Tuberculosis Research Articles

Differential requirement of formyl peptide receptor 1 in macrophages and neutrophils in the host defense against Mycobacterium tuberculosis Infection

Formyl peptide receptors (FPR), part of the G-protein coupled receptor superfamily, are pivotal in directing phagocyte migration towards chemotactic signals from bacteria and host tissues. Although their roles in acute bacterial infections are well-documented, their involvement in immunity against tuberculosis (TB) remains unexplored. Here, we investigate the functions of Fpr1 and Fpr2 in defense against Mycobacterium tuberculosis (Mtb), the causative agent of TB. Elevated levels of Fpr1 and Fpr2 were found in the lungs of mice, rabbits and peripheral blood of humans infected with Mtb, suggesting a crucial role in the immune response. The effects of Fpr1 and Fpr2 deletion on bacterial load, lung damage, and cellular inflammation were assessed in a murine TB model utilizing hypervirulent strain of Mtb from the W-Beijing lineage. While Fpr2 deletion had no impact on disease outcome, Fpr1-deficient mice demonstrated improved bacterial control, especially by macrophages. Bone marrow-derived macrophages from these Fpr1−/− mice exhibited an enhanced ability to contain bacterial growth over time. Contrarily, treating genetically susceptible mice with Fpr1-specific inhibitors caused impaired early bacterial control, corresponding with increased Mtb persistence in necrotic neutrophils. Furthermore, ex vivo assays revealed that Fpr1−/− neutrophils were unable to restrain Mtb growth, indicating a differential function of Fpr1 among myeloid cells. These findings highlight the distinct and complex roles of Fpr1 in myeloid cell-mediated immunity against Mtb infection, underscoring the need for further research into these mechanisms for a better understanding of TB immunity.

Molecular and microbiological methods for the identification of nonreplicating Mycobacterium tuberculosis.

Chronic tuberculosis (TB) disease, which requires months-long chemotherapy with multiple antibiotics, is defined by diverse pathological manifestations and bacterial phenotypes. Targeting drug-tolerant bacteria in the host is critical to achieving a faster and durable cure for TB. In order to facilitate this field of research, we need to consider the physiology of persistent MTB during infection, which is often associated with the nonreplicating (NR) state. However, the traditional approach to quantifying bacterial burden through colony enumeration alone only informs on the abundance of live bacilli at the time of sampling, and provides an incomplete picture of the replicative state of the pathogen and the extent to which bacterial replication is balanced by ongoing cell death. Modern approaches to profiling bacterial replication status provide a better understanding of inter- and intra-population dynamics under different culture conditions and in distinct host microenvironments. While some methods use molecular markers of DNA replication and cell division, other approaches take advantage of advances in the field of microfluidics and live-cell microscopy. Considerable effort has been made over the past few decades to develop preclinical in vivo models of TB infection and some are recognized for more closely recapitulating clinical disease pathology than others. Unique lesion compartments presenting different environmental conditions produce significant heterogeneity between Mycobacterium tuberculosis populations within the host. While cellular lesion compartments appear to be more permissive of ongoing bacterial replication, caseous foci are associated with the maintenance of M. tuberculosis in a state of static equilibrium. The accurate identification of nonreplicators and where they hide within the host have significant implications for the way novel chemotherapeutic agents and regimens are designed for persistent infections.

Histopathological spectrum of Cardiac Tuberculosis on autopsy: series of 11 cases

Background: Tuberculosis (TB) is leading cause of morbidity and mortality worldwide. However, this endemic disease rarely involves heart. Cardiac TB can involve any structure of heart with pericarditis is most frequent manifestation. Methods: This retrospective study was conducted at Department of Pathology from January 2012 to December 2020. Autopsy records of all cases suggestive of tuberculosis in any part of heart were selected and slides were reviewed. Results: A total of 11 cases of cardiac TB were recorded on autopsy, including 6 cases of isolated myocarditis, 2 cases of myopericarditis 2 cases of isolated pericarditis and one case of necrotizing arteritis in left coronary artery. Concomitant pulmonary TB was present in 72.7% cases. Conclusion: This study highlights that in all patients of pulmonary tuberculosis with appearance of any cardiovascular sign or symptom, cardiac TB should be suspected as one of the differentials.

Mathematical modeling suggests heterogeneous replication of Mycobacterium tuberculosis in rabbits.

How quickly Mycobacterium tuberculosis ( Mtb ) replicates and dies in lungs of infected individuals is likely to determine the outcome of the infection - either control/clearance of the bacteria by the host immune response or progression to active disease, tuberculosis ( TB ). And yet, only a few studies, primarily in mice, rigorously estimated the rates of Mtb replication and death during an in vivo infection. We infected rabbits with a novel clinical isolate of Mtb carrying an unstable, "replication clock" plasmid and followed the dynamics of bacteria over time. Interestingly, previous methods developed to estimate Mtb replication and death rates using similar data for Mtb infection of mice failed to describe our novel data on Mtb dynamics in rabbits; we showed that heterogeneous dynamics of Mtb in semi-independent subpopulations in lungs of Mtb-infected rabbits may be one explanation of this failure of the method. Our results highlight potential differences in Mtb dynamics in different mammalian hosts and suggest ways to evaluate heterogeneity of Mtb replication and death rates in vivo.

Nanopore-targeted sequencing (NTS) for intracranial tuberculosis: a promising and reliable approach

BackgroundThe World Health Organization predicted 10.6 million new tuberculosis cases and 1.5 million deaths in 2022. Tuberculous meningitis, affecting 1% of active TB cases, is challenging to diagnose due to sudden onset, vague symptoms, and limited laboratory tests. Nanopore-targeted sequencing (NTS) is an emerging third-generation sequencing technology known for its sequencing capabilities. We compared its detection efficiency with Xpert, MTB culture, PCR, and AFB smear in cerebrospinal fluid samples to highlight the substantial potential of NTS in detecting intracranial tuberculosis.MethodsThis study included 122 patients suspected of having intracranial tuberculosis at the Second Hospital of Nanjing in Jiangsu Province, China, between January 2021 and January 2024. The Univariate logistic regression and random forest regression identified risk factors and clinical markers. A chi-square test evaluated diagnostic accuracy for different image types of intracranial tuberculosis.ResultsThe research involved 100 patients with intracranial tuberculosis. Among them, 41 had tuberculous meningitis, 27 had cerebral parenchymal tuberculosis, and 32 had mixed intracranial tuberculosis. Besides, 22 patients were diagnosed with other brain conditions. In diagnosing intracranial tuberculosis, NTS demonstrated a sensitivity of 60.0% (95% CI: 49.7-69.5%) and a specificity of 95.5% (95% CI:75.1-99.8%), with an AUC value of 0.78 (95% CI: 0.71 to 0.84), whose overall performance was significantly better than other detection methods. There was no notable difference (P > 0.05) in diagnostic accuracy between NTS and the final diagnosis for intracranial tuberculosis patients with varying imaging types. Furthermore, patients who tested positive had a 31.500 (95% CI: 6.205-575.913) times higher risk of having intracranial tuberculosis compared to those with negative results.ConclusionDue to its convenience, efficiency, quick turnaround time, and real-time sequencing analysis, NTS might become a promising and reliable method for providing microbiological diagnoses for patients with intracranial tuberculosis and for screening populations at risk.

Risk of tuberculosis after achieving HIV virological suppression on antiretroviral therapy: a Danish nationwide prospective cohort study.

In countries with low tuberculosis (TB) burden, the risk of TB in people with HIV (PWH) once HIV virological suppression is achieved is not fully understood. In a nationwide cohort, we included all adult PWH from the Danish HIV Cohort initiating antiretroviral therapy (ART) (1995-2017) without prior TB disease. We used Kaplan-Meier estimation and Poisson regression to calculate TB incidence rate (IR) after six months of ART, along with associated risk factors and mortality rates (MR). Among 6,849 PWH initiating ART (median follow-up 7.4 years), 84 developed TB (IR 1.4/1000 person-year [PY]), 54 of them beyond six months of ART initiation, IR 0.97/1000 PY (95%CI:1.17-1.79): 1.95 (95%CI:1.34-2.76) in non-Danish born, 0.36 (95%CI:0.21-0.62) in Danish-born without injection drug use (IDU), and 2.95 (95%CI:1.53-5.66) in Danish-born with IDU. Danish-born with suppressed viremia, and no IDU or known TB exposures had the lowest risk (IR 0.05/1000 PY).In the adjusted analysis, being non-Danish born (aIRR 4.27[95%CI:2.36-7.72]), IDU (aIRR 4.95[95%CI:2.55-9.62]), and previous AIDS-defining events (aIRR 2.05[95%CI:1.06-3.94]) raised TB risk, while suppressed HIV-RNA (aIRR 0.58[95%CI:0.34-0.99]) reduced it. The overall MR for HIV/TB co-infected post- ART was high, at 48.9/1000 PY (95%CI:30.4-78.7). The TB risk remains elevated in PWH beyond six months of ART initiation, especially among migrants, IDU, those without suppressed HIV-RNA, and individuals exposed to high TB endemic areas or with social risk determinants of health. Conversely, PWH without these risk factors have a TB risk similar to the general population and would not require targeted TB screening strategies.

A modified BPaL regimen for tuberculosis treatment replaces linezolid with inhaled spectinamides.

The Nix-TB clinical trial evaluated a new 6 month regimen containing three oral drugs; bedaquiline (B), pretomanid (Pa), and linezolid (L) (BPaL regimen) for the treatment of tuberculosis (TB). This regimen achieved remarkable results as almost 90% of the multidrug-resistant or extensively drug-resistant TB participants were cured but many patients also developed severe adverse events (AEs). The AEs were associated with the long-term administration of the protein synthesis inhibitor linezolid. Spectinamide 1599 is also a protein synthesis inhibitor of Mycobacterium tuberculosis with an excellent safety profile, but it lacks oral bioavailability. Here, we propose to replace L in the BPaL regimen with spectinamide (S) administered via inhalation and we demonstrate that inhaled spectinamide 1599, combined with BPa --BPaS regimen--has similar efficacy to that of the BPaL regimen while simultaneously avoiding the L-associated AEs. The BPaL and BPaS regimens were compared in the BALB/c and C3HeB/FeJ murine chronic TB efficacy models. After 4-weeks of treatment, both regimens promoted equivalent bactericidal effects in both TB murine models. However, treatment with BPaL resulted in significant weight loss and the complete blood count suggested the development of anemia. These effects were not similarly observed in mice treated with BPaS. BPaL and BPa, but not the BPaS treatment, also decreased myeloid to erythroid ratio suggesting the S in the BPaS regimen was able to recover this effect. Moreover, the BPaL also increased concentration of proinflammatory cytokines in bone marrow compared to mice receiving BPaS regimen. These combined data suggest that inhaled spectinamide 1599 combined with BPa is an effective TB regimen without L-associated AEs.

Nanomaterial-mediated host directed therapy of tuberculosis by manipulating macrophage autophagy.

Tuberculosis (TB), induced by Mycobacterium tuberculosis (Mtb) infection, remains a major public health issue worldwide. Mtb has developed complicated strategies to inhibit the immunological clearance of host cells, which significantly promote TB epidemic and weaken the anti-TB treatments. Host-directed therapy (HDT) is a novel approach in the field of anti-infection for overcoming antimicrobial resistance by enhancing the antimicrobial activities of phagocytes through phagosomal maturation, autophagy and antimicrobial peptides. Autophagy, a highly conserved cellular event within eukaryotic cells that is effective against a variety of bacterial infections, has been shown to play a protective role in host defense against Mtb. In recent decades, the introduction of nanomaterials into medical fields open up a new scene for novel therapeutics with enhanced efficiency and safety against different diseases. The active modification of nanomaterials not only allows their attractive targeting effects against the host cells, but also introduce the potential to regulate the host anti-TB immunological mechanisms, such as apoptosis, autophagy or macrophage polarization. In this review, we introduced the mechanisms of host cell autophagy for intracellular Mtb clearance, and how functional nanomaterials regulate autophagy for disease treatment. Moreover, we summarized the recent advances of nanomaterials for autophagy regulations as novel HDT strategies for anti-TB treatment, which may benefit the development of more effective anti-TB treatments.

Isoniazid Hybrids As Potential Antitubercular Agents

AbstractThe rapid emergence of various forms of drug‐resistant tuberculosis (TB) has massively impacted people's health globally. According to the WHO, TB care and facilities have been downgraded by 21% since the COVID‐19 pandemic, which has further slowed down the progress toward the “End TB Strategy.” Multiple studies have shown drug‐resistant tuberculosis to be resilient to front‐line antituberculosis drugs, including isoniazid (INH), thus constantly prompting researchers worldwide to probe new potent chemical entities to replace/supplement the current artillery of anti‐TB therapeutics. The molecular hybridization (MH) technique has recently been adopted by many synthetic and medicinal chemists to combine different pharmacophoric units into a single molecular architecture which in most cases has been reported to exhibit a better pharmacological profile as compared to its precursors. The present review provides a concise account of the MH hybridization strategies directed at the structural manipulations of isoniazid to develop new anti‐TB agents and their structure‐activity relationships. Furthermore, their toxicity profiles and docking studies with relevant receptors are also briefly discussed.

UNSEEN TUBERCULOSIS: STUDY AMONG INPATIENTS OF A TERTIARY CARE HOSPITAL OF NORTH KARNATAKA

Objective: Tuberculosis (TB) remains a significant global health challenge, particularly in high-burden countries like India. However, high proportion of people never diagnosed or treated. Delayed diagnosis poses a significant threat to hospital inpatients, health-care workers, and medical trainees. Hence, systematic screening of high-risk groups, including hospital inpatients, has been recommended as a strategy to identify TB. Using signs and symptoms as an independent screening tool remains a global challenge for its relatively low accuracy. However, it could still be of value when it was used in a specific target population like inpatients of hospital. Hence, this study is aimed to determine the proportion of presumptive and active TB cases among inpatients. Methods: A hospital-based cross-sectional study was conducted among inpatients above 18 years of age admitted in non-emergency wards admitted during March to April 2023 at ESIC Hospital in Kalaburagi. A pre-existing TB diagnosis and patients admitted to critical care units were excluded. The convenient sampling method was used to recruit participants. Data were collected through using a pre-designed, semi-structured questionnaire. The patients who presented with one of the four symptoms for screening had undergone investigations such as cartridge-based nucleic acid amplification test, chest X-ray, and sputum microscopy to confirm the diagnosis, and the findings were recorded as proportion. Results: Out of 1363 inpatients, 35 (2.5%) patients had classified as presumptive TB case. Out of 35, 3 (8.57%) were found to be actual TB cases. All patients who had positive results for TB were young patients and belonged to low socioeconomic class. Two of three were rifampicin-sensitive TB cases. Conclusion: Timely screening of the patient’s is of utmost importance to avoid further spread of TB infection among inpatients. The higher prevalence of actual TB cases in younger adults needs further exploration.

Rifampicin-resistant Tuberculosis and Associated Factors Among Pulmonary Tuberculosis Patients in Mahakali Provincial Hospital, Nepal

The study aims at assessing the prevalence of RR-TB and identify associated factors among pulmonary TB patients using GeneXpert MTB/RIF assay data from January to December 2023. Tuberculosis (TB) continues to pose a significant global health threat, with rifampicin-resistant (RR) strains presenting a formidable challenge to disease control efforts. This study based the retrospective cross-sectional study conducted at Mahakali Provincial Hospital in Nepal. Out of 2587 presumptive TB cases, 11.8% were confirmed positive for TB, with males constituting a significantly higher proportion (66.1%) than females (33.9%). Among TB-positive cases, 3% showed resistance to rifampicin, predominantly affecting males (77.8%). Age group analysis revealed higher TB detection rates in the 46-60 years group, while rifampin -resistance tuberculosis (RR-TB) cases were more evenly distributed across age groups without statistical significance. Ethnicity and residential locality did not show significant associations with RR-TB. Multivariate logistic regression highlighted gender as RR-TB and associated factors among pulmonary tuberculosis patients in a Mahakali Provincial Hospital, Nepal. Rifampicin-resistant TB (RR-TB) remains a significant challenge at Mahakali Provincial Hospital, with a 3% prevalence, predominantly affecting males. Gender is a key factor in RR-TB prevalence. To manage and reduce RR-TB effectively, it is necessary to implement targeted interventions for high-risk groups, particularly males, and to enhance diagnostic capabilities.

Role of interferon-gamma release assay for screening and monitoring of latent tuberculosis infection in kidney transplant recipients

BackgroundThe reactivation of tuberculosis (TB) among kidney transplant (KT) recipients in an endemic area is of general concern. However, the epidemiology of latent TB infection (LTBI) status and its dynamic change responses have not been explored.MethodsBetween September 2020 and August 2021, a prospective study was conducted to investigate the status of LTBI in KT recipients who received a 9-month isoniazid universal prophylaxis. This status was measured using the interferon-gamma release assay (IGRA) with T-SPOT.TB before transplant, as well as at one month and nine months post-transplant.ResultsNinety-one KT recipients had a mean (SD) age of 45 (11) years, and 41% were female. Sixty-eight (75%) patients received a deceased donor allograft, and eighty-six (91%) patients received induction immunosuppressive therapy. The IGRA results were positive, borderline, negative, and indeterminate in 14 (15.4%), 6 (6.6%), 64 (70.3%), and 7 (7.8%) patients, respectively. Among 84 evaluable patients, 20 (23.8%) KT recipients were defined as having LTBI. Older age was significantly associated with LTBI (OR 1.06 [95% CI 1.01–1.12], p = 0.03). Among the 77 KT recipients who completed monitoring, 55 had negative IGRA results. Three (5.4%) KT recipients had conversion post-transplant. One of them developed pulmonary TB at 1 week after the transplant. Among the 13 patients with positive results, 8 (61.5%) remained positive, 1 (7.7%) had an indeterminate result at 1-month post-transplant and subsequently tested positive at 9 months post-transplant, and 4 (30.8%) experienced reversion to negative results throughout the study.ConclusionsIn a high TB-endemic area, one-quarter of KT recipients were reported to have LTBI, and the dynamic change of IGRA response in KT recipients is plausible post-transplant.

Analysis and dynamical transmission of tuberculosis model with treatment effect by using fractional operator

ABSTRACT Each year, millions of people die from the airborne infectious illness tuberculosis (TB). Several drug-susceptible (DS) and drug-resistant (DR) forms of the causative agent, Mycobacterium tuberculosis (MTB), are currently common in the majority of affluent and developing nations, particularly in Bangladesh, and completely drug-resistant strains are beginning to arise. The main purpose of this research is to develop and examine a non-integer-order mathematical model for the dynamics of tuberculosis transmission using the fractal fractional operator. By demonstrating characteristics such as the boundedness of solutions, positivity, and reliance of the solution on the original data, the biological well-posedness of the mathematical model formulation was investigated for TB cases from 2002 to 2017 in KPK Pakistan. Ulam-Hyres stability is also used to assess both local and global aspects of TB bacterial infection. Sensitivity analysis of the TB model with therapy was also examined. The advanced numerical technique is used to find the solution of the fractional-order system to check the impact of fractional parameters. Simulation highlights that all classes have converging qualities and retain established positions with time, which shows the actual behavior of bacterial infection with TB.

Eco-friendly Biosynthesis of Silver Nanoparticles Using Elephantorrhiza elephantina: Characterization and Antimicrobial Activity against Mycobacterium tuberculosis Surrogate Models

The emergence of multidrug-resistant (MDR) and extensively-drug resistant (XDR) Mycobacterium tuberculosis (MTB) strains have scampered efforts to arrest the tuberculosis (TB) pandemic due to treatment failures based on current drugs. The need for novel therapeutics has never been more urgent. Research is leaning towards alternative composite antimicrobials such as silver nanoparticles (AgNPs). Elephantorrhiza elephantina (E. elephantina) is an indigenous Southern African rhizomatous plant which has been used for eons in African traditional medicine for the management of TB. The purpose of this study was to biosynthesize and characterize AgNps using E. elephantina, and to evaluate their antimicrobial effectiveness against surrogate MTB species. The study also sought to screen for the participating secondary metabolites in E. elephantina acting as bio reducing, capping and stabilising agents; and to determine the toxicity of the lyophilised root extract in vivo. Qualitative phytochemical screening techniques confirmed the presence of bioactive secondary metabolites with functional groups capable of mediating in the biosynthesis of AgNPs. UV-Vis spectrometry established the identity of the nanostructures as AgNPs. Transmission electron microscopy and dynamic light scattering confirmed the AgNPs to have an average size of 44 nm, with spherical and cubic morphologies. The biosynthesised AgNPs were potent inhibitors of the model MTB species with an MIC of 19.53 µg/mL, and inhibition zones of 20mm and 18mm against Mycolicibacterium aurum and Mycolicibacterium smegmatis respectively at their MICs. Oral toxicity evaluations based on OECD guideline 425 determined the LD50 of the lyophilised E. elephantina root extract to be safe above 4000mg/kg body weight. The study concluded that biosynthesized AgNPs from E. elephantina root extract, using a one-pot green-synthesis technique, were both safe and effective, offering a promising alternative therapeutic strategy for combating multidrug-resistant TB.

Assessing infectiousness and the impact of effective treatment to guide isolation recommendations for people with pulmonary tuberculosis.

Determining the extent and duration of infectiousness of individuals with pulmonary tuberculosis (TB) is critical for various aspects of TB care, including decisions regarding isolation. Studies suggest considerable heterogeneity in infectiousness of people with pulmonary TB. Pre-treatment, measures of bacillary burden including sputum smear microscopy, culture time-to-positivity, and Xpert MTB/RIF cycle threshold (Ct) value, predict the risk of transmission to contacts. Index patients with smear negative disease pose lower infectious risk than those who have smear-positive disease, and household contact infection is more likely with index patients who have lower Xpert Ct values. Newer tools that enable detection of Mycobacterium tuberculosis complex (Mtb complex) from cough aerosol sampling and face mask sampling may be better predictors of contact infection risk. Clinical factors such as cough strength and frequency, and presence of cavitation on chest imaging, may also assist with risk prediction. Post-treatment, smear and culture status are poor predictors of infectiousness. While the exact duration of infectiousness post treatment initiation remains uncertain, data from human-to-guinea pig transmission studies and clinical studies suggest effective treatment results in a rapid decline in infectiousness, irrespective of smear or culture conversion. This is largely supported by early bactericidal activity and transcriptomic studies, and cough aerosol sampling studies, although a subset of patients may have persistent cough aerosol positivity. These findings can enable a more nuanced approach to isolation decision making, while further research studies are awaited.

Bedaquiline versus injectable containing regimens for rifampicin-resistant and multidrug-resistant tuberculosis in a reference center in Brazil – a real-world evidence study using a retrospective design

BackgroundDrug resistance (DR) is one of the several challenges to global tuberculosis (TB) control. The implementation of bedaquiline (BED) for DR-TB after more than 40 years was expected to improve treatment outcomes as well as microbiologic conversion and adverse events (AE) occurrence.MethodsRetrospective cohort study based on secondary data of patients with rifampicin-resistant (RR) or multidrug-resistant (MDR) TB reported to the Outpatient Clinic of Mycobacterial Diseases of the Thorax Diseases Institute – Federal University of Rio de Janeiro - Brazil, between 2016 and 2023. We aimed to evaluate microbiologic conversion, AE and TB treatment outcomes and compare them according to the treatment regimen used for RR/MDR-TB patients under routine conditions [Injectable Containing Regimens (ICR) versus BED Containing Regimens (BCR)]. Logistic regression and survival analysis using Cox regression and Kaplan Meier curve were used for statistical analysis.ResultsOf the 463 DR-TB patients notified during the study period, 297 (64.1%) were included for analysis (ICR = 197 and BCR = 100). Overall AEs were more frequent (83.7 vs. 16.3%, p < 0.001) and occurred earlier in the ICR group (15 days vs. 65 days, p = 0.003). There were no cases of cardiotoxicity requiring interruption of BED treatment. None of the regimens of treatment tested were associated with smear or culture conversion on Cox regression analysis (p = 0.60 and 0.88, respectively). BED-containing regimens were also associated with favorable outcomes in multivariable logistic regression [adjusted odds ratio (aOR) = 2.63, 95% confidence interval (CI)1.36–5.07, p = 0.004], as higher years of schooling, primary drug resistance, and no previous TB treatment. In the survival analysis, BCR was inversely associated with the occurrence of AE during treatment follow-up (aHR 0.24, 95% CI 0.14–0.41, p < 0.001). In addition, TB treatment regimens with BED were also associated with favorable outcomes (aHR 2.41, 95% CI 1.62–3.57, p < 0.001), along with no illicit drug use and primary drug resistance.ConclusionsThe implementation of a fully oral treatment for RR/MDR-TB in a reference center in Brazil was safe and associated with favorable outcomes under routine conditions, despite social, demographic, and behavioral factors that may influence TB treatment completion.

Analyzing nutrition risks and blood biomarkers in hospitalized patients with tuberculosis: Insights from a 2020 hospital-based study.

There exists a bidirectional relationship between tuberculosis (TB) and nutrition, wherein they mutually influence and interact causally. However, current guidance for providing nutrition support to individuals diagnosed with TB remains inadequate, leading to a significant gap in comprehensive patient care. This study aims to assess the nutrition status of patients with TB and endeavors to provide insights into early nutrition interventions for individuals vulnerable to TB-associated malnutrition. Data from 2204 newly admitted patients at Beijing Chest Hospital in 2020 were collected, with 1735 patients with confirmed TB aged ≥18 years after exclusions. Patient data, encompassing diagnosis and results from routine blood tests and biochemical analyses conducted on the day after admission, were gathered using the electronic medical records system. Nutrition risk screening was conducted using the Nutritional Risk Screening 2002 (NRS 2002) tool, and questionnaire-based assessments were administered. Statistical analyses were performed using SPSS 17.0 software. Among 1735 patients with TB, the occurrence rate of nutrition risk was 74.58%. Factors such as age ≥65 years, sputum smear positivity for TB, and concurrent illnesses significantly increased the occurrence rate of nutrition risk. Nutrition risk among patients with TB exhibited negative correlations with parameters such as body weight, hemoglobin, and serum albumin level while showing positive correlations with white blood cell count and C-reactive protein, among others. The occurrence rate of nutrition risk among patients with TB at Beijing Chest Hospital was notably high, particularly among older individuals, those with sputum smear positivity, and those with concurrent illnesses.

7180 Adrenal Histoplasmosis And Tuberculosis: Clinical Presentations And Prevalence Of Adrenal Insufficiency

Abstract Disclosure: T. Vorasayun: None. P. Pengkhum: None. T. Porntharukchareon: None. R. Plongla: None. K. Sasiprang: None. T. Snabboon: None. W.W. Parksook: None. T. Wannachalee: None. S. Sunthornyothin: None. Background: Adrenal infection is an important cause of adrenal insufficiency (AI). Commonly reported pathogens are Histoplasma capsulatum and Mycobacterium tuberculosis (TB). These two pathogens can cause similar clinical presentations, yet patients require different specific treatments. Methods: We performed a retrospective study of patients with adrenal histoplasmosis and TB at two referral centers in Bangkok, Thailand. Adrenal infection was diagnosed by proven microbiologic evidence of infection and morphologic adrenal abnormalities on cross-sectional imaging. We evaluated clinical characteristics, prevalence of AI, and treatment. Results: Of the 47 patients, 33 (70%) had adrenal histoplasmosis, 13 (28%) had adrenal TB, and 1 (2%) had coinfection with both pathogens. The majority were HIV-negative (91%) and males (whole cohort; 81%, histoplasmosis; 94%, TB; 54%, coinfection; 100%). The mean age at the diagnosis was 64 years in patients with adrenal histoplasmosis and 49 in adrenal TB. One patient with coinfection was 84 years. Extra-adrenal manifestations were 55%, 77%, and 100% in patients with adrenal histoplasmosis, TB, and coinfection, respectively. At presentation, all patients with adrenal histoplasmosis had anorexia/weight loss, while this symptom was present in 54% of patients with adrenal TB. The most common presentation in adrenal TB was hyperpigmentation (77%), while it was documented in less than half of adrenal histoplasmosis (45%). On cross-sectional imaging, the majority (83%) had bilateral adrenal abnormalities, of which 81% were mass-like. The median diameter of the adrenal lesions with histoplasmosis infection was 5.6 and 5.4 cm on the right and left adrenal glands, respectively, while the median diameter of the adrenal lesions with TB infection was 3.2 cm on both sides. The prevalence of AI was 88% in the whole cohort (83% in adrenal histoplasmosis, 100% in adrenal TB and coinfection). In patients with AI, the median 8 AM cortisol levels were 4 ug/dl (histoplasmosis; 8.0 ug/dl and TB; 2.3 ug/dl), and the median ACTH levels were 431 pg/ml (histoplasmosis; 189 pg/ml and TB; 1377 pg/ml). During a median follow-up time of 22 months, 100% received antituberculosis/antifungal agents, while only 21% underwent adrenalectomy, in which most patients were those with adrenal histoplasmosis. All patients with AI received steroid replacement, yet 11% had an adrenal crisis. There was no HPA axis recovery in any AI patients. Conclusion: There were high rates of AI in patients with adrenal histoplasmosis and/or TB. No recovery of the HPA axis was observed, even after antifungal/TB agents and without bilateral adrenalectomy. Most patients were non-HIV males and had bilateral mass-like adrenal lesions. There was a slightly higher prevalence of extra-adrenal manifestations and AI in TB, and it affected more women than histoplasmosis. Presentation: 6/3/2024

Can Primary Knee Tuberculosis Simulate the Clinical and Radiological Profile of Pigmented Villonodular Synovitis?

Can Primary Knee Tuberculosis Simulate the Clinical and Radiological Profile of Pigmented Villonodular Synovitis?

Tuberculosis Elimination Forecast for Moscow Region

The objective: to assess the possibility of tuberculosis elimination in Moscow Region by 2035.Subjects and Methods. For the study, Federal Statistical Surveillance Form No. 8 Information on Active Tuberculosis cases, and Form No. 33 Information on Tuberculosis Patients for 015-2023 were selected, rates were calculated for the average annual population in the region. Changes in tuberculosis incidence in Moscow Region were analyzed.Results. Based on results of the study on possibility to eliminate tuberculosis in Moscow Region by 2035, it has been found that if the current epidemic situation persists, it is only possible to achieve the mortality target. To achieve the target results for other rates, additional measures to prevent tuberculosis among the population are needed.