for levofloxacin, cefotaxime, and vancomycin. For CSF, the most frequent gram-negative was E. coli. In Acinetobacter baumannii, carbapenem resistance was 71.4%. The most frequent species detected for pleural fluid was E. coli; in A. baumannii, carbapenem resistance was 96.3%. Conclusion: Gram-negative bacteria, with E. coli most prevalent, are frequently recovered from CSF, blood, and pleural fluid. In S. pneumoniae, the routine, conventional methods showed good agreement in detecting resistance percentages for erythromycin, levofloxacin, and vancomycin.

Incidence of cervical intraepithelial lesions and human papilloma virus infection in female renal transplant recipients.

BACKGROUND: Female renal transplant recipients (RTR) are at high risk of human papillomavirus (HPV)-related anogenital premalignancies and cancer. The aim of this study was to estimate the incidence of cervical intraepithelial lesions (IL) and HPV infection, and their associated factors, in Mexican RTR. METHODS: This is a prospective cohort study conducted between January 2011 and December 2017. Demographic, clinical, and gynecological data were collected using a previously designed questionnaire. Gynecological examination, cervical cytology, and detection of high- and low-risk HPV DNA were undertaken prior to and after the renal transplant (RT). Colposcopically guided biopsies were obtained from patients who presented high grade squamous intraepithelial lesions (HSIL) during the follow-up period. Diagnoses were established according to the Bethesda system. RESULTS: Among 130 RTR, 62 were eligible for our study. The overall incidence of IL was 17.7% (95% CI, 8% to 27%), (11/62 patients), at 25.6 ± 10.7 months post-RT. Nine out of the eleven affected patients had low-grade squamous intraepithelial lesions (81.8%) and only two had HSIL (18.2%). The incidence of HPV infection, determined in a subgroup of 30 RTR, was 53.3% (95% CI, 35% to 71%), (16 out of 30 patients), at 18.3 ± 8.9 months post-RT. High-risk HPV genotypes were present in 62.5% of HPV positive cases (10/16). In 11 patients (36.6%), HPV infection was not associated to IL. CONCLUSIONS: HPV infection and cervical IL are common in the early posttransplant period. Our findings support the need of screening for cervical cancer to detect precancerous changes in RTR and the need of strengthening the knowledge of medical personnel on this issue.

Genotyping and spatial analysis of pulmonary tuberculosis and diabetes cases in the state of Veracruz, Mexico.

BACKGROUND: Genotyping and georeferencing in tuberculosis (TB) have been used to characterize the distribution of the disease and occurrence of transmission within specific groups and communities. OBJECTIVE: The objective of this study was to test the hypothesis that diabetes mellitus (DM) and pulmonary TB may occur in spatial and molecular aggregations. MATERIAL AND METHODS: Retrospective cohort study of patients with pulmonary TB. The study area included 12 municipalities in the Sanitary Jurisdiction of Orizaba, Veracruz, México. Patients with acid-fast bacilli in sputum smears and/or Mycobacterium tuberculosis in sputum cultures were recruited from 1995 to 2010. Clinical (standardized questionnaire, physical examination, chest X-ray, blood glucose test and HIV test), microbiological, epidemiological, and molecular evaluations were carried out. Patients were considered "genotype-clustered" if two or more isolates from different patients were identified within 12 months of each other and had six or more IS6110 bands in an identical pattern, or < 6 bands with identical IS6110 RFLP patterns and spoligotype with the same spacer oligonucleotides. Residential and health care centers addresses were georeferenced. We used a Jeep hand GPS. The coordinates were transferred from the GPS files to ArcGIS using ArcMap 9.3. We evaluated global spatial aggregation of patients in IS6110-RFLP/ spoligotype clusters using global Moran´s I. Since global distribution was not random, we evaluated "hotspots" using Getis-Ord Gi* statistic. Using bivariate and multivariate analysis we analyzed sociodemographic, behavioral, clinic and bacteriological conditions associated with "hotspots". We used STATA® v13.1 for all statistical analysis. RESULTS: From 1995 to 2010, 1,370 patients >20 years were diagnosed with pulmonary TB; 33% had DM. The proportion of isolates that were genotyped was 80.7% (n = 1105), of which 31% (n = 342) were grouped in 91 genotype clusters with 2 to 23 patients each; 65.9% of total clusters were small (2 members) involving 35.08% of patients. Twenty three (22.7) percent of cases were classified as recent transmission. Moran`s I indicated that distribution of patients in IS6110-RFLP/spoligotype clusters was not random (Moran`s I = 0.035468, Z value = 7.0, p = 0.00). Local spatial analysis showed statistically significant spatial aggregation of patients in IS6110-RFLP/spoligotype clusters identifying "hotspots" and "coldspots". GI* statistic showed that the hotspot for spatial clustering was located in Camerino Z. Mendoza municipality; 14.6% (50/342) of patients in genotype clusters were located in a hotspot; of these, 60% (30/50) lived with DM. Using logistic regression the statistically significant variables associated with hotspots were: DM [adjusted Odds Ratio (aOR) 7.04, 95% Confidence interval (CI) 3.03-16.38] and attending the health center in Camerino Z. Mendoza (aOR18.04, 95% CI 7.35-44.28). CONCLUSIONS: The combination of molecular and epidemiological information with geospatial data allowed us to identify the concurrence of molecular clustering and spatial aggregation of patients with DM and TB. This information may be highly useful for TB control programs.

Isoniazid Mono-Resistant Tuberculosis: Impact on Treatment Outcome and Survival of Pulmonary Tuberculosis Patients in Southern Mexico 1995-2010.

BACKGROUND: Isoniazid mono-resistance (IMR) is the most common form of mono-resistance; its world prevalence is estimated to range between 0.0 to 9.5% globally. There is no consensus on how these patients should be treated. OBJECTIVE: To describe the impact of IMR tuberculosis (TB) on treatment outcome and survival among pulmonary TB patients treated under programmatic conditions in Orizaba, Veracruz, Mexico. MATERIALS AND METHODS: We conducted a prospective cohort study of pulmonary TB patients in Southern Mexico. From 1995 to 2010 patients with acid-fast bacilli or culture proven Mycobacterium tuberculosis in sputum samples underwent epidemiological, clinical and microbiological evaluation. We included patients who harbored isoniazid mono-resistant (IMR) strains and patients with strains susceptible to isoniazid, rifampicin, ethambutol and streptomycin. All patients were treated following Mexican TB Program guidelines. We performed annual follow-up to ascertain treatment outcome, recurrence, relapse and mortality. RESULTS: Between 1995 and 2010 1,243 patients with pulmonary TB were recruited; 902/1,243 (72.57%) had drug susceptibility testing; 716 (79.38%) harbored pan-susceptible and 88 (9.75%) IMR strains. Having any contact with a person with TB (adjusted odds ratio (aOR)) 1.85, 95% Confidence interval (CI) 1.15-2.96) and homelessness (adjusted odds ratio (aOR) 2.76, 95% CI 1.08-6.99) were associated with IMR. IMR patients had a higher probability of failure (adjusted hazard ratio (HR) 12.35, 95% CI 3.38-45.15) and death due to TB among HIV negative patients (aHR 3.30. 95% CI 1.00-10.84). All the models were adjusted for socio-demographic and clinical variables. CONCLUSIONS: The results from our study provide evidence that the standardized treatment schedule with first line drugs in new and previously treated cases with pulmonary TB and IMR produces a high frequency of treatment failure and death due to tuberculosis. We recommend re-evaluating the optimal schedule for patients harboring IMR. It is necessary to strengthen scientific research for the evaluation of alternative treatment schedules in similar settings.

Impact of cigarette smoking on rates and clinical prognosis of pulmonary tuberculosis in Southern Mexico.

OBJECTIVES: To examine the relationship between cigarette smoking and incidence and mortality rates of pulmonary tuberculosis (TB) and treatment outcomes. MATERIALS: From 1995 to 2010, we analyzed data from 1062 patients with TB and from 2001 to 2004, 2951 contacts in Southern Mexico. Patients with acid-fast bacilli or Mycobacterium tuberculosis in sputum samples underwent epidemiological, clinical and mycobacteriological evaluation and received treatment by the local DOTS program. RESULTS: Consumers of 1-10 (LS) or 11 or more (HS) cigarettes per day incidence (1.75 and 11.79) and mortality (HS, 17.74) smoker-non-smoker rate ratios were significantly higher for smokers. Smoker population was more likely to experience unfavorable treatment outcomes (HS, adjusted OR 2.36) and retreatment (LS and HS, adjusted hazard ratio (HR) 2.14 and 2.37). Contacts that smoked had a higher probability of developing active TB (HR 2.38) during follow up. CONCLUSIONS: Results indicate the need of incorporating smoking prevention and cessation, especially among men, into international TB control strategies.

Association of diabetes and tuberculosis: impact on treatment and post-treatment outcomes.

OBJECTIVE: To determine the clinical consequences of pulmonary tuberculosis (TB) among patients with diabetes mellitus (DM). METHODS: We conducted a prospective study of patients with TB in Southern Mexico. From 1995 to 2010, patients with acid-fast bacilli or Mycobacterium tuberculosis in sputum samples underwent epidemiological, clinical and microbiological evaluation. Annual follow-ups were performed to ascertain treatment outcome, recurrence, relapse and reinfection. RESULTS: The prevalence of DM among 1262 patients with pulmonary TB was 29.63% (n=374). Patients with DM and pulmonary TB had more severe clinical manifestations (cavities of any size on the chest x-ray, adjusted OR (aOR) 1.80, 95% CI 1.35 to 2.41), delayed sputum conversion (aOR 1.51, 95% CI 1.09 to 2.10), a higher probability of treatment failure (aOR 2.93, 95% CI 1.18 to 7.23), recurrence (adjusted HR (aHR) 1.76, 95% CI 1.11 to 2.79) and relapse (aHR 1.83, 95% CI 1.04 to 3.23). Most of the second episodes among patients with DM were caused by bacteria with the same genotype but, in 5/26 instances (19.23%), reinfection with a different strain occurred. CONCLUSIONS: Given the growing epidemic of DM worldwide, it is necessary to add DM prevention and control strategies to TB control programmes and vice versa and to evaluate their effectiveness. The concurrence of both diseases potentially carries a risk of global spreading, with serious implications for TB control and the achievement of the United Nations Millennium Development Goals.

Tuberculosis in ageing: high rates, complex diagnosis and poor clinical outcomes.

BACKGROUND: worldwide, the frequency of tuberculosis among older people almost triples that observed among young adults. OBJECTIVE: to describe clinical and epidemiological consequences of pulmonary tuberculosis among older people. METHODS: we screened persons with a cough lasting more than 2 weeks in Southern Mexico from March 1995 to February 2007. We collected clinical and mycobacteriological information (isolation, identification, drug-susceptibility testing and IS6110-based genotyping and spoligotyping) from individuals with bacteriologically confirmed pulmonary tuberculosis. Patients were treated in accordance with official norms and followed to ascertain treatment outcomes, retreatment, and vital status. RESULTS: eight hundred ninety-three tuberculosis patients were older than 15 years of age; of these, 147 (16.5%) were 65 years of age or older. Individuals ≥ 65 years had significantly higher rates of recently transmitted and reactivated tuberculosis. Older age was associated with treatment failure (OR=5.37; 95% CI: 1.06-27.23; P=0.042), and death due to tuberculosis (HR=3.52; 95% CI: 1.78-6.96; P<0.001) adjusting for sociodemographic and clinical variables. CONCLUSIONS: community-dwelling older individuals participate in chains of transmission indicating that tuberculosis is not solely due to the reactivation of latent disease. Untimely and difficult diagnosis and a higher risk of poor outcomes even after treatment completion emphasise the need for specific strategies for this vulnerable group.

[Research on conventional and molecular epidemiology of tuberculosis in Orizaba, Veracruz, 1995-2008]. / Investigación sobre epidemiología convencional y molecular de tuberculosis en Orizaba, Veracruz, 1995-2008.

This study describes the achievements of the Mexican Consortium against Tuberculosis, in the Sanitary District of Orizaba, Veracruz, Mexico between 1995 and 2008. In brief, the main results can be classified as follows: 1) Conventional and molecular epidemiology (measurement of burden of disease, trends, risk factors and vulnerable groups, consequences of drug resistance, identification of factors that favor nosocomial and community transmission); 2) Development of diagnostic techniques to detect drug resistance, description of circulating clones and adaptation of simple techniques to be used in the field; 3) Evaluation of usefulness of tuberculin skin test, immunologic responses to BCG, impact of directly observed therapy for tuberculosis (DOTS), and study of immunological biomarkers and 4) Comments on ethical aspects of tuberculosis research. Additionally, we describe the impact on public policies, transference of technology, capacity building and future perspectives.

Investigación sobre epidemiología convencional y molecular de tuberculosis en Orizaba, Veracruz, 1995-2008 / Research on conventional and molecular epidemiology of tuberculosis in Orizaba, Veracruz, 1995-2008

Se describen los resultados de investigación del Consorcio Mexicano contra la Tuberculosis, en la Jurisdicción Sanitaria de Orizaba, Veracruz, entre 1995 y 2008. Las aportaciones principales de los trabajos se refieren a los siguientes rubros: 1. Epidemiología convencional y molecular (medición de la carga de la enfermedad, tendencias, factores de riesgo y grupos vulnerables; descripción de las consecuencias de la farmacorresistencia e identificación de factores que favorecen la transmisión en la comunidad y en los hospitales). 2. Desarrollo de técnicas rápidas para conservación de muestras respiratorias que permitan el aislamiento y diagnóstico de farmacorresistencia de M. tuberculosis en campo. 3. Evaluación de la prueba tuberculínica, respuesta inmunológica al Bacilo de Calmette-Guerin (BCG), biomarcadores de la respuesta inmunitaria y medidas de control. 4. Comentarios en torno a aspectos éticos de la investigación en tuberculosis. Además se describe el impacto en políticas públicas, la transferencia de tecnología, la formación de recursos humanos y las perspectivas a futuro.

This study describes the achievements of the Mexican Consortium against Tuberculosis, in the Sanitary District of Orizaba, Veracruz, Mexico between 1995 and 2008. In brief, the main results can be classified as follows: 1) Conventional and molecular epidemiology (measurement of burden of disease, trends, risk factors and vulnerable groups, consequences of drug resistance, identification of factors that favor nosocomial and community transmission); 2) Development of diagnostic techniques to detect drug resistance, description of circulating clones and adaptation of simple techniques to be used in the field; 3) Evaluation of usefulness of tuberculin skin test, immunologic responses to BCG, impact of directly observed therapy for tuberculosis (DOTS), and study of immunological biomarkers and 4) Comments on ethical aspects of tuberculosis research. Additionally, we describe the impact on public policies, transference of technology, capacity building and future perspectives.