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International Journal of Surgery Case... Jun 2024Diagnosing peritoneal tuberculosis is challenging due to unspecific clinical manifestations, particularly in immunocompromised patients with HIV/AIDS and tuberculosis...
INTRODUCTION
Diagnosing peritoneal tuberculosis is challenging due to unspecific clinical manifestations, particularly in immunocompromised patients with HIV/AIDS and tuberculosis infections.
PRESENTATION OF CASE
An Indonesian man, 26-years-old, complained of mid-abdominal colic and constipation. The patient's present state exhibited symptoms of weakness and paleness, oral candidiasis, a bloated abdomen, palpable discomfort, and shifting dullness. The ascitic fluid analysis showed increased ADA (709 U/L), and detected Mycobacterium tuberculosis using GeneXpert MTB/RIF. Radiographic examination from abdominal x-ray and CT scan revealed a small bowel obstruction. He received intestinal decompression, pain control, intravenous fluid resuscitation, and correction of electrolyte imbalance for small bowel obstruction without any indication for surgical intervention. He also receive first-line ATD for 2 months during intensive phase and 4 months for continuous phase. After a period of 2 weeks following the ATD administration, the patient began taking ARV medication on a daily basis. He showed a good prognosis 6 months following.
DISCUSSION
The diagnosis of peritoneal tuberculosis is challenging due to its unspecific manifestation and some cases are identified when complications such as small bowel obstruction appear. The ADA test and GenExpert MTB/RIF are useful instruments for promptly diagnosing tuberculosis. It is suggested to use ARV treatment in individuals with HIV/AIDS who have peritoneal tuberculosis, starting 2 weeks following ATD treatments.
CONCLUSION
Peritoneal tuberculosis with small bowel obstruction and HIV/AIDS infection is a rare case in which early diagnosis and monitoring play an important role in successful treatment.
PubMed: 38959611
DOI: 10.1016/j.ijscr.2024.109977 -
Cell Reports Jul 2024Understanding the role of B cells in tuberculosis (TB) is crucial for developing new TB vaccines. However, the changes in B cell immune landscapes during TB and their...
Understanding the role of B cells in tuberculosis (TB) is crucial for developing new TB vaccines. However, the changes in B cell immune landscapes during TB and their functional implications remain incompletely explored. Using high-dimensional flow cytometry to map the immune landscape in response to Mycobacterium tuberculosis (Mtb) infection, our results show an accumulation of marginal zone B (MZB) cells and other unconventional B cell subsets in the lungs and spleen, shaping an unconventional B cell landscape. These MZB cells exhibit activated and memory-like phenotypes, distinguishing their functional profiles from those of conventional B cells. Notably, functional studies show that MZB cells produce multiple cytokines and contribute to systemic protection against TB by shaping cytokine patterns and cell-mediated immunity. These changes in the immune landscape are reversible upon successful TB chemotherapy. Our study suggests that, beyond antibody production, targeting the regulatory function of B cells may be a valuable strategy for TB vaccine development.
PubMed: 38959109
DOI: 10.1016/j.celrep.2024.114426 -
European Journal of Clinical... Jul 2024Molecular screening for Mycobacterium tuberculosis (MTB) can lead to rapid empirical treatment inception and reduce hospitalization time and complementary diagnostic...
PURPOSE
Molecular screening for Mycobacterium tuberculosis (MTB) can lead to rapid empirical treatment inception and reduce hospitalization time and complementary diagnostic tests. However, in low-prevalence settings, the cost-benefit balance remains controversial due to the high cost.
METHODS
We used a Markov model to perform an economic analysis to evaluate the profit after implementing molecular MTB screening (Period B) compared with conventional culture testing (Period A) in respiratory samples from 7,452 consecutive subjects with presumed tuberculosis (TB).
RESULTS
The proportion of positivity was comparable between both periods (P > 0.05), with a total of 2.16 and 1.78 samples/patient requested in periods A and B, respectively (P < 0.001). The mean length of hospital stay was 8.66 days (95%CI: 7.63-9.70) in Period B and 11.51 days (95%CI: 10.15-12.87) in Period A (P = 0.001). The healthcare costs associated with diagnosing patients with presumed TB were reduced by €717.95 per patient with PCR screening. The probability of remaining hospitalized and the need for a greater number of outpatient specialty care visits were the variables with the most weight in the model.
CONCLUSION
Employing PCR as an MTB screening method in a low-prevalence setting may increase the profits to the system.
PubMed: 38958810
DOI: 10.1007/s10096-024-04880-1 -
Brazilian Journal of Medical and... 2024Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains the leading cause of mortality by a single infectious agent in the world. M. tuberculosis infection...
Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains the leading cause of mortality by a single infectious agent in the world. M. tuberculosis infection could also result in clinical chronic infection, known as latent TB infection (LTBI). Compared to the current limited treatment, several subunit vaccines showed immunotherapeutic effects and were included in clinical trials. In this study, a subunit vaccine of Ag85B with a novel mucosal adjuvant c-di-AMP (Ag85B:c-di-AMP) was delivered intranasally to a persistent M. tuberculosis H37Ra infection mouse model, which also presented the asymptomatic characteristics of LTBI. Compared with Ag85B immunization, Ag85B:c-di-AMP vaccination induced stronger humoral immune responses, significantly higher CD4+ T cells recruitment, enhanced Th1/Th2/Th17 profile response in the lung, decreased pathological lesions of the lung, and reduced M. tuberculosis load in mice. Taken together, Ag85B:c-di-AMP mucosal route immunization provided an immunotherapeutic effect on persistent M. tuberculosis H37Ra infection, and c-di-AMP, as a promising potential mucosal adjuvant, could be further used in therapeutic or prophylactic vaccine strategies for persistent M. tuberculosis infection as well as LTBI.
Topics: Animals; Adjuvants, Immunologic; Tuberculosis Vaccines; Mycobacterium tuberculosis; Mice; Disease Models, Animal; Female; Antigens, Bacterial; Acyltransferases; Vaccines, Subunit; Bacterial Proteins; Tuberculosis; Latent Tuberculosis; Mice, Inbred BALB C; Administration, Intranasal
PubMed: 38958367
DOI: 10.1590/1414-431X2024e13409 -
Journal of Medicinal Chemistry Jul 2024(Mtb), the infectious agent of tuberculosis (TB), causes over 1.5 million deaths globally every year. Host-directed therapies (HDT) for TB are desirable for their...
(Mtb), the infectious agent of tuberculosis (TB), causes over 1.5 million deaths globally every year. Host-directed therapies (HDT) for TB are desirable for their potential to shorten treatment and reduce the development of antibiotic resistance. Previously, we described a modular biomimetic strategy to identify , targeting PPM1A (IC = 1.19 μM), a metal-dependent phosphatase exploited by Mtb to survive intracellularly. restricted the survival of Mtb in macrophages and lungs of infected mice. Herein, we redesigned to create , which is a more potent inhibitor for PPM1A (IC = 180 nM). efficiently increased the level of phosphorylation of S403-p62 and the expression of LC3B-II to activate autophagy, resulting in the dose-dependent clearance of Mtb in infected macrophages. possesses a good pharmacokinetic profile and oral bioavailability ( = 74%). In vivo, is well tolerated up to 50 mg/kg and significantly reduces the bacteria burden in the spleens of infected mice.
PubMed: 38958057
DOI: 10.1021/acs.jmedchem.4c00513 -
Frontiers in Cellular and Infection... 2024Tuberculosis (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...
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSION
LAG-3 was overexpressed in TB samples. Targeting LAG-3 may represent a potential therapeutic target for tuberculosis.
Topics: Lymphocyte Activation Gene 3 Protein; Humans; Mycobacterium tuberculosis; CD8-Positive T-Lymphocytes; Tuberculosis; Animals; Antigens, CD; BCG Vaccine; Macrophages; Interleukin-2; Gene Expression Profiling; Tuberculosis, Pulmonary; Interleukin-12; Perforin; Male
PubMed: 38957797
DOI: 10.3389/fcimb.2024.1410015 -
Open Forum Infectious Diseases Jul 2024Direct whole genome sequencing (WGS) of () can be used as a tool to study drug resistance, mixed infections, and within-host diversity. However, WGS is challenging to...
BACKGROUND
Direct whole genome sequencing (WGS) of () can be used as a tool to study drug resistance, mixed infections, and within-host diversity. However, WGS is challenging to obtain from clinical samples due to low number of bacilli against a high background.
METHODS
We prospectively collected 34 samples (sputum, n = 17; bronchoalveolar lavage, n = 13; and pus, n = 4) from patients with active tuberculosis (TB). Prior to DNA extraction, we used a ligand-mediated magnetic bead method to enrich from clinical samples and performed WGS on Illumina platform.
RESULTS
was definitively identified based on WGS from 88.2% (30/34) of the samples, of which 35.3% (12/34) were smear negative. The overall median genome coverage was 15.2% (interquartile range [IQR], 7.7%-28.2%). There was a positive correlation between load of bacilli on smears and genome coverage ( < .001). We detected 58 genes listed in the World Health Organization mutation catalogue in each positive sample (median coverage, 85% [IQR, 61%-94%]), enabling the identification of mutations missed by routine diagnostics. Mutations causing resistance to rifampicin, isoniazid, streptomycin, and ethambutol were detected in 5 of 34 (14.7%) samples, including the S441A mutation that confers resistance to rifampicin, which is not covered by Xpert MTB/RIF.
CONCLUSIONS
We demonstrate the feasibility of magnetic bead-based enrichment for culture-free WGS of from clinical specimens, including smear-negative samples. This approach can also be integrated with low-cost sequencing workflows such as targeted sequencing for rapid detection of and drug resistance.
PubMed: 38957687
DOI: 10.1093/ofid/ofae320 -
Public Health Action Jun 2024The occurrence of transient culture positivity for (MTB), known as , poses significant challenges in understanding its spectrum and implications. Here, we report a case...
The occurrence of transient culture positivity for (MTB), known as , poses significant challenges in understanding its spectrum and implications. Here, we report a case of transient culture positivity, oscillating between detectable and non-detectable MTB cultures with minimal radiological features and review the literature on this phenomenon. The scarcity of scientific literature on this subject stems from the inherent impossibility of systematically studying mirage de tuberculose. Ethical and public health concerns prevent withholding treatment to monitor spontaneous reversion to negative cultures. Based on the literature, we estimate that mirage de tuberculose occurs in approximately one-third of individuals infected with MTB who exhibit no symptoms. Despite the inherently limited nature of these findings, they suggest that the significance of mirage de tuberculose may be greater than currently perceived. Managing cases of mirage de tuberculose presents formidable challenges from a public health perspective. Striking a balance between prompt treatment initiation to prevent transmission and the risk of unnecessary treatment requires careful consideration. In conclusion, mirage de tuberculose remains a poorly understood clinical entity with very limited literature available. Advancing research and interdisciplinary collaborations are essential to unravel the intricacies of this phenomenon and develop effective strategies to address its public health challenges.
PubMed: 38957505
DOI: 10.5588/pha.24.0056 -
BMC Infectious Diseases Jul 2024Tuberculosis 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... (Comparative Study)
Comparative Study
Comparison of microscopic and xpert MTB diagnoses of presumptive mycobacteria tuberculosis infection: retrospective analysis of routine diagnosis at Cape Coast Teaching Hospital.
INTRODUCTION
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.
CONCLUSION
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.
Topics: Humans; Mycobacterium tuberculosis; Retrospective Studies; Sputum; Ghana; Female; Hospitals, Teaching; Adult; Male; Microscopy; Middle Aged; Tuberculosis, Pulmonary; Young Adult; Adolescent; Sensitivity and Specificity; Aged; Molecular Diagnostic Techniques; Child; Child, Preschool
PubMed: 38956504
DOI: 10.1186/s12879-024-09566-9 -
BMC Infectious Diseases Jul 2024Multi-drug or rifamycin-resistant tuberculosis (MDR/RR-TB) is an important public health concern, including in settings with high HIV prevalence. TB drug resistance can... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Multi-drug or rifamycin-resistant tuberculosis (MDR/RR-TB) is an important public health concern, including in settings with high HIV prevalence. TB drug resistance can be directly transmitted or arise through resistance acquisition during first-line TB treatment. Limited evidence suggests that people living with HIV (PLHIV) might have an increased risk of acquired rifamycin-resistance (ARR).
METHODS
To assess HIV as a risk factor for ARR during first-line TB treatment, a systematic review and meta-analysis was conducted. ARR was defined as rifamycin-susceptibility at treatment start with rifamycin-resistance diagnosed during or at the end of treatment, or at recurrence. PubMed/MEDLINE, CINAHL, Cochrane Library, and Google Scholar databases were searched from inception to 23 May 2024 for articles in English; conference abstracts were also searched from 2004 to 2021. The Mantel-Haenszel random-effects model was used to estimate the pooled odds ratio of any association between HIV and ARR among individuals receiving first-line TB treatment.
RESULTS
Ten studies that included data collected between 1990 and 2014 were identified: five from the United States, two from South Africa and one each from Uganda, India and Moldova. A total of 97,564 individuals were included across all studies, with 13,359 (13.7%) PLHIV. Overall, 312 (0.32%) acquired rifamycin-resistance, among whom 115 (36.9%) were PLHIV. The weighted odds of ARR were 4.57 (95% CI, 2.01-10.42) times higher among PLHIV compared to HIV-negative individuals receiving first-line TB treatment.
CONCLUSION
The available data, suggest that PLHIV have an increased ARR risk during first-line TB treatment. Further research is needed to clarify specific risk factors, including advanced HIV disease and TB disease severity. Given the introduction of shorter, 4-month rifamycin-based regimens, there is an urgent need for additional data on ARR, particularly for PLHIV.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42022327337.
Topics: Humans; HIV Infections; Rifamycins; Antitubercular Agents; Tuberculosis, Multidrug-Resistant; Risk Factors; Mycobacterium tuberculosis; South Africa
PubMed: 38956461
DOI: 10.1186/s12879-024-09514-7