Retrospective validation of MetaSystems' deep-learning-based digital microscopy platform with assistance compared to manual fluorescence microscopy for detection of mycobacteria.

This study aimed to validate Metasystems' automated acid-fast bacilli (AFB) smear microscopy scanning and deep-learning-based image analysis module (Neon Metafer) with assistance on respiratory and pleural samples, compared to conventional manual fluorescence microscopy (MM). Analytical parameters were assessed first, followed by a retrospective validation study. In all, 320 archived auramine-O-stained slides selected non-consecutively [85 originally reported as AFB-smear-positive, 235 AFB-smear-negative slides; with an overall mycobacterial culture positivity rate of 24.1% (77/320)] underwent whole-slide imaging and were analyzed by the Metafer Neon AFB Module (version 4.3.130) using a predetermined probability threshold (PT) for AFB detection of 96%. Digital slides were then examined by a trained reviewer blinded to previous AFB smear and culture results, for the final interpretation of assisted digital microscopy (a-DM). Paired results from both microscopic methods were compared to mycobacterial culture. A scanning failure rate of 10.6% (34/320) was observed, leaving 286 slides for analysis. After discrepant analysis, concordance, positive and negative agreements were 95.5% (95%CI, 92.4%-97.6%), 96.2% (95%CI, 89.2%-99.2%), and 95.2% (95%CI, 91.3%-97.7%), respectively. Using mycobacterial culture as reference standard, a-DM and MM had comparable sensitivities: 90.7% (95%CI, 81.7%-96.2%) versus 92.0% (95%CI, 83.4%-97.0%) (P-value = 1.00); while their specificities differed 91.9% (95%CI, 87.4%-95.2%) versus 95.7% (95%CI, 92.1%-98.0%), respectively (P-value = 0.03). Using a PT of 96%, MetaSystems' platform shows acceptable performance. With a national laboratory staff shortage and a local low mycobacterial infection rate, this instrument when combined with culture, can reliably triage-negative AFB-smear respiratory slides and identify positive slides requiring manual confirmation and semi-quantification. IMPORTANCE: This manuscript presents a full validation of MetaSystems' automated acid-fast bacilli (AFB) smear microscopy scanning and deep-learning-based image analysis module using a probability threshold of 96% including accuracy, precision studies, and evaluation of limit of AFB detection on respiratory samples when the technology is used with assistance. This study is complementary to the conversation started by Tomasello et al. on the use of image analysis artificial intelligence software in routine mycobacterial diagnostic activities within the context of high-throughput laboratories with low incidence of tuberculosis.

Nontuberculous mycobacteria testing and culture positivity in the United States.

BACKGROUND: Nontuberculous mycobacteria (NTM) are environmental bacteria which may cause chronic lung disease. The prevalence of NTM pulmonary infection and disease has been increasing in the United States and globally. The predominant clinically relevant species of NTM in the United States are Mycobacterium avium complex (MAC) species and Mycobacterium abscessus. With the development of rapid species identification methods for NTM (e.g. PCR probes), more testing for NTM is being conducted through commercial labs, such as Laboratory Corporation of America (Labcorp), which provides deidentified real-time testing data to the Centers for Disease Control (CDC) pursuant to a data sharing agreement. Because NTM lung infections are not reportable in most states, other data sources are key to understanding NTM testing patterns, positivity rates, and species distributions to track infection trends and identify clinical care needs. METHODS: We obtained national Labcorp data for the period January 2019 through mid-April 2022. We subset the data to only respiratory samples sent for Acid Fast Bacilli (AFB) cultures. NTM positive results were defined as those which identified an NTM species and are not Mycobacterium tuberculosis, Mycobacterium bovis, or Mycobacterium gordonae. RESULTS: Overall, 112,528 respiratory samples were sent for AFB testing during the study period; 26.3% were from the Southeast U.S., identified as HSS Region IV in the Labcorp dataset, and 23.0% were from the Pacific and South Pacific region (Region IX). The culture positive prevalence ranged from 20.2% in the Southeast to 9.2% in the East North Central region (Region V). In the Southeast US, M. abscessus prevalence was 4.0%. For MAC, the highest prevalence was observed in the Mountain region (Region VII) (13.5%) and the lowest proportion was in the East South Central region (7.3%, Region III). Among positive tests, the proportion which was MAC varied from 61.8% to 88.9% and was highest in the Northeast U.S. The proportion of positive samples which were M. abscessus ranged from 3.8% to 19.7% and was highest in the Southeast. CONCLUSIONS: The Southeastern region of the U.S. has the highest rate of culture positivity in Labcorp tests for total NTM and, of all positive tests, the highest proportion of M. abscessus. These estimates may underrepresent the true number of M. abscessus infections because M. absesscus-specific probes are not commercially available and not all NTM testing in the United States is done by Labcorp. Analysis of real-time testing data from commercial laboratories may provide insights into risk factors for NTM culture positivity in 'hotspot' areas.

Pituitary tuberculoma with panhypopituitarism masquerading as a pituitary adenoma.

Tuberculosis of the hypothalamo-pituitary axis is extremely uncommon. The presentation of panhypopituitarism in a case of sellar tuberculosis is an even rarer occurrence. We present a case of a 44-year-old man who presented with complaints of headache and right-sided diminution of vision for six months. A hormone profile showed abnormal anterior pituitary assay suggestive of panhypopituitarism. Magnetic Resonance imaging of the brain showed a sellar mass measuring 1.8 × 1.5 × 1.3 cm with suprasellar extension suggestive of a pituitary adenoma. Histopathological examination showed multiple epithelioid cell granulomas along with Langhans giant cells and mixed inflammatory infiltrates against a necrotic background. Zeihl Neelson stain demonstrated the presence of acid-fast bacilli. Thus, a final diagnosis of pituitary tuberculoma was made, and the patient started on antitubercular therapy. It is extremely important to correctly diagnose sellar tuberculosis as the treatment is entirely different, and the patient usually responds well to therapy.

Clinical and imaging factors that can predict contagiousness of pulmonary tuberculosis.

BACKGROUND: Knowledge on predicting pulmonary tuberculosis (PTB) contagiosity in the hospital admission setting is limited. The objective was to assess clinical and radiological criteria to predict PTB contagiosity. METHODS: Retrospective analysis of 7 clinical, 4 chest X-ray (CXR) and 5 computed tomography (CT) signs in 299 PTB patients admitted to an urban tertiary hospital from 2008 to 2016. If the acid fact bacilli stain was positive (AFB+) on admission, the case was considered high contagiosity. RESULTS: Best predictors for high PTB contagiosity (AFB+) were haemoptysis (OR 4.33), cough (3.00), weight loss (2.96), cavitation in CT (2.75), cavitation in CXR (2.55), tree-in-bud-sign in CT (2.12), German residency of the patient (1.89), and abnormal auscultation findings (1.83). A previous TB infection reduced the risk of contagiosity statistically (0.40). Radiographic infiltrates, miliary picture, and pleural effusion were not helpful in predicting high or low contagiosity. 34% of all patients were clinically asymptomatic (20% of the highly contagious group, 50% of the low contagious group). CONCLUSION: Haemoptysis, cough and weight loss as well as cavitation and tree-in-bud sign in CXR/CT can be helpful to predict PTB contagiosity and to improve PTB management.

Evaluation of MetaSystems Automated Fluorescent Microscopy System for the Machine-Assisted Detection of Acid-Fast Bacilli in Clinical Samples.

Manual reading of fluorescent acid-fast bacilli (AFB) microscopy slides is time-intensive and technically demanding. The aim of this study was to evaluate the accuracy of MetaSystems' automated fluorescent AFB slide scanner and analyzer. Auramine O-stained slides corresponding to 133 culture-positive and 363 culture-negative respiratory (n = 284), tissue (n = 120), body fluid (n = 81), and other (n = 11) sources were evaluated with the MetaSystems Mycobacteria Scanner running the NEON Metafer AFB Module. The sensitivity and specificity of the MetaSystems platform was measured as a standalone diagnostic and as an assistant to technologists to review positive images. Culture results were used as the reference method. The MetaSystems platform failed to scan 57 (11.5%) slides. The MetaSystems platform used as a standalone had a sensitivity of 97.0% (129/133; 95% CI 92.5 to 99.2) and specificity of 12.7% (46/363; 95% CI 9.4 to 16.5). When positive scans were used to assist technologists, the MetaSystems platform had a sensitivity of 70.7% (94/133; 95% CI 62.2 to 78.3) and specificity of 89.0% (323/363; 95% CI 85.3 to 92.0). The manual microscopy method had a sensitivity of 79.7% (106/133; 95% CI 71.9 to 86.2) and specificity of 98.6% (358/363; 95% CI 96.8 to 99.6). The sensitivity of the MetaSystems platform was not impacted by smear grade or mycobacterial species. The majority (70.3%) of false positive smears had ≥2+ smear results with the MetaSystems platform. Further performance improvements are needed before the MetaSystems' automated fluorescent AFB slide reader can be used to assist microscopist in the clinical laboratory.

Evaluation of an AI-Based TB AFB Smear Screening System for Laboratory Diagnosis on Routine Practice.

The most robust and economical method for laboratory diagnosis of tuberculosis (TB) is to identify mycobacteria acid-fast bacilli (AFB) under acid-fast staining, despite its disadvantages of low sensitivity and labor intensity. In recent years, artificial intelligence (AI) has been used in TB-smear microscopy to assist medical technologists with routine AFB smear microscopy. In this study, we evaluated the performance of a TB automated system consisting of a microscopic scanner and recognition program powered by artificial intelligence and machine learning. This AI-based system can detect AFB and classify the level from 0 to 4+. A total of 5930 smears were evaluated on the performance of this automatic system in identifying AFB in daily lab practice. At the first stage, 120 images were analyzed per smear, and the accuracy, sensitivity, and specificity were 91.3%, 60.0%, and 95.7%, respectively. In the second stage, 200 images were analyzed per smear, and the accuracy, sensitivity, and specificity were increased to 93.7%, 77.4%, and 96.6%. After removing disqualifying smears caused by poor staining quality and smear preparation, the accuracy, sensitivity, and specificity were improved to 95.2%, 85.7%, and 96.9%, respectively. Furthermore, the automated system recovered 85 positive smears initially identified as negative by manual screening. Our results suggested that the automated TB system could achieve higher sensitivity and laboratory efficiency than manual microscopy under the quality control of smear preparation. Automated TB smear screening systems can serve as a screening tool at the first screen before manual microcopy.

Effectiveness of inhaled hypertonic saline application for sputum induction to improve Mycobacterium tuberculosis identification in patients with pulmonary tuberculosis.

BACKGROUND: This study assessed the effectiveness and diagnostic significance of hypertonic saline sputum induction for improving Mycobacterium tuberculosis (MTB) detection. METHODS: A prospective, randomized, open, two-arm, comparative study on MTB identification effectiveness when using inhaled sodium chloride hypertonic solution was performed in patients diagnosed with pulmonary tuberculosis (TB). Patients were randomly assigned into two groups: group 1 (inhalation group) included patients who inhaled a 7% sodium chloride solution upon admission to the hospital, and group 2 (control group) coughed up their sputum as usual. For both groups, specimens were tested by bacterioscopic, bacteriological, and molecular genetic methods. Diagnostic chest radiography was performed for all participants. RESULTS: In this study, 644 patients (mean age 42.2 years; 151 women, 23.4%) were randomly divided into two groups. Low-quality sputum samples were observed in 7.4% of patients from the inhalation group and 28.8% in the control group (p < 0.001). Acid-fast bacilli (AFB) smear was positive in 65.1% of patients from the inhalation group and 51.3% of controls (p = 0.002). A similar statistically significant situation was observed when culture methods (93.9% inhalation group and 81.9% control group, p < 0.001) and molecular genetic tests (92.2% inhalation group and 79.4% control group, p < 0.001) were used. Thus, active pulmonary TB was not verified microbiologically in 6.1% of patients from the inhalation group and in 18.1% of controls (p < 0.001). CONCLUSIONS: Hypertonic saline sputum induction improves the quality of collected samples. This method may be appropriate to increase the rate of MTB detection in sputum using microscopic, bacteriological, and molecular genetic methods for diagnosing TB on the day of specimen collection. Hypertonic saline sputum induction is suitable for middle- and low-income countries with limited resources and causes no severe adverse effects in TB patients.

Latent Tuberculosis among Human Immunodeficiency Virus (HIV) Positive Patients: Prevalence and Correlates.

BACKGROUND: Tuberculosis is the most common opportunistic infection affecting HIV-infected individuals and it remains the most common cause of death in patients with AIDS. Detection of latent tuberculosis and treatment largely prevents the development of active disease. OBJECTIVE: This study was to determine the prevalence and factors associated with latent TB in HIV-positive patients. METHODOLOGY: This is an analytical cross-sectional study which involved 160 consented patients. Active tuberculosis was excluded using signs, symptoms and laboratory tests. All participants were tested using Quantiferon TB Gold Plus test kits. Data analysed with SPSS version 25.0 included patient's demographics, clinical and laboratory features. P< 0.05 was considered significant. RESULTS: The mean age of HIV-infected patients was 42.69 ± 9.91 years and the mean age of the control was 41.29 ± 9.20 years with no significant statistical difference. The prevalence of latent tuberculosis among HIV-infected patients was found to be 22.50% while among controls was 10.0% which was statistically significant (p-0.001). CD4 cells count was observed to inversely predict latent tuberculosis (OR = 1.41; CI = 1.01-3.73) while viral load was found to directly predict latent tuberculosis (OR = 1.63; CI=1.04-4.25). CONCLUSION: The prevalence of latent tuberculosis infection is significantly higher among HIV-positive patients when compared with HIV-negative patients. Also, the prevalence of HIV infection was higher amongst the female and less educated population.

CONTEXTE: La tuberculose est l'infection opportuniste la plus courante chez les personnes infectées par le VIHet reste la cause la plus fréquente de décès chez les patients atteints du SIDA. La détection de la tuberculose latente et le traitement empêchent largement le développement de la maladie active. OBJECTIF: Cette étude visait à déterminer la prévalence et les facteurs associés à la tuberculose latente chez les personnes séropositives. MÉTHODOLOGIE: Il s'agit d'une étude transversale analytique qui a porté sur 160 patients consentants. La tuberculose active a été exclue à l'aide de signes, de symptômes et de tests de laboratoire. Tous les participants participants ont été testés à l'aide de kits de test Quantiferon TB Gold Plus. de Quantiferon TB Gold Plus. Les données analysées avec SPSS version 25.0 comprenaient les caractéristiques démographiques, cliniques et de laboratoire des patients. P< 0,05 a été a été considéré comme significatif. RÉSULTATS: L'âge moyen des patients infectés par le VIH était de 42,69 ± 9,91 ans et l'âge moyen du groupe témoin était de 41,29 ± 9,20 ans., sans différence statistic significative. La prevalence de tuberculose latente chez les patients infectés par le VIH était de 22,50 % alors qu'elle était de 10,0 % chez les témoins, ce qui était statistiquement significative (p-0,001). On a observé que le nombre de cellules CD4 de prédire de façon inverse la tuberculose latente (OR = 1,41; IC = 1,01- 3,73), tandis que la charge virale prédit directement la tuberculose latente (OR = 1,63 ; IC = 1,04-4,25). CONCLUSION: la prévalence de l'infection tuberculeuse latente est significativement plus élevée chez les patients séropositifs par rapport aux patients séronégatifs. De même, la prévalence de l'infection par le VIH était plus élevée chez les femmes et les personnes peu moins éduquée. Mots clés: Bacilles acido-alcoolo-résistants, indice de masse corporelle, extrapulmonaire, virus de l'immunodéficience humaine, interféron gamma, immunodéficience, tuberculose latente, ZiehlNeelsen.

Clinical characteristics and chest computed tomography findings related to the infectivity of pulmonary tuberculosis.

AIM: This study mainly evaluates the clinical characteristics and chest chest computed tomography (CT) findings of AFB-positive and AFB-negative pulmonary tuberculosis (PTB) patients to explore the relationship between AFB-positive and clinico-radiological findings. METHODS: A retrospective analysis of 224 hospitalized tuberculosis patients from 2018 to 2020 was undertaken. According to the AFB smear results, they were divided into AFB-positive pulmonary tuberculosis (positive by Ziehl-Neelsen staining) and AFB-negative pulmonary tuberculosis and patients' CT results and laboratory test results were analyzed. RESULTS: A total of 224 PTB patients were enrolled. AFB-positive (n = 94, 42%) and AFB-negative (n = 130, 58%). AFB-positive patients had more consolidation (77.7% vs. 53.8%, p < 0.01), cavity (55.3% vs. 34.6%, p < 0.01), calcification (38.3% vs. 20%, p < 0.01), bronchiectasis (7.5% vs. 1.5%, p < 0.05), bronchiarctia (6.4% vs. 0.8%, p < 0.05), and right upper lobe involvement (57.5% vs. 33.1%, p < 0.01), left upper lobe involvement (46.8% vs. 33.1%, p < 0.05) and lymphadenopathy (58.5% vs. 37.7%, p < 0.01). CONCLUSION: The study found that when pulmonary tuberculosis patients have consolidation, cavity, upper lobe involvement and lymphadenopathy on chest CT images, they may have a higher risk of AFB-positive tuberculosis.

[Molecular pathology of tuberculosis : Status, methodology, and limits]. / Molekularpathologie der Tuberkulose : Stellenwert, Methodik und Grenzen.

In the diagnosis of mycobacterioses, microbiological examination with culture and antibiogram, possibly in combination with molecular biological testing of the fresh material, still represents the gold standard. However, these methods are not available for formalin-fixed paraffin-embedded (FFPE) material or other fixed samples. For this reason, the first step in pathology is to attempt microscopic pathogen detection (ZN/Fite/rhodamine-auramine). Subsequently, molecular pathological examination for the detection of mycobacterial gene sequences should also be considered mandatory today. Although this has clear limits due to the material, it is nevertheless well suited, if carried out correctly, to detect a mycobacterial infection or make it unlikely. A negative result may favor an alternative diagnosis but does not completely rule out mycobacteriosis.For the therapy of tuberculosis or nontuberculous mycobacterial (NTM) disease, the reliable detection of the species and the determination of resistance is of utmost importance. With regard to therapy, the clinician cannot afford to make a false diagnosis. In case of doubt, a rebiopsy for sampling native material, particularly for microbiological testing, should be discussed.

[Histopathology of pulmonary tuberculosis]. / Histopathologie der Lungentuberkulose.

Although typical histological findings of tuberculosis are well known, the diagnosis of nonmicrobiologically proven tuberculosis with the instruments available to pathology is challenging. Indeed, necrotizing epithelioid cell granulomatosis is typical for tuberculosis, but it is also seen in a number of different infectious or noninfectious lung diseases. The tools of microscopy and molecular pathology are suitable for confirming the diagnosis or paving the way to a differential diagnosis, but molecular pathology applied to formalin-fixated and paraffin-embedded material is limited. This should be openly communicated to the referring clinician. After interdisciplinary re-evaluation of the findings, an alternative solution to confirm the diagnosis must therefore be found if the additional examinations are negative.

Diagnostic Value of PCR compared to Urine Culture for Urinary Tuberculosis in Adult Women: An Evidence-Based Case Report.

BACKGROUND: genitourinary tuberculosis (GUTB) refers to a Mycobacterium tuberculosis infection of the urinary tract with clinical manifestation masquerading as various urological diagnostic entities. With an incidence rate of 192-232 per 100,000 individuals, current diagnoses have fallen short in comparison to the total incidence. Combined with an atypical and non-specific manifestation, a high false negative rate of acid-fast bacilli (AFB) staining, and long AFB culture duration has made diagnosis difficult. We aim to gather current available evidence regarding the diagnostic performance of polymerase chain reaction (PCR) in the diagnosis of GUTB. METHODS: a literature search was conducted in four different, well-known databases using a predetermined PICO, keywords, and Boolean operators. All included articles will be subjected to rigorous appraisal according the University of Oxford's Centre for Evidence-Based Medicine (CEBM) Diagnostic Variability Criteria. Review and meta-analysis will be subjected to the QFAITH appraisal checklist to assess its quality. RESULTS: out of a total of 243 initial search results, 11 relevant studies were determined after title and abstract screening. Additionally, nine articles were excluded based on the predetermined criteria. Two fully appraised articles were included in the study: one systematic review article, revealing a heterogenous (I2 = unstated; p = unstated) result of sensitivity mean above 85% and specificity above 75%; and one cross-sectional diagnostic study that reported the use of two different PCR primers: IS6110-PCR and 16SrRNA-PCR primer with a sensitivity of 95.99% and 87.05% and specificity of 98.11% and 98.9%, respectively. CONCLUSION: current limited evidence showed that PCR could not be solely used for the diagnosis of GUTB, but its use is recommended to guide patient treatment and monitoring.

Mycobacterial Testing Trends, United States, 2009-20151.

We studied 31 US healthcare facilities to characterize trends in mycobacterial testing. During 2009-2015, testing for acid-fast bacilli increased 3.2% annually, and prevalence of pathogenic nontuberculous mycobacteria increased 4.5% annually. These increases were highest for subpopulations at high risk of infection, including older women, Asians, and patients with concurrent conditions.

GASMoC method: a phenol-free technique to detect acid-fast bacilli.

The genre Mycobacterium includes a series of pathological species, such as M. tuberculosis, which is important for pathology laboratories to detect for a correct diagnosis. The Ziehl-Neelsen technique (ZNT) is the most commonly histochemical method used to detect these bacilli and uses a heated mixture of carbol-fuchsine, which contains basic fuchsine and phenol. Whereas the former component is responsible for the pinkish staining of acid-fast mycobacteria, the role of phenol is not completely understood and it has been suggested that its exclusion does not impact the detection ability of the ZNT. Since phenol is highly toxic and induces several injuries, the goal of this study is to determine the detection capacity of mycobacteria through a method that excludes the use of phenol. Accordingly, the GASMoC method, a modified ZNT that employs a solution of aqueous basic fuchsine heated at 37 °C, was tested on histological samples positive for mycobacteria and the results were compared to that of the ZNT. Data demonstrated that the GASMoC method was able to detect acid-fast bacilli (AFB) in all analyzed cases. Remarkably, microscopic inspection of mycobacteria was easier when the GASMoC method was applied. In conclusion, our study demonstrates that AFB detection does not require phenol and that the GASMoC method, a phenol-free technique, may substitute the ZNT in pathology laboratories.

Acid and heat fastness in microsporidia: How acid fast are acid fast microsporidium?

Microsporidia are obligate spore-forming microorganisms with strong resemblance to fungi and can affect almost every organ system in immunocompetent or immunocompromised individuals. Mixed infections are also reported in immunocompromised hosts. Microsporidial spores show marked morphological variations and the small and slender forms can resemble bacilli. Modified Zeihl Neelsen (ZN) stain, cold method demonstrates them as bright red in color, leaving several spores blue or incompletely stained; thus, they are reported as weakly or variably acid fast. Variability in staining results with ZN stain and considering the fact that Mycobacterium tuberculosis, the commoner bug in developing countries is identified by its resistance to stronger acids on ZN staining, authors wished to demonstrate acid and heat fastness in microsporidium using corneal tissue specimens. Microsporidial spores stained bright red in color with conventional ZN stain, demonstrated strong acid fastness, and interestingly the staining results improved on heating. Thus, the authors conclude that they are strongly acid and heat fast and care must be warranted so that they are not misdiagnosed as Mycobacterium or other acid-fast organisms. Careful observation of morphology, battery of special stains, and molecular diagnostics should be advocated for diagnostic confirmation. To the best of the authors' knowledge, this is the first explicit report on acid and heat fastness on microsporidial spores.

Mycobacterium haemophilum skin and soft tissue infection in a kidney transplant recipient: A case report and summary of the literature.

Non-tuberculous mycobacteria are ubiquitous pathogens causing infections in immunocompromised patients. Here, we describe a kidney transplant recipient who developed skin and soft tissue infection by Mycobacterium haemophilum, complicated by tenosynovitis and fluid collection, following an injury sustained to her right foot. Her immunosuppressant dose was reduced, and she underwent prolonged antimicrobial therapy followed by surgical debridement with a favorable outcome. Non-tuberculous mycobacteria should be considered as a potential etiology of subacute skin and soft tissue infections.

Disseminated tuberculosis presenting as medium-vessel vasculitis in an immunocompromised host.

Cutaneous tuberculosis is an uncommon entity with several clinical forms recognized. Histopathologically, most cases are characterized by granulomatous inflammation and caseating necrosis, although less common findings, including vasculitis, have also been described. We report a 55-year-old male with a history of recently diagnosed dermatomyositis receiving immunosuppression with mycophenolate mofetil and prednisone, who developed multifocal soft tissue abscesses and an indurated erythematous plaque on the back. Skin biopsy of the back revealed a necrotizing medium-vessel vasculitis. Mycobacterium tuberculosis was detected in the skin via acid-fast bacilli stain and confirmed by tissue culture and polymerase chain reaction. Cutaneous findings improved rapidly with antituberculosis therapy. This case illustrates an uncommon clinical and histopathologic presentation of disseminated tuberculosis.

Window Period Prophylaxis for Children Exposed to Tuberculosis, Houston, Texas, USA, 2007-2017.

In this retrospective study, we assessed the safety of window period prophylaxis and proportion of tuberculin skin test (TST) conversions in children <5 years of age who were exposed to an adult with tuberculosis disease during 2007-2017. Children included in this study had unremarkable examination and chest radiograph findings and negative test results for TB infection. In total, 752 children (41% cohabitating with the index patient) received prophylaxis during the window period, usually directly observed therapy with isoniazid. Hepatotoxicity and tuberculosis disease did not develop in any child. TST conversion occurred in 37 (4.9%) children and was associated with the index patient being the child's parent (odds ratio 3.2, 95% CI 1.2-8.2). TST conversion was not associated with sputum smear results, culture positivity, or cohabitation. Thresholds for initiation of window prophylaxis in exposed young children should be low given the safety of medication and difficulties with risk stratification.

Added Value of Xpert MTB/RIF Ultra for Diagnosis of Pulmonary Tuberculosis in a Low-Prevalence Setting.

Xpert MTB/RIF (Xpert) for direct molecular detection of Mycobacterium tuberculosis and rifampin resistance from clinical specimens has dramatically improved the diagnosis of tuberculosis (TB). Xpert MTB/RIF Ultra (Ultra) is proposed as a substitute of Xpert with increased sensitivity and improved rifampin resistance detection. We evaluated the diagnostic performance of Ultra and Xpert for pulmonary TB diagnosis in a low-TB-burden setting. Performance of Ultra and Xpert were compared to culture on respiratory specimens from patients with suspected pulmonary TB (November 2016 to August 2018; n = 196) in Lausanne (Switzerland). Clinical data were used to investigate discrepant results. Correlation between semiquantitative result of Ultra and smear microscopy status for the detection of acid-fast bacilli (AFB) was established. The sensitivities of Xpert and Ultra were 82.9% (39/47) and 95.8% (45/47), respectively, when considering all culture-positive specimens, 100% (23/23) for both assays on smear-positive specimens, and 66.7% (16/24) and 91.7% (22/24) on smear-negative specimens. Using culture as gold standard, the specificities of Xpert and Ultra were 97.3% (145/149) and 96.64% (144/149), respectively. All the patients with Ultra-positive results with the new category "trace" were diagnosed with active TB based on clinical findings and microbiological culture. The semiquantitative results of both Xpert and of Ultra positively correlated with the semiquantitative result of AFB detection. Our data support an increased sensitivity of Ultra compared to Xpert in a low-prevalence setting. Correlation between the Ultra semiquantitative result and AFB burden can help in evaluating a patient's transmission potential.