Managing tuberculous meningitis (TBM) is challenging because of its poor prognosis and the difficulty in making an early diagnosis due to the low sensitivity of cerebrospinal fluid (CSF) polymerase chain reaction (PCR) evaluations. A 75-year-old woman presented with fatigue and multiple enlarged lymph nodes and was initially suspected of having metastatic cancer of unknown primary origin. Differential diagnoses included carcinomatous meningitis, neurosarcoidosis, and TBM, as suggested by the presence of multiple enhancing cerebral nodules. Despite 11 negative PCR evaluations, including nested PCR of CSF and biopsied lymph nodes within the first 3 days of empirical anti-tubercular treatment, TBM was eventually confirmed by CSF cultures 32 days later. This case highlights the need for repeated sampling.

Tuberculosis (TB) is a major global health burden, particularly in developing countries like India. While the most common presentation is pulmonary TB, extrapulmonary TB involving other body systems can also occur, posing diagnostic challenges. We present the case of a 24-year-old immunocompetent man from India who exhibited an uncommon and complex presentation of disseminated extrapulmonary TB. The patient had an asymptomatic brain cavitated lesion, likely tuberculoma, cervical lymphadenopathy, a small subcutaneous collection in the neck, a destructive lytic lesion in the sacrum, and a subcutaneous collection in the left gluteal/paraspinal region, all in the absence of pulmonary involvement. This combination of manifestations has not been previously reported. The presence of cervical lymphadenopathy and a slowly growing subcutaneous abscess were important clues that guided the diagnostic workup. Maintaining a high index of suspicion for TB, even in atypical presentations and immunocompetent individuals, is crucial, particularly in high-TB-burden regions. This case highlights the importance of considering disseminated extrapulmonary TB in the differential diagnosis, even in the absence of pulmonary involvement and typical risk factors. A high index of suspicion, a multidisciplinary approach, and a comprehensive diagnostic workup are essential for the timely recognition and management of these challenging conditions.

The immune system is the body\'s defense system against infection, pathogenic organisms, or foreign bodies. Human immunodeficiency virus (HIV) infection significantly reduces the number of cells involved in the immune system making the infected person prone to a greater number of infections like tuberculosis (TB). HIV infection reduces the CD4 T helper cell count and further replicates within the body. HIV-TB is a major health concern as there is more chance of progression to acquired immunodeficiency syndrome (AIDS) and the emergence of drug-resistant TB. In this case report, we see how the HIV-TB infection affects the body, significantly affecting the morbidity and mortality of the patient.

Epididymal tuberculosis is rare and often presents diagnostic difficulties. It may be indicative of a disseminated form of the infection, which is the case of our patient. A 19-year-old man, with no past medical history, was admitted for a swollen painful left scrotum that had been evolving for 8 months. He had undergone an orchiectomy and the anatomopathological examination was consistent with epididymal tuberculosis. The radiological investigations had revealed other localizations of the infection: lymphatic, pulmonary, parietal and osteoarticular tuberculosis. Anti-tuberculosis therapy was introduced. However, in the 4th month of treatment, the patient developed seizures. A cerebral magnetic resonance imaging was practiced, concluding to cerebral tuberculomas. Anti-tuberculosis treatment was continued associated to an anticonvulsant with a favourable outcome. The originality of our observation resides in the mode of revelation of a disseminated paucisymptomatic tuberculosis, by an epididymal localization, in an immunocompetent patient.

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.

OBJECTIVE: This systematic review aimed to evaluate the published cases with miliary brain lesions and their etiological factors, clinical manifestations, diagnostic procedures, and outcomes.
METHODS: A comprehensive search of PubMed, Scopus, Embase, and Google Scholar was conducted using the specified search strategy. Eligibility criteria included cases with miliary lesions in the brain confirmed through neuroimaging and various diagnostic procedures. The PRISMA guidelines were followed, and the PROSPERO registration number for the protocol is CRD42023445849.
RESULTS: Data from 130 records provided details of 140 patients. Tuberculosis was the primary cause in 93 cases (66.4%), malignancies in 36 cases (25.7%), and other causes accounted for the remaining 11% cases. Tuberculosis patients averaged 35.7 years old, while those with malignancies averaged 55.44 years. Tuberculosis symptoms primarily included fever, headache, and altered sensorium, whereas malignant cases often exhibited progressive encephalopathy, headache, and specific neurological deficits. Distinctive indicators for CNS tuberculosis were choroidal tubercles and paradoxical reactions. Additionally, 63 tuberculosis patients showed miliary lung shadows and 49 had abnormal CSF findings. For the malignancy group, 13 exhibited miliary lung lesions, and 8 had CSF abnormalities. Regarding outcomes, a significant mortality disparity was observed, with 58.3% in the malignancy group, compared to 10.8% in the tuberculosis group and 27.3% in other cases.
CONCLUSIONS: Miliary brain lesions are a crucial imaging abnormality that necessitates prompt work up. In an immunocompromised state, diagnostic possibilities of miliary brain lesions are more varied and often pose a bigger challenge.

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BACKGROUND: Severe combined immunodeficiency disease (SCID) is a rare primary immunodeficiency disease, usually manifest in the first six months of life with failure to thrive, oral thrush, recurrent respiratory infection, and chronic diarrhea.
METHODS: In three male patients, we describe an unusual presentation of SCID. They are an outcome of consanguineous marriage; all received the BCG vaccine at birth. All three cases presented with regional lymphadenopathy at three months, progressing to generalized lymphadenopathy treated with anti-tuberculous. The first and second cases were twins. The first had an uneventful history until 33 months when he developed multiple Suppurative Tuberculous lymphadenitis confirmed by biopsy. The second and the third cases were diagnosed with Disseminated Tuberculosis at 24 months as they developed fever, anemia, weight loss, tuberculous peritonitis, and lymphadenopathy confirmed by biopsy. After investigations, the first case was diagnosed as CD4, CD16 lymphopenic SCID, the second one as CD4, CD8, CD19, CD16 lymphopenic SCID with hypogammaglobulinemia and the third case as CD3, CD4, CD8 lymphopenic SCID with hypogammaglobulinemia. They received anti-Tuberculous medications, prophylactic Trimethoprim/Sulfamethoxazole, and Immunoglobulin infusion. When writing this abstract, the patients were alive and had no other bacterial, viral, or fungal infections. The twins are three years old, and the third case is 30 months old.
CONCLUSIONS: SCID may not exhibit the classical manifestation of recurrent infections. It may present only as a complication of the BCG vaccine, alarming to maintain high susceptibility in such patients, especially in a developing country, specifically in Sudan, where the BCG vaccine is usually given at birth.

Context Tuberculosis (TB) is India\'s major public health problem. The profile of childhood TB in the northeast region of India is still limited. Aim To analyze the clinical, radiological, and bacteriological profiles of children with TB at a tertiary health care facility. Materials and methods A three years retrospective descriptive analysis of children admitted to a tertiary centre with TB before the introduction of cartridge-based nucleic acid amplification test (CBNAAT) for testing. Children below 18 years who were admitted from 2012 to 2014 and were diagnosed with TB were included. Relevant data were extracted in a predesigned format and entered into a Microsoft Excel sheet. Descriptive statistic was used for analysis. The results of variables are given in proportions and means and a Chi-square test was done for the test of significance using Epi-info tools. The study was done after getting ethical approval from the institute. Results A total of 150 children were included in the analysis with a Male: Female ratio of 1.1:1. A majority of the cases were under five years (n=46) and 11 to 15 years old (n=45) with a mean age of 9.3 ± 4.4 years. Fever was a common presentation (70%). Disseminated TB was seen in 31.3%, isolated central nervous system (CNS) TB was found in 30.6%, and all CNS TB with dissemination was found in 46 cases (40.7%) making extra-pulmonary TB a common finding in our study (83.3%). Isolated pulmonary TB was seen in 16.7% and total pulmonary cases along with dissemination was seen in 60 cases (40%). A bacteriological diagnosis was made in 23%. Overall mortality was 9.3%, out of which mortality in CNS TB was 13% with a p-value of 0.004 as compared to mortality other than CNS TB which was significant and mortality in under-five years was significant with a p-value of 0.001. Conclusions Pulmonary and extra-pulmonary were both causes of admission in the pediatric age group. We found that extra-pulmonary TB was the most common cause of admission in children, with CNS manifestation and disseminated TB, being the most common presentations and significant mortality was seen in under-five years and in children diagnosed with CNS TB.

Disseminated tuberculosis is frequently associated with delayed diagnosis and a poorer prognosis.
To describe case series of disseminated TB and diagnosis delay in a low TB burden country during the COVID-19 period.
We consecutively included all patients with of disseminated TB reported from 2019 to 2021 in the reference hospital of the Northern Crown of the Metropolitan Area of Barcelona. We collected socio-demographic information, clinical, laboratory and radiological findings.
We included all 30 patients reported during the study period-5, 9, and 16 in 2019, 2020, and 2021 respectively-20 (66.7%) of whom were male and whose mean age was 41 years. Twenty-five (83.3%) were of non-EU origin. The most frequent system involvement was central nervous system (N = 8; 26.7%) followed by visceral (N = 7; 23.3%), gastro-intestinal (N = 6, 20.0%), musculoskeletal (N = 5; 16.7%), and pulmonary (N = 4; 13.3%). Hypoalbuminemia and anemia were highly prevalent (72 and 77%). The median of diagnostic delay was 6.5 months (IQR 1.8-30), which was higher among women (36.0 vs. 3.5 months; p = 0.002). Central nervous system involvement and pulmonary involvement were associated with diagnostic delay among women. We recorded 24 cured patients, two deaths, three patients with post-treatment sequelae, and one lost-to-follow up. We observed a clustering effect of patients in low-income neighborhoods (p < 0.001).
There was a substantial delay in the diagnosis of disseminated TB in our study region, which might impacted the prognosis with women affected more negatively. Our results suggest that an increase in the occurrence of disseminated TB set in motion by diagnosis delay may have been a secondary effect of the COVID-19 pandemic.