Effects of the Beijing genotype on latent tuberculosis infection, TB disease risk, and clustering of TB cases.

BACKGROUND: The Beijing genotype of Mycobacterium tuberculosis (Mtb) has sparked debate regarding its virulence and transmissibility. This study contributes to this discussion by assessing its effect on the risk of latent tuberculosis infection (LTBI), active tuberculosis (TB) disease among contacts, and clustering of known TB cases. METHODS: We conducted a retrospective cohort study using the records of 4457 culture-confirmed TB patients and their contacts (20,448) reported to the Florida Department of Health between 2009 and 2023. Univariate and multivariate analyses were used to evaluate the effect of the Beijing strain on LTBI, active TB risk among contacts, and case clustering. RESULTS: Our study revealed no significant difference in transmissibility between the Beijing and non-Beijing genotypes among contacts. LTBI prevalence was 19.9%, slightly higher in non-Beijing than Beijing genotypes (20.2% vs. 15.5%, p < 0.001). The prevalence of active TB was 1.8%, with no significant difference between the Beijing and non-Beijing genotypes (1.4% vs. 1.8%, p = 0.296). Increased LTBI risk was associated with older age, male sex, Hispanic ethnicity, multidrug-resistant TB exposure, household exposure, and a longer exposure duration. Active TB risk was higher for males, HIV-positive individuals, and contacts with more prolonged exposure to index cases. The Beijing genotype was associated with increased TB case clustering (aOR = 1.98, 95%CI: 1.53, 2.55, p < 0.001) as compared to the non-Beijing genotypes. US birthplace (aOR = 2.75, 95%CI: 2.37, 3.19, p < 0.001), pulmonary disease (aOR = 1.27, 95%CI: 1.04, 1.56, p < 0.020), cavitary TB (aOR = 1.25, 95% CI: 1.08, 1.44, p < 0.003), previous year alcohol use (aOR = 1.68, 95%CI: 1.38, 2.04, p < 0.001), and recreational drug use (aOR = 1.32, 95%CI: 1.04, 1.67, p < 0.024) were also associated with an increased risk of TB case clustering. CONCLUSION: While the Beijing genotype did not increase the risk of LTBI or active TB among contacts, it showed a higher tendency for case clustering. Hence, interventions should prioritize populations where this genotype is prevalent.

Comparison of Tuberculin Skin Testing and Interferon-γ Release Assays in Predicting Tuberculosis Disease.

Importance: Elimination of tuberculosis (TB) disease in the US hinges on the ability of tests to detect individual risk of developing disease to inform prevention. The relative performance of 3 available TB tests-the tuberculin skin test (TST) and 2 interferon-γ release assays (IGRAs; QuantiFERON-TB Gold In-Tube [QFT-GIT] and SPOT.TB [TSPOT])-in predicting TB disease development in the US remains unknown. Objective: To compare the performance of the TST with the QFT-GIT and TSPOT IGRAs in predicting TB disease in high-risk populations. Design, Setting, and Participants: This prospective diagnostic study included participants at high risk of TB infection (TBI) or progression to TB disease at 10 US sites between 2012 and 2020. Participants of any age who had close contact with a case patient with infectious TB, were born in a country with medium or high TB incidence, had traveled recently to a high-incidence country, were living with HIV infection, or were from a population with a high local prevalence were enrolled from July 12, 2012, through May 5, 2017. Participants were assessed for 2 years after enrollment and through registry matches until the study end date (November 15, 2020). Data analysis was performed in June 2023. Exposures: At enrollment, participants were concurrently tested with 2 IGRAs (QFT-GIT from Qiagen and TSPOT from Oxford Immunotec) and the TST. Participants were classified as case patients with incident TB disease when diagnosed more than 30 days from enrollment. Main Outcomes and Measures: Estimated positive predictive value (PPV) ratios from generalized estimating equation models were used to compare test performance in predicting incident TB. Incremental changes in PPV were estimated to determine whether predictive performance significantly improved with the addition of a second test. Case patients with prevalent TB were examined in sensitivity analysis. Results: A total of 22 020 eligible participants were included in this study. Their median age was 32 (range, 0-102) years, more than half (51.2%) were male, and the median follow-up was 6.4 (range, 0.2-8.3) years. Most participants (82.0%) were born outside the US, and 9.6% were close contacts. Tuberculosis disease was identified in 129 case patients (0.6%): 42 (0.2%) had incident TB and 87 (0.4%) had prevalent TB. The TSPOT and QFT-GIT assays performed significantly better than the TST (PPV ratio, 1.65 [95% CI, 1.35-2.02] and 1.47 [95% CI, 1.22-1.77], respectively). The incremental gain in PPV, given a positive TST result, was statistically significant for positive QFT-GIT and TSPOT results (1.64 [95% CI, 1.40-1.93] and 1.94 [95% CI, 1.65-2.27], respectively). Conclusions and Relevance: In this diagnostic study assessing predictive value, IGRAs demonstrated superior performance for predicting incident TB compared with the TST. Interferon-γ release assays provided a statistically significant incremental improvement in PPV when a positive TST result was known. These findings suggest that IGRA performance may enhance decisions to treat TBI and prevent TB.

Central Nervous System Tuberculosis: Risk Factors for Mortality in a Propensity Score-Matched Case-Control Study.

Background: Despite advancements in tuberculosis (TB) control and treatment in the United States (US), patients with central nervous system TB (CNS-TB) continue to experience significantly higher mortality rates than those without CNS-TB. This raises concerns regarding clinical management and the need for a deeper understanding of the risk factors contributing to these deaths. This study aimed to determine the predictors of mortality in patients with CNS-TB. Methods: We conducted a retrospective 1:2 propensity score-matched case-control study. Cases were TB patients diagnosed with TB of the meninges, brain, spinal cord, or peripheral nerves, as documented in the Florida Department of Health (FDOH) TB registry, between 2009 and 2021. Controls were TB patients without CNS-TB, also reported in the FDOH TB registry during the same timeframe. We employed conditional logistic regression models to investigate the factors contributing to mortality in cases compared with controls. Results: We analyzed data from 116 cases and 232 matched controls. Patients with CNS-TB had a 5.69-fold higher risk of death than those without CNS-TB (adjusted odds ratio [aOR], 5.69 [95% confidence interval {CI}, 2.91-11.6]). Increased risk of death was associated with human immunodeficiency virus (HIV) coinfection (aOR, 1.93 [95% CI, .82-4.37]) and diabetes (aOR, 3.13 [95% CI, 1.28-7.47]). Miliary TB and non-HIV immunosuppression were significantly associated with being a case, while cavitary TB was less likely to be associated with being a case. Conclusions: Clinical management should prioritize screening and close monitoring of patients with HIV coinfection and diabetes to improve patient outcomes.

Multicenter matched-pair study comparing BACT/ALERT® MP reagent systems for the recovery of mycobacteria from specimens other than blood.

The BACT/ALERT® MP Reagent System is a broth culture medium for optimal detection and recovery of mycobacteria from clinical samples. The MP formulation was recently modified to improve detection and recovery times. A multicenter prospective matched pair study design was conducted to validate the performance of improved MP (MP-I) versus current MP (MP-C) bottles utilizing nonsterile and normally sterile samples, except blood, from patients suspected of having mycobacterial infections. A total of 1488 clinical samples were collected to obtain 212 mycobacteria samples by either or both MP culture bottles. MP-I and MP-C sensitivities were 86.6% and 81.4%, respectively, but the difference was not significant (P = 0.163) while specificities were 96.8% and 93.8%, respectively, and that difference was significant (P = 0.002). Overall recovery was 94.34% for MP-I and 88.68% for MP-C (recovery was 100% for both bottles with 52 seeded samples). Overall performance of MP-I was better than MP-C for sensitivity, specificity, and recovery.

Retrospective Analysis of Wastewater-Based Epidemiology of SARS-CoV-2 in Residences on a Large College Campus: Relationships between Wastewater Outcomes and COVID-19 Cases across Two Semesters with Different COVID-19 Mitigation Policies.

Wastewater-based epidemiology (WBE) has been utilized for outbreak monitoring and response efforts in university settings during the coronavirus disease 2019 (COVID-19) pandemic. However, few studies examined the impact of university policies on the effectiveness of WBE to identify cases and mitigate transmission. The objective of this study was to retrospectively assess relationships between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wastewater outcomes and COVID-19 cases in residential buildings of a large university campus across two academic semesters (August 2020-May 2021) under different COVID-19 mitigation policies. Clinical case surveillance data of student residents were obtained from the university COVID-19 response program. We collected and processed building-level wastewater for detection and quantification of SARS-CoV-2 RNA by RT-qPCR. The odds of obtaining a positive wastewater sample increased with COVID-19 clinical cases in the fall semester (OR = 1.50, P value = 0.02), with higher odds in the spring semester (OR = 2.63, P value < 0.0001). We observed linear associations between SARS-CoV-2 wastewater concentrations and COVID-19 clinical cases (parameter estimate = 1.2, P value = 0.006). Our study demonstrated the effectiveness of WBE in the university setting, though it may be limited under different COVID-19 mitigation policies. As a complementary surveillance tool, WBE should be accompanied by robust administrative and clinical testing efforts for the COVID-19 pandemic response.

Lack of SARS-CoV-2 in environmental samples collected from September 2020-February 2021 in a university that followed CDC reopening guidance.

This study aimed to provide environmental surveillance data for evaluating the risk of acquiring SARS-CoV-2 in public areas with high foot traffic in a university. Air and surface samples were collected at a university that had the second highest number of COVID-19 cases among public higher education institutions in the U.S. during Fall 2020. A total of 60 samples were collected in 16 sampling events performed during Fall 2020 and Spring 2021. Nearly 9800 students traversed the sites during the study period. SARS-CoV-2 was not detected in any air or surface samples. The university followed CDC guidance, including COVID-19 testing, case investigations, and contact tracing. Students, faculty, and staff were asked to maintain physical distancing and wear face coverings. Although COVID-19 cases were relatively high at the university, the possibility of acquiring SARS-CoV-2 infections at the sites tested was low.

Application of Phylodynamic Tools to Inform the Public Health Response to COVID-19: Qualitative Analysis of Expert Opinions.

BACKGROUND: In the wake of the SARS-CoV-2 pandemic, scientists have scrambled to collect and analyze SARS-CoV-2 genomic data to inform public health responses to COVID-19 in real time. Open source phylogenetic and data visualization platforms for monitoring SARS-CoV-2 genomic epidemiology have rapidly gained popularity for their ability to illuminate spatial-temporal transmission patterns worldwide. However, the utility of such tools to inform public health decision-making for COVID-19 in real time remains to be explored. OBJECTIVE: The aim of this study is to convene experts in public health, infectious diseases, virology, and bioinformatics-many of whom were actively engaged in the COVID-19 response-to discuss and report on the application of phylodynamic tools to inform pandemic responses. METHODS: In total, 4 focus groups (FGs) occurred between June 2020 and June 2021, covering both the pre- and postvariant strain emergence and vaccination eras of the ongoing COVID-19 crisis. Participants included national and international academic and government researchers, clinicians, public health practitioners, and other stakeholders recruited through purposive and convenience sampling by the study team. Open-ended questions were developed to prompt discussion. FGs I and II concentrated on phylodynamics for the public health practitioner, while FGs III and IV discussed the methodological nuances of phylodynamic inference. Two FGs per topic area to increase data saturation. An iterative, thematic qualitative framework was used for data analysis. RESULTS: We invited 41 experts to the FGs, and 23 (56%) agreed to participate. Across all the FG sessions, 15 (65%) of the participants were female, 17 (74%) were White, and 5 (22%) were Black. Participants were described as molecular epidemiologists (MEs; n=9, 39%), clinician-researchers (n=3, 13%), infectious disease experts (IDs; n=4, 17%), and public health professionals at the local (PHs; n=4, 17%), state (n=2, 9%), and federal (n=1, 4%) levels. They represented multiple countries in Europe, the United States, and the Caribbean. Nine major themes arose from the discussions: (1) translational/implementation science, (2) precision public health, (3) fundamental unknowns, (4) proper scientific communication, (5) methods of epidemiological investigation, (6) sampling bias, (7) interoperability standards, (8) academic/public health partnerships, and (9) resources. Collectively, participants felt that successful uptake of phylodynamic tools to inform the public health response relies on the strength of academic and public health partnerships. They called for interoperability standards in sequence data sharing, urged careful reporting to prevent misinterpretations, imagined that public health responses could be tailored to specific variants, and cited resource issues that would need to be addressed by policy makers in future outbreaks. CONCLUSIONS: This study is the first to detail the viewpoints of public health practitioners and molecular epidemiology experts on the use of viral genomic data to inform the response to the COVID-19 pandemic. The data gathered during this study provide important information from experts to help streamline the functionality and use of phylodynamic tools for pandemic responses.

Assessing risk factors for latent and active tuberculosis among persons living with HIV in Florida: A comparison of self-reports and medical records.

PURPOSE: This study examined factors associated with TB among persons living with HIV (PLWH) in Florida and the agreement between self-reported and medically documented history of tuberculosis (TB) in assessing the risk factors. METHODS: Self-reported and medically documented data of 655 PLWH in Florida were analyzed. Data on sociodemographic factors such as age, race/ethnicity, place of birth, current marital status, education, employment, homelessness in the past year and 'ever been jailed' and behavioural factors such as excessive alcohol use, marijuana, injection drug use (IDU), substance and current cigarette use were obtained. Health status information such as health insurance status, adherence to HIV antiretroviral therapy (ART), most recent CD4 count, HIV viral load and comorbid conditions were also obtained. The associations between these selected factors with self-reported TB and medically documented TB diagnosis were compared using Chi-square and logistic regression analyses. Additionally, the agreement between self-reports and medical records was assessed. RESULTS: TB prevalence according to self-reports and medical records was 16.6% and 7.5% respectively. Being age ≥55 years, African American and homeless in the past 12 months were statistically significantly associated with self-reported TB, while being African American homeless in the past 12 months and not on antiretroviral therapy (ART) were statistically significantly associated with medically documented TB. African Americans compared to Whites had odds ratios of 3.04 and 4.89 for self-reported and medically documented TB, respectively. There was moderate agreement between self-reported and medically documented TB (Kappa = 0.41). CONCLUSIONS: TB prevalence was higher based on self-reports than medical records. There was moderate agreement between the two data sources, showing the importance of self-reports. Establishing the true prevalence of TB and associated risk factors in PLWH for developing policies may therefore require the use of self-reports and confirmation by screening tests, clinical signs and/or microbiologic data.

Evaluation of screen, test, & protect: A public health program to control and prevent COVID-19 at a large academic university.

Background: We evaluate the public health surveillance program, Screen, Test, and Protect (STP) designed to control and prevent COVID-19 at a large academic university in the United States. Methods: STP was established at the University of Florida in May 2020. This report details STP's full-time workforce, centralized database, and testing and vaccination programs. We evaluate the program's success in controlling COVID-19 during the 2020-2021 academic school year. Results: COVID-19 cases rose among the campus community in the first few weeks of campus reopening in Fall 2020. Test positivity levels returned to prefall semester levels within one month, however. A few additional, yet smaller, waves occurred during the 2020-2021 school year and were successfully controlled without any campus-wide closures. Conclusions: This program may serve as a framework for other institutions managing the ongoing COVID-19 crisis, in addition to setting the standard for programmatic management of future emerging infectious diseases at universities.

Multi-Faceted Approach to COVID-19 Surveillance at a Large University Campus in the Southeastern United States.

The coronavirus disease 2019 (COVID-19) pandemic continues to present unique public health challenges both within the United States and across the globe. Institutions of higher learning are tasked with preventing and responding to COVID-19 on campus while also considering implications for the surrounding communities. The process of re-opening campus, whether at full or partial capacity, has tasked these institutions with overcoming complex challenges associated with balancing the resumption of campus operations while simultaneously protecting university affiliates and surrounding community members from COVID-19 through robust surveillance, contact tracing, and testing efforts. Here, we provide a concise outline related to the development and implementation of the comprehensive and sustainable COVID-19 surveillance program at the University of Florida. We also critically discuss the successes and pitfalls of this program while also providing recommendations for the development of similar programs in the future.

Low-frequency variants in mildly symptomatic vaccine breakthrough infections presents a doubled-edged sword.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) has raised questions regarding vaccine protection against SARS-CoV-2 infection, transmission, and ongoing virus evolution. Twenty-three mildly symptomatic "vaccination breakthrough" infections were identified as early as January 2021 in Alachua County, Florida, among individuals fully vaccinated with either the BNT162b2 (Pfizer) or the Ad26 (Janssen/J&J) vaccines. SARS-CoV-2 genomes were successfully generated for 11 of the vaccine breakthroughs, and 878 individuals in the surrounding area and were included for reference-based phylogenetic investigation. These 11 individuals were characterized by infection with VOCs, but also low-frequency variants present within the surrounding population. Low-frequency mutations were observed, which have been more recently identified as mutations of interest owing to their location within targeted immune epitopes (P812L) and association with increased replicative capacity (L18F). We present these results to posit the nature of the efficacy of vaccines in reducing symptoms as both a blessing and a curse-as vaccination becomes more widespread and self-motivated testing reduced owing to the absence of severe symptoms, we face the challenge of early recognition of novel mutations of potential concern. This case study highlights the critical need for continued testing and monitoring of infection and transmission among individuals regardless of vaccination status.

Severe Acute Respiratory Syndrome Coronavirus 2 Delta Vaccine Breakthrough Transmissibility in Alachua County, Florida.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant has caused a dramatic resurgence in infections in the United Sates, raising questions regarding potential transmissibility among vaccinated individuals. METHODS: Between October 2020 and July 2021, we sequenced 4439 SARS-CoV-2 full genomes, 23% of all known infections in Alachua County, Florida, including 109 vaccine breakthrough cases. Univariate and multivariate regression analyses were conducted to evaluate associations between viral RNA burden and patient characteristics. Contact tracing and phylogenetic analysis were used to investigate direct transmissions involving vaccinated individuals. RESULTS: The majority of breakthrough sequences with lineage assignment were classified as Delta variants (74.6%) and occurred, on average, about 3 months (104 ±â€…57.5 days) after full vaccination, at the same time (June-July 2021) of Delta variant exponential spread within the county. Six Delta variant transmission pairs between fully vaccinated individuals were identified through contact tracing, 3 of which were confirmed by phylogenetic analysis. Delta breakthroughs exhibited broad viral RNA copy number values during acute infection (interquartile range, 1.2-8.64 Log copies/mL), on average 38% lower than matched unvaccinated patients (3.29-10.81 Log copies/mL, P < .00001). Nevertheless, 49% to 50% of all breakthroughs, and 56% to 60% of Delta-infected breakthroughs exhibited viral RNA levels above the transmissibility threshold (4 Log copies/mL) irrespective of time after vaccination. CONCLUSIONS: Delta infection transmissibility and general viral RNA quantification patterns in vaccinated individuals suggest limited levels of sterilizing immunity that need to be considered by public health policies. In particular, ongoing evaluation of vaccine boosters should specifically address whether extra vaccine doses curb breakthrough contribution to epidemic spread.

Applying Lean principles to create a high throughput mass COVID-19 vaccination site.

A high throughput COVID-19 vaccination site was created using Lean principles and tools. Mass-vaccination sites can achieve high output by creating a standard physical design for workspaces and standardised work protocols, and by timing each step in the vaccination process to create a value stream map that can identify and remove all wasteful steps. Reliability of the vaccination process can be assured by creating a visual checklist that monitors the individual steps as well as by building in second checks by downstream personnel. Finally, productivity can be closely monitored by recording the start and completion time for each vaccination and plotting run charts. With 78 personnel working efficiently and effectively together, a maximum throughput of 5024 injections over 10 hours was achieved. As compared with other published COVID-19 mass-vaccination sites, our site attained threefold-fourfold higher productivity. We share our approach to encourage others to reproduce our vaccination system.

Detection of SARS-CoV-2 in the gastrointestinal tract among patients with negative nasopharyngeal COVID-19 testing prior to endoscopy.

Background and study aims The clinical significance of SARS-CoV-2 RNA in the stool remains unclear. We aimed to determine whether SARS-CoV-2 is detected via real-time reverse transcriptase polymerase chain reaction (rRT-PCR) in the gastrointestinal tracts of patients scheduled for endoscopy and if the virus obtained from these clinical specimens could be isolated in culture. Patients and methods All patients underwent symptom screening and had negative nasopharyngeal testing for SARS-CoV-2 within 72 hours of their scheduled procedure. Study samples were collected via nasopharyngeal swab, rectal swab, and fluid from the upper gastrointestinal tract and/or colon based on their endoscopic procedure(s). Samples were tested for SARS-CoV-2 via rRT-PCR. SARS-CoV-2 positive specimens were isolated and cultured in Vero-E6 cells. Results 243 patients (mean age 63.1 years;54.3 % men) were enrolled from July 15, 2020 to September 2, 2020. SARS-CoV-2 testing was performed from 242 (99.6 %) nasopharyngeal, 243 (100 %) rectal, 183 (75.3 %) upper gastrointestinal tract and 73 (30 %) colon samples. SARS-CoV-2 RNA was detected in the nasopharynx and gastrointestinal specimens in one patient (0.4 %). After a 14-day incubation period, there was no evidence of virus growth in cells incubated with any of these specimens. Conclusions SARS-CoV-2 was rarely detected in the gastrointestinal tract of patients with negative nasopharyngeal testing prior to endoscopy. No live virus was detected by culture, further highlighting that presence of viral genome on its own is not sufficient proof of infectivity. PCR-based screening provides limited insight into virus infectivity and its results should be interpreted carefully as to avoid unnecessary delays in clinical care or inadvertent risk exposure.

Isolation of SARS-CoV-2 from the air in a car driven by a COVID patient with mild illness.

OBJECTIVE: To determine if viable virus could be isolated from the air within a car driven by a patient infected with SARS-CoV-2, and to assess the size range of the infectious particles. METHODS: We used a Sioutas personal cascade impactor sampler (PCIS) to screen for SARS-CoV-2 in a car driven by a COVID-19 patient. The patient, who had only mild illness without fever or cough and was not wearing a mask, drove the car for 15 min with the air conditioning turned on and windows closed. The PCIS was clipped to the sun-visor above the front passenger seat and was retrieved from the car two hours after completion of the drive. RESULTS: SARS-CoV-2 was detectable at all PCIS stages by PCR and was cultured from the section of the sampler collecting particles in the 0.25-0.50 µm size range. CONCLUSIONS: Our data highlight the potential risk of SARS-CoV-2 transmission by minimally symptomatic persons in the closed space inside of a car and suggest that a substantial component of that risk is via aerosolized virus.

Observed Face Mask Use at Six Universities - United States, September-November 2020.

Approximately 41% of adults aged 18-24 years in the United States are enrolled in a college or university (1). Wearing a face mask can reduce transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (2), and many colleges and universities mandate mask use in public locations and outdoors when within six feet of others. Studies based on self-report have described mask use ranging from 69.1% to 86.1% among adults aged 18-29 years (3); however, more objective measures are needed. Direct observation by trained observers is the accepted standard for monitoring behaviors such as hand hygiene (4). In this investigation, direct observation was used to estimate the proportion of persons wearing masks and the proportion of persons wearing masks correctly (i.e., covering the nose and mouth and secured under the chin*) on campus and at nearby off-campus locations at six rural and suburban universities with mask mandates in the southern and western United States. Trained student observers recorded mask use for up to 8 weeks from fixed sites on campus and nearby. Among 17,200 observed persons, 85.5% wore masks, with 89.7% of those persons wearing the mask correctly (overall correct mask use: 76.7%). Among persons observed indoors, 91.7% wore masks correctly. The proportion correctly wearing masks indoors varied by mask type, from 96.8% for N95-type masks and 92.2% for cloth masks to 78.9% for bandanas, scarves, and similar face coverings. Observed indoor mask use was high at these six universities with mask mandates. Colleges and universities can use direct observation findings to tailor training and messaging toward increasing correct mask use.

Optimal Testing Choice and Diagnostic Strategies for Latent Tuberculosis Infection Among US-Born People Living with Human Immunodeficiency Virus (HIV).

BACKGROUND: Increased risk of progression from latent tuberculosis infection (LTBI) to tuberculosis (TB) disease among people living with human immunodeficiency virus (HIV; PLWH) prioritizes them for LTBI testing and treatment. Studies comparing the performance of interferon gamma release assays (IGRAs) and the tuberculin skin test (TST) among PLWH are lacking. METHODS: We used Bayesian latent class analysis to estimate the prevalence of LTBI and diagnostic characteristics of the TST, QuantiFERON Gold In-Tube (QFT), and T.SPOT-TB (TSPOT) among a prospective, multicenter cohort of US-born PLWH ≥5 years old with valid results for all 3 LTBI tests using standard US cutoffs (≥5 mm TST, ≥0.35 IU/mL QFT, ≥8 spots TSPOT). We also explored the performance of varying LTBI test cutoffs. RESULTS: Among 1510 PLWH (median CD4+ count 532 cells/mm3), estimated LTBI prevalence was 4.7%. TSPOT was significantly more specific (99.7%) and had a significantly higher positive predictive value (90.0%, PPV) than QFT (96.5% specificity, 50.7% PPV) and TST (96.8% specificity, 45.4% PPV). QFT was significantly more sensitive (72.2%) than TST (54.2%) and TSPOT (51.9%); negative predictive value of all tests was high (TST 97.7%, QFT 98.6%, TSPOT 97.6%). Even at the highest cutoffs evaluated (15 mm TST, ≥1.00 IU/mL QFT, ≥8 spots TSPOT), TST and QFT specificity was significantly lower than TSPOT. CONCLUSIONS: LTBI prevalence among this cohort of US-born PLWH was low compared to non-US born persons. TSPOT's higher PPV may make it preferable for testing US-born PLWH at low risk for TB exposure and with high CD4+ counts.

Effect of mixed strain infections on clinical and epidemiological features of tuberculosis in Florida.

Mixed infections with genetically distinct Mycobacterium tuberculosis (MTB) strains within a single host have been documented in different settings; however, this phenomenon is rarely considered in the management and care of new and relapse tuberculosis (T.B.) cases. This study aims to establish the epidemiological and clinical features of mixed infections among culture-confirmed T.B. patients enrolled in tuberculosis care at the Florida Department of Health (FDOH) and measure its association with T.B. mortality. We analyzed de-identified surveillance data of T.B. cases enrolled in T.B. care from April 2008 to January 2018. Mixed MTB infection was determined by the presence of more than one Copy Number Variant (CNV) in at least one locus, based on the genotype profile pattern of at least one isolate using 24-locus Mycobacterial Interspersed Repetitive Unit-Variable Number Tandem Repeat (MIRU-VNTR). The prevalence of mixed MTB infections among the 4944 culture-confirmed TB cases included in this analysis was 2.6% (129). Increased odds of mixed infections were observed among middle-aged patients, 45-64 years (AOR = 2.38; 95% CI: 0.99, 5.69; p = 0.0513), older adults 65 years and above (AOR = 3.95; 95% CI: 1.63, 9.58; p = 0.0023) and patients with diabetes (OR = 1.77; 95% CI: 1.12, 2.80; p = 0.0150). There was no significant association between mixed infections and death. Our study provides insight into the epidemiological and clinical characteristics of patients with mixed MTB infections, which is essential in the management of T.B. patients.

Viable SARS-CoV-2 in the air of a hospital room with COVID-19 patients.

Background - There currently is substantial controversy about the role played by SARS-CoV-2 in aerosols in disease transmission, due in part to detections of viral RNA but failures to isolate viable virus from clinically generated aerosols. Methods - Air samples were collected in the room of two COVID-19 patients, one of whom had an active respiratory infection with a nasopharyngeal (NP) swab positive for SARS-CoV-2 by RT-qPCR. By using VIVAS air samplers that operate on a gentle water-vapor condensation principle, material was collected from room air and subjected to RT-qPCR and virus culture. The genomes of the SARS-CoV-2 collected from the air and of virus isolated in cell culture from air sampling and from a NP swab from a newly admitted patient in the room were sequenced. Findings - Viable virus was isolated from air samples collected 2 to 4.8m away from the patients. The genome sequence of the SARS-CoV-2 strain isolated from the material collected by the air samplers was identical to that isolated from the NP swab from the patient with an active infection. Estimates of viable viral concentrations ranged from 6 to 74 TCID50 units/L of air. Interpretation - Patients with respiratory manifestations of COVID-19 produce aerosols in the absence of aerosol-generating procedures that contain viable SARS-CoV-2, and these aerosols may serve as a source of transmission of the virus.