Background Bioaerosol-mediated transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via building ventilation systems has yet to be convincingly demonstrated. We used the South African Airborne Infections Research (AIR) facility near Pretoria to study human-to-animal (H2A) transmission of SARS-CoV-2 in newly diagnosed patients. While the facility was built to study tuberculosis transmission, this was its first adaptation to study H2A virus transmission. Methods Patients with clinically confirmed coronavirus disease 2019 were housed for up to 4 days in in the AIR facility with continuously exhausting patient ward air to hamsters housed in animal exposure rooms. After a 3-week exposure period, animals were held for an additional week to allow for antibody development. Animal sera were analyzed for anti-spike and plaque reduction activities and lung samples for pathology. Results Seven patients provided ≥400 in-residence hours over a 17-day period. Pair-housed naive golden Syrian hamsters (n = 216) received continuous exposure to mixed patient ward exhaust. Serum analyses revealed anti-SARS-CoV-2 immunoglobulin G in 58% of animals tested. Plaque reduction assays on 7 high-titer serum samples revealed neutralizing activity. Conclusions These results support the concept that viral bioaerosols generated from patients remain infectious over long-distance transport through a building ventilation system. The seroconversion among sentinel animals supports the long-held belief that airborne infections manifest as a stochastic rather than deterministic event that is subject to a threshold dose effect. Further confirmatory studies are necessary to characterize the relationship between the bioaerosol delivered and the infections that result in this controlled H2A transmission model.

Background. Most drug-resistant tuberculosis occurs due to transmission of unsuspected or ineffectively treated drug-resistant tuberculosis. The duration of treatment to stop person-to-person spread of drug-resistant tuberculosis is uncertain. We evaluated the impact of novel regimens, including BPaL (bedaquiline, 1200-mg linezolid, and pretomanid), on drug-resistant tuberculosis transmission, using the human-guinea pig (H-GP) transmission model. Methods. In experiment 1, patients initiated an optimized drug-resistant tuberculosis regimen including bedaquiline and linezolid. In experiment 2, patients initiated the BPaL regimen. We measured baseline infectivity for each cohort by exhausting ward air to one of two guinea pig exposure rooms (control group), each containing 90 guinea pigs, for 8 patient-days. Then, after 72 hours of treatment, ward air was exhausted to the second guinea pig exposure room for 8 patient-days (intervention group). The infectiousness of each cohort was compared by performing tuberculin skin tests in guinea pigs at baseline (before treatment) and 6 weeks after the exposure period. Results. In experiment 1, before treatment, 5 patients with drug-resistant tuberculosis infected 24 of 90 guinea pigs (26.7%) (control group). After treatment (72 hours after drug initiation), the same patients infected 25 of 90 guinea pigs (27.8%) (intervention group) (P > .99). In experiment 2, before treatment, 9 patients with drug-resistant tuberculosis infected 40 of 90 guinea pigs (44.4%) (control group). After treatment (beginning 72 hours after drug initiation), the same patients infected 0 of 90 guinea pigs (0%) (intervention group) (P < .0001). Conclusions. In this study, drug-resistant tuberculosis drug regimens, including bedaquiline and standard-dose linezolid for 72 hours, did not decrease drug-resistant tuberculosis transmission. In contrast, transmission was rapidly and completely inhibited in patients treated with BPaL for 72 hours, suggesting an early and profound impact on transmission.

Both probabilistic and deterministic models for prediction of infection transmission risk are potentially useful in understanding and controlling airborne infection transmission. The Wells-Riley model, developed by Edward Riley and colleagues, estimates infection transmission risk using the concept of quantum/quanta, proposed by Wells to circumvent the unknown factor of infectious dose. This model has been extensively used by researchers in recent years, and some have attempted to modify it to overcome its limitations and expand its applications. In some cases, however, researchers have misunderstood the concept of quanta and the mathematical requirements of the Wells-Riley model, leading to inappropriate uses and flawed modifications.A quantum is defined as the unknown average number of infectious particles required to initiate an infection in a susceptible host. Although a quantum of infection can be one or more infectious particles, Wells clearly understood that inhaled infectious particles normally cause infection as if by a single particle that reaches its target and overcomes host defenses.Since infection occurs as if by just one of an unknown number of infectious particles, integer values are used to count the number of quanta. This enabled Riley to derive the Wells-Riley model equation from a discrete probability distribution, representing the likelihood of inhaling at least one quantum. Revisiting these definitions in greater detail in this study enables an examination of the limitations of studies that have used or modified this model and provides valuable insights for future research.

Determining the extent and duration of infectiousness of people with pulmonary tuberculosis (PWPTB) is critical for various aspects of tuberculosis care, including decisions regarding isolation. Studies suggest considerable heterogeneity in infectiousness of PWPTB. Pretreatment, measures of bacillary burden, including sputum smear microscopy, culture time to positivity, and Xpert MTB/RIF cycle threshold (Ct) value, predict the risk of transmission to contacts. Index patients with smear-negative disease pose lower infectious risk than those who have smear-positive disease, and household contact infection is more likely with index patients who have lower Xpert Ct values. Newer tools that enable detection of Mycobacterium tuberculosis complex from cough aerosol sampling and face mask sampling may be better predictors of contact infection risk. Clinical factors such as cough strength and frequency, and presence of cavitation on chest imaging, may also assist with risk prediction. Posttreatment, smear and culture status are poor predictors of infectiousness. While the exact duration of infectiousness post-treatment initiation remains uncertain, data from human-to-guinea pig transmission studies and clinical studies suggest that effective treatment results in a rapid decline in infectiousness, irrespective of smear or culture conversion. This is largely supported by early bactericidal activity and transcriptomic studies, as well as cough aerosol sampling studies, although a subset of patients may have persistent cough aerosol positivity. These findings can enable a more nuanced approach to isolation decision making while further research studies are awaited.

Tuberculosis (TB) transmission in healthcare facilities is common in high-incidence countries. Yet, the optimal approach for identifying inpatients who may have TB is unclear. We evaluated the diagnostic accuracy of qXR (Qure.ai, India) computer-aided detection (CAD) software versions 3.0 and 4.0 (v3 and v4) as a triage and screening tool within the FAST (Find cases Actively, Separate safely, and Treat effectively) transmission control strategy. We prospectively enrolled two cohorts of patients admitted to a tertiary hospital in Lima, Peru: one group had cough or TB risk factors (triage) and the other did not report cough or TB risk factors (screening). We evaluated the sensitivity and specificity of qXR for the diagnosis of pulmonary TB using culture and Xpert as primary and secondary reference standards, including stratified analyses based on risk factors. In the triage cohort (n = 387), qXR v4 sensitivity was 0.91 (59/65, 95% CI 0.81-0.97) and specificity was 0.32 (103/322, 95% CI 0.27-0.37) using culture as reference standard. There was no difference in the area under the receiver-operating-characteristic curve (AUC) between qXR v3 and qXR v4 with either a culture or Xpert reference standard. In the screening cohort (n = 191), only one patient had a positive Xpert result, but specificity in this cohort was high (>90%). A high prevalence of radiographic lung abnormalities, most notably opacities (81%), consolidation (62%), or nodules (58%), was detected by qXR on digital CXR images from the triage cohort. qXR had high sensitivity but low specificity as a triage in hospitalized patients with cough or TB risk factors. Screening patients without cough or risk factors in this setting had a low diagnostic yield. These findings further support the need for population and setting-specific thresholds for CAD programs.

Far-UVC radiation between 200 and 230 nm is a promising technology for reducing airborne disease transmission. Previous work with far-UVC lamps has demonstrated the efficacy of far-UVC radiation to inactivate bacteria and viruses while presenting minimal human health hazards. While far-UVC intentionally exposes the occupied space, effectively disinfecting air between occupants, installations must still ensure that occupant eye and skin exposure is within the recommended daily limits. This study examines far-UVC-sensitive films for measuring the dose received by occupants within two real-world far-UVC installations. The film is characterized for accuracy, angular response, wavelength response, and sources of uncertainty in film response, and used to obtain individual exposure doses that account for both the non-uniform irradiance and the unique motion of individuals within the space. Dosimetry results using the films, which account for the time-weighted average exposure of an occupant, ranged from 10% to 49% of the maximum calculated stationary dose based on peak irradiance measurements. Results from this study spotlight the need to incorporate time-weighted average considerations into the design and safety assessment of far-UVC installations to ultimately operate far-UVC technology with its full potential to prevent the spread of potentially fatal infectious diseases.

Closing the TB diagnostic gap is an urgent priority, for which non-sputum-based tests are needed. We evaluated the diagnostic accuracy of Aeonose, an exhaled breath test (EBT), as a TB triage test.Patients with cough or TB risk factors admitted to a tertiary hospital in Lima, Peru, were prospectively enrolled and underwent EBT. We evaluated EBT sensitivity and specificity for diagnosing pulmonary TB using culture and Xpert as primary and secondary reference standards and conducted stratified analyses based on risk factors.EBT sensitivity was 85% (95% CI 72.9–93.4), and specificity was 51% (95% CI 46.0–56.6) in the training cohort (n = 417). EBT sensitivity was 70% (95% CI 47.1–86.8), and specificity was 54% (95% CI 44.8–63.6) in the validation cohort (n = 139) using the culture reference standard, with higher sensitivity (78%) when using the Xpert reference standard (n = 156). Sensitivity (60%) and specificity (48%) were lower when patients with prior TB were included. In a subset of participants randomly selected for interviews, 94% (15/16) preferred EBT to sputum-based testing.EBT had moderate sensitivity and low specificity as a TB triage test in this hospitalised cohort with cough or risk factors. Diagnostic accuracy was lower in people with prior TB.

Background Respiratory isolation of people with pulmonary tuberculosis (TB), including after treatment initiation, is used to prevent community-based transmission; yet guidelines on duration are limited and implementation is heterogeneous. This systematic review synthesized evidence on respiratory isolation for TB to inform National TB Coalition of America guidelines.Methods After searching 6 databases, 8 reviewers screened and extracted data in duplicate on effects of respiratory isolation compared to no isolation or masking. Studies were stratified by outcomes: TB infection or disease in contacts, mortality, hospitalization duration, patient and health system costs, and impact on mental health or stigma. We used a convergent integrated approach to synthesize quantitative and qualitative findings and assess limitations.Results Seventeen studies were included. There were limited data directly comparing isolation to non-isolation interventions, including effects after treatment initiation. One randomized controlled trial suggested treatment in a sanatorium versus at home did not affect TB incidence in contacts. Modeling studies suggest isolation may reduce transmission but relied on various assumptions, and isolation was implemented alongside other interventions. Descriptive, mixed-methods, and qualitative studies described adverse impacts of isolation on employment, education, food/housing security, and mental health due to transmission fears, stigma, and social isolation. Impacts were compounded in marginalized groups including Indigenous and incarcerated persons.Conclusions Data to support current isolation practices, particularly after effective treatment initiation, to reduce TB transmission in communities are limited. Public health guidance should weigh the negative impacts on people with TB against decreased community transmission to make evidence-based decisions about respiratory isolation. There are limited data on the effects of respiratory isolation, particularly after treatment initiation, to prevent community-based tuberculosis transmission. Isolation adversely affects employment, education, food/housing security, and mental health. Isolation decisions should weigh benefits and risks for patients and communities.

The COVID-19 pandemic has created an urgent need to utilize existing and develop new intervention technologies for SARS-CoV-2 inactivation on surfaces and in the air. Ultraviolet (UV) technology has been shown to be an effective antimicrobial intervention. Here a study was conducted to determine the efficacy of commercially available UV and blue light-based devices for inactivating HCoV-229E, a surrogate of SARS-CoV-2. The results indicate that two UV devices designed for surface disinfection, with doses of 8.07 mu J/cm(2) for the 254 nm device and 20.61 mu J/cm(2) for the 275 nm device, were efficient in inactivating 4.94 logs of surface inoculated HCoV-229E. Additionally, a 222 nm UV device with intended ceiling-based operation was effective in inactivating 1.7 logs of the virus inoculated on surface, with a dose of 6 mJ/cm(2). A ceiling-based device designed to emit blue light at 405 nm was found to produce 89% reduction in HCoV-229E inoculated on a surface for a dose of 78 J/cm(2). Finally, the UV based 222 nm device was found to produce a 90% reduction in the concentration of airborne HCoV-229E, at a 55 mu J/cm(2) dose. These results are indicative of the great potential of using UV based technology for the control of SARS-CoV-2.Implications: An important avenue of arresting COVID-19 and future pandemics caused by infectious pathogens is through environmental disinfection. To this effect, the study presented here evaluates commercially available UV and blue light based antimicrobial devices for their ability to kill the human coronavirus HCoV-229E, a surrogate of SARS-CoV-2, on surfaces and in air. The results indicate that two handheld UV devices produced complete inactivation of surface viral inoculum and a UVC ceiling based device produced 1 log reduction in HCoV-229E in air. These results imply the efficacy of UV technology as an antimicrobial tool, especially for rapid disinfection of indoor air.

Abstract Background The duration of respiratory isolation for infectious tuberculosis (TB) is based on limited data and expert opinion. Yet the impact of isolation on persons with TB and public health programs is significant. This systematic review synthesized evidence on public health and patient-important outcomes of respiratory isolation for TB to inform revised National TB Controllers Association guidelines. Methods We searched PubMed, EMBASE, CINAHL, Web of Science, Cochrane Central and WHO-Global Index Medicus using terms for TB and respiratory isolation (Figure). Eight reviewers screened abstracts, full-texts, and extracted data in pairs. Inclusion criteria were data on effects of respiratory isolation compared to no isolation or masking. Studies were stratified by outcomes: TB infection or TB disease in contacts, mortality, hospitalization duration, patient and health system costs, and impact on mental health or stigma. A convergent mixed methods approach was used to integrate quantitative and qualitative findings and assess limitations. Results After screening 3640 publications, 17 studies: randomized controlled trial (1), quasi-experimental (1), cohort (1), modelling (3), mixed-methods studies (3), and qualitative (8), were included. The trial (conducted in the 1950s) suggested treatment in isolation in a sanatorium versus at home did not affect TB infection (22% versus 23%) or disease incidence (11% versus 10.5%) in contacts (Table 1). Modelling studies suggest isolation may reduce transmission, including drug-resistant TB, but highlighted isolation is rarely implemented without other interventions, including treatment or masking. Many studies described adverse impacts of isolation on employment, education, food/housing security, and mental health due to transmission fears, stigma and social isolation (Tables 2 & 3). Impacts were compounded in marginalized groups such as indigenous and incarcerated persons. Conclusion Data to support current isolation practices, particularly once effective treatment is started, to reduce TB transmission in communities are limited. Public health guidance should consider the negative impacts on persons with TB against the potential for transmission reduction to facilitate evidence-based decisions about respiratory isolation. Disclosures All Authors: No reported disclosures

We performed studies investigating the feasibility of human to animal (H2A) model system to test whether patient generated respiratory bioaerosols hold infective capacity when traversing long distance airborne transport within the built environment. South African patients, clinically confirmed by facemask sampling to be exhaling SARS-CoV-2 genomic sequence, were recruited and housed for multiple days in a clinical ward with a uniquely designed building ventilation system continuously channeling exhaust airflow to individual microisolator animal caging units located proximal but segregated from clinic space (University of Pretoria AIR facility).

This study used Computational Fluid Dynamics (CFD) to investigate air disinfection for SARS-CoV-2 by the Upper-Room Germicidal Ultraviolet (UR-GUV), with focus on ceiling impact. The study includes three indoor settings, i.e., low (airport bus), medium (classroom) and high (rehearsal room) ceilings, which were ventilated with 100% clean air (CA case), 80% air-recirculation with a low filtration (LF case), and 80% air-recirculation with a high filtration (HF case). According to the results, using UR-GUV can offset the increased infection risk caused by air recirculation, with viral concentrations in near field (NF) and far field (FF) in the LF case similar to those in the CA case. In the CA case, fraction remaining (FR) was 0.48-0.73 with 25% occupancy rate (OR) and 0.49-0.91 with 45% OR in the bus, 0.41 in NF and 0.11 in FF in the classroom, and 0.18 in NF and 0.09 in FF in the rehearsal room. Obviously, UR-GUV performance in NF can be improved in a room with a high ceiling where FR has a power relationship with UV zone height. As using UR-GUV can only extend the exposure time to get infection risk of 1% (T1%) to 8 min in NF in the classroom, and 47 min in NF in the rehearsal room, it is necessary to abide by social distancing in the two rooms. In addition, T1% in FF was calculated to be 18.3 min with 25% OR and 21.4% with 45% OR in the airport bus, showing the necessity to further wear a mask.

Objective: To evaluate the effect of the FAST (Find cases Actively, Separate safely, Treat effectively) strategy on time to tuberculosis diagnosis and treatment for patients at a general hospital in a tuberculosis-endemic setting. Design: Prospective cohort study with historical controls. Participants: Patients diagnosed with pulmonary tuberculosis during hospitalization at Hospital Nacional Hipolito Unanue in Lima, Peru. Methods: The FAST strategy was implemented from July 24, 2016, to December 31, 2019. We compared the proportion of patients with drug susceptibility testing and tuberculosis treatment during FAST to the 6-month period prior to FAST. Times to diagnosis and tuberculosis treatment were also compared using Kaplan-Meier plots and Cox regressions. Results: We analyzed 75 patients diagnosed with pulmonary tuberculosis through FAST. The historical cohort comprised 76 patients. More FAST patients underwent drug susceptibility testing (98.7% vs 57.8%; OR, 53.8; P < .001), which led to the diagnosis of drug-resistant tuberculosis in 18 (24.3%) of 74 of the prospective cohort and 4 (9%) of 44 of the historical cohort (OR, 3.2; P = .03). Overall, 55 FAST patients (73.3%) started tuberculosis treatment during hospitalization compared to 39 (51.3%) controls (OR, 2.44; P = .012). FAST reduced the time from hospital admission to the start of TB treatment (HR, 2.11; 95% CI, 1.39-3.21; P < .001). Conclusions: Using the FAST strategy improved the diagnosis of drug-resistant tuberculosis and the likelihood and speed of starting treatment among patients with pulmonary tuberculosis at a general hospital in a tuberculosis-endemic setting. In these settings, the FAST strategy should be considered to reduce tuberculosis transmission while simultaneously improving the quality of care.

BACKGROUND:High rates of tuberculosis (TB) transmission occur in hospitals in high-incidence countries, yet there is no validated way to evaluate the impact of hospital design and function on airborne infection risk. We hypothesized that personal ambient carbon dioxide (CO2) monitoring could serve as a surrogate measure of rebreathed air exposure associated with TB infection risk in health workers (HWs). METHODS:We analyzed baseline and repeat (12-month) interferon-γ release assay (IGRA) results in 138 HWs in Cape Town, South Africa. A random subset of HWs with a baseline negative QuantiFERON Plus (QFT-Plus) underwent personal ambient CO2 monitoring. RESULTS:Annual incidence of TB infection (IGRA conversion) was high (34%). Junior doctors were less likely to have a positive baseline IGRA than other HWs (OR, 0.26; P = .005) but had similar IGRA conversion risk. IGRA converters experienced higher median CO2 levels compared to IGRA nonconverters using quantitative QFT-Plus thresholds of ≥0.35 IU/mL (P < .02) or ≥1 IU/mL (P < .01). Median CO2 levels were predictive of IGRA conversion (odds ratio [OR], 2.04; P = .04, ≥1 IU/mL threshold). Ordinal logistic regression demonstrated that the odds of a higher repeat quantitative IGRA result increased by almost 2-fold (OR, 1.81; P = .01) per 100 ppm unit increase in median CO2 levels, suggesting a dose-dependent response. CONCLUSIONS:HWs face high occupational TB risk. Increasing median CO2 levels (indicative of poor ventilation and/or high occupancy) were associated with higher likelihood of HW TB infection. Personal ambient CO2 monitoring may help target interventions to decrease TB transmission in healthcare facilities and help HWs self-monitor occupational risk, with implications for other airborne infections including coronavirus disease 2019.

Aerosol transmission is now widely accepted as the principal way that COVID-19 is spread, as has the importance of ventilation-natural and mechanical. But in other than healthcare facilities, mechanical ventilation is designed for comfort, not airborne infection control, and cannot achieve the 6 to 12 room air changes per hour recommended for airborne infection control. More efficient air filters have been recommended in ventilation ducts despite a lack of convincing evidence that SARS-CoV-2 virus spreads through ventilation systems. Most transmission appears to occur in rooms where both an infectious source COVID-19 case and other susceptible occupants share the same air. Only two established room-based technologies are available to supplement mechanical ventilation: portable room air cleaners and upper room germicidal UV air disinfection. Portable room air cleaners can be effective, but performance is limited by their clean air delivery rate relative to room volume. SARS-CoV-2 is highly susceptible to GUV, an 80-year-old technology that has been shown to safely, quietly, effectively and economically produce the equivalent of 10 to 20 or more air changes per hour under real life conditions. For these reasons, upper room GUV is the essential engineering intervention for reducing COVID-19 spread.

Background Healthcare workers (HWs) have at least twice the risk of tuberculosis (TB) compared to the general population. There is growing emphasis on latent TB infection (LTBI) in high-risk populations. Yet we know little about HWs' perspectives of LTBI testing and treatment to inform implementation in high-incidence settings. We developed a qualitative networked approach to analyze HWs' perspectives on LTBI testing and treatment. Methods We conducted 22 in-depth interviews with nurse and physician stakeholders, who had been recruited as part of a larger study evaluating TB transmission risk in HWs at Tygerberg Hospital, Cape Town, South Africa. We performed open coding to identify emergent themes and selective coding to identify relevant text citations. We used thematic analysis to inductively derive the CARD (Constraints, Actions, Risks, Desires) framework. Results All HWs desired to avoid developing TB but few felt this was actionable. Despite LTBI knowledge gaps, safety and cost concerns, most HWs reported hypothetical willingness to take LTBI treatment. The CARD framework showed that desire and action related to LTBI testing and treatment was clearly framed by the interactions between constraints, administrative action, and risk. The surprise HWs described on receiving a negative LTBI (Quantiferon-Plus) result suggests LTBI testing may recalibrate HWs' perceptions regarding the futility of actions to reduce their TB risk. Conclusions LTBI testing and treatment are acceptable to HWs and could counteract the perceived inevitability of occupational TB infection that currently may limit risk reduction action. This should be coupled with administrative leadership and infrastructural support. The CARD analytic framework is a helpful tool for implementation scientists to understand current practices within complex health systems. Application of CARD could facilitate the development of contextually-relevant interventions to address important public health problems such as occupational TB.