Tuberculosis Infection Control Research Articles

Comprehensive identification of immuno-related transcriptional signature for active pulmonary tuberculosis by integrated analysis of array and single cell RNA-seq

BackgroundTuberculosis (TB) continues to be a major cause of morbidity and mortality worldwide. However, the molecular mechanism underlying immune response to human infection with Mycobacterium tuberculosis (Mtb) remains unclear. Assessing changes in transcript abundance in blood between health and disease on a genome-wide scale affords a comprehensive view of the impact of Mtb infection on the host defense and a reliable way to identify novel TB biomarkers. MethodsWe combined expression profiling by array and single cell RNA-sequencing (scRNA-seq) via 10X Genomics platform to better illustrate the immuno-related transcriptional signature of TB and explore potential diagnostic markers for differentiating TB from latent tuberculosis infection (LTBI) and healthy control (HC). FindingsPathway analysis based on differential expressed genes (DEGs) revealed that immune transcriptional profiling could effectively differ TB with LTBI and HC. Following WGCNA and PPI network analysis based on DEGs, we screened out three key immuno-related hub genes (ADM, IFIT3 and SERPING1) highly associated with TB. Further validation found only ADM expression significantly increased in TB patients in both adult and children's datasets. By comparing the scRNA-seq datasets from TB, LTBI and HC, we observed a remarkable elevated expression level and proportion of ADM in TB Myeloid cells, further supporting that ADM expression changes could distinguish patients with TB from LTBI and HC. Besides, the hsa-miR-24–3p-NEAT1-ADM-CEBPB regulation pathway might be one of the critical networks regulating the pathogenesis of TB. Although further investigation in a larger cohort is warranted, we provide useful and novel insight to explore the potential candidate genes for TB diagnosis and intervention. InterpretationWe propose that the expression of ADM in peripheral blood could be used as a novel biomarker for differentiating TB with LTBI and HC.

Estimating waiting times, patient flow, and waiting room occupancy density as part of tuberculosis infection prevention and control research in South African primary health care clinics.

Transmission of respiratory pathogens, such as Mycobacterium tuberculosis and severe acute respiratory syndrome coronavirus 2, is more likely during close, prolonged contact and when sharing a poorly ventilated space. Reducing overcrowding of health facilities is a recognised infection prevention and control (IPC) strategy; reliable estimates of waiting times and 'patient flow' would help guide implementation. As part of the Umoya omuhle study, we aimed to estimate clinic visit duration, time spent indoors versus outdoors, and occupancy density of waiting rooms in clinics in KwaZulu-Natal (KZN) and Western Cape (WC), South Africa. We used unique barcodes to track attendees' movements in 11 clinics, multiple imputation to estimate missing arrival and departure times, and mixed-effects linear regression to examine associations with visit duration. 2,903 attendees were included. Median visit duration was 2 hours 36 minutes (interquartile range [IQR] 01:36-3:43). Longer mean visit times were associated with being female (13.5 minutes longer than males; p<0.001) and attending with a baby (18.8 minutes longer than those without; p<0.01), and shorter mean times with later arrival (14.9 minutes shorter per hour after 0700; p<0.001). Overall, attendees spent more of their time indoors (median 95.6% [IQR 46-100]) than outdoors (2.5% [IQR 0-35]). Attendees at clinics with outdoor waiting areas spent a greater proportion (median 13.7% [IQR 1-75]) of their time outdoors. In two clinics in KZN (no appointment system), occupancy densities of ~2.0 persons/m2 were observed in smaller waiting rooms during busy periods. In one clinic in WC (appointment system, larger waiting areas), occupancy density did not exceed 1.0 persons/m2 despite higher overall attendance. In this study, longer waiting times were associated with early arrival, being female, and attending with a young child. Occupancy of waiting rooms varied substantially between rooms and over the clinic day. Light-touch estimation of occupancy density may help guide interventions to improve patient flow.

Health worker experiences of implementing TB infection prevention and control: A qualitative evidence synthesis to inform implementation recommendations.

Implementation of TB infection prevention and control (IPC) measures in health facilities is frequently inadequate, despite nosocomial TB transmission to patients and health workers causing harm. We aimed to review qualitative evidence of the complexity associated with implementing TB IPC, to help guide the development of TB IPC implementation plans. We undertook a qualitative evidence synthesis of studies that used qualitative methods to explore the experiences of health workers implementing TB IPC in health facilities. We searched eight databases in November 2021, complemented by citation tracking. Two reviewers screened titles and abstracts and reviewed full texts of potentially eligible papers. We used the Critical Appraisals Skills Programme checklist for quality appraisal, thematic synthesis to identify key findings and the GRADE-CERQual method to appraise the certainty of review findings. The review protocol was pre-registered on PROSPERO, ID CRD42020165314. We screened 1062 titles and abstracts and reviewed 102 full texts, with 37 studies included in the synthesis. We developed 10 key findings, five of which we had high confidence in. We describe several components of TB IPC as a complex intervention. Health workers were influenced by their personal occupational TB risk perceptions when deciding whether to implement TB IPC and neglected the contribution of TB IPC to patient safety. Health workers and researchers expressed multiple uncertainties (for example the duration of infectiousness of people with TB), assumptions and misconceptions about what constitutes effective TB IPC, including focussing TB IPC on patients known with TB on treatment who pose a small risk of transmission. Instead, TB IPC resources should target high risk areas for transmission (crowded, poorly ventilated spaces). Furthermore, TB IPC implementation plans should support health workers to translate TB IPC guidelines to local contexts, including how to navigate unintended stigma caused by IPC, and using limited IPC resources effectively.

Estimating the contribution of transmission in primary healthcare clinics to community-wide TB disease incidence, and the impact of infection prevention and control interventions, in KwaZulu-Natal, South Africa

BackgroundThere is a high risk of Mycobacterium tuberculosis (Mtb) transmission in healthcare facilities in high burden settings. WHO guidelines on tuberculosis (TB) infection prevention and control (IPC) recommend a range...

World Tuberculosis Day 2022: aligning COVID-19 and tuberculosis innovations to save lives and to end tuberculosis

World Tuberculosis Day 2022: aligning COVID-19 and tuberculosis innovations to save lives and to end tuberculosis

Knowledge and practice of nurses regarding tuberculosis infection control in selected tertiary hospital

Tuberculosis caused by a microorganism called Mycobacterium tuberculosis. The undiagnosed or unsuspected patient with tuberculosis is the primary risk to health care workers and to the general population. The major risks for TB infection are through close contact to the infectious case before diagnosis. The objective of the study was to assess the level of knowledge and practice of nurses regarding tuberculosis infection control. This cross sectional study was conducted in Chest Diseases Hospital, Khulna and Khulna Medical College Hospital, Khulna. From 1st January to 31st December, 2020. Purposive sampling was adopted and semi-structured questionnaire was used to collect information from the respondents. Two hundred twenty-four (224) participants involve in the study. We found that the majority of the respondent’s age were 31-40 years, Female 99.6%, and 45% were Muslim. Majority 87.1% were senior staff nurse and 87.5% were diploma in nursing. Among the respondents 64.7% had good knowledge and 71.0% had good practice respectively. Most of the respondents (74.1%, n=181) had no training on TBIC. Significant statistical difference was found regarding professional education and knowledge (p=.002). This cross-sectional study revealed a majority of the respondents were found to have good TBIC knowledge and practices. More TBIC program should be enhanced among nurses whose knowledge and practice were poor. It can also be used to benchmark the evaluation of TBIC interventions, especially in setting where TBIC guideline have not been optimally implemented. It is recommended that training on TBIC should be provided to nurses.

Mycobacterium tuberculosis infection and disease in healthcare workers in a tertiary referral hospital in Bandung, Indonesia.

Healthcare workers (HCWs), especially in high tuberculosis (TB) incidence countries, are at risk of Mycobacterium tuberculosis infection and TB disease, likely due to greater exposure to TB cases and variable implementation of infection control measures. We aimed to estimate the prevalence of tuberculin skin test (TST) positivity, history of TB and to identify associated risk factors in HCWs employed at a tertiary referral hospital in Bandung, Indonesia. A cross-sectional study was conducted from April to August 2018. A stratified sample of the HCWs were recruited, screened by TST, assessed for TB symptoms, history of TB disease and possible risk factors. Prevalence of positive TST included diagnosis with TB after starting work. HCWs with TB disease diagnosed earlier were excluded. Survey weights were used for all analyses. Possible risk factors were examined using logistic regression; adjusted odds ratios and 95% confidence intervals (CI) are presented. Of 455 HCWs recruited, 42 reported a history of TB disease (25 after starting work) and 395 had a TST result. The prevalence of positive TST was 76.9% (95% CI 72.6-80.8%). The odds increased by 7% per year at work (95% CI 3-11%) on average, with a rapid rise in TST positivity up to 10 years of work and then a plateau with around 80% positive. A high proportion of HCWs had a history of TB or were TST positive, increasing with longer duration of work. A package of TB infection control measures is needed to protect HCWs from Mycobacterium tuberculosis infection.

Knowledge and Practice on Prevention and Control of Tuberculosis Among Nurses Working in a Regional Hospital, Nepal.

IntroductionTuberculosis (TB) is a highly prevalent communicable disease in Nepal. All health personnel who care for such patients are at high risk of developing tuberculosis. It is very necessary for all healthcare providers, especially nurses, who spend a lot of time with such patients, to have adequate knowledge and correct practice on the occupational safety measures to maintain health and prevent transmission of the disease. This study was carried out to assess the knowledge and practice of nurses in the prevention and control of TB infection.MethodThis study was a cross-sectional study conducted on nurses working in all wards and Outpatient Departments (OPDs) of Western Regional Hospital, Pokhara, Nepal. A complete enumeration of the respondents was performed, and data were collected consecutively, using a semi-structured self-administered questionnaire, from all nurses working in all the wards and OPDs of the hospital. The predictors of knowledge of TB infection prevention and control (TBIPC) were assessed using binary logistic regression.ResultsThe study findings showed that a majority of nurses had an inadequate level of knowledge and poor practice of prevention and control of TB. Regarding practice, none of the nurses reported the use of an N95 mask or a respirator during care of the patients with TB and all the nurses reported that they used chemical disinfectant (virex) to clean the room and the surfaces. However, none of them reported the use of fumigation or ultraviolet irradiation for disinfection. Nurses who were 40 years and older (p = 0.001, adjusted odds ratio (AOR) = 5.965, CI = 2.083–17.457) and who were currently working in the wards with isolation rooms demonstrated higher odds for knowledge on TBIPC (p = 0.010, AOR = 2.686, CI = 1.264–5.710).ConclusionsThis study showed that a majority of nurses had an inadequate level of knowledge and implemented poor safety measures for the prevention and control of tuberculosis. This increases their risk of being infected with TB infection and cross-transmission. It is recommended that the hospital plan and conduct the necessary education/training for nurses to update their knowledge, develop the organizational structure and policies, and establish a system to support and monitor the practice of health workers on the prevention and control of TB, and maintain the health and safety of nurses caring for patients with TB.

Preparedness of tertiary care hospitals to implement the national TB infection prevention and control guidelines in Bangladesh: A qualitative exploration.

In high tuberculosis (TB) burden countries, health settings, including non-designated TB hospitals, host many patients with pulmonary TB. Bangladesh's National TB Control Program aims to strengthen TB infection prevention and control (IPC) in health settings. However, there has been no published literature to date that assessed the preparedness of hospitals to comply with the recommendations. To address this gap, our study examined healthcare workers knowledge and attitudes towards TB IPC guidelines and their perceptions regarding the hospitals' preparedness in Bangladesh. Between January to December 2019, we conducted 16 key-informant interviews and four focus group discussions with healthcare workers from two public tertiary care hospitals. In addition, we undertook a review of 13 documents [i.e., hospital policy, annual report, staff list, published manuscript]. Our findings showed that healthcare workers acknowledged the TB risk and were willing to implement the TB IPC measures but identified key barriers impacting implementation. Gaps were identified in: policy (no TB policy or guidelines in the hospital), health systems (healthcare workers were unaware of the guidelines, lack of TB IPC program, training and education, absence of healthcare-associated TB infection surveillance, low priority of TB IPC, no TB IPC monitoring and feedback, high patient load and bed occupancy, and limited supply of IPC resources) and behavioural factors (risk perception, compliance, and self and social stigma). The additional service-level gap was the lack of electronic medical record systems. These findings highlighted that while there is a demand amongst healthcare workers to implement TB IPC measures, the public tertiary care hospitals have got key issues to address. Therefore, the National TB Control Program may consider these gaps, provide TB IPC guidelines to these hospitals, assist them in developing hospital-level IPC manual, provide training, and coordinate with the ministry of health to allocate separate budget, staffing, and IPC resources to implement the control measures successfully.

Examining pulmonary TB patient management and healthcare workers exposures in two public tertiary care hospitals, Bangladesh.

Implementation of tuberculosis (TB) infection prevention and control (IPC) guidelines in public tertiary care general hospitals remain challenging due to limited evidence of pulmonary TB (PTB) patients' duration of hospital stay and management. To fill this evidence gap, this study examined adult PTB patient management, healthcare workers' (HCWs) exposures and IPC practices in two public tertiary care hospitals in Bangladesh.Between December 2017 and September 2019, a multidisciplinary team conducted structured observations, a hospital record review, and in-depth interviews with hospital staff from four adult medicine wards.Over 20 months, we identified 1,200 presumptive TB patients through the hospital record review, of whom 263 were confirmed PTB patients who stayed in the hospital, a median of 4.7 days without TB treatment and possibly contaminated the inpatients wards. Over 141 observation hours, we found a median of 3.35 occupants present per 10 m2 of floor space and recorded a total of 17,085 coughs and 316 sneezes: a median of 3.9 coughs or sneezes per 10 m2 per hour per ward. Only 8.4% of coughs and 21% of sneezes were covered by cloths, paper, tissues, or by hand. The HCWs reportedly could not isolate the TB patients due to limited resources and space and could not provide them with a mask. Further, patients and HCWs did not wear any respirators.The study identified that most TB patients stayed in the hospitals untreated for some duration of time. These PTB patients frequently coughed and sneezed without any facial protection that potentially contaminated the ward environment and put everyone, including the HCWs, at risk of TB infection. Interventions that target TB patients screening on admission, isolation of presumptive TB patients, respiratory hygiene, and HCWs' use of personal protective equipment need to be enhanced and evaluated for acceptability, practicality and scale-up.

Tuberculosis infection control in health care facilities in Enugu State, Nigeria: a cross-sectional facility-based study.

Introductionovertime, tuberculosis (TB) has remained the most common opportunistic infection among people living with HIV (PLHIV). Proper implementation of TB infection control (TBIC) practices in health care facilities can curb TB menace among PLHIV and the public. We assessed the implementation of TB infection control in health care facilities offering Anti-Retroviral Therapy (ART) in Enugu State, Nigeria.Methodswe employed a cross-sectional research design and assessed TB infection control practices in nine State owned public health care facilities offering antiretroviral therapy (ART) services for PLHIV. A 23 item World Health Organization (WHO) checklist for infection control in health care facilities was used to collect data. We assessed the five minimum standards as well as the four sets of TB infection control (TBIC) measures. Frequencies, percentages and chi square statistic were used to analyze data.Resultsonly four (44%) health care facilities that provides ART services studied in Enugu State implemented TBIC practices. Higher proportion of the rural and secondary facilities implemented TBIC although the difference is not statistically significant (p>0.05). Implementation was better with the administrative controls while the personal protective equipment was almost non-existent.Conclusionless than half of the facilities offering ART services in the Enugu State have TB infection control measures. We therefore recommend that in order to reduce TB infection among PLHIV, the issue of proper TBIC in health care facilities need urgent attention. Materials provision, staff training and retraining are issues that must be tackled to achieve the aim of reduction of TB infection among PLHIV, health care workers and the public.

ДИНАМИКА ЛЕКАРСТВЕННОЙ УСТОЙЧИВОСТИ ВОЗБУДИТЕЛЕЙ ТУБЕРКУЛЁЗА ВО ВРЕМЯ ПАНДЕМИИ НОВОЙ КОРОНАВИРУСНОЙ ИНФЕКЦИИ В Г. ДУШАНБЕ: НЕОБХОДИМОСТЬ ПРИНЯТИЯ СРОЧНЫХ МЕР

Objective: To study the frequency and structure of primary and secondary drug resistance in M. tuberculosis (MTB) and risk factors for primary multidrug/rifampicin resistance (MDR/RR) in MTB before (Group I: 2018-2019) and during the COVID-19 pandemic (Group II: 2019-2020) in Dushanbe in patients with pulmonary tuberculosis (PTB). Methods: A cohort retrospective study included all patients with PTB tested for susceptibility to anti-tuberculosis drugs (ATD). Odds ratio (OR), 95% confidence interval (95% CI), and p-value were used to determine the significance of the association between frequency and drug susceptibility spectrum (DSS) in groups I and II; risk ratio (RR) was applied to assess a possible association between exposure and outcome. Results: The study included 559 newly diagnosed and 87 previously treated patients. Primary MDR/RR MTB was found in 21.1%, secondary – in 39.8% of patients: in group I, patients with primary MDR/RR MTB constituted 22.4%, secondary – 34.7%; in group II, the prevalence of secondary MDR/RR MTB was found to be three times higher than that of the primary resistance (OR=2.97; 95% CI=1.67-5.27, p&lt;0.001) due to a decrease in the prevalence of primary MDR/RR MTB (19.5%) and an increase in the secondary MDR/RR MTB (47.4%). There was a statistically significant increase in the frequency of primary drug resistance to fluoroquinolones in group II compared with group I: OR=2.58 for levofloxacin (p=0.003) and OR=2.31 for moxifloxacin (p=0.027). An increase in primary MDR/RR MTB was found among healthcare workers in group II (RR=3.21; 95% CI=1.50-6.89; p=0.05), which was statistically significant in patients with diabetes mellitus in both groups: group I (RR=1.83; p=0.035) and group II (OR=2.68; p&lt;0.001). Conclusion: The current high prevalence of primary and secondary MDR, the increase in monoresistance during the COVID-19 pandemic, and the association of MDR with employment in healthcare institutions raise concerns regarding the quality of implementation of tuberculosis (TB) infection control measures in Dushanbe. The increased frequency of resistance to fluoroquinolones requires immediate action to control their prescription. It is recommended to improve anti-TB standards among patients with diabetes mellitus. Keywords: Drug resistance, M. tuberculosis, risk factors for multidrug resistance, COVID-19.

Investigation of miRNA and cytokine expressions in latent tuberculosis infection and active tuberculosis.

In tuberculsosis (TB), miRNA has been used as a biomarker to distinguish between healthy individuals and TB patients. The aim of this study was to investigate (i) the association of the miRNA and cytokine expression levels, the course of tuberculosis infection, clinical forms and response to treatment, and (ii) the effects of genotypic features of bacteria on the course of tuberculosis and the relationship between miRNA and cytokine expressions and bacterial genotypes. A total of 200 cases (100: culture positive active tuberculosis, 50: quantiferon positive latent tuberculosis infection and 50: quantiferon negative healthy controls) were included in the study. For the tuberculosis group at the time of admission and after treatment, for the latent tuberculosis infection and healthy control groups at the time of admission, miRNA and cytokine expressions were determined. Genotyping of M.tuberculosis isolates was performed by spoligotyping method. While, in the comparison of miRNA expressions between the pretreatment patient group and the healthy control group, there was a statistically significant decrease in the expression of miR-454-3p, miR-15a-5p, miR-590-5p, miR-381, and miR-449a in the Pulmonary TB group, there was no significant change in miRNA expression in extrapulmonary TB patients. When the cytokine expressions of the patient group and the healthy control group were compared before treatment, the expressions of all cytokines in the patient group decreased. However, the only cytokine that showed a significantly lower expression was IL12A in PTB patients. There is no significant relationship between the clinical course of the disease, cytokine and miRNA expression, and the genotype of the bacteria.

Knowledge, Attitude, and Practices Regarding Childhood Tuberculosis Screening and Management among Healthcare Providers in Al-Medinah Al-Munawara, Saudi Arabia

Among infectious illnesses, tuberculosis (TB) has the highest fatality rate. The likelihood of infection spreading from patients to healthcare providers is two times higher than in the general population. The primary risk factor for contracting TB is close proximity to an infected individual prior to diagnosis. The research assessed health workers’ knowledge, attitude, and practice of TB infection control in Saudi Arabia. The study used a cross-sectional approach based on an online survey. The research was carried out throughout the months of May to July 2022 in Al Madinah Al-Munawara. The questionnaire included demographic’s and work variables, knowledge regarding pediatric TB etiology, transmission, symptoms, lymph node characteristics, and diagnostic criteria. Also, the participants’ perspectives and practice patterns on contact investigation, TB diagnostic tools, laboratory services, presumptive TB diagnostic referrals, and TB treatment were evaluated. The study included 558 healthcare workers (HCWs) from various specialists. HCWs exhibited sound knowledge, and positive attitudes in comparison to those with minimal experience in diagnosing TB in children TB as 31.2% had excellent knowledge, 22.6% good, 18.5% mediocre, and 27.8% bad. The majority of responders (49.1%) had a positive attitude, while only 33.2% had correct and full practice routines. Immediate action is required to increase HCW awareness, capacity, and skills to ensure an accurate diagnosis. In the identification of TB cases, certain crucial information gaps were discovered. This study also highlights the significance of clinical experience and frequent interactions with tuberculosis patients in clinical practice as a pathway to competency-based learning by practice. Keywords: healthcare workers, knowledge, tuberculosis, diagnosis, practice, KSA.

Tuberculosis Infection Control Practice among Antiretroviral (ART) Clinics in North Central Nigeria

Tuberculosis Infection Control Practice among Antiretroviral (ART) Clinics in North Central Nigeria

Tuberculosis infection control measures and knowledge in primary health centres in Bandung, Indonesia.

Health care workers (HCWs) in low- and middle-income countries (LMICs) continue to have an unacceptably high prevalence and incidence of Mycobacterium tuberculosis infection due to high exposure to tuberculosis (TB) cases at health care facilities and often inadequate infection control measures. This can contribute to an increased risk of transmission not only to HCWs themselves but also to patients and the general population. We assessed implementation of TB infection control measures in primary health centres (PHCs) in Bandung, Indonesia, and TB knowledge among HCWs. A cross-sectional study was conducted between May and November 2017 amongst a stratified sample of the PHCs, and their HCWs, that manage TB patients in Bandung. Questionnaires were used to assess TB infection control measures plus HCW knowledge. Summary statistics, linear regression and the Kruskal-Wallis test were used for analysis. The median number of TB infection control measures implemented in 24 PHCs was 21 of 41 assessed. Only one of five management controls was implemented, 15 of 24 administrative controls, three of nine environmental controls and one of three personal respiratory protection controls. PHCs with TB laboratory facilities and high TB case numbers were more likely to implement TB infection control measures than other PHCs (p=0.003). In 398 HCWs, the median number of correct responses for knowledge was 10 (IQR 9-11) out of 11. HCWs had good TB knowledge. TB infection control measures were generally not implemented and need to be strengthened in PHCs to reduce M. tuberculosis transmission to HCWs, patients and visitors.

Using system dynamics modelling to estimate the costs of relaxing health system constraints: a case study of tuberculosis prevention and control interventions in South Africa.

Health system constraints are increasingly recognized as an important addition to model-based analyses of disease control interventions, as they affect achievable impact and scale. Enabling activities implemented alongside interventions to relax constraints and reach the intended coverage may incur additional costs, which should be considered in priority setting decisions. We explore the use of group model building, a participatory system dynamics modelling technique, for eliciting information from key stakeholders on the constraints that apply to tuberculosis infection prevention and control processes within primary healthcare clinics in South Africa. This information was used to design feasible interventions, including the necessary enablers to relax existing constraints. Intervention and enabler costs were then calculated at two clinics in KwaZulu-Natal using input prices and quantities from the published literature and local suppliers. Among the proposed interventions, the most inexpensive was retrofitting buildings to improve ventilation (US$1644 per year), followed by maximizing the use of community sites for medication collection among stable patients on antiretroviral therapy (ART; US$3753) and introducing appointments systems to reduce crowding (US$9302). Enablers identified included enhanced staff training, supervision and patient engagement activities to support behaviour change and local ownership. Several of the enablers identified by the stakeholders, such as obtaining building permissions or improving information flow between levels of the health systems, were not amenable to costing. Despite this limitation, an approach to costing rooted in system dynamics modelling can be successfully applied in economic evaluations to more accurately estimate the ‘real world’ opportunity cost of intervention options. Further empirical research applying this approach to different intervention types (e.g. new preventive technologies or diagnostics) may identify interventions that are not cost-effective in specific contexts based on the size of the required investment in enablers.

Whole genome sequencing reveals large deletions and other loss of function mutations in Mycobacterium tuberculosis drug resistance genes.

Drug resistance in Mycobacterium tuberculosis , the causative agent of tuberculosis disease, arises from genetic mutations in genes coding for drug-targets or drug-converting enzymes. SNPs linked to drug resistance have been extensively studied and form the basis of molecular diagnostics and sequencing-based resistance profiling. However, alternative forms of functional variation such as large deletions and other loss of function (LOF) mutations have received much less attention, but if incorporated into diagnostics they are likely to improve their predictive performance. Our work aimed to characterize the contribution of LOF mutations found in 42 established drug resistance genes linked to 19 anti-tuberculous drugs across 32689 sequenced clinical isolates. The analysed LOF mutations included large deletions (n=586), frameshifts (n=4764) and premature stop codons (n=826). We found LOF mutations in genes strongly linked to pyrazinamide (pncA), isoniazid (katG), capreomycin (tlyA), streptomycin (e.g. gid) and ethionamide (ethA, mshA) (P<10−5), but also in some loci linked to drugs where relatively less phenotypic data is available [e.g. cycloserine, delaminid, bedaquiline, para-aminosalicylic acid (PAS), and clofazimine]. This study reports that large deletions (median size 1115 bp) account for a significant portion of resistance variants found for PAS (+7.1% of phenotypic resistance percentage explained), pyrazinamide (+3.5%) and streptomycin (+2.6%) drugs, and can be used to improve the prediction of cryptic resistance. Overall, our work highlights the importance of including LOF mutations (e.g. large deletions) in predicting genotypic drug resistance, thereby informing tuberculosis infection control and clinical decision-making.

Lessons Learned During the COVID-19 Pandemic to Strengthen TB Infection Control: A Rapid Review.

Over the past 5 years, substantial global investment has resulted in reduced TB incidence rates by 9% and mortality rates by 14%. However, the coronavirus disease (COVID-19) pandemic has hindered access and availability of TB services to maintain robust TB control. The objective of this rapid review was to describe the challenges to be addressed and recommendations to strengthen health system preparedness for optimal TB control across low- and middle-income countries during and after the COVID-19 pandemic. Five databases were used to systematically search for relevant articles published in 2020. The 5-step framework proposed by Arskey and O'Malley and adapted by Levac et al. guided the review process. Thematic analysis with grounded theory principles was used to summarize themes from selected articles and integrate analyses with barriers reported from authors' previous TB research. Of the 218 peer-reviewed articles, 20 articles met the inclusion criteria. Four emerging themes described challenges: (1) unprepared health system leadership and infrastructure, (2) coexisting health priorities, (3) insufficient health care workforce support for continued training and appropriate workplace environments, and (4) weak connections to primary health centers hindering community engagement. Four recommendations were highlighted: (1) ensuring leadership and governance for sustainable national health budgets, (2) building networks of community stakeholders, (3) supporting health care workforce training and safe workplace environments, and (4) using digital health interventions for TB care. National health systems must promote patient-centered TB care, implement ethical community interventions, support operational research, and integrate appropriate eHealth applications. TB program managers and primary care practitioners can serve as instrumental leaders and patient advocates to deliver high-quality and sustainable TB care that leads to achieving the targets of the End TB Strategy.

Organisational Culture and Mask-Wearing Practices for Tuberculosis Infection Prevention and Control among Health Care Workers in Primary Care Facilities in the Western Cape, South Africa: A Qualitative Study.

Background: Although many healthcare workers (HCWs) are aware of the protective role that mask-wearing has in reducing transmission of tuberculosis (TB) and other airborne diseases, studies on infection prevention and control (IPC) for TB in South Africa indicate that mask-wearing is often poorly implemented. Mask-wearing practices are influenced by aspects of the environment and organisational culture within which HCWs work. Methods: We draw on 23 interviews and four focus group discussions conducted with 44 HCWs in six primary care facilities in the Western Cape Province of South Africa. Three key dimensions of organisational culture were used to guide a thematic analysis of HCWs’ perceptions of masks and mask-wearing practices in the context of TB infection prevention and control. Results: First, HCW accounts address both the physical experience of wearing masks, as well as how mask-wearing is perceived in social interactions, reflecting visual manifestations of organisational culture in clinics. Second, HCWs expressed shared ways of thinking in their normalisation of TB as an inevitable risk that is inherent to their work and their localization of TB risk in specific areas of the clinic. Third, deeper assumptions about mask-wearing as an individual choice rather than a collective responsibility were embedded in power and accountability relationships among HCWs and clinic managers. These features of organisational culture are underpinned by broader systemic shortcomings, including limited availability of masks, poorly enforced protocols, and a general lack of role modelling around mask-wearing. HCW mask-wearing was thus shaped not only by individual knowledge and motivation but also by the embodied social dimensions of mask-wearing, the perceptions that TB risk was normal and localizable, and a shared underlying tendency to assume that mask-wearing, ultimately, was a matter of individual choice and responsibility. Conclusions: Organisational culture has an important, and under-researched, impact on HCW mask-wearing and other PPE and IPC practices. Consistent mask-wearing might become a more routine feature of IPC in health facilities if facility managers more actively promote engagement with TB-IPC guidelines and develop a sense of collective involvement and ownership of TB-IPC in facilities.