Knowledge gaps and research priorities for understanding the transmission of Mycobacterium tuberculosis and other airborne infections

Despite 5 years of SARS-CoV-2 research, as well as decades of research on tuberculosis (TB), large gaps remain in understanding the transmission of airborne pathogens. Our aim was to delineate these gaps. Understanding them would enable evidence-based, practical efforts to reduce transmission. Building upon the 2017 Roadmap for TB Transmission Science, we interviewed experts in the field and identified six salient topics harboring holes in knowledge that impede prevention and control efforts. These include 1) fundamental elements of aerobiology, 2) detecting and measuring infectious respiratory particles directly in the air, 3) the infectiousness of asymptomatic TB (by extension, other lung infections) and 4) of calm tidal breathing – including their contributions to global epidemiology, 5) the role of ‘superspreading’ in disease incidence, and 6) the duration of infectiousness of highly drug-resistant TB treated with the newest, all-oral short-course regimens. Based on an extensive literature review, we update advances in science since 2017 and then summarize knowledge gaps and research priorities. Several recent systematic reviews all noted the relatively low quality of published research, so there is an overriding need for high-quality studies to provide evidence for national and international entities upon which to base recommendations, guidelines, and standards

Management of patients with multidrug-resistant/extensively drug-resistant tuberculosis in Europe: a TBNET consensus statement.

The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) substantially challenges TB control, especially in the European Region of the World Health Organization, where the highest prevalence of MDR/XDR cases is reported. The current management of patients with MDR/XDR-TB is extremely complex for medical, social and public health systems. The treatment with currently available anti-TB therapies to achieve relapse-free cure is long and undermined by a high frequency of adverse drug events, suboptimal treatment adherence, high costs and low treatment success rates. Availability of optimal management for patients with MDR/XDR-TB is limited even in the European Region. In the absence of a preventive vaccine, more effective diagnostic tools and novel therapeutic interventions the control of MDR/XDR-TB will be extremely difficult. Despite recent scientific advances in MDR/XDR-TB care, decisions for the management of patients with MDR/XDR-TB and their contacts often rely on expert opinions, rather than on clinical evidence. This document summarises the current knowledge on the prevention, diagnosis and treatment of adults and children with MDR/XDR-TB and their contacts, and provides expert consensus recommendations on questions where scientific evidence is still lacking

Experience with UV-C Air Disinfection in Some Russian Hospitals^†

Although the environmental control measure of ultraviolet germicidal irradiation (UVGI) for disinfection has not been widely used in the United States and some parts of the world in the past few decades, this technology has been well applied in Russia. UVGI technology has been particularly useful with regard to limiting TB transmission in medical facilities. There is good evidence that UV-C (180−280 nm) air disinfection can be a helpful intervention in reducing transmission of the SARS-CoV-2 virus

Antimicrobial drug resistance and infection prevention/control: lessons from tuberculosis

Antimicrobial drug resistance (AMR) is increasing rapidly worldwide, causing an estimated 700,000 deaths annually over the past decade, en route to becoming the leading global threat to public health by 2050 with an estimated 10 million deaths per year (more than heart disease, cancer, and stroke), while reducing global wealth by US$100 trillion. Yet AMR has not received the attention and action required to change this trajectory. Appropriate infection prevention and control (IPC) measures are needed to prevent transmission of infections to healthcare workers (HCWs), other patients, families, and the general public. In this review, we discuss a notable case study of AMR: highly drug-resistant tuberculosis (TB) has emerged repeatedly over the past 70 years as new drugs have been introduced, leading to new diagnostics, therapeutics, funding, public health strategies, and, in high-income countries, effective IPC measures that curtailed transmission. We review current efforts to control and prevent AMR using the example of drug-resistant tuberculosis to highlight important themes including laboratory systems, surveillance, control and prevention of healthcare-associated infections (especially among HCWs), better coordination across disciplines and diseases, and powerful advocacy/social change initiatives grounded in social and behavioral sciences. These strategies are the foundation of an effective response to the AMR threat to public health.</jats:p

Impact of GeneXpert MTB/RIF® on treatment initiation and outcomes of RIF-resistant and RIF-susceptible TB patients in Vladimir TB dispensary, Russia

Abstract Background The main advantage of GeneXpert MTB/RIF® (Xpert) molecular diagnostic technology is the rapid detection of M.tuberculosis DNA and mutations associated with rifampicin (RIF) resistance for timely initiation of appropriate treatment and, consequently, preventing further transmission of the disease. We assessed time to treatment initiation and treatment outcomes of RIF-resistant and RIF-susceptible TB patients diagnosed and treated in Vladimir TB Dispensary, Russia in 2012, before and after implementation of GeneXpert MTB/RIF® diagnostic technology. Methods All adult patients suspected of having TB during February–December 2012 underwent a clinical examination, chest x-ray, microscopy, culture, and phenotypic drug susceptibility testing (DST). Starting August 2012 Xpert diagnostic technology became available in the facility. We used logistic regression to compare treatment outcomes in pre-Xpert and post-Xpert periods. Kaplan-Meier curves and log-rank test were used to compare the time to treatment initiation between the groups. Results Of 402 patients screened for TB during February–December 2012, 338 were diagnosed with TB (280 RIF-susceptible, 58 RIF-resistant). RIF-resistant patients in the post-Xpert group started treatment with second-line drugs (SLD) earlier than those in pre-Xpert group (median 11 vs. 37 days, Log-rank p = 0.02). The hazard ratio for time to SLD treatment initiation was significantly higher in post-Xpert group (HR:2.06; 95%CI:1.09,3.89) compared to pre-Xpert group. Among the 53/58 RIF-resistant TB patients with available treatment outcome, 28 (53%) had successful outcomes (cured/completed treatment) including 15/26 (58%) in post-Xpert group versus 13/27 (48%) in pre-Xpert group. The observed difference, however, was not statistically significant (OR:0.69; 95%CI:0.23,2.06). Among RIF-susceptible TB cases time to treatment initiation was not significantly different between the groups (2 vs. 3 days, Log-rank p = 0.73). Of 252/280 RIF-susceptible TB cases with treatment outcome, 199 (79%) cases had successful outcome including 94/114 (82%) in post-Xpert group versus 105/138 (76%) in pre-Xpert group (OR:0.68; 95%CI:0.36,1.26). Conclusion We observed that availability of Xpert for initial diagnosis significantly reduced the time to SLD treatment for RIF-resistant patients in the Vladimir TB Dispensary. Although implementation of rapid diagnostics did not improve treatment outcomes, early diagnosis of MDR-TB is important for selection of appropriate treatment regimen and prevention of transmission of drug-resistant strains of TB. </jats:sec

Additional Drug Resistance of Multidrug-Resistant Tuberculosis in Patients in 9 Countries

Data from a large multicenter observational study of patients with multidrug-resistant tuberculosis (MDR TB) were analyzed to simulate the possible use of 2 new approaches to treatment of MDR TB: a short (9-month) regimen and a bedaquiline-containing regimen. Of 1,254 patients, 952 (75.9%) had no resistance to fluoroquinolones and second-line injectable drugs and thus would qualify as candidates for the 9-month regimen; 302 (24.1%) patients with resistance to a fluoroquinolone or second-line injectable drug would qualify as candidates for a bedaquiline-containing regimen in accordance with published guidelines. Among candidates for the 9-month regimen, standardized drug-susceptibility tests demonstrated susceptibility to a median of 5 (interquartile range 5–6) drugs. Among candidates for bedaquiline, drug-susceptibility tests demonstrated susceptibility to a median of 3 (interquartile range 2–4) drugs; 26% retained susceptibility to <2 drugs. These data may assist national TB programs in planning to implement new drugs and drug regimens