Isolated Unilateral Testicular Tuberculosis in a Young, Immunocompetent Patient: A Case Report.

Testicular or epididymal tuberculosis is a rare form of extrapulmonary tuberculosis. Extrapulmonary tuberculosis of any form is very difficult to diagnose by microscopy because it is usually paucibacillary. Therefore, molecular methods play a major role in the diagnosis of extrapulmonary tuberculosis. We present a rare case of unilateral testicular tuberculosis in a 23-year-old immunocompetent patient with no history of contact with a known tuberculosis case. He presented to us with swelling on his testis for one month and a discharging sinus in the left testis for 15 days, along with an intermittent fever for a week. A pus swab from the discharging sinus of the testis was sent to microbiology, where a cartridge-based nucleic acid amplification test (CBNAAT) was done, which detected Mycobacterium tuberculosis complex (MTBC), but resistance to rifampicin was not detected. A line probe assay was also done on the sample for first-line drugs, and no resistance was detected for rifampicin or isoniazid. The patient was started on first-line drugs in the intensive phase, and after the completion of two months of treatment, the patient's discharge stopped and he showed clinical improvement. Being a young patient, if he had not been diagnosed and treated as early as possible, it could have led to infertility. This again emphasizes the importance of molecular methods for the diagnosis of extrapulmonary tuberculosis.

Tuberculosis-targeted next-generation sequencing and machine learning: An ultrasensitive diagnostic strategy for paucibacillary pulmonary tuberculosis and tuberculous meningitis.

BACKGROUND: Existing diagnostic approaches for paucibacillary tuberculosis (TB) are limited by the low sensitivity of testing methods and difficulty in obtaining suitable samples. METHODS: An ultrasensitive TB diagnostic strategy was established, integrating efficient and specific TB targeted next-generation sequencing and machine learning models, and validated in clinical cohorts to test plasma cfDNA, cerebrospinal fluid (CSF) DNA collected from tuberculous meningitis (TBM) and pediatric pulmonary TB (PPTB) patients. RESULTS: In the detection of 227 samples, application of the specific thresholds of CSF DNA (AUC = 0.974) and plasma cfDNA (AUC = 0.908) yielded sensitivity of 97.01 % and the specificity of 95.65 % in CSF samples and sensitivity of 82.61 % and specificity of 86.36 % in plasma samples, respectively. In the analysis of 44 paired samples from TBM patients, our strategy had a high concordance of 90.91 % (40/44) in plasma cfDNA and CSF DNA with both sensitivity of 95.45 % (42/44). In the PPTB patient, the sensitivity of the TB diagnostic strategy yielded higher sensitivity on plasma specimen than Xpert assay on gastric lavage (28.57 % VS. 15.38 %). CONCLUSIONS: Our TB diagnostic strategy provides greater detection sensitivity for paucibacillary TB, while plasma cfDNA as an easily collected specimen, could be an appropriate sample type for PTB and TBM diagnosis.

Diagnostic value of tNGS vs Xpert MTB/RIF in childhood TB.

Objectives: To evaluate the diagnostic value of targeted next generation sequencing (tNGS) in childhood tuberculosis (TB) and compare the accuracy with Xpert MTB/RIF method. Methods: Children aged ≤18 years with symptoms suggestive of TB during July 2021 to December 2022 at Beijing Children's Hospital were included, and the performances of tNGS and Xpert were evaluated. Results: A total of 103 children with suspected TB were recruited, including 72 discharge diagnosis of TB and 31 non-TB cases. The mean age was 7.37 ± 4.77 years, and 62.1 % were male. The most common type of specimens was gastric aspirate (GA) (59, 57.3 %). Among all the 72 TB patients, tNGS showed higher sensitivity than Xpert, but the difference was not significant (34.7 %, 25/72 vs 20.8 %, 15/72; P = 0.063). The specificities of tNGS and Xpert were 87.1 % (27/31) and 96.8 % (30/31), respectively (P = 0.162). Among different types of specimen, the highest sensitivity of tNGS on sputum and pus was observed (80.0 %, 4/5), followed by pleural effusion (50.0 %, 2/4). One rifampin resistance and one protionamide resistance were detected in bacteriologically confirmed TB by tNGS. Conclusion: tNGS had a higher sensitivity but lower specificity compared to Xpert in diagnosis of children TB. tNGS yielded higher sensitivity than Xpert on gastric aspirate and sputum and pus.

Comparison of Conventional Methods with Newer Diagnostic Modalities to Detect Genital Tuberculosis in Infertile Women.

Background: Genital tuberculosis is one of the leading causes of female infertility. Paucibacillary nature of the disease in the female genital system often makes its diagnosis difficult. No single test has been able to accurately diagnose genital tuberculosis. In this study we aim to compare conventional diagnostic tests for tuberculosis like Acid Fast Bacilli (AFB) Staining, Lowenstein Jensen (LJ) Culture and Histopathology with newer tests like PCR, MGIT 960, GeneXpert. Methods: This study included 67 infertile women from Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi. They were subjected to detailed history and routine investigations, namely Haemogram, ESR, Mantoux test, Chest X-ray and pelvic ultrasound to look for the findings of tuberculosis. A premenstrual endometrial aspirate was taken and was subjected to the AFB Staining, LJ Culture, Histopathology, PCR, MGIT 960, Gene Xpert, and the test results were compared. Result and Conclusion: 35.8% (24/67) of women were diagnosed with genital tuberculosis using the diagnostic criteria. With culture as the gold standard, the positivity of genital TB was 19.4% (13/67). Majority of infertile patients with low index of suspicion clinically were positive for genital tuberculosis. Therefore, all the patients of infertility should be routinely evaluated for genital tuberculosis. PCR and MGIT 960 have shown promising results in the newer methods. LJ culture and histopathology are still the most reliable and available diagnostic methods. The usefulness of AFB Staining and GeneXpert remains questionable.

Dermoscopy and clinicopathology features in diagnosing paucibacillary leprosy: Case series.

A wide variety of leprosy clinical manifestations poses an early diagnostic challenge. Currently, various diagnostic modalities have been developed to optimize the definite diagnostic of leprae. Leprosy diagnosis was established based on the presence of either hypopigmented or reddish skin lesions accompanied with loss of sensation, peripheral nerve involvement, and a positive skin-slit smear (SSS) test result for acid-fast bacilli. Resemblance of leprosy skin lesions to excessively many other differential diagnoses, unclear nerve involvement, and negative results of SSS in paucibacillary (PB) leprosy become a diagnostic veil to clinicians. Furthermore, an additional modality for PB leprosy is needed as an important way to prevent misdiagnoses and complications of leprosy. Commonly, a biopsy or polymerase chain reaction examination is performed to exclude other similarly presenting diseases. Dermoscopy examination, the noninvasive technique that allows a better examination to visualize skin lesions, along with clinicopathology features of skin lesions can help to establish the diagnosis of PB leprosy.

A new droplet digital PCR assay: improving detection of paucibacillary smear-negative pulmonary tuberculosis.

OBJECTIVES: Smear-negative pulmonary TB (PTB) is difficult to diagnose. Current diagnosis and treatment monitoring methods have inherent limitations. Droplet digital PCR (ddPCR) is a new technique with high sensitivity. This study presents a novel ddPCR for rapid and sensitive identification of Mycobacterium tuberculosis (MTB). METHODS: MTB DNA was detected in respiratory specimens from suspected PTB cases using ddPCR assay, which was directed at two different locations within IS6110. We, for the first time, evaluated the clinical diagnostic ability of this ddPCR for paucibacillary smear-negative PTB. RESULTS: A total of 605 PTB suspects were recruited, including 263 patients with confirmed PTB (84.03% from smear-negative PTB) and 342 without PTB. The sensitivity and specificity of IS6110 ddPCR were 61.22% (95% confidence interval (CI) 55.00-67.10%) and 95.03% (95% CI 92.20-97.10%) for total PTB and 57.92% (95% CI 51.10-64.50%) and 94.57% (95% CI 91.20-96.90%) for smear-negative PTB. ddPCR assay outperformed Xpert MTB/RIF (53.08% vs 28.46%, P = 0.020) in smear-negative PTB detection. Furthermore, effective anti-TB treatment was linked to significantly lower IS6110 copies detected by ddPCR. CONCLUSION: Herein, we developed and validated a highly sensitive and robust ddPCR assay for MTB quantification in respiratory specimens, which improves diagnosis and therapeutic effect evaluation of smear-negative PTB.

Utility of RNTCP (NTEP) guidelines in microbiological confirmation of pediatric tuberculosis.

OBJECTIVE: To estimate the proportion of microbiologically confirmed disease among children diagnosed with tuberculosis using RNTCP guidelines. MATERIALS AND METHODS: Retrospective chart review of a cohort of 151 children (aged between 1 month and 18 years) diagnosed with Tuberculosis between December 2016 and June 2020 at a pediatric department of a tertiary care hospital. We collected information on AFB (Acid Fast Bacillus) smear and Cartridge Based Nucleic Acid Amplification Test (CB NAAT) results. RESULTS: Out of 151 children with a diagnosis of Tuberculosis, 66 (44%) children were found to have microbiologically confirmed disease. Confirmatory rate was almost equal in children less than <5 and >5 years (48% vs 52%). Confirmatory rate did not differ between pulmonary and extra pulmonary samples (49% and 53%). Cartridge Based Nucleic Acid Amplification Test outperformed AFB by 10%, which was statistically significant (p = .000 by fisher exact test). CONCLUSION: Although considered paucibacillary in nature, microbiological confirmation can be obtained in almost up to half of children with a diagnosis of TB by using RNTCP guidelines. Neither young age nor type of TB is a deterrent to bacteriologically confirm TB in children.

Utility of Multi-target Nested PCR and ELISPOT Assays for the Detection of Paucibacillary Leprosy: A Possible Conclusion of Clinical Laboratory Misdiagnosis.

The diagnosis of paucibacillary (PB) leprosy often possesses a diagnostic challenge, especially for pure neuritic and lesser skin lesions with the zero bacillary load, requiring a sensitive and accurate diagnostic tool. We have included 300 clinically diagnosed new leprosy cases (comprising 98 PB cases) and analyzed the sensitivity and specificity of PB leprosy cases by nested PCR with folP, gyrA, rpoB, RLEP, and 16SrRNA and Enzyme-linked Immunospot Assay test (ELISPOT) with MMPII, NDO-BSA, and LID-1 antigens by detecting interferon gamma (IFN-γ) release. The overall positivity rates of genes tested in 300 clinical specimens were identified as 55% of 16SrRNA, 59% of RLEP, 59.3% of folP, 57.3% of rpoB, 61% of gyrA while 90% of nested folP, 92.6% of nested rpoB, and 95% of nested gyrA, and 285 (95%) of at least one gene positive cases. For PB specimens, 95% PCR positivity was achieved by three tested genes in nested PCR. The data obtained from ELISPOT for three antigens were analyzed for IFN-γ expression with 600 subjects. Among 98 PB leprosy cases, the sensitivity of MMP II, LID-1, and NDO-BSA was 90%, 87%, and 83%, respectively, and the specificity was 90%, 91%, and 86%, respectively. The total number of cases positive for at least one antigen was 90 (91.8%) in PB, which is significantly higher than that in multibacillary (MB) leprosy (56.7%). The combination of multi-targets nested PCR and ELISPOT assay provides a specific tool to early clinical laboratory diagnosis of PB leprosy cases. The two assays are complementary to each other and beneficial for screening PB patients.

Tween 80 Improves the Acid-Fast Bacilli Quantification in the Magnetic Nanoparticle-Based Colorimetric Biosensing Assay (NCBA).

Despite its reduced sensitivity, sputum smear microscopy (SSM) remains the main diagnostic test for detecting tuberculosis in many parts of the world. A new diagnostic technique, the magnetic nanoparticle-based colorimetric biosensing assay (NCBA) was optimized by evaluating different concentrations of glycan-functionalized magnetic nanoparticles (GMNP) and Tween 80 to improve the acid-fast bacilli (AFB) count. Comparative analysis was performed on 225 sputum smears: 30 with SSM, 107 with NCBA at different GMNP concentrations, and 88 with NCBA-Tween 80 at various concentrations and incubation times. AFB quantification was performed by adding the total number of AFB in all fields per smear and classified according to standard guidelines (scanty, 1+, 2+ and 3+). Smears by NCBA with low GMNP concentrations (≤1.5 mg/mL) showed higher AFB quantification compared to SSM. Cell enrichment of sputum samples by combining NCBA-GMNP, incubated with Tween 80 (5%) for three minutes, improved capture efficiency and increased AFB detection up to 445% over SSM. NCBA with Tween 80 offers the opportunity to improve TB diagnostics, mainly in paucibacillary cases. As this method provides biosafety with a simple and inexpensive methodology that obtains results in a short time, it might be considered as a point-of-care TB diagnostic method in regions where resources are limited.

Xpert MTB/RIF Ultra assay for the detection of Mycobacterium tuberculosis in people with negative conventional Xpert MTB/RIF but chest imaging suggestive of tuberculosis in Dhaka, Bangladesh.

BACKGROUND: The World Health Organization is considering substituting Xpert MTB/RIF (Xpert) with Xpert MTB/RIF Ultra (Ultra) for tuberculosis (TB) diagnosis, but supportive evidence is scarce, particularly among people more likely (presumptive) to have paucibacillary pulmonary TB (PTB). METHODS: During January-July 2018, presumptive PTB patients visiting TB Screening and Treatment Centres of Dhaka for routine chest X-ray (CXR) and conventional Xpert were enrolled. Sputum specimens were additionally tested with microscopy, culture, and Ultra. Specimens with "Trace call" by Ultra (Ultra-trace) were retested. Yield and diagnostic accuracy using various approaches to Ultra-trace and concordance of Ultra with bacteriological-positive PTB were assessed. RESULTS: Altogether, 1,083 participants (104 'Xpert-positive'; 979 'Xpert-negative and CXR-suggestive') were enrolled. All Xpert-positives and 900 (92%) Xpert-negatives were concordant with Ultra, however, seventy-nine (8.1%) Xpert-negative specimens tested positive with Ultra; 37 (46.8%) were categorically positives, and 42 (53.2%) were Ultra-trace. Sixteen of the 42 were retested, of whom eight (50.1%) Ultra-trace turned categorically positive, leading to 45 (4.6%) additionally detected by Ultra. Ultra sensitivity and specificity were 93.9% and 94.6%, and it additionally detected 5.4% more TB patients with a concordance of 94.6% (kappa, □=0.78) compared to any bacteriologically positive specimen (microscopy, culture, or Xpert). CONCLUSION: Ultra exhibited improved detection and accuracy among Xpert-negatives in a cohort with a high likelihood of PTB.

Utility of EBUS-TBNA in diagnosing mediastinal tuberculous lymphadenitis in East London.

OBJECTIVES: To characterise and describe the diagnostic utility of Endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) in intrathoracic tuberculosis in a cohort of patients with mediastinal lymphadenopathy of unknown aetiology. METHODS: Consecutive patients with intrathoracic lymphadenopathy undergoing EBUS-TBNA between 2012 and 2016 were identified. Demographic data, biopsy cytopathology and mycobacteriology results, HIV and vitamin D status, susceptibility results and final diagnoses were recorded. Pre- and post-procedure probability scores were assigned to each case to reflect the probability of tuberculosis. RESULTS: 315 cases were identified; 54 (17.1%) had tuberculosis and 261 (82.9%) had a non-tuberculosis diagnosis. amongst TB cases, the sensitivity of EBUS-TBNA was 59.3% (95% CI 45.06-72.14), specificity 100% (95% CI 98.19-100) and the negative predictive value (NPV) was 92.23% (95% CI 88.31-94.95). 19/54 (35%) TB cases were confirmed by EBUS mycobacterial culture and 13/54 (24.1%) by cytopathology.  33 (61.1%) of the TB cases, had a low to medium pre-test probability score assigned prior to EBUS-TBNA. Amongst EBUS culture-confirmed cases, we found a resistance rate of 10.5% to one or more first line TB drugs, with one case of multi-drug resistant TB. CONCLUSIONS: We confirmed the utility of EBUS-TBNA in the diagnosis of intrathoracic tuberculosis in an undifferentiated cohort of patients with mediastinal lymphadenopathy of unknown aetiology and advocate sending samples for mycobacterial culture in all cases in high tuberculosis incidence areas.

Updates in Pediatric Tuberculosis in International Settings.

Childhood tuberculosis (TB) has been underreported and underrepresented in TB statistics across the globe. Contributing factors include health system barriers, diagnostic barriers, and community barriers leading to an underdetected epidemic of childhood tuberculosis. Despite considerable progress in childhood TB management, there is a concerning gap in policy and practice in high-burden countries leading to missed opportunities for active case detection, early diagnosis and treatment of TB exposure, and infection and disease in children regardless of human immunodeficiency virus status. Bridging this gap requires multisectoral coordination and political commitment along with an eye to research and innovation with potential to scale.

A case report of leprosy reaction combined with bullous pemphigoid after treatment of paucibacillary leprosy / 上海预防医学

ObjectiveTo investigate the clinical characteristics of leprosy-related neuritis with bullous pemphigoid after treatment of paucibacillary leprosy. MethodsThe treatment of leprosy reaction combined with bullous pemphigoid of a cured case of leprosy was analysed. ResultsFive years after standard treatment for leprosy， erythema and vesicles appeared in the limbs without obvious inducement， and the disease became more and more severe. With clinical diagnosis and pathological examination， pemphigoid was confirmed， and the patients were given hormone treatment for leprosy reaction and anti-immunotherapy， as well as symptomatic supportive treatment. ConclusionLeprosy reaction and pemphigoid are both related to immunity， but the occurrence of both at the same time is relatively rare， so in the clinical process we should attach great importance to early detection， early diagnosis and prompt treatment to prevent further harm to the patient.

Abdominal tuberculosis: Clinical profile and outcome.

Background: Tuberculosis (TB) is common form of communicable disease in India. Abdominal TB is one of the most common yet misdiagnosed forms of extrapulmonary TB. It is missed due to its similarity to other conditions such as Crohn's disease and nonspecific clinical presentation. Methods: Medical records of 317 patients who were diagnosed with abdominal TB from August 2015 to December 2020 were reviewed retrospectively from our prospectively maintained database. Results: Among 317 patients, 167 (52.7%) were male. Median age of presentation was 45 (8-85) years. Luminal involvement was seen in most of the patients (n = 157, 49.5%), followed by peritoneal (n = 63, 19.8%), mixed (n = 42, 13.2%), solid visceral (n = 30, 9.4%), and nodal (n = 25, 7.8%) involvement. Two hundred and sixty-one (82.3%) showed complete response. Seven (2.2%) patients died and 5 (1.6%) patients lost to follow-up. Median duration of treatment was 28 (25-52) weeks. Drug-induced liver injury was identified in 30 (9.5%) patients. Median follow-up duration was 32 (1-70) months. Conclusion: Abdominal TB is quite a diagnostic challenge due its vague clinical symptoms, nonspecific radiological features, and poor sensitivity and specificity of diagnostic tests. Hence, clinicians should have a high index of suspicion to diagnose and treat this treatable yet lethal condition promptly. Most cases respond very well to medical management and a small fraction requires surgical intervention if diagnosed early.

Altered cytokine profiles in relapsed paucibacillary leprosy: a case report.

BACKGROUND: Individuals with relapses of leprosy should be monitored carefully, however, with respect to paucibacillary (PB) leprosy, it is sometimes difficult to make a definitive diagnosis of relapse, because the bacillary index is often negative. To evaluate the usefulness of cytokine profiling in a patient with relapsed PB leprosy who tested negative for anti-phenolic glycolipid-I antibodies, we analyzed the Mycobacterium leprae protein-induced cytokine expression in peripheral blood mononuclear cells of the patient. CASE PRESENTATION: An 89-year-old-male relapsed PB patient, first treated for leprosy over 50 years prior, was examined. In April 2012, he noticed three skin lesions consisting of annular erythema in the thighs. Slit skin smear tests were negative, and skin biopsies revealed a pathology of indeterminate-to-borderline tuberculoid leprosy. He received 600 mg of rifampicin once per month and 75 mg of dapsone daily for 12 months. The annular erythemas disappeared after starting treatment. Before treatment, and 6 and 12 months after starting treatment, the Th1/Th2 cytokine profiles in the supernatant of mononuclear cells from the patient before and after stimulation with Mycobacterium leprae soluble protein (MLS) were examined using a Cytometric Bead Array (CBA) Human Th1/Th2 Cytokine Kit II. The CBA Enhanced Sensitivity Flex Set system was applied to detect small amounts of cytokines in the serum just before treatment and one year before relapse. In the culture supernatant, just before treatment, increases in IFN-γ level and the IFN-γ/IL-10 ratio and a decreased IL-6 level were observed without stimulation. Upon stimulation with MLS, just before treatment, both the IFN-γ and TNF levels increased markedly, and twelve months after starting treatment, the IFN-γ and TNF levels decreased greatly. In the serum, just before treatment, increases in IFN-γ and TNF levels and the IFN-γ/IL-10 ratio were evident compared with those measured one year before relapse. CONCLUSIONS: Cytokine profiling using culture supernatants and serum samples may be useful for the diagnosis of relapsed PB leprosy.

Renaissance of Hansen's Disease in Post-Elimination Era in North India: A Retrospective Clinico-Bacteriological Study.

Introduction Hansen's disease is a chronic infectious disease caused by Mycobacterium leprae. India declared the elimination of leprosy in December 2005, but a slow resurgence of the disease still continues in several parts of India. The diagnosis of leprosy is primarily clinical but slit-skin smear microscopy aids in an accurate diagnosis. There are very few studies on clinico-bacteriological patterns of leprosy at this post-elimination phase. Aim This study aimed to analyze the clinical and bacteriological findings of newly diagnosed cases of Hansen's disease in the post-elimination era. Materials and methods This is a descriptive, hospital-based, retrospective study of newly diagnosed cases of Hansen's disease, enrolled in the Hansen's disease clinic attached to the dermatology outpatient department (OPD) of a tertiary care hospital in North India. A retrospective chart review of newly diagnosed cases of leprosy for a period of one year was done. Information about demographics, clinical characteristics, spectrum of disease, and slit skin smear data of patients were collected. Statistical analysis was performed using SPSS Version 16.0 (Chicago, IL, SPSS Inc.). Result A total of 116 patients were included of which 68.1% (79) were males. The age of patients ranged from 7 to 72 years and children (<15 years) constituted 6% (7/116) of all cases. The most common clinical spectrum was borderline lepromatous leprosy 37.9% (44/116) followed by lepromatous leprosy 32.8% (38/116). Out of 116 cases, 39.6% of cases showed slit-skin smear positivity. Conclusion The study brings forth evidence on the slow re-emergence of leprosy in India. In this study, multibacillary cases outnumber the paucibacillary cases; also, childhood cases were encountered indicating active community spread of the disease in the "post-elimination era." There is an urgent need to step up the surveillance for Hansen's disease to curb the further spread of the bacilli in the community.

Diagnostic yield of post-bronchoscopy sputum for diagnosing pauci-bacillary pulmonary tuberculosis.

BACKGROUND: A few studies have mentioned that post-bronchoscopy sputum (PBS) could improve the diagnostic yield in pauci-bacillary pulmonary tuberculosis (PTB). Therefore, we evaluated the diagnostic yield of PBS for diagnosing pauci-bacillaryPTB. METHODS: Clinical data of immunocompromised adult patients with pauci-bacillary PTB were retrospectively retrieved at a tertiary hospital in Seoul, South Korea over a 5-year period. We analyzed patients who underwent bronchoscopy examinations for diagnosing pauci-bacillary PTB. RESULTS: Ninety patients were finally analyzed. Of these patients, 76 patients were tested with PBS. Six (8%) of these patients had positive results on AFB smear of PBS alone. Additionally, 52 patients (68%) had positive results on mycobacterial culture and 12 (16%) had positive results on mycobacterial culture of PBS exclusively. Therefore, in this study population, a total of 18 patients (20%) were finally diagnosed as having PTB with PBS results only, even though AFB smear microscopy and culture of other specimens had negative results. CONCLUSIONS: PBS could improve the diagnostic yield by 20% when diagnosing pauci-bacillary PTB. In addition, about 8% of the patients could be diagnosed rapidly because of AFB smear microscopy positivity for PBS. Therefore, PBS use should be considered as a complementary diagnostic approach in patients with suspected pauci-bacillary PTB.

Clinical profiles and outcomes of pulmonary tuberculosis patients with delayed treatment at a tertiary hospital in South Korea.

BACKGROUND: Data on the clinical characteristics of delayed treatment initiation among pulmonary tuberculosis (TB) patients are lacking. Thus, this study aimed to identify the factors associated with delayed treatment in culture-confirmed pulmonary TB and to assess outcomes of delayed treatment. METHODS: We retrospectively evaluated 151 patients with culture-confirmed pulmonary TB between 2015 and 2017. Delayed and timely treatment was defined as initiation of anti-TB treatment after and before the identification of Mycobacterium tuberculosis complex isolate, respectively. Factors related to delayed treatment, such as comorbidities, clinical presentation, and patterns of initial healthcare use, were collected. We analyzed whether delayed treatment was associated with all-cause mortality using a multivariate binary logistic regression model adjusted for age, sex, cardiovascular disease, and malignancy. RESULTS: In total, 55 (36.4%) patients had delayed treatment. The median length between the first medical visit and treatment initiation was 9 days. Compared with timely treatment, delayed treatment was associated with no initial visit to a non-pulmonary department [adjusted odds ratio (aOR) =10.49, 95% confidence interval (CI), 2.56-42.93] and absence of nucleic acid amplification test (aOR =7.54, 95% CI, 2.75-20.67). After adjusting for age, sex, cardiovascular disease, and solid malignancies, delayed treatment was significantly associated with all-cause mortality (aOR =3.79, 95% CI, 1.36-10.58). The most frequent possible cause of delayed treatment was the doctor's low suspicion of active TB disease. CONCLUSIONS: Given that delayed treatment is associated with worse outcomes in South Korea, targeted interventions to increase awareness on TB in the healthcare community are necessary for additional mycobacterial tests and consults of suspicious patients to TB specialists.

Performance of Xpert MTB/RIF Ultra assay on respiratory and extra-respiratory samples in a high-resource setting with a low tuberculosis prevalence.

The Xpert MTB/RIF assay is a molecular assay that has improved the detection of tuberculosis and rifampicin resistance. However, its sensitivity is limited in patients with paucibacillary disease. Xpert MTB/RIF Ultra has been developed to resolve this limitation. We compared the performance of Xpert Ultra with that of culture for detection of Mycobacterium tuberculosis and rifampicin resistance. We reviewed laboratory records for 848 respiratory and 419 extrarespiratory samples that were processed between April 2018 and October 2019. The sensitivity, specificity, negative predictive value, and positive predictive value of Xpert Ultra were 94.8%, 98%, 98.8%, and 91.3% for respiratory samples and 83.8%, 96.9%, 98.4% and 72.1% for nonrespiratory ones. We found 26 culture-negative/Ultra-positive samples. Most of them have low bacillary burden and more than half belonged to patients with history of tuberculosis. Xpert Ultra demonstrates excellent diagnostic accuracy for tuberculosis detection, including paucibacillary specimens. In patients with history of tuberculosis, PCR results should be interpreted carefully.

Tuberculoid Leprosy Masquerading as Erythema Induratum.

Introduction: Erythema Induratum (EI) is a relatively rare dermatologic disorder affecting subcutaneous fat tissue, which is often associated with Mycobacterium tuberculosis. This report details the presentation, diagnosis and management in a 70-year-old female who presented with a painful erythematous annular rash at the clinic. The rash was later diagnosed as EI associated with Mycobacterium leprae, one rarely seen in literature. Discussion: EI is a rare form of panniculitis that typically presents as a recurrent grouping of tender nodules and plaques on the posterior aspect of the lower legs. Although EI is considered idiopathic in most cases, it can be associated with M. leprae. Given the atypical presentation of a rash, a biopsy was done. It showed epithelioid granulomatous dermatitis with lobar panniculitis. A DNA polymerase chain reaction (PCR) was also sent and revealed the presence of M. leprae. Treatment of EI without association with M. leprae includes potassium iodide, non-steroidal anti-inflammatory drugs (NSAIDs), rest, elevation, compression and, in severe cases, systemic immunosupressives. If tuberculoid leprosy is confirmed, the attending physician is encouraged to consult the infectious disease department as treatment varies with presentation. Conclusions: This case details the diagnosis and management involved in a case of tuberculoid leprosy masquerading as EI. Management of the EI involved NSAIDs and potassium iodide. The leprosy was treated with dapsone and rifampin in conjunction with an infectious disease consultation. Our case highlights the importance of relying on a strong clinical suspicion based on a patient's social history in order to diagnose rare entities accurately.