Tuberculosis Burden Research Articles

An insight into the burden of drug-resistant tuberculosis in children.

An insight into the burden of drug-resistant tuberculosis in children.

Sociocultural understanding of Tuberculosis and implications for care-seeking among adults in the province of Zambezia, Mozambique: Qualitative research.

Mozambique has a high burden of Tuberculosis (TB) with an incidence of 368 per 100,000 population in 2020, coupled with a low all-form TB detection rate. The COVID-19 pandemic has exacerbated delays in timely diagnosis and treatment of new TB cases. Promoting active TB case finding is a national priority in Mozambique. We conducted qualitative research to explore factors influencing TB testing in Zambezia province in Mozambique. One-to-one, semi-structured, audio-recorded telephone interviews were conducted to explore TB-related knowledge, and barriers and facilitators to TB testing. A sample of two TB Program staff, two community providers of TB services, and 19 community members (10 women and 9 men) was recruited, with support from provincial government TB staff, from four districts in Zambezia with a high TB burden. Interviews were transcribed verbatim, and thematic analysis was conducted. The Mozambican National Bioethics Committee for Health approved the study protocol. Our study highlights that knowledge about TB symptoms and its causes is low, which could delay timely TB testing. Sociocultural beliefs often implicate certain types of sexual activity and women as causes of TB symptoms; for example, having sex with a widow who has not been traditionally purified, or with a woman who has had an abortion. Therefore, people usually tend to first seek care from traditional healers instead of going to a health facility. Additionally, stigma associated with HIV and TB also delays care seeking. Gender-related disparities in TB care seeking were also evident. This study provides valuable insights into how healthcare seeking for TB is influenced by sociocultural understanding of symptoms and gender dynamics. Therefore, interventions to promote timely and appropriate care seeking for TB should be contextually tailored, culturally appropriate, and gender sensitive.

Computational analysis of RNA methyltransferase Rv3366 as a potential drug target for combating drug-resistant Mycobacterium tuberculosis.

Mycobacterium tuberculosis (M.tb) remains a formidable global health threat. The increasing drug resistance among M.tb clinical isolates is exacerbating the current tuberculosis (TB) burden. In this study we focused on identifying novel repurposed drugs that could be further investigated as potential anti-TB drugs. We utilized M.tb RNA methyltransferase Rv3366 (spoU) as a potential drug target due to its imperative activity in RNA modification and no structural homology with human proteins. Using computational modeling approaches the structure of Rv3366 was determined followed by high throughput virtual screening of Food and Drug Administration (FDA) approved drugs to screen potential binders of Rv3366. Molecular dynamics (MD) simulations were performed to assess the drug-protein binding interactions, complex stability and rigidity. Through this multi-step structure-based drug repurposing workflow two promising inhibitors of Rv3366 were identified, namely, Levodopa and Droxidopa. This study highlights the significance of targeting M.tb RNA methyltransferases to combat drug-resistant M.tb. and proposes Levodopa and Droxidopa as promising inhibitors of Rv3366 for future pre-clinical investigations.

Challenge of ending TB in China: tuberculosis control in primary healthcare sectors under integrated TB control model–a systematic review and meta-analysis

BackgroundChina has the third-largest burden of tuberculosis (TB) cases in the world with great challenges towards ending TB. Primary health care (PHC) sectors play a critical role in TB prevention and control in communities under the Chinese integrated TB control model. However, there is a lack of comprehensive review of research evidence on TB control in PHC sectors under the integrated TB control model in China.MethodsThis review was conducted following the PRISMA guidelines. Articles published from 2012 to January 2022 were searched from four international and three Chinese databases. Studies conducted inside mainland China and relevant with TB control service in PHC sectors under the integrated model were included. After study selection, data extraction, and quality assessment, the meta-analysis was performed with RevMan using a random-effect model.When I2 was more than 50%, subgroup analysis was performed to explore possible reasons for heterogeneity. We also conducted a post hoc sensitivity analysis for outcomes after meta-analysis by exclusion of studies with a high risk of bias or classified as low quality.ResultsForty-three studies from 16 provinces/municipalities in China were included in this review, and most studies included were of medium quality. PHC sectors in East China delivered TB control service better overall than that in West China, especially in tracing of patients and TB case management (TCM). In meta-analyses, both the pooled arrival rate of tracing and pooled TCM rate in East China were higher than those in West China. TB patients had a low degree of willingness to receive TCM provided by healthcare workers in PHC sectors nationwide, especially among migrant TB patients. There were 9 studies reporting factors related to TB control service in PHC sectors, 6 (2 in East and 4 in West China) of which indentified several characteristics of patients as associated factors. The context of PHC sectors was demonstrated to influence delivery of TB control service in PHC sectors in 5 studies (3 in East, 1 in Middle and 1 in West China). Most studies on strategies to promoting TB control services in PHC sectors were conducted in East China and some of these studies identified several online and offline interventions and strategies improving patients’ treatment compliance [pooled OR (95% CI): 7.81 (3.08, 19.19] and awareness of TB [pooled OR (95% CI): 6.86 (2.16, 21.72)].ConclusionIt is of urgent need to improve TB control in PHC sector in China, particularly in West China. Formative and implementation research with rigorous design are necessary to develop comprehensive, context-specific, and patient-centered TB control strategies to promote ending TB in China.

Tailored treatment for tuberculosis in transgender individuals: a call for a patient-centered approach from a large Italian cohort.

Tuberculosis (TB) diagnosis and management in special populations remain challenging. Data about TB and transgender individuals is scarce, and strategies aimed at reducing the TB burden in this at-risk group are needed. We conducted an observational monocentric study from a national reference center for TB, including transgender individuals with active TB in a low-TB burden country (Italy), over 34 years (1990-2023). Sixty-six transgender males and two transgender females (median age 30 years, interquartile range 26-38 years, 65 migrants) were included. Most patients (38/66, 57.6%) lived in poor social conditions. 65.2% (43/66) of patients were people living with HIV. Multidrug- and rifampicin-resistant tuberculosis and isoniazid-resistant TB were diagnosed in five (7.6%) and three (4.5%) patients, respectively. The overall treatment success rate was 72.7% (48/66 patients), with differences observed according to social conditions. Our study highlights the need for a tailored approach to increase treatment success in this at-risk population.

Latent and active tuberculosis development in patients with rheumatoid arthritis receiving biologic disease-modifying antirheumatic drugs: A single-center prospective study.

Biologics have revolutionized the treatment of rheumatoid arthritis (RA) in recent years. However, data from clinical trials and actual clinical practice have shown that biologics currently in use may constitute a risk factor for reactivation of tuberculosis (TB) in patients with latent TB infection. Therefore, screening for latent and active TB infection is mandatory before initiating biologic therapy in patients with RA. This prospective study aimed to analyze the clinical characteristics of patients with RA receiving biologic disease-modifying antirheumatic drugs at Bach Mai Hospital, Vietnam, between 2017 and 2022, and to identify factors affecting the occurrence of active and latent TB infection among these patients. Over a 12-month follow-up period, latent TB infection was confirmed in 20% of the total 180 included patients, while 3 (1.7%) patients developed active TB (one case of pulmonary, pleural, and gluteal TB each). History of TB risk factor exposure and lack of education were significantly associated with the occurrence of active and latent TB infection, with odds ratios (95% confidence intervals [CIs]) of 1.98 (1.78; 2.2) and 1.45 (1.31; 1.6), respectively. Follow-up duration and number of X-ray, computed tomography, bronchoscopy, and sputum acid-fast bacteria examinations were identified as factors that can aid in the early diagnosis of latent TB, with odds ratios (95% CIs) of 1.00 (1; 1.01), 1.02 (1; 1.05), 1.12 (1.11; 1.2), 1.11 (1.09; 1.2), and 1.13 (1.09; 1.17), respectively. Our study showed that, in countries with high TB burden like Vietnam, latent TB infection has high prevalence among patients with RA. We also provide useful information for the screening, monitoring, and treatment of latent and active TB infection in patients with RA.

Clinical research progress of novel antituberculosis drugs on multidrug-resistant tuberculosis.

Multidrug-resistant tuberculosis (MDR-TB) has become a critical challenge to public health, and the prevention and treatment of MDR-TB are of great significance in reducing the global burden of tuberculosis. How to improve the effectiveness and safety of chemotherapy for MDR-TB is a pressing issue that needs to be addressed in tuberculosis control efforts. This article provides a comprehensive review of the clinical application of new antituberculosis drugs in MDR-TB, aiming to provide a scientific basis for the prevention and treatment strategy of MDR-TB.

ZNFX1 promotes AMPK-mediated autophagy against Mycobacterium tuberculosis by stabilizing Prkaa2 mRNA.

Tuberculosis has the highest mortality rate worldwide for a chronic infectious disease caused by a single pathogen. RNA-binding proteins (RBPs) are involved in autophagy - a key defense mechanism against Mycobacterium tuberculosis (M. tuberculosis) infection - by modulating RNA stability and forming intricate regulatory networks. However, the functions of host RBPs during M. tuberculosis infection remain relatively unexplored. Zinc finger NFX1-type containing 1 (ZNFX1), a conserved RBP critically involved in immune deficiency diseases and mycobacterial infections, is significantly upregulated in M. tuberculosis-infected macrophages. Here, we aimed to explore the immunoregulatory functions of ZNFX1 during M. tuberculosis infection. We observed that Znfx1 knockout markedly compromised the multifaceted immune responses mediated by macrophages. This compromise resulted in reduced phagocytosis, suppressed macrophage activation, increased M. tuberculosis burden, progressive lung tissue injury, and chronic inflammation in M. tuberculosis-infected mice. Mechanistic investigations revealed that the absence of ZNFX1 inhibited autophagy, consequently mediating immune suppression. ZNFX1 critically maintained AMPK-regulated autophagic flux by stabilizing protein kinase AMP-activated catalytic subunit alpha 2 mRNA, which encodes a key catalytic α subunit of AMPK, through its zinc finger region. This process contributed to M. tuberculosis growth suppression. These findings reveal a function of ZNFX1 in establishing anti-M. tuberculosis immune responses, enhancing our understanding of the roles of RBPs in tuberculosis immunity and providing a promising approach to bolster antituberculosis immunotherapy.

Health Screening Strategies for Artisanal and Small-Scale Miners for Tuberculosis, Human Immunodeficiency Virus and Silicosis: A Case of the USAID-Supported Kunda Nqob'iTB Project in Zimbabwe.

Artisanal and small-scale mining is characterized by excessive exposure to physical, chemical, ergonomic, psychosocial and biological hazards. There is a high burden of tuberculosis (TB), human immunodeficiency virus (HIV) infections and silicosis among artisanal and small-scale miners (ASMs). The aim of this project report is to describe lessons learned from strategies implemented to reach ASMs with screening services for TB, HIV and silicosis in Zimbabwe through the Kunda-Nqob'i TB (KNTB) project supported by the United States Agency for International Development (USAID). The intervention package for screening ASMs for TB, HIV and silicosis included service provision through two occupational health clinics at two provincial hospitals and a mobile workplace-based screening (WBS) facility at the mining sites. From 1 October 2020 to 30 September 2023, 10,668 ASMs were screened, with a high number of cases of silicosis (21%) and TB (7.4%). There was a high burden of HIV (30%) in ASMs attending the occupational health clinics. The two occupational health clinics screened 3453 ASMs, while the mobile WBS activities screened 7215 ASMs during the period. A total of 370 healthcare workers (doctors/clinical officers, nurses, environmental health technicians and district tuberculosis and Leprosy control officers) were trained on TB and the fundamental diagnostic principles of silicosis. The KNTB project has been successful in reaching out to many ASMs operating in remote and hard-to-reach mining areas. The KNTB project has brought to light the positive health-seeking behavior of ASMs operating in remote areas. The project has brought to the fore the effectiveness of multi-stakeholder engagement and collaboration in reaching out to ASMs in remote areas with health screening services. There is a high burden of TB, HIV and silicosis in ASMs. Screening for TB, HIV and silicosis using workplace-based screening and occupational health clinics is an effective strategy and should be rolled out to all areas with high artisanal and small-scale mining activity.

Genetic structure and drug resistance of <i>Mycobacterium tuberculosis</i> strains in the Kemerovo Region — Kuzbass

Background. Kemerovo Region has a high burden of tuberculosis (TB) with incidence rates twice the national average. The circulating variants of Mycobacterium tuberculosis significantly influence the TB epidemic process. Screening of epidemically significant variants of the pathogen in areas with a high burden of TB underlies epidemiological diagnosis and is necessary for the development of effective prevention measures. However, the population structure of M. tuberculosis in the Kemerovo Region — Kuzbass is poorly understood.
 Aims: to study genetic heterogeneity and phenotypic resistance to anti-tuberculosis drugs of M. tuberculosis strains in the Kemerovo Region.
 Materials and methods. The MIRU-VNTR genotyping of 163 M. tuberculosis strains isolated from TB patients in the Kemerovo Region in March–October 2022 was carried out. Cultivation of M. tuberculosis, drug susceptibility testing, and isolation of genomic DNA were carried out by standard methods. Genotypic identification was performed using MIRU-VNTR (24 loci) typing. In parallel, express genotyping was carried out: identification of isolates of the Beijing genotype (by RD105/207) and non-Beijing; subtyping Beijing using real-time PCR tests for detection of Central Asian Russian and B0/W148; identification of the non-Beijing group by real-tine PCR RT tests for LAM, S, Ural.
 Results. The isolates of the Beijing genotype (67.5%) were found to dominate both among newly diagnosed (64.4%) and previously treated patients (88.5%). MIRU-VNTR typing revealed 75 profiles, of which 94-32 (35.3%) and 100-32 (15.7%) were the most abundant and belonged to the Beijing genotype. Overall, 39.9% and 20.9% of isolates, respectively, were assigned to the Beijing Central Asian Russian and B0/W148 epidemic clusters, which differed significantly in MDR levels (50.8% and 85.3%, respectively; p = 0.005). The second most common were strains of the genetic family of the Euro-American lineage (L4) (31.9%): LAM (6.7%) Ural (7.4%) Haarlem (4.9%) and L4-unclassified (12.9%), MDR among of these minor genotypes was significantly lower than among Beijing genotype strains, and amounted to 11.5% (p 0.001). Strains from HIV-TB patients (56.4% of the total sample) carried an MDR profile more often (54.8%) compared to TB cases without HIV infection (35.2%) (p = 0.005), which may be due to higher proportion of Beijing genotype strains in the HIV-TB group (75.0% vs. 57.7%; p = 0.026). Complete comparability of the SNP analysis (in-house tests) to identify the main genotypes and epidemically significant Beijing subtypes was shown, which made it possible to characterize 75.5% of the sample by the express method.
 Conclusions. The molecular genetic screening carried out in the Kemerovo Region revealed the heterogeneity of the M. tuberculosis population, which was dominated by strains of the Beijing genotype, with the frequency of subtypes comparable with other territories of the Siberian Federal District.

Features which discriminate between tuberculosis and haematologic malignancy as the cause of pleural effusions with high adenosine deaminase

BackgroundAdenosine deaminase (ADA) is a useful biomarker for the diagnosis of tuberculous pleurisy (TBP). However, pleural effusions with high ADA can also be caused by other diseases, particularly hematologic malignant pleural effusion (hMPE). This study aimed to investigate the features that could differentiate TBP and hMPE in patients with pleural effusion ADA ≥ 40 IU/L.MethodsThis was a retrospective observational study of patients with pleural effusion ADA ≥ 40 IU/L, conducted at a Korean tertiary referral hospital with an intermediate tuberculosis burden between January 2010 and December 2017. Multivariable logistic regression analyses were performed to investigate the features associated with TBP and hMPE, respectively.ResultsAmong 1134 patients with ADA ≥ 40 IU/L, 375 (33.1%) and 85 (7.5%) were diagnosed with TBP and hMPE, respectively. TBP and hMPE accounted for 59% (257/433) and 6% (27/433) in patients with ADA between 70 and 150 IU/L, respectively. However, in patients with ADA ≥ 150 IU/L, they accounted for 7% (9/123) and 19% (23/123), respectively. When ADA between 40 and 70 IU/L was the reference category, ADA between 70 and 150 IU/L was independently associated with TBP (adjusted odds ratio [aOR], 3.11; 95% confidence interval [CI], 1.95–4.95; P < 0.001). ADA ≥ 150 IU/L was negatively associated with TBP (aOR, 0.35; 95% CI, 0.14–0.90; P = 0.029) and positively associated with hMPE (aOR, 13.21; 95% CI, 5.67–30.79; P < 0.001). In addition, TBP was independently associated with lymphocytes ≥ 35% and a lactate dehydrogenase (LD)/ADA ratio < 18 in pleural effusion. hMPE was independently associated with pleural polymorphonuclear neutrophils < 50%, thrombocytopenia, and higher serum LD. A combination of lymphocytes ≥ 35%, LD/ADA < 18, and ADA < 150 IU/L demonstrated a sensitivity of 0.824 and specificity of 0.937 for predicting TBP.ConclusionIn patients with very high levels of pleural effusion ADA, hMPE should be considered. Several features in pleural effusion and serum may help to more effectively differentiate TBP from hMPE.

Isoniazid Monoresistance and Antituberculosis Treatment Outcome in Persons With Pulmonary Tuberculosis in Brazil.

The high burden of drug-resistant tuberculosis (TB) is a problem to achieve the goals of the End TB Strategy by 2035. Whether isoniazid monoresistance (Hr) affects anti-TB treatment (ATT) outcomes remains unknown in high-burden countries. We evaluated determinants of ATT outcome among pulmonary TB cases reported to the National Notifiable Disease Information System (SINAN) between June 2015 and June 2019, according to drug sensitivity testing (DST) results. Binomial logistic regression models were employed to evaluate whether Hr was associated with an unfavorable ATT outcome: death or failure, compared to cure or treatment completion. Among 60 804 TB cases reported in SINAN, 21 197 (34.9%) were included in the study. In this database, the frequency of unfavorable outcomes was significantly higher in those with Hr in contrast to isoniazid-sensitive persons with pulmonary TB (9.1% vs 3.05%; P < .001). Using a binomial logistic regression model, Hr was independently associated with unfavorable outcomes (odds ratio, 3.34 [95% confidence interval, 2.06-5.40]; P < .001). Hr detected prior to ATT was predictive of unfavorable outcomes at the national level in Brazil. Our data reinforce the need for high-TB-burden countries to prioritize DST to detect Hr. Effective treatment regimens for Hr-TB are needed to improve outcomes.

Exploring private sector perspectives on barriers and facilitators in availing tuberculosis care cascade services: a qualitative study from the Indian state

IntroductionThe private sector plays an important role in tuberculosis (TB) elimination by providing access to quality TB care services like diagnosis and treatment, advocacy for preventive measures, innovation to address challenges in TB elimination, vaccines etc. The study aims to understand the perspectives of private practitioners on patients’ TB care cascade to reinforce existing interventions by assuring the quality of care to TB patients.MethodsThe study utilized a qualitative design through in-depth interviews of private practitioners and was conducted in Ranchi and Purbi Singhbhum District of Jharkhand State from March-August 2021. The pilot-tested, semi-structured, open-ended interview guide questionnaire collected information from private practitioners on various aspects of the TB care cascade. The data from the provider interviews were transcribed into multiple codes and themes on the TB program. An inductive analysis was carried out with a focus on content credibility to eliminate bias. Ethical approval was received from the Institutional Ethics Committee of the Indian Institute of Public Health Gandhinagar (IIPHG), India. Written consent was taken from the private practitioners involved in the study. ResultIn-depth interviews of 17 private practitioners reveal various factors contributing to delays in TB care cascades, especially delay in access to TB diagnosis and TB Care, delay in providing treatment once after diagnosis and poor adherence to the TB treatment. According to the perception of private practitioners, there was an array of client, provider and system side factors affecting the TB care cascade gaps positively and negatively. Positive aspects mainly emerged from interviews: strong governance, consistent supply chain management, innovative PPP models and financial schemes reducing out-of-pocket expenditure (OOPE). Various factors affecting the TB care cascade negatively include awareness among the patient, socio-economic status, approach and decision-making power of providers, adverse effects of drugs, staff capacity building, etc. ConclusionsEngaging private practitioner in TB elimination efforts is critical to achieving global targets and reducing the burden of TB. The study helps to determine geography-specific barriers and facilitators of the TB care cascade to achieve the aim of providing universal access to TB healthcare with the inclusion of private practitioners.

Multiple cytokine analysis based on QuantiFERON-TB gold plus in different tuberculosis infection status: an exploratory study

BackgroundMore efficient and convenient diagnostic method is a desperate need to reduce the burden of tuberculosis (TB). This study explores the multiple cytokines secretion based on QuantiFERON-TB Gold Plus (QFT-Plus), and screens for optimal cytokines with diagnostic potential to differentiate TB infection status.MethodsTwenty active tuberculosis (ATB) patients, fifteen patients with latent TB infection (LTBI), ten patients with previous TB and ten healthy controls (HC) were enrolled. Whole blood samples were collected and stimulated by QFT-Plus TB1 and TB2 antigens. The levels of IFN-γ, TNF-α, IL-2, IL-6, IL-5, IL-10, IP-10, IL-1Ra, CXCL-1 and MCP-1 in supernatant were measured by Luminex bead-based multiplex assays. The receiver operating characteristic curve was used to evaluate the diagnostic accuracy of cytokine for distinguishing different TB infection status.ResultsAfter stimulation with QFT-Plus TB1 and TB2 antigens, the levels of all cytokines, except IL-5 in TB2 tube, in ATB group were significantly higher than that in HC group. The levels of IL-1Ra concurrently showed the equally highest AUC for distinguishing TB infection from HC, followed by the levels of IP-10 in both TB1 tube and TB2 tube. Moreover, IP-10 levels displayed the largest AUC for distinguishing ATB patients from non-ATB patients. Meanwhile, the levels of IP-10 also demonstrated the largest AUC in both TB1 tube and TB2 tube for distinguishing ATB patients from LTBI.ConclusionsIn addition to conventional detection of IFN-γ, measuring IP-10 and IL-1Ra based on QFT-Plus may have the more tremendous potential to discriminate different TB infection status.

Care pathways of individuals with tuberculosis before and during the COVID-19 pandemic in Bandung, Indonesia.

The COVID-19 pandemic is thought to have undone years' worth of progress in the fight against tuberculosis (TB). For instance, in Indonesia, a high TB burden country, TB case notifications decreased by 14% and treatment coverage decreased by 47% during COVID-19. We sought to better understand the impact of COVID-19 on TB case detection using two cross-sectional surveys conducted before (2018) and after the onset of the pandemic (2021). These surveys allowed us to quantify the delays that individuals with TB who eventually received treatment at private providers faced while trying to access care for their illness, their journey to obtain a diagnosis, the encounters individuals had with healthcare providers before a TB diagnosis, and the factors associated with patient delay and the total number of provider encounters. We found some worsening of care seeking pathways on multiple dimensions. Median patient delay increased from 28 days (IQR: 10, 31) to 32 days (IQR: 14, 90) and the median number of encounters increased from 5 (IQR: 4, 8) to 7 (IQR: 5, 10), but doctor and treatment delays remained relatively unchanged. Employed individuals experienced shorter delays compared to unemployed individuals (adjusted medians: -20.13, CI -39.14, -1.12) while individuals whose initial consult was in the private hospitals experienced less encounters compared to those visiting public providers, private primary care providers, and informal providers (-4.29 encounters, CI -6.76, -1.81). Patients who visited the healthcare providers >6 times experienced longer total delay compared to those with less than 6 visits (adjusted medians: 59.40, 95% CI: 35.04, 83.77). Our findings suggest the need to ramp up awareness programs to reduce patient delay and strengthen private provide engagement in the country, particularly in the primary care sector.

Applicability of artificial intelligence-based computer-aided detection (AI–CAD) for pulmonary tuberculosis to community-based active case finding

BackgroundArtificial intelligence-based computer-aided detection (AI–CAD) for tuberculosis (TB) has become commercially available and several studies have been conducted to evaluate the performance of AI–CAD for pulmonary tuberculosis (TB) in clinical settings. However, little is known about its applicability to community-based active case-finding (ACF) for TB.MethodsWe analysed an anonymized data set obtained from a community-based ACF in Cambodia, targeting persons aged 55 years or over, persons with any TB symptoms, such as chronic cough, and persons at risk of TB, including household contacts. All of the participants in the ACF were screened by chest radiography (CXR) by Cambodian doctors, followed by Xpert test when they were eligible for sputum examination. Interpretation by an experienced chest physician and abnormality scoring by a newly developed AI–CAD were retrospectively conducted for the CXR images. With a reference of Xpert-positive TB or human interpretations, receiver operating characteristic (ROC) curves were drawn to evaluate the AI–CAD performance by area under the ROC curve (AUROC). In addition, its applicability to community-based ACFs in Cambodia was examined.ResultsTB scores of the AI–CAD were significantly associated with the CXR classifications as indicated by the severity of TB disease, and its AUROC as the bacteriological reference was 0.86 (95% confidence interval 0.83–0.89). Using a threshold for triage purposes, the human reading and bacteriological examination needed fell to 21% and 15%, respectively, detecting 95% of Xpert-positive TB in ACF. For screening purposes, we could detect 98% of Xpert-positive TB cases.ConclusionsAI–CAD is applicable to community-based ACF in high TB burden settings, where experienced human readers for CXR images are scarce. The use of AI–CAD in developing countries has the potential to expand CXR screening in community-based ACFs, with a substantial decrease in the workload on human readers and laboratory labour. Further studies are needed to generalize the results to other countries by increasing the sample size and comparing the AI–CAD performance with that of more human readers.

Incidence of Tuberculosis Among Immigrants in Korea Who Participated in a Latent Tuberculosis Infection Screening Program.

With a rapid decrease in tuberculosis (TB) incidence, the significance of latent tuberculosis infection (LTBI) has been underscored in South Korea. Although South Korea does not have a high proportion of immigrants compared to other countries, there is a growing argument that it should actively embrace immigrants as a solution to address issues of low birth rates and population aging. This study aimed to assess TB incidence among immigrants who participated a pilot LTBI screening program in South Korea. Records of immigrants participated in a pilot LTBI screening program in South Korea between 2018 and 2019 were linked with Korean National TB Surveillance System to determine TB development. Participants underwent interferon-gamma release assay (IGRA) and chest X-rays. Standardized incidence ratios (SIRs) stratified by age, country of origin's TB burden was calculated with a reference group of general South Korean population. Of a total of 9,517 participants, 14 TB cases were identified. Participants with positive IGRA results who did not initiate LTBI treatment showed TB incidence of 312.5 per 100,000 person-years, whereas those with negative results showed TB incidence of 34.4 per 100,000 person-years, resulting in an incidence rate ratio of 9.08 (95% confidence interval [CI], 2.50-32.99). SIR of TB among total participants including those with negative IGRA results was 2.60 (95% CI, 1.54-4.38; P < 0.001), whereas SIR among those with positive IGRA results was 5.86 (95% CI, 3.15-10.89; P < 0.001). In the calculation of SIR among participants with positive IGRA results, those aged under 35 from high TB-burden countries or intermediate TB-burden countries showed a high SIR (18.08; 95% CI, 2.55-128.37; P = 0.004), and 11.30 (95% CI, 2.82-45.16; P < 0.001), respectively). Contrary to previous reports that suggest the majority of elderly population with a positive IGRA result were due to remote infection and had a lower TB risk compared to younger ages, SIR among those aged 65 or over from intermediate TB-burden countries was 6.15 (95% CI, 0.87-43.69; P = 0.069), which was comparable to that in younger participants aged between 35 and 49 (SIR, 4.87; 95% CI, 1.22-19.49; P = 0.025) or those aged between 50 and 64 (SIR, 4.62; 95% CI, 1.73-12.31; P = 0.002). Young immigrants with positive IGRA results from countries with high or intermediate TB burden showed a relatively high TB risk compared to a general South Korea population. In addition, unexpected high TB risk was observed among elderly immigrants with positive IGRA results. In establishing future policies for LTBI in immigrants in South Korea, screenings should primarily focus on younger age group (who aged under 35). Additionally, further research is needed on the high TB risk observed in elderly immigrants.

Burden of tuberculosis in underserved populations in South Africa: A systematic review and meta-analysis.

Identifying case-finding strategies to reduce tuberculosis (TB) incidence in high-burden countries requires better knowledge of the disease burden in key contributing populations and settings. To inform South Africa's National Tuberculosis Strategic Plan 2023-2028, we conducted a systematic review of active TB disease and latent TB infection (LTBI) prevalence and incidence in underserved populations, defined as those living in informal settlements, townships, or impoverished communities. We identified articles published from January 2010 to December 2023, assessed study quality, and conducted a meta-analysis to estimate pooled TB and LTBI prevalence stratified by HIV status. We calculated prevalence ratios for underserved populations compared to the overall South African population. The search yielded 726 unique citations. We identified 22 studies reporting TB prevalence (n = 12), TB incidence (n = 5), LTBI prevalence (n = 5), and/or LTBI incidence (n = 2) eligible for the review, including six high-quality studies. Meta-analysis demonstrated a high prevalence of TB disease among persons living without HIV (2.7% 95% CI 0.1 to 8.5%) and persons living with HIV (PLWH) (22.7%, 95% CI 15.8 to 30.4%), but heterogeneity was high (I2 = 95.5% and 92.3%, p-value<0.00). LTBI prevalence was high among persons living without HIV (44.8%, 95% 42.5 to 47%) with moderate heterogeneity (I2 = 14.6%, p-value = 0.31), and lower among PLWH (33%, 95% CI 22.6 to 44.4%) based on one study. Compared to the national average, underserved populations of persons living without HIV had a 4-fold higher TB prevalence and a 3.3-fold higher LTBI prevalence. Underserved PLWH had a 31-fold higher TB prevalence than the national average, but similar LTBI prevalence as measured in one study. Our findings illustrate that underserved populations in South Africa have a substantially higher TB and LTBI prevalence than the general population, making targeted TB interventions potentially beneficial. More research is needed to explore the heterogeneous TB epidemiology in South Africa.

Proportion of active tuberculosis among HIV-infected children after antiretroviral therapy in Ethiopia: A systematic review and meta-analysis.

Despite effectiveness of antiretroviral therapy in reducing mortality of opportunistic infections among HIV infected children, however tuberculosis (TB) remains a significant cause for morbidity and attributed for one in every three deaths. HIV-infected children face disproportionate death risk during co-infection of TB due to their young age and miniatures immunity makes them more vulnerable. In Ethiopia, there is lack of aggregated data TB and HIV mortality in HIV infected children. We conducted an extensive systematic review of literature using Preferred Reporting of Systematic Review and Meta-Analysis (PRISMA) guideline. Five electronic databases were used mainly Scopus, PubMed, Medline, Web of Science, and Google scholar for articles searching. The pooled proportion of TB was estimated using a weighted inverse variance random-effects meta-regression using STATA version-17. Heterogeneity of the articles was evaluated using Cochran's Q test and I2 statistic. Subgroup analysis, sensitivity test, and Egger's regression were conducted for publication bias. This met-analysis is registered in Prospero-CRD42024502038. In the final met-analysis report, 13 out of 1221 articles were included and presented. During screening of 6668 HIV-infected children for active TB occurrence, 834 cases were reported after ART was initiated. The pooled proportion of active TB among HIV infected children was found 12.07% (95% CI: 10.71-13.41). In subgroup analysis, the Oromia region had 15.6% (95%CI: 10.2-20.6) TB burden, followed by southern Ethiopia 12.8% (95%CI: 10.03-15.67). During meta-regression, missed isoniazid Preventive therapy (IPT) (OR: 2.28), missed contrimoxazole preventive therapy (OR: 4.26), WHO stage III&IV (OR: 2.27), and level of Hgb ≤ 10gm/dl (OR = 3.11.7) were predictors for active TB. The systematic review found a higher proportion of active TB in HIV-infected children in Ethiopia compared to estimated rates in end TB strategy. To prevent premature death during co-infection, implement effective TB screening and cases tracing strategies in each follow up is needed.

Epidemiology of multi-drug resistant Tuberculosis in the western region of Kenya.

Multidrug-resistant tuberculosis (TB) (MDR-TB), or TB that is simultaneously resistant to both isoniazid (INH) and rifampicin (RIF), is a barrier to successful TB control and treatment. Stratified data on MDR-TB, particularly in the high-burden western Kenya region, remain unknown. This data is important to monitor the efficacy of TB control and treatment efforts. Herein, we determined the molecular epidemiology of drug-resistant TB and associated risk factors in western Kenya. This was a non-experimental, population-based, cross-sectional study conducted between January and August 2018. Morning sputum samples of individuals suspected of pulmonary TB were collected, processed, and screened for Mycobacterium tuberculosis (Mtb) and drug resistance using line probe assay (LPA) and Mycobacterium growth indicator tubes (MGIT) culture. MGIT-positive samples were cultured on brain heart infusion (BHII) agar media, and the presence of Mtb was validated using Immunochromatographic assay (ICA). Drug sensitivity was performed on MGIT and ICA-positive but BHI-negative samples. Statistical significance was set at P < 0.05. Of the 622 Mtb isolates, 536 (86.2%) were susceptible to RIF and INH. The rest, 86 (13.83%), were resistant to either drugs or both. A two-sample proportional equality test revealed that the MDR-TB prevalence in western Kenya (5%) did not vary significantly from the global MDR-TB estimate (3.9%) (P = 0.196). Men comprised the majority of susceptible and resistant TB (75.9% and 77.4%%, respectively). Also, compared with healthy individuals, the prevalence of HIV was significantly higher in MDR-TB patients (35.9% vs 5.6%). Finally, TB prevalence was highest in individuals aged 25-44 years, who accounted for 58.4% of the total TB cases. Evidently, the prevalence of MDRTB in western Kenya is high. Particular attention should be paid to men, young adults, and those with HIV, who bear the greatest burden of resistant TB. Overall, there is a need to refine TB control and treatment programs in the region to yield better outcomes.