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TB affects around 10.6 million people each year and there are now around 155 million TB survivors. TB and its treatments can lead to permanently impaired health and wellbeing. In 2019, representatives of TB affected communities attending the '1 st International Post-Tuberculosis Symposium´ called for the development of clinical guidance on these issues. This clinical statement on post-TB health and wellbeing responds to this call and builds on the work of the symposium, which brought together TB survivors, healthcare professionals and researchers. Our document offers expert opinion and, where possible, evidence-based guidance to aid clinicians in the diagnosis and management of post-TB conditions and research in this field. It covers all aspects of post-TB, including economic, social and psychological wellbeing, post TB lung disease (PTLD), cardiovascular and pericardial disease, neurological disability, effects in adolescents and children, and future research needs.

Introduction: Hydrocephalus occurs in 85% of patients with tuberculous meningitis (TBM). Ventriculoperitoneal shunt (VPS) insertion is first-line treatment for relieving increased intercranial pressure. VPS obstruction secondary to increased protein levels in cerebrospinal fluid (CSF) is a known complication., Objective: To ascertain if there is a difference in protein levels 1) between cranial and lumbar CSF, and to quantify levels associated with VPS obstruction, and 2) obtained from lumbar puncture vs. ventricular CSF., Method: A 30-year retrospective analysis was undertaken. CSF protein levels were statistically analysed to determine correlation between these levels and VPS obstruction., Results: Of 214 children and 376 adults who underwent VPS insertion for TBM, respectively 27.5% and 25.5% sustained blocked VPS. The mean protein level in CSF collected from the non-obstructed group was 1.76 g/l, compared to 2.94 g/l in the obstructed group. The mean CSF protein level from intraoperative ventricular vs. lumbar puncture samples in the VPS obstruction group was respectively 2.471 g/l and 2.474 g/l., Conclusion: Patients with increased protein levels in CSF are at a high risk of VPS blockage. In these patients, temporary measures should be employed until CSF protein levels decrease.

Background: The diagnosis of tuberculous meningitis (TBM) in children is often delayed, with disastrous consequences. The Integrated Management of Childhood Illness (IMCI) strategy aims to ensure the accurate assessment of ill children using simple yet reliable clinical signs., Methods: We conducted a retrospective observational study of 30 consecutive children aged 3 months to 5 years diagnosed with TBM at Tygerberg Hospital, Cape Town, South Africa. Clinical records were reviewed to assess diagnostic delay and identify IMCI indicators that were present at the time of initial presentation., Results: Six patients (20%) presented with stage I, 6 (20%) with stage II and 18 (60%) with stage III TBM. Recent contact with an adult TB source case was recorded in 21 (70%) cases. The median number of health care visits before hospital admission was 4.0 (range 1-6). At the first health care visit, 21 (70%) had potential TB features and recent contact with an adult household TB source case., Conclusion: Adequate implementation of IMCI clinical indicators is essential to ensure earlier diagnosis and prompt treatment initiation in children with TBM, as the majority of cases present with advanced disease. Recent contact with an adult TB source case is an important consideration.

Background: Bacteriological confirmation of tuberculous meningitis (TBM) is problematic, and rarely guides initial clinical management. A uniform TBM case definition has been proposed for research purposes., Methods: We prospectively enrolled patients aged 3 months to 13 years with meningitis confirmed using cerebrospinal fluid analysis at Tygerberg Hospital, Cape Town, South Africa. Criteria that differentiated TBM from other causes were explored and the accuracy of a probable TBM score assessed by comparing bacteriologically confirmed cases to 'non-TBM' controls., Results: Of 139 meningitis patients, 79 were diagnosed with TBM (35 bacteriologically confirmed), 10 with bacterial meningitis and 50 with viral meningitis. Among those with bacteriologically confirmed TBM, 15 were Mycobacterium tuberculosis culture-positive and 20 were culture-negative but positive on GenoType(®) MTBDRplus or Xpert(®) MTB/RIF; 18 were positive on only a single commercial nucleic acid amplification test. A probable TBM score provided a sensitivity of 74% (95%CI 57-88) and a specificity of 97% (95%CI 86-99) compared to bacteriologically confirmed TBM., Conclusion: A probable TBM score demonstrated excellent specificity compared to bacteriological confirmation. However, 26% of children with TBM would be missed due to the limited accuracy of the case definition. Further prospective testing of an algorithm-based approach to TBM is advisable before recommendation for general clinical practice.

Background: Tuberculous meningitis (TBM) is diagnosed based on a combination of clinical, laboratory and radiological findings, including signs suggestive of tuberculosis (TB) on a standard chest X-ray (CXR)., Methods: We describe the radiological features suggestive of intrathoracic TB in children diagnosed with TBM during a prospective evaluation of TBM suspects seen at Tygerberg Children's Hospital, Cape Town, South Africa., Results: Of 84 children treated for TBM, 31 (37%) had 'definite' TBM, 45 (55%) 'probable' TBM and 8 (9%) 'possible' TBM. In total, 37 (44%) TBM patients had CXR findings suggestive of TB, 9 (11%) with disseminated (miliary) TB. Only 1 in 4.39 children aged ≤3 years with TBM had suggestive CXR findings. The presence of complicated intrathoracic lymph node disease was significantly higher in children aged ≤3 years (OR 21.69, 95%CI 2.73-172.67, P < 0.01). Among 6 human immunodeficiency virus infected children, 3 (50%) had intrathoracic lymphadenopathy., Conclusion: The majority of the children with TBM, including the very young, did not have signs suggestive of TB on CXR.

Background: Early treatment is critical to reducing tuberculous meningitis (TBM) related morbidity and mortality. Diagnosis based on cerebrospinal fluid (CSF) culture is impractical due to slow turnaround times, while microscopy has poor sensitivity. Enhanced detection methods are essential to guide early treatment initiation, especially in vulnerable young children., Methods: We assessed the diagnostic accuracy of the GenoType(®) MTBDRplus and Xpert(®) MTB/RIF assays on CSF collected from paediatric meningitis suspects prospectively enrolled at Tygerberg Hospital, Cape Town, South Africa. Fluorescent auramine-O microscopy, liquid culture for Mycobacterium tuberculosis, GenoType and Xpert assays were performed on all CSF samples., Results: Of 101 meningitis suspects, 55 were diagnosed with TBM and 46 served as non-TBM controls. Using a pre-defined TBM case definition as reference standard, sensitivities and specificities were 4% and 100% for fluorescent microscopy, 22% and 100% for culture, 33% and 98% for GenoType, 26% and 100% for Xpert, 22% and 100% for microscopy and culture combined and 49% and 98% for GenoType and Xpert combined. Culture, GenoType and Xpert combined performed best, with 56% sensitivity and 98% specificity., Conclusion: Although commercial nucleic-acid amplification tests performed on CSF revealed incrementally improved diagnostic accuracy, providing rapid microbiological confirmation, they cannot serve as a rule-out test.

Setting: Tuberculous meningitis (TBM) is a severe complication of tuberculosis (TB) predominantly affecting young children. Early initiation of treatment is important to prevent morbidity and mortality associated with TBM, emphasising the importance of early diagnosis. Among the most promising new methods for diagnosing TB are antigen-detection assays based on the detection of lipoarabinomannan (LAM)., Objective: To evaluate the diagnostic value of a commercial, antigen-capture enzyme-linked immunosorbent assay (ELISA) test based on the detection of LAM in urine for the early diagnosis of TBM in children., Method: A cross-sectional study in which urine samples from paediatric patients with suspected TBM attending the Tygerberg Children's Hospital, Cape Town, South Africa, were tested for LAM., Results: Complete data were available for 50 of 56 patients with suspected TBM. TBM was diagnosed in 21 (42%) patients and excluded in 29 (58%). The LAM ELISA had a sensitivity of 4.8% and a specificity of 93.1%. Serial measurements in the first 2 weeks after treatment initiation did not improve test performance., Conclusion: We have shown that urinary LAM detection was of little value for the diagnosis of TBM in a cohort of paediatric patients with suspected TBM.