Regional and National Trends in Tuberculosis Research in South Asian Association for Regional Cooperation Countries: Post-COVID-19 Pandemic Machine Learning Factorial Analysis.

BACKGROUND: The number of tuberculosis (TB)-related morbidities and mortalities is still high in the South-east Asian region. This study was performed to characterize and visualize the post-coronavirus disease 2019 (COVID-19) TB research in South Asian Association for Regional Cooperation (SAARC). METHODS: The Web of Science Core Collection database was utilized. A total of 4822 documents were included in the final analysis according to the predefined eligibility criteria. The data were exported to the R package and VOSviewer software for factorial analysis and network visualization, respectively. RESULTS: The included documents were published in English between 2020 and 2024 in 1255 journals. These documents were authored by 17005 authors (3.53 authors/document). The authors collaboration index was noticed 3.61. In total, 74.16% documents were published as the article. The highest number of documents were published in 2022 (n = 1089). The documents published in 2020 received the highest number of mean total citations per article (n = 8.64). The most published journal was Cureus Journal of Medical Science (n = 228). The most prolific author was Gupta A (n = 115). The most active institution was the All India Institute of Medical Sciences (n = 587). The top most trending topics were Mycobacterium tuberculosis, TB elimination, molecular docking, extrapulmonary TB, Cartridge Based Nucleic Acid Amplification Test, and multidrug resistance. India was the most productive country and had the strongest research collaboration with the United States of America (USA), the United Kingdom (UK), and South Africa. Pakistan was mainly collaborating with the USA, the UK, Saudi Arabia, and China. The India and Pakistan collaboration was observed only in 66 documents. CONCLUSION: There is a poor output of scientific publication on TB in most SAARC countries. However, it is recognized that India has produced the highest number of scientific publications. The detection of undiagnosed post-COVID-19 pandemic TB cases is crucial to control further cases in the region. An effective regional cooperation should be established among institutions, universities, and countries to achieve the World Health Organization End TB goals.

Tuberculosis or Nontuberculosis? A Case of Mycobacterial Skin Infection.

Bacteria other than Mycobacterium tuberculosis and Mycobacterium leprae are known as nontuberculous mycobacteria (NTM), and the frequency of clinically symptomatic forms is increasing day by day. Mycobacterium fortuitum, a rapidly reproducing NTM, causes various clinical signs such as skin soft-tissue infection, surgical site infection, and disseminated infection in immunosuppressed patients. Although progress can be made in terms of diagnosis when growth is detected in culture, it is quite difficult to distinguish between infection and contamination. There is no place for antituberculosis treatment in the treatment of M. fortuitum. Antibiotics such as quinolones, trimethoprim-sulfamethoxazole, linezolid, doxycycline, clarithromycin, azithromycin, imipenem, tigecycline, linezolid, and amikacin are recommended at least in dual combination therapy. In this case presentation, the diagnosis and treatment of a 2-year skin soft-tissue infection with M. fortuitum growth in culture will be discussed.

Stigma and discrimination by healthcare providers towards patients diagnosed with HIV and tuberculosis: A study from India.

Background High levels of human HIV and tuberculosis (TB) stigma have been reported among healthcare workers (HCWs). Methods We compared HIV and TB stigma scores reported by nursing students and ward staff from hospitals across India. Transmission worry (TW) and intent to discriminate (ID) for HIV and TB were captured using a validated stigma scale. Results A total of 3733 individuals were interviewed. Nursing students and ward staff expressed higher TW while carrying out high- and low-risk tasks on patients with HIV compared to TB. Mean scores were 2.1 and 1.86 among nursing students; 1.82 and 1.79 among ward staff (all p<0.001). Both groups expressed a significantly higher ID against patients with HIV compared to TB (mean percentage: 75.6 and 70.3 among nursing students; and 81.8 and 78.8 among ward staff; all p<0.001). Conclusion TB stigma has implications for providing quality TB care. Training of HCWs regarding transmission dynamics, the importance of standard precautions during patient care, regardless of diagnosis is essential.

Clinical characteristics and pregnancy outcomes in pregnant women with TB: a retrospective cohort study.

PURPOSE: The influence of pregnancy on tuberculosis (TB) has not been well studied. This study aimed to investigate the demographics, clinical characteristics and outcomes of pregnant-related TB compared with the general population with TB. METHODS: We retrospectively analysed medical records of women during pregnancy or within six months postpartum with active TB who were admitted to the West China Hospital between 2011 and 2022. According to age, gender and admission time, the general population with active TB was matched at a ratio of 1:2, and the demographics, clinical characteristics and outcomes were compared. RESULTS: All the participants in both the pregnant and non-pregnant groups were females, averaging 26 years old, with a majority of Han nationality (72.4% vs. 69.5%, respectively). The two groups were comparable (p < .05). Pregnant TB cases showed higher rates of fever (61% vs. 35%), dyspnoea (39.9% vs. 18.7%), neurological symptoms (34.4% vs. 11.0%) and miliary TB (24.5% vs. 10.9%) compared to non-pregnant cases (p < .05). Additionally, the pregnant group exhibited lower red blood cell counts (3.62 × 109/L vs. 4.37 × 109/L), lower albumin levels (31.20 g/L vs. 40.40 g/L) and elevated inflammatory markers (p < .05). Pregnant women with TB had severe outcomes, with 16.3% requiring intensive care unit (ICU) care and a 3.3% TB-related mortality rate - higher than local averages. In contrast, the non-pregnant group had lower rates (0.8% for ICU admission, and no TB-related deaths). Moreover, active TB during pregnancies led to a high rate of spontaneous abortion (34.1%), with military pulmonary TB identified as the sole risk factor for severe TB in pregnancies (OR: 3.6; 95% CI: 1.15, 11.34). CONCLUSIONS: Manifestations of TB in pregnant women differ from those in the general population with TB. Pregnancy complicated with active TB greatly harms the mother and foetus and requires special attention in the future.

PPE59 antibodies in tuberculous patients and potential use for diagnosis when assayed with other rapid biomarkers.

BACKGROUND: PPE 59, which is absent from bacillus Calmette Guérin (BCG) strains, seems to induce a humoral immune response in patients with tuberculosis (TB). Additional studies are needed to better evaluate this protein in immune response to tuberculosis. OBJECTIVES: To evaluate the response of antibodies to PPE59 in TB individuals, its combination with IgG response to other, previously tested mycobacterial antigens (Ag) and with sputum smear microbiology (SM) results. METHODS: We have cloned and expressed the rv3429 gene that encodes PPE59, then IgG, IgM, and IgA against PPE59 antigens measured by enzyme-linked immunosorbent assay (ELISA) in 212 sera samples obtained from the following subject cohorts: TB residents from Italy (79) and in Brazil (52); and an all-Brazilian cohort of 55 patients with other respiratory disorders; 10 patients infected with non-tuberculous mycobacteria, and 16 asymptomatic subjects. Drawing on results from a previous study(17) of serum samples from Brazilian subjects tested for IgG by ELISA against mycobacterial antigens ESAT-6, 16kDa, MT10.3, MPT-64 and 38kDa, the results were analysed in combination with those of the PPE59 and SM tests. FINDINGS: Keeping the specificity rate at 97%, the overall PPE59 IgA sensitivity was 42.7%, while IgG and IgM showed lower performance (p < 0.0001). Combining PPE59 IgA/16kDa IgG results increased sensitivity to 71%, and even higher rates when the results were combined with SM results (86.5%, p = 0.001), at 88.9% specificity. Positive IgA was associated with pulmonary image alterations of high TB probability (p < 0.05). MAIN CONCLUSIONS: Tests with TB patients found a moderate frequency of positivity for PPE59 IgA. However, the higher level of sensitivity attained in combination with PPE59 IgA/16kDa IgG/SM results unheard of before, although imperfect, suggests that this may be a potential additional tool for rapid detection of TB in low-resource areas.

Genetic diversity within diagnostic sputum samples is mirrored in the culture of Mycobacterium tuberculosis across different settings.

Culturing and genomic sequencing of Mycobacterium tuberculosis (MTB) from tuberculosis (TB) cases is the basis for many research and clinical applications. The alternative, culture-free sequencing from diagnostic samples, is promising but poses challenges to obtain and analyse the MTB genome. Paradoxically, culture is assumed to impose a diversity bottleneck, which, if true, would entail unexplored consequences. To unravel this paradox we generate high-quality genomes of sputum-culture pairs from two different settings after developing a workflow for sequencing from sputum and a tailored bioinformatics analysis. Careful downstream comparisons reveal sources of sputum-culture incongruences due to false positive/negative variation associated with factors like low input MTB DNA or variable genomic depths. After accounting for these factors, contrary to the bottleneck dogma, we identify a 97% variant agreement within sputum-culture pairs, with a high correlation also in the variants' frequency (0.98). The combined analysis from five different settings and more than 100 available samples shows that our results can be extrapolated to different TB epidemic scenarios, demonstrating that for the cases tested culture accurately mirrors clinical samples.

Rapid lateral flow test for Mycobacterium tuberculosis complex and non-tuberculous mycobacteria differentiation.

The diagnosis of mycobacterial infections, including both the Mycobacterium tuberculosis complex (MTBC) and non-tuberculous mycobacteria (NTM), poses a significant global medical challenge. This study proposes a novel approach using immunochromatographic (IC) strip tests for the simultaneous detection of MTBC and NTM. Traditional methods for identifying mycobacteria, such as culture techniques, are hindered by delays in distinguishing between MTBC and NTM, which can affect patient care and disease control. Molecular methods, while sensitive, are resource-intensive and unable to differentiate between live and dead bacteria. In this research, we developed unique monoclonal antibodies (mAbs) against Ag85B, a mycobacterial secretory protein, and successfully implemented IC strip tests named 8B and 9B. These strips demonstrated high concordance rates with conventional methods for detecting MTBC, with positivity rates of 93.9% and 85.9%, respectively. For NTM detection, the IC strip tests achieved a 63.2% detection rate compared to culture methods, considering variations in growth rates among different NTM species. Furthermore, this study highlights a significant finding regarding the potential of MPT64 and Ag85B proteins as markers for MTBC detection. In conclusion, our breakthrough method enables rapid and accurate detection of both MTBC and NTM bacteria within the BACTEC MGIT system. This approach represents a valuable tool in clinical settings for distinguishing between MTBC and NTM infections, thereby enhancing the management and control of mycobacterial diseases. KEY POINTS: • Panel of mAbs for differentiating MTB versus NTM • IC strips for diagnosing MTBC and NTM after the BACTEC MGIT • Combined detection of MTP64 and Ag85B enhances diagnostic accuracy.

A decline in tuberculosis diagnosis, treatment initiation and success during the COVID-19 pandemic, using routine health data in Cape Town, South Africa.

BACKGROUND: Coronavirus disease (COVID-19) negatively impacted tuberculosis (TB) programs which were already struggling to meet End-TB targets globally. We aimed to quantify and compare diagnosis, treatment initiation, treatment success, and losses along this TB care cascade for drug-susceptible TB in Cape Town, South Africa, prior to and during COVID-19. METHODS: This observational study used routine TB data within two predefined cohorts: pre-COVID-19 (1 October 2018-30 September 2019) and during-COVID-19 (1 April 2020-31 March 2021). The numbers of people diagnosed, treated for TB and successfully treated were received from the Western Cape Provincial Health Data Centre. Pre and post treatment loss to follow up and cascade success rates (proportion of individuals diagnosed with an outcome of treatment success) were calculated and compared across cohorts, disaggregated by sex, age, HIV status, TB treatment history and mode of diagnosis. RESULTS: There were 27,481 and 19,800 individuals diagnosed with drug-susceptible TB in the pre- and during-COVID-19 cohorts respectively, a relative reduction of 28% (95% CI [27.4% - 28.5%]). Initial loss to follow up increased from 13.4% to 15.2% (p<0.001), while post treatment loss increased from 25.2% to 26.1% (p < 0.033). The overall cascade success rate dropped by 2.1%, from 64.8% to 62.7% (p< 0.001). Pre- and during-COVID-19 cascade success rates were negatively associated with living with HIV and having recurrent TB. CONCLUSIONS: An already poorly performing TB program in Cape Town was negatively impacted by the COVID-19 pandemic. There was a substantial reduction in the number of individuals diagnosed with drug-susceptible. Increases in pre-and post-treatment losses resulted in a decline in TB cascade success rates. Strengthened implementation of TB recovery plans is vital, as health services now face an even greater gap between achievements and targets and will need to become more resilient to possible future public health disruptions.

Effects of low dose computed tomography (LDCT) on lung cancer screening on incidence and mortality in regions with high tuberculosis prevalence: A systematic review.

BACKGROUND: Lung cancer screening (LCS) using low-dose computed tomography (LDCT) is a strategy for early-stage diagnosis. The implementation of LDCT screening in countries with a high prevalence/incidence of tuberculosis (TB) is controversial. This systematic review and meta-analysis aim to identify whether LCS using LDCT increases early-stage diagnosis and decreases mortality, as well as the false-positive rate, in regions with a high prevalence of TB. METHODS/DESIGN: Studies were identified by searching BVS, PUBMED, EMBASE, and SCOPUS. RCT and cohort studies (CS) that show the effects of LDCT in LC screening on mortality and secondary outcomes were eligible. Two independent reviewers evaluated eligibility and a third judged disagreements. We used the Systematic Review Data Repository (SRDR+) to extract the metadata and record decisions. The analyses were stratified by study design and incidence of TB. We used the Cochrane "Risk of bias" assessment tool. RESULTS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) were used. Thirty-seven papers were included, referring to 22 studies (10 RCTs and 12 cohorts). Few studies were from regions with a high incidence of TB (One RCT and four cohorts). Nonetheless, the evidence is compatible with European and USA studies. RCTs and CS also had consistent results. There is an increase in early-stage (I-II) diagnoses and reduced LC mortality in the LCDT arm compared to the control. Although false-positive rates varied, they stayed within the 20 to 30% range. DISCUSSION: This is the first meta-analysis of LDCT for LCS focused on its benefits in regions with an increased incidence/prevalence of TB. Although the specificity of Lung-RADS was higher in participants without TB sequelae than in those with TB sequelae, our findings point out that the difference does not invalidate implementing LDCT LCS in these regions. TRIAL REGISTRATION: Systematic review registration Systematic review registration PROSPERO CRD42022309581.

[Disseminated tuberculosis with osteomyelitis of the right little finger as the first manifestation: a case report].

The clinical data of a child with disseminated tuberculosis with osteomyelitis of the right little finger as the first manifestation who was admitted to Tianjin Children's Hospital on April 8, 2023 were retrospectively analyzed. The child, a 14-year-old female, presented with osteomyelitis of the right little finger as the first manifestation. She still had recurrent fever after focal incision and drainage. She was referred to our hospital. The samples from multiple sites were positive for molecular biology detection of Mycobacterium tuberculosis. She was considered as disseminated tuberculosis and was given anti-tuberculosis treatment. The child has recovered well. Pediatric disseminated tuberculosis has variable clinical manifestations and lacks specificity. It is often misdiagnosed and has a high mortality rate. Clinicians should improve their understanding of the disease and ensure early diagnosis and treatment.

A multicentre study to evaluate the diagnostic performance of a novel CAD software, DecXpert, for radiological diagnosis of tuberculosis in the northern Indian population.

Tuberculosis (TB) is the leading cause of mortality among infectious diseases globally. Effectively managing TB requires early identification of individuals with TB disease. Resource-constrained settings often lack skilled professionals for interpreting chest X-rays (CXRs) used in TB diagnosis. To address this challenge, we developed "DecXpert" a novel Computer-Aided Detection (CAD) software solution based on deep neural networks for early TB diagnosis from CXRs, aiming to detect subtle abnormalities that may be overlooked by human interpretation alone. This study was conducted on the largest cohort size to date, where the performance of a CAD software (DecXpert version 1.4) was validated against the gold standard molecular diagnostic technique, GeneXpert MTB/RIF, analyzing data from 4363 individuals across 12 primary health care centers and one tertiary hospital in North India. DecXpert demonstrated 88% sensitivity (95% CI 0.85-0.93) and 85% specificity (95% CI 0.82-0.91) for active TB detection. Incorporating demographics, DecXpert achieved an area under the curve of 0.91 (95% CI 0.88-0.94), indicating robust diagnostic performance. Our findings establish DecXpert's potential as an accurate, efficient AI solution for early identification of active TB cases. Deployed as a screening tool in resource-limited settings, DecXpert could enable early identification of individuals with TB disease and facilitate effective TB management where skilled radiological interpretation is limited.

Performance evaluation of the national tuberculosis control program 2016-2020: Souss-Massa region, Morocco.

BACKGROUND: Tuberculosis constitutes a public health problem in Morocco. In an environment where results-based management and the evaluation of public policies become an imperative; the evaluation of the performance of the national tuberculosis control program finds its interest. OBJECTIVES: This study aims to analyze the performance of the tuberculosis control program in the Souss Massa region, based on the systemic approach model over a five-year period 2016-2020. METHODS: This is a descriptive secondary data analysis carried out in the Souss-Massa region in southern Morocco over a five year period 2016-2020. Data collection was carried out through the health information system of the NTCP and the various periodic reports produced by the primary health care establishments and diagnostic centers for tuberculosis and respiratory diseases, the delegations and the regional health directorate of the Ministry of Health. RESULTS: The incidence of tuberculosis has fluctuated between 63 and 72 cases/100,000 inhabitants; the average number of cases detected is 1871 cases per year; the survey completion rate is 57.10%; the therapeutic success rate varies between 82% and 89%, the treatment failure rate varies between 0.62% and 2.32%; the death rate varies between 0.63% and 2.92%; the failure rate for tuberculosis/HIV cases is between 3.10% and 6.09%. CONCLUSIONS: The results of the program tracer indicators at the level of the Souss-Massa region show that the latter combs to achieve the target objectives.

My tuberculosis epidemiology journey: Implications for TB program interventions, activities and strategy.

Key learnings from some landmark studies that the author has been associated with and their implications on program strategies are highlighted. Learnings from prevalence surveys provide justification for active TB Case finding (ACF), role of Chest X-ray screening, justification of the elderly as a key vulnerable population and suggest re-think of the methods of sub-national certification for progress towards tuberculosis free status. Risk of infection studies suggest 14 million people acquiring new tuberculous infection each year in India suggesting a re-think on the targets for TB elimination. Justification is given for 'TB deaths averted' as a parameter for monitoring program impact, reviving risk of infection surveys using CyTB and higher emphasis on careful analysis of routine surveillance data for monitoring epidemiological trends rather than oft-repeated surveys. The modelling outputs suggest higher focus on reducing transmission of infection in urban and reducing treatment delay in rural areas and the need to scale up active case finding and TB preventive treatment in order to achieve End TB targets. Case finding studies justify upfront molecular diagnostics, need to confirm a single sputum result by another specimen or radiology during ACF and futility of X-ray based diagnosis during ACF. High rates of recurrence with intermittent treatment regimen providing evidence in favor of daily regimen, role of family centric approach to nutritional supplementation to prevent TB mortality and reduce TB incidence among household contacts are highlighted besides the need to address high proportion of families suffering catastrophic expenses during pre-treatment period.

Management of tuberculosis patients and the role of forensic medicine in COVID-19 pandemic.

Tuberculosis and Coronaviral disease-19 had a global impact in 2020 and still predominating, both infectious diseases similar to the lethal pandemics spread in one route, likely airborne transmission, the infected person could spread to healthy people. However, tuberculosis slightly varies from COVID-19. Though the primordial disease of the tuberculosis epidemic has had a vast impact on this society, besides the COVID-19 pandemic with other co-morbidities, conditions faced numerous complications. This review exemplified the impact of two lethal diseases in changing patient care, diagnostic issues, and forensic sciences roles. The diagnosis of tuberculosis with a massive concern due to standard testing methods, leading to inaccuracy, sensitivity, and prolonged time consumption. In addition, unavailability of testing kits, equipment failure, over-crowd in hospitals and fewer healthcare workers, a prolonged testing period, and finally, anxiety about COVID-19. Also, the contribution of forensic sciences in the autopsy of the exact cause of infectious diseases is crucial. Likewise, during this pandemic, there has been a drastic reduction in tuberculosis incidence in high-burden countries and a synergistic effect of both diseases. So, this review summarized the overall burden of tuberculosis management during COVID-19 and followed the guidelines of various nations' healthcare authorities to mitigate the consequences of tuberculosis diagnosis and prognosis during the pandemic.

Tubercular pyomyositis: A case series.

Tuberculosis is one of the endemic diseases in India. Tuberculosis can involve almost every organ of the body, however isolated muscle involvement is considered rare. We hereby report a series of three cases of tubercular pyomyositis to highlight the importance of high clinical suspicion in endemic countries like India, in both immunocompetent and immunocompromised individuals, presenting with persistent fever and musculoskeletal symptoms. A timely diagnosis with effective drainage and antitubercular therapy helps in good functional recovery.

Evaluation of mycobacterial microscopy and culture results from clinical samples: A five-year analysis.

Introduction: Ehrlich-Ziehl-Neelsen (EZN) staining and culture methods are often used to diagnose tuberculosis. This study aimed to determine the acidfast bacteria (AFS) positivity rates in various clinical samples sent to our laboratory over five years and the growth and resistance rates in two different (solid and liquid) cultures and compare them with the data from Türkiye and the world. Materials and Methods: A total of 62.456 clinic samples were accepted in the microbiology laboratory between 2019 and 2024. The mycobacterial culture was performed by searching for acid-resistant bacilli microscopically and parallel inoculation media [solid Löwenstein-Jensen (L-J) and MGIT 960 liquid]. Those growing in the MGIT 960 system were identified using BD MGIT TBC Identification test kits that detect the MPT64 antigen. AFS and MPT64 antigenpositive samples were identified as Mycobacterium tuberculosis complex (MTBC) while AFS-positive samples and MPT64 antigen-negative results were classified as non-tuberculous mycobacteria (NTM). Drug susceptibility testing was performed with the BACTEC MGIT 960 SIRE kit. Susceptibility to NTM samples was not performed. Result: Out of a total of 120.829 samples, 95.101 were lung samples and 25.728 were extrapulmonary samples. AFS positivity was detected in 2961 (2.4%) samples. MTBC grew in 6854 (5.6%) samples, and NTM grew in 1506 (1.24%) samples. Contamination was detected in 7171 (5.9%) media. Two thousand one hundred and sixty-nine susceptibility tests were performed. Considering antibiotic resistance rates, isoniazid resistance was detected in 154 (7%), rifampicin resistance in 140 (6.4%), ethambutol resistance in 18 (0.8%), and streptomycin resistance in 120 (0.5%) samples. All four-drug resistance was observed in 91 (4.1%) samples. AFP positivity and resistance rates for rifampicin have decreased significantly, while there have been no significant changes in NTM rates over the years. Conclusions: When our data was determined, the sensitivity of microscopy was low. It is understood that mycobacterial culture and microscopy must be evaluated together to exclude tuberculosis infection. The high mycobacterial culture positivity rate, which is 5.6%, is due to the high number of follow-up patients and new referrals. It is seen that the change in sensitivity rates is due to the period of the COVID-19 epidemic, and it is similar to World Health Organization (WHO) data.

A serum B-lymphocyte activation signature is a key distinguishing feature of the immune response in sarcoidosis compared to tuberculosis.

Sarcoidosis and tuberculosis (TB) are two granulomatous diseases that often share overlapping clinical features, including uveitis. We measured 368 inflammation-related proteins in serum in both diseases, with and without uveitis from two distinct geographically separated cohorts: sarcoidosis from the Netherlands and TB from Indonesia. A total of 192 and 102 differentially expressed proteins were found in sarcoidosis and active pulmonary TB compared to their geographical healthy controls, respectively. While substantial overlap exists in the immune-related pathways involved in both diseases, activation of B cell activating factor (BAFF) signaling and proliferation-inducing ligand (APRIL) mediated signaling pathways was specifically associated with sarcoidosis. We identified a B-lymphocyte activation signature consisting of BAFF, TNFRSF13B/TACI, TRAF2, IKBKG, MAPK9, NFATC1, and DAPP1 that was associated with sarcoidosis, regardless of the presence of uveitis. In summary, a difference in B-lymphocyte activation is a key discriminative immunological feature between sarcoidosis/ocular sarcoidosis (OS) and TB/ocular TB (OTB).