BACKGROUND: Ocular tuberculosis (TB) affects 1-2% of patients with TB, with TB uveitis being the most common. This series aims to look at different manifestations of tuberculosis associated uveitis and the different tests used to make a presumptive or definitive diagnosis.
METHODS: Patients diagnosed with TB related uveitis in Hong Kong SAR between 2017 and 2020 were reviewed. Demographics, clinical features, investigations and treatments of patients were collected.
RESULTS: Fifteen eyes in 10 patients with a mean age 57.30 ± 10.17 years were included. The ocular manifestations on presentation included anterior uveitis (50%), posterior uveitis (40%) and panuveitis (10%), where 70% of them were unilateral and 30% were bilaterally infected; on subsequent visits the manifestations further developed into posterior uveitis (40%), panuveitis (40%) and anterior uveitis (20%), where 50% of them were unilateral and 50% bilateral infected. Tuberculosis tests were positive in 5 out of 7 Mantoux tests, 4 out of 4 T-SPOT TB tests, 3 out of 4 QuantiFERON-TB gold tests, 1 out of 1 lymph node biopsy, 0 out of 9 chest x-rays, and no aqueous fluid polymerase chain reaction (PCR) was tested. Vision impairing complications were seen in 6 patients where retinal vasculitis was most commonly seen. With anti-TB treatment prescribed in 9 patients, side effects occurred in 5 patients, including ocular hypertension, disc swelling, and hepatitis.
CONCLUSIONS: Ocular TB infections may manifest in various forms, and can involve different parts of the eye. Bilateral involvement of TB is commonly presented, and both eyes should be evaluated at every follow up. When TB is suspected in a patient, diagnostic confirmation requires multimodal investigations where a negative chest x-ray is not useful in ruling out ocular TB infections, especially in an endemic region like Hong Kong. In these patients, it is crucial to have a high index of suspicion for TB, even when they do not demonstrate classical respiratory signs and symptoms of TB.

UNASSIGNED: Drug-resistant tuberculosis (DR-TB) is a threat to tuberculosis (TB) control. Extra-pulmonary forms of DR-TB (DR-epTB) are not well characterized. This review summarizes the clinical features, resistance patterns and treatment outcomes of DR-epTB.
UNASSIGNED: We searched EMBASE to identify studies that reported drug-resistance among extra-pulmonary TB sites. All age groups were included in this review. Studies which did not describe drug-resistance patterns at extra-pulmonary TB sites were excluded. We summarized the proportion of resistance to individual anti-TB drugs as well as multi-drug resistant (MDR), pre-extensively drug resistant (pre-XDR) and extensively drug-resistant (XDR) TB.
UNASSIGNED: Eighteen studies with a total of 10,222 patients with extra-pulmonary TB of whom 1,236 (12.0%) had DR-epTB, were included in this review. DR-epTB was mostly reported in young people aged 28 to 46 years. While TB meningitis is the most commonly studied form, adenitis is the commonest form of DR-epTB reported in 21% to 47%. Central nervous system TB (3.8% to 51.6%), pleural TB (11.3% to 25.9%), skeletal TB (9.4% to 18.1%), abdominal TB (4.3% to 6.5%), and disseminated TB (3.8%) are also encountered. The HIV co-infection rate is reported to be 5.0% to 81.3% while 2.6% to 25.4 % have diabetes mellitus. Clinical symptoms of DR-epTB are consistent with morbidity in the affected body system. Among patients with DR-epTB, the proportion of MDR TB was 5% to 53% while that for pre-XDR TB and XDR TB was 3% to 40% and 4% to 33%, respectively. Treatment success is achieved in 26% to 83% of patients with DR-epTB while death, treatment loss-to-follow up, and treatment failure occur in 2% to 76%, 7% to 15%, and 0% to 4% respectively. Patients with DR-epTB were reported to have poorer outcomes than those with pulmonary DR-TB and extra-pulmonary drug-susceptible TB.
UNASSIGNED: Clinical features of DR-epTB are similar to those observed among people with drug-susceptible EPTB but patients with DR-epTB post worse treatment outcomes.

BACKGROUND: Although genitourinary Tuberculosis (GUTB) is the second commonest source of extrapulmonary TB in most countries, the reported rate of GUTB in Sri Lanka remains low. The characteristics of GUTB in Sri Lanka have not been studied and documented so far. We aimed to study the clinical and imaging characteristics, treatment modalities and outcome of GUTB in Sri Lanka.
METHODS: Data collected from patients treated by a single urological surgeon in two institutes consecutively over a period of 21 years were analysed. All patients with a microbiological and/or histopathological diagnosis of GUTB were included. Median duration of follow-up was 24 months (range: 6-96).
RESULTS: There were 82 patients and 45 (54.9%) were men. The median age was 51 (range: 26-75) years. Most patients (39%, n = 32) had vague non-specific symptoms at presentation. Common specific symptoms at presentation were haematuria (15.8%, n = 13) and scrotal manifestations (15.8%, n = 13). Mantoux test was done in 70 patients and was > 10 mm in 62 (88.5%). Erythrocyte sedimentation rate was available in 69 patients and was > 30 mm in 54 (78.3%) patients. Chest x-ray and x-ray kidney-ureter-bladder (KUB) abnormalities were detected in 9 (11%) and 6 (7.3%) respectively. CT-urography was performed in 72 patients and abnormalities were detected in 57 (79%) patients. Forty-two patients underwent cystoscopy and 73.8% (n = 31) had abnormal findings. Microbiological diagnosis was feasible in 43 (52.4%) and rest were diagnosed histopathologically. Commonest organs involved were kidney (64.6%, n = 53), ureter (51.2%, n = 42), bladder (43.9%, n = 36) and testis/epididymis (15.8%, n = 13). One patient had TB of the prostate. All were treated primarily with anti-TB drugs however, 50 (61%) required ancillary therapeutic interventions. The majority of interventions were reconstructive surgeries (n = 20, 24.4%) followed by excisional surgeries (n = 19, 23.2%) and drainage procedures (n = 11, 13.4%). Seven patients developed serious adverse reactions to anti-TB drugs. Five patients developed a thimble bladder with disabling storage symptoms. Eight patients had deranged renal functions at diagnosis and three patients developed progressive deterioration of renal function and two patients died of end stage renal disease.
CONCLUSIONS: The combination of urine for acid-fast bacilli, Mantoux test, CT-Urography, cystoscopy and histopathology is necessary to diagnose GUTB in resource-poor settings. Most ureteric strictures, non-functioning kidneys and epididymal masses need surgical treatment. Long-term follow up is essential to detect progressive deterioration of renal function.

Isolated tuberculous dactylitis is a rare form of extra-pulmonary tuberculosis that frequently eludes assessment and constitutes diagnostic challenges. This case reminds physicians of keeping tuberculosis (TB) as a differential when dealing with chronic finger ulcers to avoid devastating consequences.

Matrix metalloproteinases (MMPs) are crucial for tissue remodeling and repair and are expressed in diverse infections, whereas tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors of MMPs. However, the interaction of MMPs and TIMPs in tuberculous lymphadenitis (TBL), an extra-pulmonary form of tuberculosis (EPTB) and helminth (Hel+) coinfection is not known. Therefore, this present study investigates the levels of circulating MMPs (1, 2, 3, 7, 8, 9, 12, 13) and TIMPs (1, 2, 3, 4) in TBL individuals with helminth (Strongyloides stercoralis [Ss], hereafter Hel+) coinfection and without helminth coinfection (hereafter, Hel-). In addition, we have also carried out the regression analysis and calculated the MMP/TIMP ratios between the two study groups. We describe that the circulating levels of MMPs (except MMP-8 and MMP-12) were elevated in TBL-Hel+ coinfected individuals compared to TBL-Hel- individuals. Similarly, the systemic levels of TIMPs (1, 2, 3, 4) were increased in TBL-Hel+ compared to TBL-Hel- groups indicating that it is a feature of helminth coinfection per se. Finally, our multivariate analysis data also revealed that the changes in MMPs and TIMPs were independent of age, sex, and culture status between TBL-Hel+ and TBL-Hel- individuals. We show that the MMP-2 ratio with all TIMPs were significantly associated with TBL-helminth coinfection. Thus, our results describe how helminth infection has a profound effect on the pathogenesis of TBL and that both MMPs and TIMPs could dampen the immunity against the TBL-Hel+ coinfected individuals.

Extra-pulmonary tuberculosis (EPTB), caused by Mycobacterium tuberculosis, is the leading cause of communicable disease-related deaths in people with human immunodeficiency virus (HIV) worldwide and in South Africa. Mycobacterium tuberculosis disseminates haematogenously from an active primary lung focus and may affect extra-pulmonary sites in up to 15% of patients. Extra-pulmonary TB may present with a normal chest radiograph, which often causes a significant diagnostic dilemma. This review describes the main sites of involvement in EPTB, which is illustrated by local imaging examples.

OBJECTIVE: To investigate the possibility of combining tuberculosis (TB)-interferon (IFN)-γ release assays (IGRAs) with lymphocyte enumeration for diagnosis of Mycobacterium tuberculosis infection.
METHODS: We performed a retrospective study of 166 TB patients [68 patients with pulmonary tuberculosis TB (PTB) and 98 patients with extra-pulmonary TB (EPTB)] diagnosed in our hospital between January 2016 and May 2018 along with 377 non-TB patients. The diagnostic performance of the TB-IGRA was evaluated using receiver operating characteristic (ROC) curves. Youden\'s index was used to determine the optimal cut-off threshold.
RESULTS: IFN-γ release in patients with PTB and EPTB were dramatically higher compared with non-TB patients (203.58±18.00 pg/mL, 201.83±14.56 pg/mL and 32.12±4.36 pg/mL, respectively). IFN-γ release was positively correlated with lymphocyte counts and percentages in patients with PTB (r = 0.252 and r = 0.278, respectively) and EPTB (r = 0.229 and r = 0.298, respectively). No correlation was observed in non-TB patients. The area under the ROC curve for TB-IGRA was 0.884. When the optimal cut-off value for IFN-γ (14 pg/mL, Youden\'s index 0.661) was applied, the sensitivity was 88.6% and the specificity was 77.5%.
CONCLUSIONS: Combining TB-IGRA with lymphocyte enumeration was effective for diagnosis of early-stage Mycobacterium tuberculosis infection.

This study was conducted to evaluate the characteristics, treatment outcome and risk factors associated with 223 drug-resistant tuberculosis (DR-TB) cases in the State of Qatar. A descriptive records-based retrospective study was conducted on patients registered at Communicable Disease Centre (CDC), Qatar to all consecutive microbiologically confirmed tuberculosis cases for the period January 2010 - March 2015. Demographic, clinical data, drug-resistance pattern of isolated mycobacteria and treatment outcome was assessed for the patient who completed their treatment in Qatar. Of 3301 patients with positive M. tuberculosis culture were analyzed; 223 (6.7%) were resistant to at least one drug. The overall prevalence of multi-d rug resistant TB (MDR-TB) was 1.2% (n = 38) of patients. A former resident of Indian sub contents was the most common demographic characteristic observed (64.1%). The outcome of treatment was assessed for 85 resistant cases with follow-up after completion of treatment. Cure and relapse rates were 97.6%, and 2.4%, respectively. Drug-resistant TB in Qatar is influenced by migration where the patients were probably infected. Rapid sputum sampling performed in the early stages of the disease, patient isolation, and drug-susceptibility testing should be the standard of care.

BACKGROUND: There were 10 million new cases of tuberculosis (TB) in 2017. To eliminate TB, it is necessary to diagnose active TB and latent tuberculosis infection (LTBI). Diagnosis of paucibacillary disease and in extrapulmonary TB (EPTB) remains challenging; low mycobacterial load can be missed by microbiological or molecular based confirmation; EPTB, can be misdiagnosed due to absence of site specific specimens for testing. Interferon gamma release assays (IGRA) use T cell-based Interferon-gamma (IFN-γ) to identify infection with M. tuberculosis (MTB) but cannot discriminate between active and LTBI. We investigated how IGRA was being used in a high burden low resource setting.
METHODS: We conducted a retrospective review of 149 consecutive cases received for QuantiFERON-TB Gold In-Tube Assay (QFT-GIT) testing in routine clinical service.
RESULTS: Fifty-six cases were QFT-GIT positive and 93 were QFT-GIT negative. Thirty-six per cent of QFT-GIT tested cases had active TB. Of QFT-GIT positive cases, 59% patients had active TB; 10 with pulmonary and 23 with extra-pulmonary TB. The remaining 41% QFT-positive cases were LTBI. Of the QFT-GIT negative cases, 22% had active TB. Co-morbid conditions were present in 37% of QFT-GIT positive and 60% of QFT-GIT negative cases.
CONCLUSIONS: Our study shows that IGRA is being used as an adjunct test for active TB in this population. It highlights the complexity of interpreting QFT-GIT results particularly for QFT-GIT negative cases when ruling out MTB infection.

Background: The diagnostic utility of the Mycobacteria tuberculosis lipoarabinomannan (TB-LAM) antigen lateral flow assay on cerebrospinal fluid (CSF) for the diagnosis of tuberculous meningitis (TBM) has not been extensively studied and the few published studies have conflicting results. Methods: Lumbar CSF from 59 HIV-positive patients with suspected TBM was tested with TB-LAM and Xpert MTB/Rif Ultra. The diagnostic performance of CSF TB-LAM was compared to positive CSF Xpert MTB/Rif Ultra (definite TBM) and a composite reference of probable or definite TBM according to the uniform case definition.  Results: Of 59 subjects, 12 (20%) had definite TBM and five (9%) had probable TBM. With reference to definite TBM, CSF TB-LAM assay had a diagnostic sensitivity of 33% and specificity of 96%. When compared to a composite reference of definite or probable TBM, the sensitivity was 24% and specificity was 95%. There were two false positive tests with TB-LAM (3+ grade). In-hospital mortality in CSF TB-LAM positive patients was 17% compared to 0% in those with definite TBM by Xpert MTB/Rif Ultra but negative LAM. Conclusions: Lumbar CSF TB-LAM has a poor performance in diagnosing TBM. Both urine TB-LAM and Xpert Ultra should be further investigated in the diagnosis of TBM.