Global Tuberculosis Research Articles

FACTORS CONTRIBUTING TO PULMONARY TB TREATMENT LOST TO FOLLOW-UP IN DEVELOPING COUNTRIES: AN OVERVIEW.

Despite the available treatment options, pulmonary tuberculosis (TB) remains a leading cause of disease-related deaths worldwide. Treatment non-adherence/lost to follow-up (LTFU), particularly in developing countries, is a continuous concern. LTFU prolongs TB infectiousness and contributes to TB treatment failure, relapse, and death. Furthermore, LTFU also delays global TB eradication by promoting TB spread and drug-resistant TB strain development.[1] The purpose of this paper is to give an overview of the commonly observed risk factors associated with TB treatment LTFU in developing countries. A literature survey was done of studies published in the past decade, which evaluated the risk factors for LTFU in TB patients, specifically in developing countries. Furthermore, some prospective TB treatment adherence initiatives and the feasibility of these initiatives within developing countries were assessed.[3]. Several variables, including socio-demographic, patient-related, TB disease and other health-related-factors, healthcare and system determinants, as well as treatment-related factors, were identified to increase the risk of TB treatment LTFU. More recently applied adherence interventions in developing countries, show potential for implementation on a larger scale. Successful TB treatment is contingent on treatment adherence, and by addressing these persisting LTFU risk factors, treatment adherence in developing countries may be improved.

Tingkat pengetahuan mahasiswa profesi terhadap Pencegahan dan pengendalian infeksi tuberkulosis : Kajian pada RSGM-P FKG Universitas Trisakti (Laporan Penelitian)

Background: Tuberculosis is a chronic granulomatous disease caused by Mycobacterium tuberculosis bacteria. Globally, tuberculosis still becomes a threat to public health, with approximately 11 million infected cases every year. Based on WHO in Global Tuberculosis Report 2020, Indonesia (8.5%) becomes the second-highest country after India (27%). As one of the health workers with a high risk of being infected with tuberculosis, dental students are important to have good knowledge about the prevention and control of tuberculosis infection as one attempt to prevent the risk of tuberculosis infection in dental practices. Objective: To find out an overview of dental students’ knowledge level towards the prevention and control of tuberculosis infection in Dental and Oral Hospital of the Faculty of Dentistry, Trisakti University. Method: This study was a descriptive observational research with a cross-sectional study approach and was conducted by distributing questionnaires to 92 dental students who entered the clinical clerkship in 2019 and 2020. Results: The results show that 42.39% of students have a high knowledge level, 28.26% have a moderate knowledge level, and 29.35% have a low knowledge level. Conclusion: In this study can be concluded that the knowledge level of dental students who entered the clinical clerkship in 2019 and 2020 is still inadequate.

ROLE OF FIBEROPTIC BRONCHOSCOPY IN DIAGNOSIS OF SPUTUM NEGATIVE PULMONARY TUBERCULOSIS

Tuberculosis is a disease caused by Mycobacterium tuberculosis. It is a systemic disease, predominantly affecting the lungs. Globally, tuberculosis affects around 10.4 million people per year, and kills around million of them, with the majority of patients presenting with pulmonary disease. One of the key challenges to global tuberculosis control is correct diagnosis. The diagnosis of Pulmonary Tuberculosis can be obtained from microscopy and culture of a number of different sources including expectorated sputum, induced sputum, gastric washings and bronchoscopy. Fiberoptic bronchoscopy (FOB) can provide an early conrmative diagnosis in such patients. Among the bronchoscopic materials, bronchoalveolar lavage (BAL) is the best diagnostic material for the diagnosis of PTB.

Progress towards the 2020 milestones of the end TB strategy in Cambodia: estimates of age and sex specific TB incidence and mortality from the Global Burden of Disease Study 2019

BackgroundCambodia was recently removed from the World Health Organization’s (WHO’s) top 30 high tuberculosis (TB) burden countries. However, Cambodia’s TB burden remains substantial, and the country is on the WHO’s new global TB watchlist. We aimed to examine the levels and trends in the fatal and non-fatal TB burden in Cambodia from 1990 to 2019, assessing progress towards the WHO End TB interim milestones, which aim to reduce TB incidence rate by 20% and TB deaths by 35% from 2015 to 2020.MethodsWe leveraged the Global Burden of Disease 2019 (GBD 2019) analytical framework to compute age- and sex-specific TB mortality and incidence by HIV status in Cambodia. We enumerated TB mortality utilizing a Bayesian hierarchical Cause of Death Ensemble modeling platform. We analyzed all available data sources, including prevalence surveys, population-based tuberculin surveys, and TB cause-specific mortality, to produce internally consistent estimates of incidence and mortality using a compartmental meta-regression tool (DisMod-MR 2.1). We further estimated the fraction of tuberculosis mortality among individuals without HIV coinfection attributable to the independent effects of alcohol use, smoking, and diabetes.ResultsIn 2019, there were 6500 (95% uncertainty interval 4830–8680) deaths due to all-form TB and 50.0 (43.8–57.8) thousand all-form TB incident cases in Cambodia. The corresponding age-standardized rates were 53.3 (39.9–69.4) per 100,000 population for mortality and 330.5 (289.0–378.6) per 100,000 population for incidence. From 2015 to 2019, the number of all-form TB deaths decreased by 11.8% (2.3–21.1), while the age-standardized all-form TB incidence rate decreased by 11.1% (6.3–15.6). Among individuals without HIV coinfection in 2019, alcohol use accounted for 28.1% (18.2–37.9) of TB deaths, smoking accounted for 27.0% (20.2–33.3), and diabetes accounted for 12.5% (7.1–19.0). Removing the combined effects of these risk factors would reduce all-form TB deaths by 54.2% (44.2–62.2).DiscussionDespite significant progress in reducing TB morbidity and mortality since 1990, Cambodia is not on track to achieve the 2020 WHO End TB interim milestones. Existing programs in Cambodia can benefit from liaising with risk factor control initiatives to accelerate progress toward eliminating TB in Cambodia.

Tuberculosis infections during the COVID-19 pandemic: Comparing USA and global tuberculosis in 2019 and 2020

Background: Tuberculosis (TB) was the worldwide leading cause of mortality from a single infectious agent before the coronavirus disease 2019 (COVID-19) pandemic. The incidence of TB infections has continually declined since 2000, but the COVID-19 pandemic has reversed this trend. In 2020, global health officials reported a 21% drop in documented cases relative to TB cases in 2019. Although previous studies evaluated the impact of the COVID-19 pandemic on global TB cases, we are not aware of reports that compared U.S. and global TB cases during the COVID-19 pandemic. Objective: To analyze prepandemic and pandemic volumes of TB cases within the United States and compare findings with global TB volumes. Methods: This descriptive study used data from the Centers for Disease Control and Prevention to compare reported TB cases in the United States in 2019 and 2020. TB cases from the United States were compared with data about global TB cases. Results: The COVID-19 pandemic was associated with decreased TB testing and cases in the United States. The five states with the highest number of TB cases remained the same in 2019 and 2020, and included California, Texas, New York, Florida, and New Jersey. In these states, TB predominantly occurred in non‐U.S.-born residents and most patients solely presented with pulmonary manifestations. In the United States, the most substantial risk factor for TB was diabetes mellitus. Conclusion: The COVID-19 pandemic decreased access to TB services and discouraged patients from seeking TB care, which inadvertently disrupted international and U.S. TB surveillance systems. Given the decline in documented TB cases, leaders may need to anticipate an increase in TB cases and begin to aggressively reallocate resources to improve TB detection and care to mitigate the recent changes.

A systematic review and meta-analysis of active case finding for tuberculosis in India.

Active case finding (ACF) for tuberculosis (TB) is the cornerstone case-finding strategy in India's national TB policy. However, ACF strategies are highly diverse and pose implementation challenges in routine programming. We reviewed the literature to characterise ACF in India; assess the yield of ACF for different risk groups, screening locations, and screening criteria; and estimate losses to follow-up (LTFU) in screening and diagnosis. We searched PubMed, EMBASE, Scopus, and the Cochrane library to identify studies with ACF for TB in India from November 2010 to December 2020. We calculated 1) weighted mean number needed to screen (NNS) stratified by risk group, screening location, and screening strategy; and 2) the proportion of screening and pre-diagnostic LTFU. We assessed risk of bias using the AXIS tool for cross-sectional studies. Of 27,416 abstracts screened, we included 45 studies conducted in India. Most studies were from southern and western India and aimed to diagnose pulmonary TB at the primary health level in the public sector after screening. There was considerable heterogeneity in risk groups screened and ACF methodology across studies. Of the 17 risk groups identified, the lowest weighted mean NNS was seen in people with HIV (21, range 3-89, n=5), tribal populations (50, range 40-286, n=3), household contacts of people with TB (50, range 3-undefined, n=12), people with diabetes (65, range 21-undefined, n=3), and rural populations (131, range 23-737, n=5). ACF at facility-based screening (60, range 3-undefined, n=19) had lower weighted mean NNS than at other screening locations. Using the WHO symptom screen (135, 3-undefined, n=20) had lower weighted mean NNS than using criteria of abnormal chest x-ray or any symptom. Median screening and pre-diagnosis loss-to-follow-up was 6% (IQR 4.1%, 11.3%, range 0-32.5%, n=12) and 9.5% (IQR 2.4%, 34.4%, range 0-86.9%, n=27), respectively. For ACF to be impactful in India, its design must be based on contextual understanding. The narrow evidence base available currently is insufficient for effectively targeting ACF programming in a large and diverse country. Achieving case-finding targets in India requires evidence-based ACF implementation. WHO Global TB Programme.

Implementing molecular tuberculosis diagnostic methods in limited-resource and high-burden countries.

Tuberculosis (TB) is one of the deadliest infectious diseases in the world with more than a million people dying of TB each year. Accurate and timely TB diagnosis has the potential to alleviate the global TB burden; therefore, one of the pillars of the End TB Strategy developed by the World Health Organization (WHO) is the early diagnosis of TB, including universal drug-susceptibility testing (DST). The WHO emphasises the importance of DST before treatment initiation, using molecular WHO-recommended rapid diagnostic tests (mWRDs). Currently available mWRDs are nucleic acid amplification tests, line probe assays, whole genome sequencing, and targeted next-generation sequencing. However, implementing the sequencing mWRDs in routine laboratories in low-income countries is constrained by the existing infrastructure, high cost, the specialised skills needed, data storage, and the current delay in results compared with other routine methods. These limitations are pronounced in resource-limited settings, which often have a high TB burden and need for innovative TB diagnostic technologies. In this article we propose several possible solutions, like adapting infrastructure capacity to needs, advocating for lowering costs, building bioinformatics and laboratory capacity, and increasing the use of open-access resources for software and publications.

Potential Impact of Long-Acting Products on the Control of Tuberculosis: Preclinical Advancements and Translational Tools in Preventive Treatment.

A key component of global tuberculosis (TB) control is the treatment of latent TB infection. The use of long-acting technologies to administer TB preventive treatment has the potential to significantly improve the delivery and impact of this important public health intervention. For example, an ideal long-acting treatment could consist of a single dose that could be administered in the clinic (ie, a "1-shot cure" for latent TB). Interest in long-acting formulations for TB preventive therapy has gained considerable traction in recent years. This article presents an overview of the specific considerations and current preclinical advancements relevant for the development of long-acting technologies of TB drugs for treatment of latent infection, including attributes of target product profiles, suitability of drugs for long-acting formulations, ongoing research efforts, and translation to clinical studies.

Computer-Aided Diagnosis Using Hybrid Technique for Fastened and Accurate Analysis of Tuberculosis Detection with Adaboost and Learning Vector Quantization

Background: The concept of tuberculosis diagnosis plays a significant role in the current world since, in accordance with the Global Tuberculosis (TB) Report in 2019, more than one million cases are reported per year in India. Various tests are available even then the chest X-ray is the most significant one, devoid of which the diagnosis will be incomplete. By the usage of computationally designed algorithms, various clinical, as well as diagnostic functions, were built in ancient poster anterior chest radiographs. The Digital image (X-ray) may be an essential medium for examining and annotating patient’s demographics coverage in the screening of TB via chest radiography. Results: Even though several medicines are available to cure TB, diagnosis with accuracy is a major challenge. So, we have introduced a fastened technique with the merged combination of Adaptive Boosting (AdaBoost) and learning vector quantization (LVQ) for determining TB in an easier way with the input chest X-ray image of a person with the aid of computer-aided diagnosis with greatest accuracy, precision, recall and F1 values. This finest technique got an accuracy of 94.73% when compared to the prior conventional methods used such as SVM and Convolutional Neural Network. Conclusions: Tuberculosis detection can be done in a meaningful way with the aid of MATLAB simulation using Computer Aided Diagnosis. The algorithms Adaboost and LVQ works best with the datasets for around 400 chest X-ray images for detecting the normal and abnormal images conditions for the detection of the disease for a patient suspected to have TB, in a fraction of seconds.

The Effect of the COVID-19 Pandemic on Pulmonary Tuberculosis Control in the Selected Upazila Health Complexes of Dhaka Division, Bangladesh.

Despite the enormous disruption of tuberculosis (TB) services reported globally, Bangladesh's impact is not well documented. We aimed to assess the effect of the COVID-19 pandemic on the TB control program in Bangladesh from patients' and service providers' perspectives. We conducted a cross-sectional study from November-December 2021 at six conveniently selected Upazila Health Complexes (UHC) of the Dhaka division, Bangladesh. We conducted face-to-face interviews among 180 pulmonary TB service recipients and all TB service providers working in the selected UHC. We also reviewed TB registries from each UHC. All data were summarized using descriptive statistics tools. We found a 31% reduction in presumptive TB cases during 2021 compared to 2020. Other TB services, such as testing, were reduced by 16-36% during the same period. Service receivers reported a lack of transportation (95%), and a lack of adequate human resources (89%) as critical barriers to receiving and providing TB service, respectively. The findings of our study showed substantial interruption of TB service delivery during the COVID-19 pandemic, threatening the recent progress and pushback from achieving the 2035 End TB targets. Early mitigation of TB service delivery through adopting remote follow-ups using digital health technology and integrating COVID-19 and TB screening is essential for the continuity of essential TB services and achieving global TB targets.

COVID-19 and global childhood tuberculosis notifications

Globally, an estimated 1·2 million cases of tuberculosis disease each year occur in children younger than 15 years, and around 67 million children have tuberculosis infection, putting them at the risk of developing tuberculosis disease.1 Tuberculosis in childhood was historically neglected in surveillance efforts, with national tuberculosis programmes focusing primarily on cases of microscopically smear-positive tuberculosis, which is more common among older adolescents or adults. The diagnosis of tuberculosis in children is made challenging by low suspicion among health-care providers, reliance on sputum microscopy, which has very low sensitivity (ranging from 1–14%), children's difficulty in producing sputum, or disease with low bacillary load.

Global impact of COVID-19 on childhood tuberculosis: an analysis of notification data

There is concern that the COVID-19 pandemic has damaged global childhood tuberculosis management. Quantifying changes in childhood tuberculosis notifications could support more targeted interventions to restore childhood tuberculosis services. We aimed to use time-series modelling to evaluate the impact of COVID-19 on child tuberculosis notifications. Annual tuberculosis case notification data reported to WHO by 215 countries were used to calculate annual notification counts for the years 2014-20, stratified by age groups (0-4, 5-14, and ≥15 years) and sex. We used time-series modelling to predict notification counts for 2020, and calculated differences between these predictions and observed notifications in 2020 for each of the six WHO regions and at the country level for 30 countries with high tuberculosis burden. We assessed associations between these differences and the COVID-19 stringency index, a measure of COVID-19 social impact. From 2014 to 2019, annual tuberculosis notification counts increased across all age groups and WHO regions. More males than females in the 0-4 years age group and ≥15 years age group had notifications in all years from 2014 to 2020 and in all WHO regions. In the 5-14 years age group, more females than males were notified globally in all years, although some WHO regions had higher notifications from males than females. In 2020, global notifications were 35·4% lower than predicted (95% prediction interval -30·3 to -39·9; 142 525 observed vs 220 794 predicted notifications [95% prediction interval 204 509 to 237 078]) for children aged 0-4 years, 27·7% lower (-23·4 to -31·5; 256 398 vs 354 578 [334 724 to 374 431]) in children aged 5-14 years, and 18·8% lower (-15·4 to -21·9; 5 391 753 vs 6 639 547 [6 375 086 to 6 904 007]) for people aged 15 years or older. Among those aged 5-14 years, the reduction in observed relative to predicted notifications for 2020 was greater in males (-30·9% [-24·8 to -36·1]) than females (-24·5% [-18·1 to -29·9]). Among 28 countries with high tuberculosis burden, no association was observed between the stringency of COVID-19 restrictions and the relative difference in observed versus predicted notifications. Our findings suggest that COVID-19 has substantially affected childhood tuberculosis services, with the youngest children most affected. Although children have mostly had fewer severe health consequences from COVID-19 than have adults, they have been disproportionately affected by the effects of the pandemic on tuberculosis care. Observed sex differences suggest that targeted interventions might be required. As countries rebuild health systems following the COVID-19 pandemic, it is crucial that childhood tuberculosis services are placed centrally within national strategic plans. Medical Research Council.

Characteristics of Drug-sensitive and Drug-resistant Tuberculosis Cases among Adults at Tuberculosis Referral Hospitals in Indonesia.

As Indonesia's rifampin resistance testing rates are lower than global testing rates per the 2020 WHO global tuberculosis (TB) report, prevalence of multidrug-resistant TB may be underestimated. Our study aimed to evaluate prevalence and patterns of TB drug resistance (DR) within Indonesia. We conducted a cross-sectional analysis of baseline data collected from 2017-2018 as part of a cohort study of adults with presumed pulmonary TB at 7 DR-TB referral hospitals in Indonesia. Bacteriological examinations (acid-fast bacilli, GeneXpert, sputum culture) and drug-susceptibility testing were performed following the guidelines of the National TB Program. Of 447 participants with complete bacteriological examinations, 312 (69.8%) had positive sputum cultures for Mycobacterium tuberculosis. The proportion of MDR and pre-extensively drug-resistant was higher in previously treated compared with newly diagnosed participants (52.5% [73/139] versus 15% [26/173]). Compared with drug-sensitive case, drug-resistant TB was associated with cavities. Given the difference between rates of DR in TB referral hospitals from our study compared with the WHO survey in 2019 that showed 17.7% and 3.3% DR among previously treated and newly diagnosed participants globally, further characterization of Indonesia's TB epidemiology in the general population is needed. Strategies, including public policies to optimize case finding, strengthen capacity for resistance testing, and prevent loss to follow-up will be critical to reduce the burden of TB in Indonesia.

Prevalence, associated factors and rifampicin resistance pattern of pulmonary tuberculosis among HIV-positive patients attending antiretroviral treatment clinic at East Gojjam Zone, Ethiopia: An institution-based cross-sectional study

BackgroundDrug-resistant tuberculosis (TB) threatens global TB care and prevention, and it remains a major public health concern in many countries particularly in sub-Saharan countries. Pulmonary TB is the most common serious opportunistic infection on HIV-positive patients and it is the leading cause of death among HIV-positive patients in developing countries. Ethiopia is one of the high TB burden countries with high morbidity and mortality. ObjectiveTo determine the prevalence, associated factors and rifampicin resistance of pulmonary TB among HIV-positive attending antiretroviral treatment clinic at East Gojjam. MethodsHospital-based cross-sectional study was conducted at Debre Markos Referral Hospital, from February to June 2019. A total of 112 HIV-positive TB suspected patients were included using convenient sampling techniques and a bacteriological confirmation test for tuberculosis was performed using Gene-Xpert MTB/RIF assay from a spot sputum sample. Viral load was determined by using a quantitative real-time polymerase chain reaction (RT-PCR) from the blood sample. Socio-demographic and clinical data were collected by face-to-face interview using a semi-structured questionnaire. The data were analyzed by using Statistical Package for Social Sciences (SPSS) software (version 24). ResultOut of the 112 study participants, the prevalence of Pulmonary TB was 11.6 %. Among TB positives 23.1 % were rifampicin resistant. Rifampicin resistance was 100 % among female patients. Having family members treated for pulmonary TB (P = 0.003, [AOR = 4.5; 95 % CI = 3.59–58.8]), cigarette smoking (P = 0.039, [AOR = 2.18; 95 %CI = 1.17–40.5]), being on WHO HIV disease clinical stage II (P = 0.024, [AOR = 1.81; 95 %CI = 1.50–30.99]), and having viral load (1000–9999) RNA copies/ml (P = 0.031, [AOR = 1.54; 95 %CI = 1.32–31.41]) were found to be significantly associated with pulmonary TB. ConclusionThe prevalence of pulmonary TB and rifampicin resistance was high among HIV patients. Having family members treated for Pulmonary TB, history of cigarette smoking, WHO HIV clinical stage, and high viral load were associated risk factors for TB. Therefore, strengthening awareness creation on TB transmission, drug resistance, and treatment adherence are essential. Moreover, early screening and treatment are vital for preventing the transmission and occurrence of drug-resistant TB among study populations.

Tuberculosis (TB) Mucosal Vaccines: Current Efforts and Future Approaches

It is now known that the existing vaccination, Bacille Calmette-Guérin (BCG), is unable to stop the global Tuberculosis (TB) epidemic, and TB continues to pose a serious threat to public health [1]. Mycobacterium tuberculosis (Mtb), the causing agent, enters the body by inhalation, causing TB predominantly a respiratory infection [1]. Therefore, there is solid evidence to support the idea that a mucosally administered TB vaccination would be more successful than one administered systemically. Our team in Universiti Sains Malaysia (USM) has been working with several organisations in conjunction with Malaysia’s National Vaccine Roadmap (PPVN) to address this problem as well as the government's goal to produce vaccines that are high-quality, efficient, and secure following the guidelines established by the National Pharmaceutical Regulatory Agency (NPRA).
 Therefore, the development of TB mucosal vaccines over the past few years for worldwide as well as in USM is outlined in this presentation. It aims to discuss immunological and practical factors in the development of mucosal vaccines and emphasises some of the current and future approaches in USM.
 As a result, it is acknowledged globally that matching the path of infection with the path of immunisation is an appealing strategy for the development of TB vaccines. Several approaches have been made in USM to produce a vaccine candidate that significantly induces mucosal immunity. The design of the study showed the manipulation of IgA, which is a hallmark of mucosal immunity, with multi-epitopes of TB to produce IgA: TB recombinant protein by using goat’s milk as a bioreactor. The concept of oral immunisation in-vivo also is an important approach in our effort to maximise the production of the immune system at the point of entry of bacteria.
 In a conclusion, as a boost to a prior respiratory or systemic immunisation, the mucosal method might be more effective. In addition to systemic immunity obtained by injected vaccines, vaccines to induce pathogen-specific IgA are being developed to provide a first line of defence at these entry sites. Therefore, combining these concepts into developing new recombinant vaccine against TB would be a promising alternative.

Prediabetes and risk of active tuberculosis: a cohort study from Northern Taiwan.

Diabetes mellitus (DM) is a well-established risk factor for active tuberculosis (TB) infection. Despite the worldwide rapid increase in the prevalence of prediabetes, its impact on the risk of active TB remains largely unknown. This study aimed to investigate the relationship between prediabetes and risk of active TB in a large cohort study. A total of 119 352 participants were screened from a community-based health screening programme in Northern Taiwan. Diabetes mellitus and prediabetes were defined by baseline fasting plasma glucose (FPG) and prescription of anti-diabetic drugs. Incident cases of active TB were identified from the National Tuberculosis Registry. Kaplan-Meier curves and Cox regression analysis were employed to estimate the hazard ratios for prediabetes and DM compared with normoglycaemia. Spline regression was performed to investigate the dose-response relationship between FPG level and risk of TB disease. At baseline, 27 404 (22.96%) participants had prediabetes and 10 943 (9.17%) participants had DM. After an average follow-up of 7.2 years, 322 TB cases occurred. The adjusted hazard ratio of developing active TB disease was 0.73 [95% confidence interval (CI) 0.55-0.97] for prediabetic and 1.48 (95% CI 1.11-1.98) for diabetic participants compared with normoglycaemic individuals. Spline regression revealed a U-shaped association between FPG level and risk of active TB disease, with the lowest risk at FPG around110 mg/dl. Sensitivity analyses were conducted to exclude factors such as potential confounders (including body mass index), misclassification of glycaemic level, and selection bias, and results showed that those factors could not explain the lower risk of active TB. Prediabetes was associated with a 27% reduced risk of active TB disease compared with normoglycaemia. The biological mechanism of this inverse association and its implication for global nutrition transition and TB control should be further investigated.

Divergence in pace of decline in tuberculosis rates among migrants versus non-migrants in Ireland from 2011 to 2020

BackgroundDespite declining tuberculosis crude incidence rates (CIRs) in Ireland, the CIR among migrants remains five times higher than among non-migrants. We analysed notifications from the Irish tuberculosis surveillance system to compare the epidemiology of active tuberculosis among migrants with non-migrants in Ireland from 2011 to 2020 to inform future prevention and control strategies. MethodsWe analysed cases by individuals, place, and time, defining migrants as being diagnosed in Ireland and born outside Ireland. We calculated CIRs per 100 000 population using population denominators stratified by country of birth, defining high tuberculosis incidence as more than 40 per 100 000 population. We did temporal trend analysis using negative-binomial regression. FindingsA total of 3158 cases were notified, of which 1461 (46·3%) were migrants. Annual CIRs declined from 25·2 to 13·6 per 100 000 population among migrants (incidence rate ratio [IRR] 0·95 [95% CI 0·94–0·97]) and from 5·6 to 1·8 per 100 000 population among non-migrants (0·91 [0·89–0·93]). Median age was 34 years among migrants and 53 years among non-migrants. Male-to-female ratio was 1·3 among migrants and 1·7 among non-migrants. Migrants had significantly higher odds of any drug resistance (odds ratio [OR] 1·7 [95% CI 1·2–2·6]), multidrug resistance (19·4 [5·0–166]), and HIV co-infection (4·0 [2·5–6·9]), but lower odds of being linked to an outbreak (OR 0·28 [95% CI 0·21–0·37]) or sputum positive (0·76 [0·61–0·93]). Migrants originated from 96 countries, 82% originated from high tuberculosis incidence countries compared with 23% of the Irish population. The top ten migrant source countries differed when ranked by case numbers versus CIR. Four countries had a higher CIR in Ireland than in those reported by WHO for their country of origin. InterpretationThe pace of tuberculosis decline in migrants is slower than in non-migrants, with elevated CIRs among migrant subpopulations that might indicate underserved communities. A renewed focus on migrant health strategy is required to achieve the global tuberculosis elimination goal. FundingHealth Service Executive, Ireland.

A revolution in the management of multidrug-resistant tuberculosis

The detection of multidrug-resistant (MDR) tuberculosis (resistance to rifampicin and isoniazid) or rifampicin-resistant tuberculosis has increased by about 20% annually over the past decade (2009–2018); drug-resistant tuberculosis underpins about 15–20% of global tuberculosis mortality.1,2 In some countries, such as Russia and Belarus, almost half of all patients with tuberculosis have rifampicin-resistant tuberculosis.3 Unmet needs and challenges concerning drug-resistant tuberculosis include suboptimal diagnosis (about 60% of cases remain undiagnosed), inadequate access to effective drugs (about 30% of patients receive appropriate treatment), and poor treatment outcomes (treatment success is achieved in only about 60% of patients).

M. tuberculosis curli pili (MTP) facilitates a reduction of microbicidal activity of infected THP-1 macrophages during early stages of infection

Mycobacterium tuberculosis (M. tuberculosis) curli pili (MTP) is a surface located adhesin, which is involved in the initial point-of-contact between the pathogen and the host. Host-pathogen interaction is essential for establishing infection. M. tuberculosis has the ability to infect various host lung cell types, which includes both the epithelial cells and macrophages, and subsequent differences in their cellular function will be evident in their metabolic profiles. Understanding the differences between these cell types and their individual metabolic response to M. tuberculosis infection, with and without the presence of the MTP, will aid to better elucidate the role of this adhesin in modulating metabolic pathways during infection. This may further contribute to the development of improved diagnostic and therapeutic interventions, much needed at present in order to improve control the global tuberculosis (TB) epidemic. This study used a two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GC×GC-TOFMS) metabolomics approach to compare the metabolite profiles of A549 epithelial cells to that of THP-1 macrophages, infected with M. tuberculosis, in the presence and absence of MTP. Significant metabolites were identified using various univariate and multivariate statistical analysis. A total of 44, 40, 50 and 34 metabolites were differentially detected when comparing the (a) uninfected A549 epithelial cells to uninfected THP-1 macrophages, (b) wild-type infected A549 epithelial cells to wild-type infected THP-1 macrophages, (c) ∆mtp-infected A549 epithelial cells to ∆mtp-infected THP-1 macrophages (d) complement-infected A549 epithelial cells to complement-infected THP-1 macrophages, respectively. These included metabolites that were involved in amino acid metabolism, fatty acid metabolism, general central carbon metabolism, and nucleic acid metabolism. In the absence of the M. tuberculosis MTP adhesin, the THP-1 macrophages predominantly displayed higher concentrations of amino acids and their metabolic intermediates, than the A549 epithelial cells. The deletion of MTP from M. tuberculosis in the host infection models potentially elicited a pro-inflammatory phenotype, particularly in the macrophage model. In the presence of MTP, the metabolite profile changes indicate potential regulation of host defence mechanisms, accompanied by a reduction in microbicidal abilities of host cells. Hence MTP can be considered a virulence factor of M. tuberculosis. Therefore, blocking MTP interaction with the host may facilitate a faster pathogen clearance during the initial stages of infection, and potentially enhance current therapeutic interventions.

Exploring the Impact of the COVID-19 Pandemic on Tuberculosis Care and Prevention

The COVID-19 pandemic has set back the global tuberculosis (TB) response by several years. In 2020, access to TB prevention and care declined sharply, with TB notifications dropping by 18% compared to 2019. Declines were more pronounced in children, with a 24% drop in 0-14 year-olds and a 28% drop in 0-4 year-olds. As a result, in 2020 the number of deaths due to TB increased to 1.5 million across all ages, reversing a decade-long declining trend. Progress toward the UN High Level Meeting targets for 2022 is at risk, including the targets related to children for TB and drug-resistant TB treatments, and TB preventive therapy. Nonetheless, ending TB by 2030 as envisaged in the Sustainable Development Goals (SDGs) is still possible, but requires increased investments in accelerated case detection, subclinical TB, preventive therapy and an effective vaccine. Investing in TB could prepare the world better for fighting a future airborne pandemic.