UNASSIGNED: The impact of previous SARS-CoV-2 infection on the systemic immune response during tuberculosis (TB) disease has not been explored.
UNASSIGNED: An observational, cross-sectional cohort was established to evaluate the systemic immune response in persons with pulmonary tuberculosis with or without previous SARS-CoV-2 infection. Those participants were recruited in an outpatient referral clinic in Rio de Janeiro, Brazil. TB was defined as a positive Xpert-MTB/RIF Ultra and/or a positive culture of Mycobacterium tuberculosis from sputum. Stored plasma was used to perform specific serology to identify previous SARS-CoV-2 infection (TB/Prex-SCoV-2 group) and confirm the non- infection of the tuberculosis group (TB group). Plasmatic cytokine/chemokine/growth factor profiling was performed using Luminex technology. Tuberculosis severity was assessed by clinical and laboratory parameters. Participants from TB group (4.55%) and TB/Prex-SCoV-2 (0.00%) received the complete COVID-19 vaccination.
UNASSIGNED: Among 35 participants with pulmonary TB, 22 were classified as TB/Prex-SCoV-2. The parameters associated with TB severity, together with hematologic and biochemical data were similar between the TB and TB/Prex-SCoV-2 groups. Among the signs and symptoms, fever and dyspnea were significantly more frequent in the TB group than the TB/Prex-SCoV-2 group (p < 0,05). A signature based on lower amount of plasma EGF, G-CSF, GM-CSF, IFN-α2, IL-12(p70), IL-13, IL-15, IL-17, IL-1β, IL-5, IL-7, and TNF-β was observed in the TB/Prex-SCoV-2 group. In contrast, MIP-1β was significantly higher in the TB/Prex-SCoV-2 group than the TB group.
UNASSIGNED: TB patients previously infected with SARS-CoV-2 had an immunomodulation that was associated with lower plasma concentrations of soluble factors associated with systemic inflammation. This signature was associated with a lower frequency of symptoms such as fever and dyspnea but did not reflect significant differences in TB severity parameters observed at baseline.

BACKGROUND: Growing evidence suggests that chronic inflammation caused by tuberculosis (TB) may increase the incidence of diabetes. However, the relationship between post-TB pulmonary abnormalities and diabetes has not been well characterized.
METHODS: We analyzed data from a cross-sectional study in KwaZulu-Natal, South Africa, of people 15 years and older who underwent chest X-ray and diabetes screening with hemoglobin A1c testing. The analytic sample was restricted to persons with prior TB, defined by either (1) a self-reported history of TB treatment, (2) radiologist-confirmed prior TB on chest radiography, and (3) a negative sputum culture and GeneXpert. Chest X-rays of all participants were evaluated by the study radiologist to determine the presence of TB lung abnormalities. To assess the relationships between our outcome of interest, prevalent diabetes (HBA1c ≥6.5%), and our exposure of interest, chest X-ray abnormalities, we fitted logistic regression models adjusted for potential clinical and demographic confounders. In secondary analyses, we used the computer-aided detection system CAD4TB, which scores X-rays from 10 to 100 for detection of TB disease, as our exposure interest, and repeated analyses with a comparator group that had no history of TB disease.
RESULTS: In the analytic cohort of people with prior TB (n = 3,276), approximately two-thirds (64.9%) were women, and the average age was 50.8 years (SD 17.4). The prevalence of diabetes was 10.9%, and 53.0% of people were living with HIV. In univariate analyses, there was no association between diabetes prevalence and radiologist chest X-ray abnormalities (OR 1.23, 95%CI 0.95-1.58). In multivariate analyses, the presence of pulmonary abnormalities was associated with an 29% reduction in the odds of prevalent diabetes (aOR 0.71, 95%CI 0.53-0.97, p = 0.030). A similar inverse relationship was observed for diabetes with each 10-unit increase in the CAD4TB chest X-ray scores among people with prior TB (aOR 0.92, 95%CI 0.87-0.97; p = 0.002), but this relationship was less pronounced in the no TB comparator group (aOR 0.96, 95%CI 0.94-0.99).
CONCLUSIONS: Among people with prior TB, pulmonary abnormalities on digital chest X-ray are inversely associated with prevalent diabetes. The severity of radiographic post-TB lung disease does not appear to be a determinant of diabetes in this South African population.

BACKGROUND: Pakistan has significantly strengthened its capacity for active case finding (ACF) for tuberculosis (TB) that is being implemented at scale in the country. However, yields of ACF have been lower than expected, raising concerns on its effectiveness in the programmatic setting. Distribution of TB in communities is likely to be spatially heterogeneous and targeting of ACF in areas with higher TB prevalence may help improve yields. The primary aim of SPOT-TB is to investigate whether a policy change to use a geographically targeted approach towards ACF supported by an artificial intelligence (AI) software, MATCH-AI, can improve yields in Pakistan.
METHODS: SPOT-TB will use a pragmatic, stepped wedge cluster randomised design. A total of 30 mobile X-ray units and their field teams will be randomised to receive the intervention. Site selection for ACF in the intervention areas will be guided primarily through the use of MATCH-AI software that models subdistrict TB prevalence and identifies potential disease hotspots. Control areas will use existing approaches towards site selection that are based on staff knowledge, experience and analysis of historical data. The primary outcome measure is the difference in bacteriologically confirmed incident TB detected in the intervention relative to control areas. All remaining ACF-related procedures and algorithms will remain unaffected by this trial.
BACKGROUND: Ethical approval has been obtained from the Health Services Academy, Islamabad, Pakistan (7-82/IERC-HSA/2022-52) and from the Common Management Unit for TB, HIV and Malaria, Ministry of Health Services, Regulation and Coordination, Islamabad, Pakistan (26-IRB-CMU-2023). Findings from this study will be disseminated through publications in peer-reviewed journals and stakeholder meetings in Pakistan with the implementing partners and public-sector officials. Findings will also be presented at local and international medical and public health conferences.
BACKGROUND: NCT06017843.

Following Mycobacterium tuberculosis infection, alveolar macrophages are initially infected but ineffectively restrict bacterial replication. The distribution of M. tuberculosis among different cell types in the lung changes with the onset of T cell immunity when the dominant infected cellular niche shifts from alveolar to monocyte-derived macrophages (MDM). We hypothesize that changes in bacterial distribution among different cell types is driven by differences in T cell recognition of infected cells and their subsequent activation of antimicrobial effector mechanisms. We show that CD4 and CD8 T cells efficiently eliminate M. tuberculosis infection in alveolar macrophages, but they have less impact on suppressing infection in MDM, which may be a bacterial niche. Importantly, CD4 T cell responses enhance MDM recruitment to the lung. Thus, the outcome of infection depends on the interaction between the T cell subset and the infected cell; both contribute to the resolution and persistence of the infection.

UNASSIGNED: Antiretroviral hair drug levels are currently being used to monitor adherence to HIV treatment. There is currently a dearth of literature on the preferred technique(s) of hair harvest for medical testing in the context of African multicultural settings.
UNASSIGNED: To explore the preferred techniques(s) of hair harvest for medical testing among TB patients.
UNASSIGNED: We used a descriptive phenomenological approach to conduct interviews for 15 TB patients from the 06th through the 24th of June 2022. Data was organized by N-VIVO version 10 and analysed step by step using a thematic analytical approach.
UNASSIGNED: Participants aged <30 years were more knowledgeable, positively perceived, and experienced about the salon-based hair cutting technique compared to those aged≥30 years old. Participants aged ≥30 had experience, flexibility to use, and were knowledgeable in all three techniques, Overall, for all age categories (<30,30-40 and >40 years), majority of the respondents were knowledgeable, flexible and experienced in using all the three techniques.
UNASSIGNED: The majority of TB patients were knowledgeable, experienced and flexible about the hair cutting techniques however, efforts are needed to educate the youth that hair for medical testing can be cut by any of the three techniques without changing their cosmetic look.

UNASSIGNED: The current six months regimen for drug-susceptible tuberculosis (TB) is long, complex, and requires adherence monitoring. TB hair drug level assay is one innovative approach to monitor TB treatment adherence however, its acceptability in the context of African multi-cultural settings is not known.
UNASSIGNED: To determine the acceptability of hair harvest and testing as a TB therapeutic drug monitoring method.
UNASSIGNED: The study explored perceptions, and lived experiences among TB patients with regard to using hair harvest and testing as a method of tuberculosis therapeutic drug monitoring in the context of their cultural beliefs, and faith. We used a descriptive phenomenological approach.
UNASSIGNED: Four main themes emerged namely: participants\' perceptions about the cultural meaning of their body parts; perceptions about hair having any medical value or meaning; perceptions about hospitals starting to use hair harvest and testing for routine hospital TB treatment adherence monitoring; and perceived advantages and disadvantages of using hair for treatment adherence monitoring. Overall, we found that using hair to monitor adherence was acceptable to TB patients provided the hair was harvested and tested by a medical worker.
UNASSIGNED: Hair harvest for medical testing is acceptable to TB patients on the condition that it is conducted by a medical worker.

UNASSIGNED: Tuberculosis (TB) persists as a global health challenge, with its treatment hampered by the side effects of long-term combination drug therapies and the growing issue of drug resistance. Therefore, the development of novel therapeutic strategies is critical. This study focuses on the role of immune checkpoint molecules (ICs) and functions of CD8+ T cells in the search for new potential targets against TB.
UNASSIGNED: We conducted differential expression genes analysis and CD8+ T cell functional gene analysis on 92 TB samples and 61 healthy individual (HI) samples from TB database GSE83456, which contains data on 34,603 genes. The GSE54992 dataset was used to validated the findings. Additionally, a cluster analysis on single-cell data from primates infected with mycobacterium tuberculosis and those vaccinated with BCG was performed.
UNASSIGNED: The overexpression of LAG-3 gene was found as a potentially important characteristic of both pulmonary TB (PTB) and extrapulmonary TB (EPTB). Further correlation analysis showed that LAG-3 gene was correlated with GZMB, perforin, IL-2 and IL-12. A significant temporal and spatial variation in LAG-3 expression was observed in T cells and macrophages during TB infection and after BCG vaccination.
UNASSIGNED: LAG-3 was overexpressed in TB samples. Targeting LAG-3 may represent a potential therapeutic target for tuberculosis.

BACKGROUND: Tuberculosis is a global health problem that causes 1. 4 million deaths every year. It has been estimated that sputum smear-negative diagnosis but culture-positive pulmonary TB diagnosis contribute to 12.6% of pulmonary TB transmission. TB diagnosis by smear microscopy smear has a minimum detection limit (LOD) of 5,000 to 10,000 bacilli per milliliter (CFU/ml) of sputum result in missed cases and false positives. However, GeneXpert technology, with a LOD of 131-250 CFU/ml in sputum samples and its implementation is believe to facilitate early detection TB and drug-resistant TB case. Since 2013, Ghana health Service (GHS) introduce GeneXpert MTB/RIF diagnostic in all regional hospitals in Ghana, however no assessment of performance between microscopy and GeneXpert TB diagnosis cross the health facilities has been reported. The study compared the results of routine diagnoses of TB by microscopy and Xpert MTB from 2016 to 2020 at the Cape Coast Teaching Hospital (CCTH).
METHODS: The study compared routine microscopic and GeneXpert TB diagnosis results at the Cape Coast Teaching Hospital (CCTH) from 2016 to 2020 retrospectively. Briefly, sputum specimens were collected into 20 mL sterile screw-capped containers for each case of suspected TB infection and processed within 24 h. The samples were decontaminated using the NALC-NaOH method with the final NaOH concentration of 1%. The supernatants were discarded after the centrifuge and the remaining pellets dissolved in 1-1.5 ml of phosphate buffer saline (PBS) and used for diagnosis. A fixed smears were Ziehl-Neelsen acid-fast stain and observed under microscope and the remainings were used for GeneXpert MTB/RIF diagnosis. The data were analyze using GraphPad Prism.
RESULTS: 50.11% (48.48-51.38%) were females with an odd ratio (95% CI) of 1.004 (0.944-1.069) more likely to report to the TB clinic for suspected TB diagnosis. The smear-positive cases for the first sputum were 6.6% (5.98-7.25%), and the second sputum was 6.07% (5.45-6.73%). The Xpert MTB-RIF diagnosis detected 2.93% (10/341) (1.42-5.33%) in the first and 5.44% (16/294) (3.14-8.69%) in the second smear-negative TB samples. The prevalence of Xpert MTB-RIF across smear positive showed that males had 56.87% (178/313) and 56.15% (137/244) and females had 43.13% (135/313) and 43.85% (107/244) for the first and second sputum. Also, false negative smears were 0.18% (10/5607) for smear 1 and 0.31% (16/5126) for smear 2.
CONCLUSIONS: In conclusion, the study highlights the higher sensitivity of the GeneXpert assay compared to traditional smear microscopy for detecting MTB. The GeneXpert assay identified 10 and 16 positive MTB from smear 1 and smear 2 samples which were microscopic negative.

OBJECTIVE: To evaluate cytokine profiles and interferon-gamma release assay (IGRA) for their diagnostic capabilities in the differentiation of tuberculosis (TB) from non-TB conditions, as well as smear-negative pulmonary tuberculosis (SNPT) from smear-positive pulmonary tuberculosis (SPPT).
METHODS: A total of 125 participants were included, 77 of whom had TB and 48 who didn\'t, and demographic, clinical, and laboratory data were collected, including cytokine levels and IGRA results. The TB patients were further divided into 2 subgroups: SNPT (n=42) and SPPT (n=35).
RESULTS: Compared to non-TB, the TB group had lower BMI, higher WBC, neutrophils, monocytes, ESR and CRP (p<0.05). TB patients showed higher IL-2, IL-6, IFN-γ, IL-8 (p<0.001) and higher IGRA positivity (88.3% versus [vs.] 29.2%, p<0.001). Between SNPT and SPPT, moderate effect sizes were observed for IFN-α, IL-2, IL-10, IL-8 (Cohen\'s d 0.59-0.76), with lower IGRA positivity in SNPT (81.0% vs. 97.1%, p=0.015). ROC analysis indicated IFN-α, IL-2, IL-10, IL-8 had moderate accuracy for SNPT diagnosis (AUCs 0.668-0.734), and combining these improved accuracy (AUC 0.759, 80% sensitivity, 64.2% specificity).
CONCLUSIONS: A multi-biomarker approach combining these cytokines demonstrates enhanced diagnostic accuracy for tuberculosis.

UNASSIGNED: Neutrophils play a complex and important role in the immunopathology of TB. Data suggest they are protective during early infection but become a main driver of immunopathology if infection progresses to active disease. Neutrophils are now recognized to exist in functionally diverse states, but little work has been done on how neutrophil states or subsets are skewed in TB disease.
UNASSIGNED: To address this, we carried out comprehensive phenotyping by flow cytometry of neutrophils in the blood and airways of individuals with active pulmonary TB with and without HIV co-infection recruited in Durban, South Africa.
UNASSIGNED: Active TB was associated with a profound skewing of neutrophils in the blood toward phenotypes associated with activation and apoptosis, reduced phagocytosis, reverse transmigration, and immune regulation. This skewing was also apparently in airway neutrophils, particularly the regulatory subsets expressing PDL-1 and LOX-1. HIV co-infection did not impact neutrophil subsets in the blood but was associated with a phenotypic change in the airways and a reduction in key neutrophil functional proteins cathelicidin and arginase 1.
UNASSIGNED: Active TB is associated with profound skewing of blood and airway neutrophils and suggests multiple mechanisms by which neutrophils may exacerbate the immunopathology of TB. These data indicate potential avenues for reducing neutrophil-mediated lung pathology at the point of diagnosis.