High mortality in adults hospitalized for active tuberculosis in a low HIV prevalence setting.

BACKGROUND: This study aims to evaluate the outcomes of adults hospitalized for tuberculosis in a higher-income region with low HIV prevalence. METHODS: A retrospective cohort study was conducted on all adults hospitalized for pulmonary and/or extrapulmonary tuberculosis in an acute-care hospital in Hong Kong during a two-year period. Microscopy and solid-medium culture were routinely performed. The diagnosis of tuberculosis was made by: (1) positive culture of M. tuberculosis, (2) positive M. tuberculosis PCR result, (3) histology findings of tuberculosis infection, and/or (4) typical clinico-radiological manifestations of tuberculosis which resolved after anti-TB treatment, in the absence of alternative diagnoses. Time to treatment ('early', started during initial admission; 'late', subsequent periods), reasons for delay, and short- and long-term survival were analyzed. RESULTS: Altogether 349 patients were studied [median(IQR) age 62(48-77) years; non-HIV immunocompromised conditions 36.7%; HIV/AIDS 2.0%]. 57.9%, 16.3%, and 25.8% had pulmonary, extrapulmonary, and pulmonary-extrapulmonary tuberculosis respectively. 58.2% was smear-negative; 0.6% multidrug-resistant. 43.4% developed hypoxemia. Crude 90-day and 1-year all-cause mortality was 13.8% and 24.1% respectively. 57.6% and 35.8% received 'early' and 'late' treatment respectively, latter mostly culture-guided [median(IQR) intervals, 5(3-9) vs. 43(25-61) days]. Diagnosis was unknown before death in 6.6%. Smear-negativity, malignancy, chronic lung diseases, and prior exposure to fluoroquinolones (adjusted-OR 10.6, 95%CI 1.3-85.2) delayed diagnosis of tuberculosis. Failure to receive 'early' treatment independently predicted higher mortality (Cox-model, adjusted-HR 1.8, 95%CI 1.1-3.0). CONCLUSIONS: Mortality of hospitalized tuberculosis patients is high. Newer approaches incorporating methods for rapid diagnosis and initiation of anti-tuberculous treatment are urgently required to improve outcomes.

Childhood tuberculosis in southern Taiwan, with emphasis on central nervous system complications.

BACKGROUND/PURPOSE: Childhood tuberculosis (TB) continues to be a major public health problem in Taiwan. Taiwan remains a highly endemic area despite neonatal Bacillus Calmette-Guérin (BCG) vaccination and the availability of anti-TB therapy. The presentation is highly variable and it is often difficult to make an accurate diagnosis. This study was designed to evaluate the demographic, clinical, and laboratory findings and outcomes of TB in children with emphasis on central nervous system (CNS) complications. METHODS: The medical records of 80 children diagnosed with TB at a medical center in southern Taiwan over the past 24 years (1988-2012) were reviewed. RESULTS: Among them, 48.8% (39/80) had pulmonary TB, 27.5% (22/80) had isolated extrapulmonary TB, and 23.7% (19/80) had disseminated TB. Most infected cases were aged either < 4 years or > 12 years. TB contact history was found in 42.5% (34/80) cases. Fourteen (17.5%) of the cases had CNS involvement. The most common presentations were fever (85.7%), signs of increased intracranial pressure (71.4%), drowsiness (64.3%), and focal neurological signs (57.1%). The major radiological findings were tuberculoma (50%), basilar enhancement (41.6%), infarction (41.6%), hydrocephalus (16.6%), and transverse myelitis (16.6%). The case fatality of CNS TB was 14.3% and 21.4% had neurologic sequelae. CONCLUSION: Findings suggest that positive exposure history and suspicious clinical presentations are important clues for further confirmatory laboratory and image studies in childhood TB. CNS TB usually presented as part of disseminated TB in children. Early diagnosis and treatment may lead to favorable outcomes in CNS TB.

Tuberculosis infections of the central nervous system.

The causative agent of Tuberculosis meningitis is Mycobacterium tuberculosis, which is the bacteria that causes pulmonary tuberculosis. Proliferating into the central nervous system occurs from other sites of infection within the body. Brain damage can result from the infection that may lead to abnormal behavior, mental impairments, motor type paralysis, and seizures. Tuberculosis infections of the central nervous system are a serious and often fatal disease predominantly impacting young children, and is thought to be the most devastating form of the disease. Isoniazid is the only first line bactericidal agent that easily crosses the blood-brain barrier and achieves concentrations in cerebrospinal fluid similar to those in serum. Rifampicin, ethambutol, and streptomycin all penetrate into the cerebrospinal fluid poorly, and even in the setting of meningeal inflammation. As much as one-third of the current world's population may be infected with tuberculosis. Tuberculosis infection of the central nervous system is a serious type of extrapulmonary proliferation of this disease . In developing countries, it has high predominance in children. Pathological manifestations of cerebral tuberculosis occur, of which the most common is tuberculous meningitis, followed by tuberculoma, tuberculous abscess, cerebral miliary tuberculosis, tuberculous encephalopathy, tuberculous encephalitis, and tuberculous arteritis. Brain abscesses of Mycobacterium tuberculosis can induce seizures and coma leading to death and complicated due to multiorgan failure. Rapid diagnosis and early intervention is vital for successful outcome for patients. Further studies are required to understand the proliferation of tuberculosis meningitis in addition to the elucidation of new therapeutic drugs for the successful clinical treatment of this deadly disease.

Prognostic factors predicting a fatal outcome in HIV-negative children with neurotuberculosis.

OBJECTIVE: To identify prognostic factors predicting a fatal outcome in HIV-negative children with neurotuberculosis based on clinical, epidemiological, and laboratory findings. METHOD: The clinical records of all in-patients diagnosed with neurotuberculosis from 1982 to 2005 were evaluated retrospectively. The following prognostic parameters were examined: gender, age, close contact with a tuberculosis-infected individual, vaccination for bacillus Calmette-Guérin, purified protein derivative (PPD) of tuberculin results, concomitant miliary tuberculosis, seizures, CSF results, and hydrocephalus. RESULTS: One hundred forty-one patients diagnosed with neurotuberculosis were included. Seventeen percent of the cases resulted in death. The factors that were correlated with a negative outcome included lack of contact with a tuberculosis-infected individual, negative PPD reaction, coma, and longer hospitalisation time. A multiple logistic regression analysis was performed to identify which of these factors most often resulted in death. CONCLUSION: Coma at diagnosis, lack of tuberculosis contact, and a non-reactive PPD were the most important predictors of fatality in patients with neurotuberculosis.

Prognostic factors predicting a fatal outcome in HIV-negative children with neurotuberculosis / Fatores prognósticos de letalidade da neurotuberculose em crianças HIV-negativas

OBJECTIVE: To identify prognostic factors predicting a fatal outcome in HIV-negative children with neurotuberculosis based on clinical, epidemiological, and laboratory findings. METHOD: The clinical records of all in-patients diagnosed with neurotuberculosis from 1982 to 2005 were evaluated retrospectively. The following prognostic parameters were examined: gender, age, close contact with a tuberculosis-infected individual, vaccination for bacillus Calmette-Guérin, purified protein derivative (PPD) of tuberculin results, concomitant miliary tuberculosis, seizures, CSF results, and hydrocephalus. RESULTS: One hundred forty-one patients diagnosed with neurotuberculosis were included. Seventeen percent of the cases resulted in death. The factors that were correlated with a negative outcome included lack of contact with a tuberculosis-infected individual, negative PPD reaction, coma, and longer hospitalisation time. A multiple logistic regression analysis was performed to identify which of these factors most often resulted in death. CONCLUSION: Coma at diagnosis, lack of tuberculosis contact, and a non-reactive PPD were the most important predictors of fatality in patients with neurotuberculosis.

OBJETIVO: Identificar elementos prognósticos para a letalidade da neurotuberculose na criança, a partir das manifestações clínicas, dados epidemiológicos e laboratoriais. MÉTODO: Registros de pacientes internados durante o período de 1982 a 2005 foram retrospectivamente avaliados. Os elementos prognósticos considerados foram: sexo, idade, história de contato íntimo com indivíduo com tuberculose, vacinação com o bacilo de Calmette-Guérin (BCG), teste tuberculínico (PPD), concomitância de tuberculose miliar, convulsões, resultados da análise do LCR e presença de hidrocefalia. RESULTADOS: 141 pacientes com diagnóstico de neurotuberculose foram incluídos. Dezessete por cento dos pacientes foram a óbito. Os fatores associados ao óbito foram história negativa de contágio, ausência de reatividade ao teste de PPD, coma e tempo de internação prolongado. Análise por regressão logística múltipla foi usada para investigar as relações entre os elementos prognósticos e o desfecho óbito. CONCLUSÃO: Os fatores prognósticos na previsão de óbito nos pacientes com neurotuberculose foram a presença de coma no momento do diagnóstico, a ausência de história de contágio e a ausência de reação ao PPD.

Treatment outcome of neuro tuberculosis patients put on DOTS--an observation study from the field.

BACKGROUND: Effectiveness of intermittent Short Course Chemotherapy for Neuro Tuberculosis has not been well studied. There are only few reported studies on this issue in the world literature under filed conditions. Neurologists all over India are reluctant to accept Directly Observed Treatment Short course for neuro tuberculosis since its introduction in India. AIM: Assessing effectiveness of Revised National TB Control Programme (RNTCP-DOTS) regimens among neuro tuberculosis patients registered under the programme. METHODS: All the neuro tuberculosis patients referred to RNTCP for treatment were included in the study. Study population included only those patients diagnosed at higher centre and referred to RNTCP during the period Jan - Dec 2002, Alappuzha District. Diagnostic Algorithm as per RNTCP guidelines was strictly followed and treatment outcome and follow-up status were taken from tuberculosis register. No pediatric age group was included in the study. RESULTS: A total of 32 cases registered for DOTS regimen were included in the study, of whom 29 completed the treatment and all were asymptomatic at the end of treatment (85%). All patients received treatment as DOTS, but only 70% received actual DOTS. All patients were given nine months intermittent regimen as per RNTCP guidelines. Five patients died during the treatment (14%). This result shows that DOTS under field programme conditions are efficient in curing Neuro Tuberculosis. CONCLUSION: Good result was obtained with intermittent short course chemotherapy under programme conditions in neurotuberculosis.

Mortality associated with central nervous system tuberculosis.

BACKGROUND: Tuberculosis (TB) of the central nervous system (CNSTB) is associated with higher mortality rates than other forms of TB. Epidemiologic associations with and prognostic indicators of CNSTB have not been assessed in a large US population-based study. METHODS: Between 1995 and 2004 and using a population-based active surveillance study, we compared patients with CNSTB to patients with TB affecting sites other than CNS (non-CNSTB) with respect to sociodemographic, clinical and Mycobacterium tuberculosis genotype variables. Risk factors associated with mortality at 180 days were compared between the 2 groups. RESULTS: We enrolled 92 patients with CNSTB and 3570 with non-CNSTB. HIV co-infection was present in 31 (33.7%) of the CNSTB cases. In a Cox proportion hazard model, we found that CNSTB patients who died within 180 days were more likely to be older (HR 1.06, 95% CI 1.02-1.10), have a positive MTB culture from a CNS source (HR 5.11, 95% CI 1.06-24.62) and have hydrocephalus (HR 10.62, 95% CI 3.28-34.36) than patients who survived CNSTB. HIV co-infection association with mortality was not statistically significant (HR 1.74, 95% CI 0.35-8.62). CONCLUSIONS: In our cohort, hydrocephalus was the most important predictor of mortality post-CNSTB diagnosis.

Risk factors for mortality among patients with extrapulmonary tuberculosis at an academic inner-city hospital in the US.

Despite an overall decrease in numbers of tuberculosis (TB) cases in the US, the proportion of extrapulmonary TB cases has increased. The study objective was to determine the most important predictors of all-cause mortality among patients with extrapulmonary TB. A retrospective chart review of adult extrapulmonary TB cases registered between 01/1995 and 12/2001 at Grady Memorial Hospital (a 1,000 bed, public inner-city hospital in Atlanta) was performed. Risk factors for death within 12 months after diagnosis of extrapulmonary TB were identified in multivariate analysis using log-binomial regression model. A total of 212 cases of extrapulmonary TB were identified; 100 (47%) were HIV-infected. The majority of patients were male (68%) and African-American (84%); mean age was 40 years. The most common sites of extrapulmonary TB were: lymph node (26%), pleural (21%), disseminated (20%), and central nervous system (CNS) or meningeal (16%). All-cause mortality rate in patients with extrapulmonary TB was 15% (21% among HIV-seropositive and 9% among HIV-uninfected patients, p = 0.02). In multivariate analysis, independent predictors of mortality included disseminated disease (PR = 4.66, 95% CI 1.93-11.24) and CNS/meningeal extrapulmonary TB (PR = 4.29, 95% CI 1.78-10.33), controlling for HIV infection. Extrapulmonary TB continues to be a persistent problem in the inner city and is associated with high mortality rates, especially among HIV-infected. Disseminated disease and the presence of CNS/meningeal TB are associated with poor prognosis.

CNS tuberculosis: a longitudinal analysis of epidemiological and clinical features.

In a prospective Canadian cohort of 82 764 patients with tuberculosis (TB), the risk of developing central nervous system manifestations of TB (CNS-TB) (1%) was higher among younger, female, Aboriginal and foreign-born persons (P < 0.005), together with an elevated mortality risk (RR 4.23), compared to controls with only pulmonary TB. TB detection was lower in the CNS-TB group (P < 0.005), while the likelihood of being cured was also reduced (P < 0.005). CNS-TB remains a serious complication of TB in the industrialised world.

Tuberculosis of the central nervous system in children: 32 years survey.

AIM: In order to study the impact of clinical and diagnostic parameters on the clinical outcome of children with central nervous system tuberculosis (CNS-TB), we retrospectively reviewed all cases of CNS-TB diagnosed over a 32-year period at the Children's Hospital of Palermo, Italy. METHODS: Data were collected with regard to the clinical, laboratory and demographic characteristics of patients, as well as the results of radiological investigations and data on clinical outcome. In relation to the date of introduction of new diagnostic methods (indirect as well direct) and to the change of treatment periods, the authors compared the clinical outcome of patients admitted prior and after 1984. They also classified the patients into 3 different stages of illness according to the severity of the disease on admission. RESULTS: We identified 80 patients with CNS-TB. The mean age of the children was 3 years with 54% of patients younger than 5 years. The contact source was documented in 40 patients (50%). The mean duration of symptoms prior to admission was 22 days (range 5 days - 3 months). Mantoux skin test was positive on admission in 50 patients (62%). CSF smear microscopy and culture were positive in 29% and 45% of patients respectively. PCR for Mycobacterium tuberculosis introduced in 1994 was positive in 11 out of 13 tested patients. Determination of CSF gdT lymphocytes composition applied in 7 patients shows a predominance of Vg9/Vd2 T lymphocytes. Fifteen subjects (19%) died; 11 (13%) suffered from permanent sequelae. The died children and those with permanent sequelae were younger than the others (p<0.05). Prior to 1984, none of the patients were identified during early stage of illness and 4 out of 37 patients with stage II illness died. After 1985, 44% of children were in stage I and 2 out of 4 patients with stage III died (p<0.05). CONCLUSIONS: Stage of disease and young age are still the decisive factors in the clinical outcome of children with CNS-TB. The availability of new advanced methods has improved the identification of patients with CNS-TB in stage I and therefore the possibility of an early treatment of such patients.

[Cerebromeningeal tuberculosis: 15 pediatric cases]. / Tuberculose cérébroméningée: à propos de 15 cas pédiatriques.

Fifteen patients (9 girls and 6 boys) with different forms of cerebromeningeal tuberculosis (meningitis: 13 cases, tuberculoma: 2 cases) was reported. Their mean age was 6 years (4 months to 14 years). The initial diagnosis was difficult. Half patients had meningism, abnormal mental state and defects signs. The cerebrospinal fluid (CSF) leukocyte count was > 20/mm3, protein > 1 g/l (66%) and glucose < 2.2 mmol/l (80%). BK was isolated in 7 patients. Five patients (33%) died. Major neurological sequelae developed in 5 patients and 5 patients completely recovered. Factors predicting fatal outcome and permanent sequelae were: diagnosis delay, altered level of consciousness, hypotrophy and low glucose level in CSF.

[Central nervous system tuberculosis in children: 2. Treatment and outcome]. / Tuberculose do sistema nervoso central em crianças: 2. Tratamento e evolução.

Neurologic damage is usual after central nervous system (CSN) tuberculosis recovery. Treatment is long, difficult and prone to complications. Many factors are enrolled as prognostic determinants. This study aimed to describe the treatment and outcome of 52 children with CNS tuberculosis of a tertiary pediatric hospital. All of them received standard triple drug regimen, and 41 (78.8%) received corticosteroids as adjunctive therapy. Hydrocephalus was common (28 of 41 tested), but only 8 (15.4%) patients underwent ventricular shunt surgery. Hepatotoxicity to anti tuberculosis drugs occurred in 32 (61.5%) cases, but in only 3 (9.4%) drug substitution was necessary. There were 8 (15.4%) deaths and 24 (46.1%) cases developed neurologic damage after therapy. Patients who did not receive steroids during treatment and those with advanced neurological involvement at diagnosis showed a tendency to worse prognosis.

Tuberculose do sistema nervoso central em crianças: 2. Tratamento e evoluçäo / Central nervous system tuberculosis in children: 2. Treatment and outcome

Sequelas neurológicas näo säo raras após o tratamento da tuberculose do sistema nervoso central (SNC), que é longo, trabalhoso e sujeito a complicações. Vários fatores säo implicados como determinantes de prognóstico. O objetivo deste estudo foi analisar o tratamento e a evoluçäo de 52 crianças com tuberculose do SNC de um hospital pediátrico terciário. A maioria dos pacientes (41 ou 78,8 por cento) utilizou corticosteróides associados ao esquema tríplice. A ocorrência de hidrocefalia foi comum (28 de 41 testados), porém apenas 8 (15,4 por cento) necessitaram de derivaçäo liquórica. Hiponatremia ocorreu em um terço dos casos testados. Hepatotoxicidade ao esquema tríplice aconteceu em 32 casos (61,5 por cento), porém apenas 3 (9,4 por cento) necessitaram de substituiçäo destas drogas. Ocorreram 8 (15,4 por cento) óbitos e 24 (46,1 por cento) casos desenvolveram sequelas ao fim do tratamento. Houve tendência de pior prognóstico entre os pacientes que näo usaram corticosteróides e os que apresentavam doença avançada ao diagnóstico