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In settings with high tuberculosis (TB) endemicity, distinct genotypes of the Mycobacterium tuberculosis complex (MTBC) often differ in prevalence. However, the factors leading to these differences remain poorly understood. Here we studied the MTBC population in Dar es Salaam, Tanzania over a six-year period, using 1,082 unique patient-derived MTBC whole-genome sequences (WGS) and associated clinical data. We show that the TB epidemic in Dar es Salaam is dominated by multiple MTBC genotypes introduced to Tanzania from different parts of the world during the last 300 years. The most common MTBC genotypes deriving from these introductions exhibited differences in transmission rates and in the duration of the infectious period, but little differences in overall fitness, as measured by the effective reproductive number. Moreover, measures of disease severity and bacterial load indicated no differences in virulence between these genotypes during active TB. Instead, the combination of an early introduction and a high transmission rate accounted for the high prevalence of L3.1.1, the most dominant MTBC genotype in this setting. Yet, a longer co-existence with the host population did not always result in a higher transmission rate, suggesting that distinct life-history traits have evolved in the different MTBC genotypes. Taken together, our results point to bacterial factors as important determinants of the TB epidemic in Dar es Salaam.

Background Growing evidence suggests an important contribution of airborne transmission to the overall spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), in particular via smaller particles called aerosols. However, the contribution of school children to SARS-CoV-2 transmission remains uncertain. The aim of this study was to assess transmission of airborne respiratory infections and the association with infection control measures in schools using a multiple-measurement approach. Methods and findings We collected epidemiological (cases of Coronavirus Disease 2019 (COVID-19)), environmental (CO.sub.2, aerosol and particle concentrations), and molecular data (bioaerosol and saliva samples) over 7 weeks from January to March 2022 (Omicron wave) in 2 secondary schools (n = 90, average 18 students/classroom) in Switzerland. We analyzed changes in environmental and molecular characteristics between different study conditions (no intervention, mask wearing, air cleaners). Analyses of environmental changes were adjusted for different ventilation, the number of students in class, school and weekday effects. We modeled disease transmission using a semi-mechanistic Bayesian hierarchical model, adjusting for absent students and community transmission. Molecular analysis of saliva (21/262 positive) and airborne samples (10/130) detected SARS-CoV-2 throughout the study (weekly average viral concentration 0.6 copies/L) and occasionally other respiratory viruses. Overall daily average CO.sub.2 levels were 1,064 ± 232 ppm (± standard deviation). Daily average aerosol number concentrations without interventions were 177 ± 109 1/cm.sup.3 and decreased by 69% (95% CrI 42% to 86%) with mask mandates and 39% (95% CrI 4% to 69%) with air cleaners. Compared to no intervention, the transmission risk was lower with mask mandates (adjusted odds ratio 0.19, 95% CrI 0.09 to 0.38) and comparable with air cleaners (1.00, 95% CrI 0.15 to 6.51). Study limitations include possible confounding by period as the number of susceptible students declined over time. Furthermore, airborne detection of pathogens document exposure but not necessarily transmission. Conclusions Molecular detection of airborne and human SARS-CoV-2 indicated sustained transmission in schools. Mask mandates were associated with greater reductions in aerosol concentrations than air cleaners and with lower transmission. Our multiple-measurement approach could be used to continuously monitor transmission risk of respiratory infections and the effectiveness of infection control measures in schools and other congregate settings., Author(s): Nicolas Banholzer 1, Kathrin Zürcher 1, Philipp Jent 2, Pascal Bittel 3, Lavinia Furrer 3, Matthias Egger 1,4,5, Tina Hascher 6, Lukas Fenner 1,* 1 Introduction The spread of [...]

Introduction: Identification of persons living with human immunodeficiency virus (HIV)-associated tuberculosis (TB) at increased risk for unfavourable TB outcomes would inform efforts to improve such outcomes. We sought to identify factors associated with a decreased risk of unfavourable TB treatment outcomes among people living with HIV-infection (PLHIV) in low- and middle-income countries (LMIC), with a specific focus on directly observed therapy (DOT) compared with self-administered therapy (SAT) during the continuation phase of anti-TB therapy. Methods: We conducted a retrospective cohort study among adults diagnosed with HIV-associated TB in Africa, Asia and the Americas from 2012 to 2013; data were collected from 2012 to 2016. Unfavourable TB treatment outcomes (death during TB treatment, and TB treatment failure or recurrence) were defined according to World Health Organization criteria. Receipt of DOT was obtained at the site level and defined as [greater than or equal to]5 days of DOT per week. The person administering DOT and treatment location varied by site. Lack of receipt of DOT was defined as SAT. Multivariable logistic regression estimated the adjusted odds of unfavourable TB treatment outcomes. Results: Among 1862 adults with HIV-associated TB included, 252 (13.5%) had unfavourable TB outcomes (226 deaths, 26 recurrences/failures). Overall, 1825 (98%) received DOT in the intensive phase and 1617 (87%) received DOT in the continuation phase. DOT in the continuation phase was not significantly associated with unfavourable TB outcomes (aOR 1.43, 95% CI 0.86 to 2.38) compared to SAT. Body mass index (BMI) change during anti-TB treatment (per 2 units increase, aOR 0.74, 95% CI 0.68 to 0.82) and CD[4.sup.+] count at TB diagnosis (200 vs. 50 cells/[micro]L, aOR 0.54, 95% CI 0.39 to 0.73) were both independently associated with decreased odds of unfavourable TB treatment outcomes. Conclusions: In this large, international cohort of people living with HIV-associated TB in LMIC who received intensive phase DOT, DOT during the continuation phase of anti-TB therapy was not associated with a decreased odds of unfavourable TB treatment outcomes compared to SAT. Randomized trials evaluating the effect of continuation-phase DOT on TB outcomes among PLHIV are needed. Keywords: tuberculosis; directly observed therapy; body mass index; human immunodeficiency virus infection; antiretroviral therapy, 1 | INTRODUCTION Tuberculosis (TB) remains a serious public health problem, particularly among people living with human immunodeficiency virus (PLHIV). TB is the leading cause of death among PLHIV worldwide, [...]

: Introduction: Dolutegravir is being scaled up globally as part of antiretroviral therapy (ART), but for people with HIV and tuberculosis co‐infection, its use is complicated by a drug–drug interaction with rifampicin requiring an additional daily dose of dolutegravir. This represents a disadvantage over efavirenz, which does not have a major drug–drug interaction with rifampicin. We sought to describe HIV clinic practices for prescribing concomitant dolutegravir and rifampicin, and characterize virologic outcomes among patients with tuberculosis co‐infection receiving dolutegravir or efavirenz. Methods: Within the four sub‐Saharan Africa regions of the International epidemiology Databases to Evaluate AIDS consortium, we conducted a site survey (2021) and a cohort study (2015–2021). The cohort study used routine clinical data and included patients newly initiating or already receiving dolutegravir or efavirenz at the time of tuberculosis diagnosis. Patients were followed from tuberculosis diagnosis until viral suppression ( Results: In the survey, 86 of 90 (96%) HIV clinics in 18 countries reported prescribing dolutegravir to patients who were receiving rifampicin as part of tuberculosis treatment, with 77 (90%) reporting that they use twice‐daily dosing of dolutegravir, of which 74 (96%) reported having 50 mg tablets available to accommodate twice‐daily dosing. The cohort study included 3563 patients in 11 countries, with 67% newly or recently initiating ART. Among patients receiving dolutegravir (n = 465), the cumulative incidence of viral suppression was 58.9% (95% confidence interval [CI]: 54.3–63.3%), switching ART regimen was 4.1% (95% CI: 2.6–6.2%) and loss to program/death was 23.4% (95% CI: 19.7–27.4%). Patients receiving dolutegravir had improved viral suppression compared with patients receiving efavirenz who had a tuberculosis diagnosis before site dolutegravir availability (adjusted subdistribution hazard ratio [aSHR]: 1.47, 95% CI: 1.28–1.68) and after site dolutegravir availability (aSHR 1.28, 95% CI: 1.08–1.51). Conclusions: At a programmatic level, dolutegravir was being widely prescribed in sub‐Saharan Africa for people with HIV and tuberculosis co‐infection with a dose adjustment for the drug–drug interaction with rifampicin. Despite this more complex regimen, our cohort study revealed that dolutegravir did not negatively impact viral suppression., INTRODUCTION Dolutegravir, an integrase strand transfer inhibitor (InSTI), is recommended as part of preferred antiretroviral therapy (ART) regimens for people with HIV (PWH) [1, 2]. Globally, HIV treatment programs are [...]

Background Using a multiple-measurement approach, we examined the real-world effectiveness of portable HEPA air filtration devices (air cleaners) in a school setting. Methods We collected data over 7 weeks during winter 2022/2023 in 2 Swiss secondary school classes: environmental (CO2, particle concentrations), epidemiologic (absences related to respiratory infections), audio (coughing), and molecular (bioaerosol and saliva samples). Using a crossover design, we compared particle concentrations, coughing, and risk of infection with and without air cleaners. Results All 38 students participated (age, 13 – 15 years). With air cleaners, mean particle concentration decreased by 77% (95% credible interval, 63% − 86%). There were no differences in CO2 levels. Absences related to respiratory infections were 22 without air cleaners vs 13 with them. Bayesian modeling suggested a reduced risk of infection, with a posterior probability of 91% and a relative risk of 0.73 (95% credible interval, 0.44 – 1.18). Coughing also tended to be less frequent (posterior probability, 93%), indicating that fewer symptomatic students were in class. Molecular analysis detected mainly non–SARS-CoV-2 viruses in saliva (50/448 positive) but not in bioaerosols (2/105) or on the HEPA filters of the air cleaners (4/160). The molecular detection rate in saliva was similar with and without air cleaners. Spatiotemporal analysis of positive saliva samples identified several likely transmissions. Conclusions Air cleaners improved air quality and showed potential benefits in reducing respiratory infections. Airborne detection of non–SARS-CoV-2 viruses was rare, suggesting that these viruses may be more difficult to detect in the air. Future studies should examine the importance of close contact and long-range transmission and the cost-effectiveness of using air cleaners. [ABSTRACT FROM AUTHOR]

Introduction: Extrapulmonary tuberculosis (EPTB) is difficult to confirm bacteriologically and requires specific diagnostic capacities. Diagnosis can be especially challenging in under-resourced settings. We studied diagnostic modalities and clinica outcomes of EPTB compared to pulmonary tuberculosis (PTB) among HIV-positive adults in antiretroviral therapy (ART) programmes in low- and middle-income countries (LMIC). Methods: We collected data from HIV-positive TB patients (>16 years) in 22 ART programmes participating in the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium in sub-Saharan Africa, Asia-Pacific, and Caribbean, Centra and South America regions between 2012 and 2014. We categorized TB as PTB or EPTB (EPTB included mixed PTB/EPTB). We used multivariable logistic regression to assess associations with clinical outcomes. Results and Discussion: We analysed 2695 HIV-positive TB patients. Median age was 36 years (interquartile range (IQR) 30 to 43), 1102 were female (41%), and the median CD4 count at TB treatment start was 114 cells/pL (IQR 40 to 248). Overall, 1930 had PTB (72%), and 765 EPTB (28%). Among EPTB patients, the most frequently involved sites were the lymph nodes (24%), pleura (15%), abdomen (11%) and meninges (6%). The majority of PTB (1123 of 1930, 58%) and EPTB (582 of 765, 76%) patients were diagnosed based on clinical criteria. Bacteriological confirmation (using positive smear microscopy, culture, Xpert MTB/RIF, or other nucleic acid amplification tests result) was obtained in 897 of 1557 PTB (52%) and 183 of 438 EPTB (42%) patients. EPTB was not associated with higher mortality compared to PTB (adjusted odd ratio (aOR) 1.0, 95% CI 0.8 to 1.3), but TB meningitis was (aOR 1.9, 95% CI 1.0 to 3.1). Bacteriological confirmation was associated with reduced mortality among PTB patients (aOR 0.7, 95% CI 0.6 to 0.8) and EPTB patients (aOR 0.3 95% CI 0.1 to 0.8) compared to TB patients with a negative test result. Conclusions: Diagnosis of EPTB and PTB at ART programmes in LMIC was mainly based on clinical criteria. Greater availability and usage of TB diagnostic tests would improve the diagnosis and clinical outcomes of both EPTB and PTB. Keywords: extrapulmonary tuberculosis; pulmonary tuberculosis; tuberculosis; HIV-positive patients; low- and middle-income countries; diagnostics; mortality; lost to follow-up, 1 | INTRODUCTION In low- and middle-income countries (LMIC), tuberculosis (TB) accounts for approximately 40% of HIV/AIDS-related deaths among adults, and half of those TB cases are undiagnosed at the [...]

Introduction: Chronic immune activation due to ongoing HIV replication may lead to impaired immune responses against opportunistic infections such as tuberculosis (TB). We studied the role of HIV replication as a risk factor for incident TB after starting antiretroviral therapy (ART). Methods: We included all HIV-positive adult patients ([greater than or equal to]16 years) in care between 2000 and 2014 at three ART programmes in South Africa. Patients with previous TB were excluded. Missing CD4 cell counts and HIV-RNA viral loads at ART start (baseline) and during follow-up were imputed. We used parametric survival models to assess TB incidence (pulmonary and extrapulmonary) by CD4 cell and HIV-RNA levels, and estimated the rate ratios for TB by including age, sex, baseline viral loads, CD4 cell counts, and WHO clinical stage in the model. We also used Poisson general additive regression models with time-updated CD4 and HIV-RNA values, adjusting for age and sex. Results: We included 44,260 patients with a median follow-up time of 2.7 years (interquartile range [IQR] 1.0-5.0); 3,819 incident TB cases were recorded (8.6%). At baseline, the median age was 34 years (IQR 28-41); 30,675 patients (69.3%) were female. The median CD4 cell count was 156 cells/[micro]L (IQR 79-229) and the median HIV-RNA viral load 58,000 copies/mL (IQR 6,000-240,000). Overall TB incidence was 26.2/1,000 person-years (95% confidence interval [CI] 25.3-27.0). Compared to the lowest viral load category (0-999 copies/mL), the adjusted rate ratio for TB was 1.41 (95% CI 1.15-1.75, p < 0.001) in the highest group (>10,000 copies/mL). Time-updated analyses for CD4/HIV-RNA confirmed the association of viral load with the risk for TB. Conclusions: Our results indicate that ongoing HIV replication is an important risk factor for TB, regardless of CD4 cell counts, and underline the importance of early ART start and retention on ART. Keywords: tuberculosis; HIV; antiretroviral treatment; viral load; CD4 cell count; time-updated; incidence; opportunistic infection; prediction, Introduction In 2014, almost 1.5 million people died from tuberculosis (TB), and an estimated 9.6 million developed the disease worldwide [1]. TB is now the leading cause of death from [...]