215 research outputs found

    Importance of differentiating Mycobaterium bovis in tuberculous meningitis

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    The aim of the article is to describe the principal findings among patients with M.tuberculosis and M. bovis CNS infection. Mycobacterium tuberculosis is one of the most common infectious agents that cause death and neurological sequelae around the world. Most of the complications of CNS TB can be attributed to a delay in the diagnosis. Unfortunately, there are no specific diagnostic tools to support an early diagnosis. Other prognostic factors different from delay in treatment have not been identified. Clinical, radiological and laboratory characteristics were analyzed retrospectively from the medical files of all the patients admitted with the diagnoses of tuberculosis. Of 215 patients admitted with systemic tuberculosis, 64 (30%) had a neurological infection. Positive cultures were found in 54 (84%) cases, 18 (33%) in the CSF and the rest in other fluids or tissues. Adenosin deaminase (ADA) enzyme determination was more sensitive than M. tuberculosis PCR in the CSF for supporting an early diagnosis. In addition to a later clinical stage and treatment lag, positive CSF cultures (P=0.001) and the presence of M. bovis (P=0.020) were prognostic factors for a worse outcome. Neither older age, the presence of tuberculomas versus meningeal enhancement, or HIV co-infection, was associated to a worse prognosis. The isolation of M. bovis subspecies was more common that previously reported, and it was associated to the development of parenchymal lesions (P=0.032) when compared to M. tuberculosis. In this study, positive CSF cultures for M. tuberculosis and further identifying M. bovis species were additional prognostic factors for worse outcome. Positive cultures in systemic fluids other than CSF, even when the patient had no obvious systemic manifestations, and ADA determination in the CSF were noteworthy diagnostic tools for the diagnosis

    rpoB Gene mutations in rifampin-resistant Mycobacterium tuberculosis identified by polymerase chain reaction single-stranded conformational polymorphism.

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    The use of polymerase chain reaction-single-stranded conformational polymorphism (PCR-SSCP) to study rpoB gene mutations in rifampin-resistant (RIFr) Mycobacterium tuberculosis has yielded contradictory results. To determine the sensitivity of this method, we analyzed 35 RIFr strains and 11 rifampin-susceptible (RIFs) strains, using the DNA sequencing of the core region of rpoB for comparison. Of the RIFr, 24 had a PCR-SSCP pattern identical to that of H37Rv; the other 11 had four different patterns. The 11 RIFs had PCR-SSCP patterns identical to that of H37Rv. The sensitivity of the assay was 31.4%; its specificity was 100%. We observed a strong correlation between the degree of resistance and the type of mutation

    Tuberculosis-Related Deaths within a Well-Functioning DOTS Control Program

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    To describe the molecular epidemiology of tuberculosis (TB)-related deaths in a well-managed program in a low-HIV area, we analyzed data from a cohort of 454 pulmonary TB patients recruited between March 1995 and October 2000 in southern Mexico. Patients who were sputum acid-fast bacillus smear positive underwent clinical and mycobacteriologic evaluation (isolation, identification, drug-susceptibility testing, and IS6110-based genotyping and spoligotyping) and received treatment from the local directly observed treatment strategy (DOTS) program. After an average of 2.3 years of follow-up, death was higher for clustered cases (28.6 vs. 7%, p=0.01). Cox analysis revealed that TB-related mortality hazard ratios included treatment default (8.9), multidrug resistance (5.7), recently transmitted TB (4.1), weight loss (3.9), and having less than 6 years of formal education (2). In this community, TB is associated with high mortality rates

    Expression of USP18 and IL2RA is increased in individuals receiving latent tuberculosis treatment with isoniazid

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    Background. The treatment of latent tuberculosis infection (LTBI) in individuals at risk of reactivation is essential for tuberculosis control. However, blood biomarkers associated with LTBI treatment have not been identified. Methods. Blood samples from tuberculin skin test (TST) reactive individuals were collected before and after one and six months of isoniazid (INH) therapy. Peripheral mononuclear cells (PBMC) were isolated, and an in-house interferon-γ release assay (IGRA) was performed. Expression of chemokine ligand 4 (CCL4), chemokine ligand 10 (CXCL10), chemokine ligand 11 (CXCL11), interferon alpha (IFNA), radical S-adenosyl methionine domain-containing 2 (RSAD2), ubiquitin-specific peptidase 18 (USP18), interferon-induced protein 44 (IFI44), interferon-induced protein 44 like (IFI44L), interferon-induced protein tetratricopeptide repeats 1(IFIT1), and interleukin 2 receptor subunit alpha (IL2RA) mRNA levels were assessed by qPCR before, during, and after INH treatment. Results. We observed significantly lower relative abundances of USP18, IFI44L, IFNA, and IL2RA transcripts in PBMC from IGRA-positive individuals compared to levels in IGRA-negative individuals before INH therapy. Also, relative abundance of CXCL11 was significantly lower in IGRA-positive than in IGRA-negative individuals before and after one month of INH therapy. However, the relative abundance of CCL4, CXCL10, and CXCL11 mRNA was significantly decreased and that of IL2RA and USP18 significantly increased after INH therapy, regardless of the IGRA result. Our results show that USP18, IFI44L, IFIT1, and IL2RA relative abundances increased significantly, meanwhile the relative abundance of CCL4, CXCL11, and IFNA decreased significantly after six months of INH therapy in TST-positive individuals. Conclusions. Changes in the profiles of USP18, IL2RA, IFNA, CCL4, and CXCL11 expressions during INH treatment in TST-positive individuals, regardless of IGRA status, are potential tools for monitoring latent tuberculosis treatment

    Epidemiology of Candidemia in Latin America: A Laboratory-Based Survey

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    Background: the epidemiology of candidemia varies depending on the geographic region. Little is known about the epidemiology of candidemia in Latin America.Methods: We conducted a 24-month laboratory-based survey of candidemia in 20 centers of seven Latin American countries. Incidence rates were calculated and the epidemiology of candidemia was characterized.Results: Among 672 episodes of candidemia, 297 (44.2%) occurred in children (23.7% younger than 1 year), 36.2% in adults between 19 and 60 years old and 19.6% in elderly patients. the overall incidence was 1.18 cases per 1,000 admissions, and varied across countries, with the highest incidence in Colombia and the lowest in Chile. Candida albicans (37.6%), C. parapsilosis (26.5%) and C. tropicalis (17.6%) were the leading agents, with great variability in species distribution in the different countries. Most isolates were highly susceptible to fluconazole, voriconazole, amphotericin B and anidulafungin. Fluconazole was the most frequent agent used as primary treatment (65.8%), and the overall 30-day survival was 59.3%.Conclusions: This first large epidemiologic study of candidemia in Latin America showed a high incidence of candidemia, high percentage of children, typical species distribution, with C. albicans, C. parapsilosis and C. tropicalis accounting for the majority of episodes, and low resistance rates.independent medical grant from Pfizer Inc.Univ Fed Rio de Janeiro, Univ Hosp, Rio de Janeiro, BrazilUniv Fed Parana, Hosp Clin, BR-80060000 Curitiba, Parana, BrazilHosp Escuela Tegucigalpa, Tegucigalpa, HondurasHosp Clin Jose San Martin, Buenos Aires, DF, ArgentinaUniv Nacl Colombia, Dept Internal Med, Bogota, ColombiaPontificia Univ Catolica Ecuador, Fac Med, Hosp Vozandes, Quito, EcuadorHosp Vargas de Caracas, Caracas, VenezuelaCtr Med Caracas, Caracas, VenezuelaUniv Chile, Fac Med, Dept Pediat, Hosp Luis Calvo Mackenna, Santiago 7, ChileUniv Desarrollo, Clin Alemana, Dept Med, Infect Dis Unit, Santiago, ChileInst Nacl Ciencias Med & Nutr Salvador Zubiran, Mexico City, DF, MexicoUniv Peruana Cayetano Heredia, Dept Med, Lima, PeruUniversidade Federal de São Paulo, Escola Paulista Med, Div Infect Dis, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Div Infect Dis, São Paulo, BrazilWeb of Scienc

    Analysis of loss to follow-up in 4099 multidrug-resistant pulmonary tuberculosis patients

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    Loss to follow-up (LFU) of 2 consecutive months contributes to the poor levels of treatment success in multidrug-resistant tuberculosis (MDR-TB) reported by TB programmes. We explored the timing of when LFU occurs by month of MDR-TB treatment and identified patient-level risk factors associated with LFU. We analysed a dataset of individual MDR-TB patient data (4099 patients from 22 countries). We used Kaplan–Meier survival curves to plot time to LFU and a Cox proportional hazards model to explore the association of potential risk factors with LFU. Around one-sixth (n=702) of patients were recorded as LFU. Median (interquartile range) time to LFU was 7 (3–11) months. The majority of LFU occurred in the initial phase of treatment (75% in the first 11 months). Major risk factors associated with LFU were: age 36–50 years (HR 1.3, 95% CI 1.0–1.6; p=0.04) compared with age 0–25 years, being HIV positive (HR 1.8, 95% CI 1.2–2.7; p<0.01) compared with HIV negative, on an individualised treatment regimen (HR 0.7, 95% CI 0.6–1.0; p=0.03) compared with a standardised regimen and a recorded serious adverse event (HR 0.5, 95% CI 0.4–0.6; p<0.01) compared with no serious adverse event. Both patient- and regimen-related factors were associated with LFU, which may guide interventions to improve treatment adherence, particularly in the first 11 months

    Surveillance of Candida spp Bloodstream Infections: Epidemiological Trends and Risk Factors of Death in Two Mexican Tertiary Care Hospitals

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    Introduction: Larger populations at risk, broader use of antibiotics and longer hospital stays have impacted on the incidence of Candida sp. bloodstream infections (CBSI).Objective: To determine clinical and epidemiologic characteristics of patients with CBSI in two tertiary care reference medical institutions in Mexico City.Design: Prospective and observational laboratory-based surveillance study conducted from 07/2008 to 06/2010.Methods: All patients with CBSI were included. Identification and antifungal susceptibility were performed using CLSI M27-A3 standard procedures. Frequencies, Mann-Whitney U test or T test were used as needed. Risk factors were determined with multivariable analysis and binary logistic regression analysis.Results: CBSI represented 3.8% of nosocomial bloodstream infections. Cumulative incidence was 2.8 per 1000 discharges (incidence rate: 0.38 per 1000 patient-days). C. albicans was the predominant species (46%), followed by C. tropicalis (26%). C. glabrata was isolated from patients with diabetes (50%), and elderly patients. Sixty-four patients (86%) received antifungals. Amphotericin-B deoxycholate (AmBD) was the most commonly used agent (66%). Overall mortality rate reached 46%, and risk factors for death were APACHE II score >= 16 (OR = 6.94, CI95% = 2.34-20.58, p<0.0001), and liver disease (OR = 186.11, CI95% = 7.61-4550.20, p = 0.001). Full susceptibility to fluconazole, AmBD and echinocandins among C. albicans, C. tropicalis, and C. parapsilosis was observed.Conclusions: the cumulative incidence rate in these centers was higher than other reports from tertiary care hospitals from Latin America. Knowledge of local epidemiologic patterns permits the design of more specific strategies for prevention and preemptive therapy of CBSI.Pfizer Inc.Salvador Zubiran Natl Inst Med Sci & Nutr, Dept Med, Mexico City, DF, MexicoHosp Escuela Tegucigalpa, Tegucigalpa, HondurasUniversidade Federal de São Paulo, Escola Paulista Med, Div Infect Dis, São Paulo, BrazilNatl Canc Inst, Div Infect Dis, Mexico City, DF, MexicoUniv Nacl Colombia, Dept Internal Med, Bogota, ColombiaUniv Peruana Cayetano Heredia, Dept Med, Lima, PeruHosp Vargas Caracas, Caracas, VenezuelaCtr Med Caracas, Caracas, VenezuelaUniv Fed Rio de Janeiro, Univ Hosp, Rio de Janeiro, BrazilUniv Texas Med Sch Houston, Mem Hermann Texas Med Ctr, Dept Med, Houston, TX USAUniv Fed Parana, Hosp Clin, BR-80060000 Curitiba, Parana, BrazilUniv Chile, Fac Med, Hosp Luis Calvo Mackenna, Dept Pediat, Santiago 7, ChileUniv Desarrollo, Clin Alemana, Dept Med, Santiago, ChileHosp Clin Jose San Martin, Infect Dis Unit, Buenos Aires, DF, ArgentinaPontificia Univ Catolica Ecuador, Fac Med, Hosp Vozandes, Quito, EcuadorUniversidade Federal de São Paulo, Escola Paulista Med, Div Infect Dis, São Paulo, BrazilPfizer Inc.: INF-168Web of Scienc
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