BACKGROUND: HIV-associated tuberculosis (TB) contributes disproportionately to global tuberculosis mortality. Patients hospitalised at the time of the diagnosis of HIV-associated disseminated TB are typically severely ill and have a high mortality risk despite initiation of tuberculosis treatment. The objective of the study is to assess the safety and efficacy of both intensified TB treatment (high dose rifampicin plus levofloxacin) and immunomodulation with corticosteroids as interventions to reduce early mortality in hospitalised patients with HIV-associated disseminated TB.
METHODS: This is a phase III randomised controlled superiority trial, evaluating two interventions in a 2 × 2 factorial design: (1) high dose rifampicin (35 mg/kg/day) plus levofloxacin added to standard TB treatment for the first 14 days versus standard tuberculosis treatment and (2) adjunctive corticosteroids (prednisone 1.5 mg/kg/day) versus identical placebo for the first 14 days of TB treatment. The study population is HIV-positive patients diagnosed with disseminated TB (defined as being positive by at least one of the following assays: urine Alere LAM, urine Xpert MTB/RIF Ultra or blood Xpert MTB/RIF Ultra) during a hospital admission. The primary endpoint is all-cause mortality at 12 weeks comparing, first, patients receiving intensified TB treatment to standard of care and, second, patients receiving corticosteroids to those receiving placebo. Analysis of the primary endpoint will be by intention to treat. Secondary endpoints include all-cause mortality at 2 and 24 weeks. Safety and tolerability endpoints include hepatoxicity evaluations and corticosteroid-related adverse events.
CONCLUSIONS: Disseminated TB is characterised by a high mycobacterial load and patients are often critically ill at presentation, with features of sepsis, which carries a high mortality risk. Interventions that reduce this high mycobacterial load or modulate associated immune activation could potentially reduce mortality. If found to be safe and effective, the interventions being evaluated in this trial could be easily implemented in clinical practice.
BACKGROUND: ClinicalTrials.gov NCT04951986. Registered on 7 July 2021 https://clinicaltrials.gov/study/NCT04951986.

Tuberculosis (TB) is the most common and fatal opportunistic co-infection among HIV-infected individuals. While TB-associated mortality predominantly occurs in the first 90 days after admission, such a correlation remains unclear in HIV/TB co-infected patients. Thus, we aimed to investigate the 90-day mortality and associated risk factors among HIV/TB co-infected patients in China.
Adult patients with HIV and a newly confirmed TB diagnosis admitted to the Shanghai Public Health Clinical Center between September 2009 and August 2017 were enrolled. Clinical and laboratory characteristics, key treatments and outcomes were collected retrospectively. The associations between different factors and early mortality were analysed.
Of the 485 laboratory-confirmed HIV/TB patients [median (range) age = 39 (19-79) years], 413 (85.15%) were male. Diagnosis was confirmed by culture, pathology and acid-fast bacilli smear alone in 362 (74.6%), 6 (1.2%) and 117 (24.1%) patients, respectively. Multiple drug-/rifampin-resistant TB was detected in 21 (5.8%) of the 367 patients with a positive culture. Rifampin or rifabutin was administered to 402 (82.9%) patients. Additionally, 66 (13.6%) and 86 (17.7%) died within 90 days and 1 year of admission, respectively. Of the 64 TB-related deaths, 59 (92.2%) occurred within 90 days of admission. In Cox regression, central nervous system (CNS) TB [odds ratio (OR) = 2.49, 95% confidence interval (CI): 1.46-4.23, P < 0.001], no antiretroviral therapy (ART) within 3 months after admission (OR = 11, 95% CI: 6.4-18.9, P < 0.001), and plasma albumin level < 25 g/L (OR = 1.91, 95% CI: 1.07-3.40, P = 0.021) were associated with early death.
Tuberculosis co-infection was prevalent and fatal in HIV-infected patients, with most deaths occurring within 90 days of admission. Early mortality was associated with CNS-TB, no ART, and serum albumin level < 25 g/L.

UNASSIGNED: The main purpose of this study was to describe the demographic and clinical features of cryptic disseminated TB; it was also aimed to shed light on diagnostic test, procedure results, organ involvement, and outcomes of cryptic disseminated TB in patients with confirmed disseminated TB.
UNASSIGNED: We performed a secondary post hoc analysis of collected data from our previous study entitled \"Disseminated Tuberculosis among Adult Patients Admitted to Hamad General Hospital, Qatar: A Five-Year Hospital-Based Study\" with modified objectives. This study included patients admitted from January 1, 2006 to December 31, 2010.
UNASSIGNED: Twenty-three patients were recruited with non-miliary patterns on chest x-ray. Their mean age was 34.4±12.6 years and 15 (65.6%) were males. The mean duration of illness was 46.13±48.4 days and the most common presenting symptom was fever in 20 patients (87%), while 3 (13%) patients had underlying medical conditions with diabetes mellitus 2 (8.7%), being the most common. Bronchoalveolar lavage (BAL) and bronchial wash (BW) fluids were Acid-fast bacilli (AFB) positive in 1/4 (25%) of the cases and culture-positive for Mycobacterium tuberculosis (M. tuberculosis) in 4/4 (100%) of all the cases. Two patients (8.7%) had positive sputum smear, while 18 (78.3%) patients had positive culture for M. tuberculosis. All except one patient completed their treatment in Qatar. One patient died one month after the start of antituberculous treatment.
UNASSIGNED: Cryptic disseminated TB should be suspected when a patient from TB-endemic countries develops unexplained fever and cough despite normal or non-miliary pattern chest radiograph. Moreover, respiratory specimen cultures should be obtained from these patients, regardless of the symptoms presented and the initial site of the involved organ.

UNASSIGNED: RA and its medication, especially TNF-α inhibitors, increase the risk of clinical tuberculosis (TB) infection. We aimed to investigate the clinical manifestations, incidence and temporal changes in TB occurring concurrently with rheumatic diseases (RDs) between 1995 and 2007.
UNASSIGNED: We combined the register of the Social Insurance Institution of Finland and the National Infectious Disease Register to find adult patients with reimbursed DMARDs and with a TB notification between 1995 and 2007. After reviewing the medical records, we described their clinical manifestations and medications, explored TB incidence trends using Poisson regression, and compared the incidence of TB with that of the general population.
UNASSIGNED: We identified 291 patients with both TB and rheumatic disease (RD), 196 of whom had RA. Between 1995 and 2007, the incidence of TB in adult RD decreased from 58.8 to 30.0 per 100 000 (trend P < 0.001, average marginal effect -3.4/100 000 per year, 95% CI -4.4, -2.4). Compared with the general population, the incidence was ∼4-fold. Among RD patients, pulmonary TB was the most common form of TB (72.6%). Disseminated TB was present in 56 (19.6%) patients.
UNASSIGNED: The incidence of TB among RD patients was ∼4-fold that of the general population, and it declined between 1995 and 2007. Disseminated TB was present in nearly 20% of patients.

Computed tomography (CT) of the thorax is the imaging modality of choice to detect or demonstrate lesions suggestive of active pulmonary tuberculosis. We aimed to evaluate the imaging abnormalities detected on CT of the thorax in patients with tuberculous meningitis (TBM).
In this prospective study, we enrolled consecutive newly-diagnosed patients with TBM. Patients were subjected to detailed clinical evaluation and laboratory investigations including MRI of brain and thoracic CT. Patients were administered WHO recommended treatment and followed-up for 6 months. At 6 months, disability assessment was done.
We included 81 patients. Fifty-six patients (69.1%) had abnormalities in CT of thorax. Miliary tuberculosis was seen in 10 (18%) patients. Centrilobular nodules were the commonest parenchymal abnormality seen in 23 (41%) patients. Pleural abnormalities and mediastinal lymphadenopathy were seen in 8 (14%) and 47 (84%) patients, respectively. On multivariate analysis, meningeal enhancement (OR = 3.5, 95%CI 1.2-9.8, P = 0.017) and CBNAAT positivity (OR = 8.7, 95%CI 1.0-73.0, P = 0.045) were independently associated with an abnormal CT of thorax. The sensitivity and specificity of CT thorax in identifying definite cases (CB-NAAT positive) of TBM were found to be 93.33% and 36.36%, respectively. Positive predictive value and negative predictive value of abnormal CT thorax in predicting definite TBM were 25% and 96%, respectively.
CT thorax abnormalities were noted in approximately two-thirds of TBM patients, and were more frequent in definite TBM cases. CT thorax abnormalities helped in upgrading the diagnostic certainty level, in many patients with tuberculous meningitis, from possible to probable.

To investigate the characteristics and associated factors for Mycobacterium tuberculosis (TB) infection in patients with systemic lupus erythematosus (SLE) from Southern China. A retrospective study of 1108 patients admitted to the First Affiliated Hospital of Sun Yat-Sen University from January 2007 to December 2017 was performed. Demographic and clinical characteristics, laboratory data, and radiographic manifestations were recorded. A total of 59 (5.3%) lupus patients with active TB were included. Pulmonary TB occurred in 41 (69.5%) patients. Single lobe involvement was showed in 14 (34.1%) patients. Multi-lobar involvement, including miliary TB (36.6%), was presented in 27 (65.8%) patients. Lower lobe involvement accounted for 31 (75.6%) of the cases. Extrapulmonary TB occurred in 18 (30.5%) patients. Nearly one-third (35.6%) of the patients developed disseminated TB. T-SPOT.TB assay was performed in 23 patients and positive in 18 patients (78.3%). Nineteen patients (32.2%) had co-infection with TB and other pathogens, most of which were bacterial-associated (52.6%). Lymphopenia was predominant in TB-infected patients, especially in those with disseminated TB. Multivariate logistic regression analysis found that lymphopenia [odds ratio (OR) = 2.19, 95% confidence interval (CI) 1.03-4.63, P = 0.04] and the accumulated doses of glucocorticoid (GC) (OR = 2.32, 95% CI 1.69-3.20, P < 0.001) were associated with TB. TB infection is a common comorbidity in patients with SLE. Manifestations of pulmonary computed tomography (CT) scan are relatively atypical. Co-infection with TB and other pathogens is not rare. Lymphopenia and the accumulated doses of GC are associated with TB infection in lupus patients.