Tuberculous dactylitis—an easily missed diagnosis

The prevalence of tuberculosis (TB) continues to rise worldwide. Current migration patterns and increased travel to high-prevalence TB countries will result in more frequent presentations of less common forms of TB. Tuberculous dactylitis, a form of tuberculous osteomyelitis, is well recognised in countries with a high prevalence of TB. We provide a systematic review of all published cases of tuberculous dactylitis in children and adolescents and describe a case to illustrate the typical features of the disease. Our review revealed 37 cases of tuberculous dactylitis in children and adolescents, all reported in the last 17years. Children less than 10 years of age are most frequently affected and the hand is the most commonly affected site. Concurrent pulmonary TB is present in a fifth of cases and systemic symptoms are usually absent. Positive TST and IGRA support the presumptive diagnosis, but cannot be used as rule-out tests. The definitive diagnosis relies on the detection M. tuberculosis by PCR or culture. Treatment should comprise of a standard three to four drug anti-tuberculous regimen. The optimal treatment duration remains unknown. Surgery has a limited role in the treatment in general but may play a supportive role, and curettage of the cavity has been recommended for avascular lesion

Bacille Calmette-Guerin (BCG) vaccine and the COVID-19 pandemic : responsible stewardship is needed

CITATION: Schaaf, H. S. et al. 2020. Bacille Calmette-Guerin (BCG) vaccine and the COVID-19 pandemic : responsible stewardship is needed. International Journal of Tuberculosis and Lung Disease, 4(7):732-734, doi:10.5588/ijtld.20.0267.The original publication is available at https://www.theunion.org/what-we-do/journals/ijtldWe believe that responsible stewardship of the bacille Calmette-Guérin (BCG) vaccine in the context of the COVID-19 epidemic is urgently needed. Live attenuated BCG is currently the only licensed vaccine to protect against tuberculosis (TB). Neonatal BCG vaccination has proven efficacy in protecting infants and young children against life-threatening disseminated forms of TB, including TB meningitis and miliary TB.Post-prin

Current use and acceptability of novel diagnostic tests for active tuberculosis: a worldwide survey

Objective: To determine the current use and potential acceptance (by tuberculosis experts worldwide) of novel rapid tests for the diagnosis of tuberculosis that are in line with World Health Organization target product profiles. Methods: A multilingual survey was disseminated online between July and November of 2016. Results: A total of 723 individuals from 114 countries responded to the survey. Smear microscopy was the most commonly used rapid tuberculosis test (available to 90.9% of the respondents), followed by molecular assays (available to 70.7%). Only a small proportion of the respondents in middle-and low-income countries had access to interferon-gamma-release assays. Serological and lateral flow immunoassays were used by more than a quarter (25.4%) of the respondents. Among the respondents who had access to molecular tests, 46.7% were using the Xpert assay overall, that proportion being higher in lower middle-income countries (55.6%) and low-income countries (76.6%). The data also suggest that there was some alignment of pricing for molecular assays. Respondents stated they would accept novel rapid tuberculosis tests if available, including molecular assays (acceptable to 86.0%) or biomarker-based serological assays (acceptable to 81.7%). Simple biomarker-based assays were more commonly deemed acceptable in middle-and lowincome countries. Conclusions: Second-generation molecular assays have become more widely available in high-and low-resource settings. However, the development of novel rapid tuberculosis tests continues to be considered important by tuberculosis experts. Our data also underscore the need for additional training and education of end users

Gauging U.S. Emergency Medical Services Workers' Willingness to Respond to Pandemic Influenza Using a Threat- and Efficacy-Based Assessment Framework

Emergency Medical Services workers' willingness to report to duty in an influenza pandemic is essential to healthcare system surge amidst a global threat. Application of Witte's Extended Parallel Process Model (EPPM) has shown utility for revealing influences of perceived threat and efficacy on non-EMS public health providers' willingness to respond in an influenza pandemic. We thus propose using an EPPM-informed assessment of EMS workers' perspectives toward fulfilling their influenza pandemic response roles.We administered an EPPM-informed snapshot survey about attitudes and beliefs toward pandemic influenza response, to a nationally representative, stratified random sample of 1,537 U.S. EMS workers from May-June 2009 (overall response rate: 49%). Of the 586 respondents who met inclusion criteria (currently active EMS providers in primarily EMS response roles), 12% indicated they would not voluntarily report to duty in a pandemic influenza emergency if asked, 7% if required. A majority (52%) indicated their unwillingness to report to work if risk of disease transmission to family existed. Confidence in personal safety at work (OR = 3.3) and a high threat/high efficacy ("concerned and confident") EPPM profile (OR = 4.7) distinguished those who were more likely to voluntarily report to duty. Although 96% of EMS workers indicated that they would probably or definitely report to work if they were guaranteed a pandemic influenza vaccine, only 59% had received an influenza immunization in the preceding 12 months.EMS workers' response willingness gaps pose a substantial challenge to prehospital surge capacity in an influenza pandemic. "Concerned and confident" EMS workers are more than four times as likely to fulfill pandemic influenza response expectations. Confidence in workplace safety is a positively influential modifier of their response willingness. These findings can inform insights into interventions for enhancing EMS workers' willingness to respond in the face of a global infectious disease threat

Performance of QuantiFERON-TB Gold Plus assays in children and adolescents at risk of tuberculosis: a cross-sectional multicentre study

Introduction: The QuantiFERON-TB Gold Plus (QFT-Plus) assay, which features two antigen-stimulated tubes (TB1 and TB2) instead of a single tube used in previous-generation interferon-gamma release assays (IGRAs), was launched in 2016. Despite this, data regarding the assay’s performance in the paediatric setting remain scarce. This study aimed to determine the performance of QFT-Plus in a large cohort of children and adolescents at risk of tuberculosis (TB) in a low-burden setting. Methods: Cross-sectional, multicentre study at healthcare institutions participating in the Spanish Paediatric TB Research Network, including patients <18 years who had a QFT-Plus performed between September 2016 and June 2020. Results: Of 1726 patients (52.8% male, median age: 8.4 years), 260 (15.1%) underwent testing during contact tracing, 288 (16.7%) on clinical/radiological suspicion of tuberculosis disease (TBD), 649 (37.6%) during new-entrant migrant screening and 529 (30.6%) prior to initiation of immunosuppressive treatment. Overall, the sensitivity of QFT-Plus for TBD (n=189) and for latent tuberculosis infection (LTBI, n=195) was 83.6% and 68.2%, respectively. The agreement between QFT-Plus TB1 and TB2 antigen tubes was excellent (98.9%, κ=0.961). Only five (2.5%) patients with TBD had discordance between TB1 and TB2 results (TB1+/TB2−, n=2; TB1−/TB2+, n=3). Indeterminate assay results (n=54, 3.1%) were associated with young age, lymphopenia and elevated C reactive protein concentrations. Conclusions: Our non-comparative study indicates that QFT-Plus does not have greater sensitivity than previous-generation IGRAs in children in both TBD and LTBI. In TBD, the addition of the second antigen tube, TB2, does not enhance the assay’s performance substantially

Comprehensive plasma proteomic profiling reveals biomarkers for active tuberculosis

BACKGROUND. Tuberculosis (TB) kills more people than any other infection, and new diagnostic tests to identify active cases are required. We aimed to discover and verify novel markers for TB in nondepleted plasma. / METHODS. We applied an optimized quantitative proteomics discovery methodology based on multidimensional and orthogonal liquid chromatographic separation combined with high-resolution mass spectrometry to study nondepleted plasma of 11 patients with active TB compared with 10 healthy controls. Prioritized candidates were verified in independent UK (n = 118) and South African cohorts (n = 203). / RESULTS. We generated the most comprehensive TB plasma proteome to date, profiling 5022 proteins spanning 11 orders-of-magnitude concentration range with diverse biochemical and molecular properties. We analyzed the predominantly low–molecular weight subproteome, identifying 46 proteins with significantly increased and 90 with decreased abundance (peptide FDR ≤ 1%, q ≤ 0.05). Verification was performed for novel candidate biomarkers (CFHR5, ILF2) in 2 independent cohorts. Receiver operating characteristics analyses using a 5-protein panel (CFHR5, LRG1, CRP, LBP, and SAA1) exhibited discriminatory power in distinguishing TB from other respiratory diseases (AUC = 0.81). / CONCLUSION. We report the most comprehensive TB plasma proteome to date, identifying novel markers with verification in 2 independent cohorts, leading to a 5-protein biosignature with potential to improve TB diagnosis. With further development, these biomarkers have potential as a diagnostic triage test. / FUNDING. Colciencias, Medical Research Council, Innovate UK, NIHR, Academy of Medical Sciences, Program for Advanced Research Capacities for AIDS, Wellcome Centre for Infectious Diseases Research

Interferon-Gamma Release Assays Differentiate Between Mycobacterium avium Complex and Tuberculous Lymphadenitis in Children

OBJECTIVES: To assess the performance of interferon-gamma release assays (IGRAs) in the differential diagnosis between Mycobacterium avium complex (MAC) and tuberculosis (TB) in children affected with subacute/chronic submandibular/cervical lymphadenitis. STUDY DESIGN: Multicenter observational study comparing children with microbiologically-confirmed MAC lymphadenitis from the European NontuberculouS MycoBacterial Lymphadenitis in childrEn (ENSeMBLE) study with children with TB lymphadenitis from the Spanish Network for the Study of Pediatric TB (pTBred) database. RESULTS: Overall, 78 patients with MAC and 34 with TB lymphadenitis were included. Among MAC cases, 44/74 (59.5%) had positive tuberculin skin test (TST) results at the 5 mm cutoff, compared with 32/33 (97%) TB cases (p<0.001); at the 10 mm cutoff TST results were positive in 23/74 (31.1%) vs. 26/31 (83.9%), respectively (P < .001). IGRA results were positive in only 1/32 (3.1%) MAC cases who had undergone IGRA testing, compared with 21/23 (91.3%) TB cases (p<0.001). Agreement between TST and IGRA results was poor in MAC (23.3%;κ=0.017), but good in TB cases (95.6%;κ=0.646). IGRAs had a specificity of 96.9% (95%CI:84.3-99.8%), positive predictive value (PPV) of 95.4% (95%CI:78.2-99.8%), and negative predictive value (NPV) of 93.9% (95%CI:80.4-98.9%) for TB lymphadenitis. CONCLUSIONS: In contrast to TST, IGRAs have high specificity, NPV and PPV for TB lymphadenitis in children with subacute/chronic lymphadenopathy, and consequently can help to discriminate between TB and MAC disease. Therefore, IGRAs are useful tools in the diagnostic work-up of children with lymphadenopathy, particularly when culture- and PCR-results are negative

Invasive Propionibacterium acnes infections in a non-selective patient cohort: clinical manifestations, management and outcome

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Purpose An increasing number of reports suggest that Propionibacterium acnes can cause serious invasive infections. Currently only limited data exist regarding the spectrum of invasive P. acnes infections. Methods Non-selective cohort study at a tertiary hospital in the UK over a nine-year-period (2003-2012) investigating clinical manifestations, risk factors, management and outcome of invasive P. acnes infections. Results Forty-nine cases were identified; the majority were neurosurgical infections and orthopaedic infections (n=28 and n=15, respectively). Only two cases had no predisposing factors; all neurosurgical and 93.3% of orthopaedic cases had a history of previous surgery and/or trauma. Foreign material was in situ at the infection site in 59.3% and 80.0% of neurosurgical and orthopaedic cases, respectively. All neurosurgical and orthopaedic cases required one or more surgical interventions to treat P. acnes infection, with or without concomitant antibiotic therapy; the duration of antibiotic therapy was significantly longer in the group of orthopaedic cases (median 53 versus 19 days; p=0.0025). All tested P. acnes isolates were susceptible to penicillin, ampicillin and chloramphenicol; only one was clindamycin-resistant. Conclusions Neurosurgical and orthopaedic infections account for the majority of invasive P. acnes infections. The majority of cases have predisposing factors, including previous surgery and/or trauma; spontaneous infections are rare. Foreign material is commonly present at the site of infection, indicating that the pathogenesis of invasive P. acnes infections likely involves biofilm formation. Since invasive P. acnes infections are associated with considerable morbidity, further studies are needed to establish effective prevention and optimal treatment strategies