Search Results (95)

Background/Objectives: Tuberculosis (TB) and HIV co-infection pose significant challenges in resource-limited settings, contributing to multi-drug-resistant TB when treatment fails. This study aimed to identify determinants of TB treatment outcomes among HIV/TB co-infected patients in Lusaka, Zambia. Methods: A retrospective cohort study was conducted at Chilenje, Chipata, and Chawama level one hospitals, using systematic sampling to select 586 patient files. Data were analyzed with SPSS version 23, employing descriptive statistics, chi-square tests, and hierarchical logistic regression. Results: Among the study population (n = 586), consisting predominantly of working-age adults (25–44 years: 61.6%) and males (56.5%), treatment success was 81.3%, with a 12.5% mortality rate across treatment phases. Baseline smear-negative TB, viral load (100,000–199,999 copies/mL), diabetes without hypertension, and negative smear at follow-up independently predicted treatment outcomes. Higher treatment failure odds were linked to smear-negative TB, high viral load, and hypertension–diabetes comorbidity, while CD4 count and HIV treatment status showed no independent effects. Conclusions: These findings underscore the influence of viral load, TB type, comorbidities, and sputum conversion on treatment success, emphasizing the need for targeted monitoring and integrated care, particularly in the continuation phase, to enhance outcomes in this vulnerable population. Full article

Despite continuous and extensive global efforts in the fight against tuberculosis (TB), this infectious disease continues to exert a tremendous burden on public health concerns and deaths worldwide. TB, caused by the bacterial species Mycobacterium tuberculosis, is highly frequent in people living with HIV. The continuing epidemics of both chronic infections and the emergence of antimicrobial resistance, as well as the lack of effective diagnostic tools and drug–drug interactions, pose major challenges in the fight against these pathogens. Developing a wide range of host-directed therapies may improve treatment outcomes, helping alleviate the morbidity and mortality associated with both infections. In this review, we discuss the identification and development of new host-directed strategies based on protease inhibitors and their clinical relevance as adjunctive treatment. In the context of therapeutic agents with novel mechanisms, selective protease inhibitors, including saquinavir (SQV) and cystatins (CstC and CstF), are valuable targets that may provide effective therapeutic solutions for controlling Mtb and HIV coinfection. Full article

Background/Objectives: HIV and Mycobacterium tuberculosis (M.tb) co-infection presents a major global health burden. The immune response to M.tb is largely orchestrated by cluster of differentiation 4-positive (CD4⁺) T cells, with CD8⁺ T cells playing an auxiliary role. This study aims to investigate the immunometabolic response of CD4⁺ and CD8⁺ T cells to M.tb antigens, analysed using metabolomics, to elucidate metabolic shifts that may influence immune function in an HIV+ environment. Methods: Whole blood samples from newly diagnosed, treatment-naïve HIV+ individuals were stimulated with M.tb antigens early secreted antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10) using the QuantiFERON^® (QFT) Gold Plus assay. Following incubation, plasma samples were analysed through untargeted nuclear magnetic resonance (1^H-NMR) spectroscopy. Metabolomic data were processed using MetaboAnalyst, with differential metabolites identified through multivariate statistical analyses. Results: Metabolic profiling of PBMCs revealed distinct differences in response to M.tb antigens between CD4⁺ and CD4⁺/CD8⁺ T-cell activation. CD4⁺ T cells exhibited enhanced glycolysis, with elevated levels of metabolites that are linked largely to the Warburg effect. Additionally, vitamin D levels were found to correlate with certain metabolites, suggesting a role in modulating immune responses. Conclusions: These findings suggest a complex interplay between immune cell metabolism and activation in HIV+ individuals. The study demonstrates that HIV and M.tb co-infection significantly influences the broader metabolic profile of peripheral blood mononuclear cells (PBMCs), highlighting the altered metabolic pathways that are critical in immune responses and disease progression. These findings contribute to the understanding of immunometabolism in co-infection and emphasise the need for further research into targeted metabolic interventions. Full article

Tuberculosis (TB) continues to be a major public health challenge in low- and middle-income countries (LMICs), where high burdens of coinfections exacerbate the disease’s impact. In 2023, an estimated 8.2 million people were newly diagnosed with tuberculosis worldwide, reflecting an increase from 7.5 million in 2022 and 7.1 million in 2019. In LMICs, limited access to healthcare, inadequate nutrition, and poor living conditions contribute to higher coinfection rates among TB patients, leading to delayed diagnosis and treatment, which in turn exacerbates disease severity and facilitates transmission. This narrative review synthesizes the epidemiology, clinical implications, diagnostic challenges, and management strategies related to TB coinfections with viral pathogens including HIV, SARS-CoV-2, and influenza, bacteria such as Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa, fungi such as Aspergillus and Candida species, and parasites. This review highlights that overlapping symptoms, immune system compromise, and socioeconomic barriers in LMICs lead to delayed diagnoses and suboptimal treatment outcomes, while also addressing the challenges of managing drug interactions particularly in HIV–TB coinfections and underscoring the need for integrated diagnostic approaches, improved treatment regimens, and strengthened healthcare systems, thereby consolidating current evidence to inform future research priorities and policy interventions aimed at reducing the overall burden of TB and its coinfections in resource-limited settings. Full article

Background/Objectives: Tuberculosis (TB) and SARS-CoV-2 share similar symptoms and transmission routes. In early 2021, USAID and Stop TB Partnership recommended an integrated approach for simultaneous COVID-19 and TB testing in high TB burden countries for individuals with respiratory symptoms. In this evaluation, we tested a single sputum for both SARS-CoV-2 and Mycobacterium tuberculosis complex (MTBC) from participants at two healthcare facilities in South Africa. The diagnostic accuracy of the Xpert Xpress SARS-CoV-2 (Xpress) assay using a sputum swab capture method was assessed by comparing the results with routine SARS-CoV-2 testing, while also determining the prevalence of TB and TB-COVID-19 co-infection in the study population. Methods: A total of 2274 individuals were screened for enrolment. Eligibility included the presence of respiratory symptoms, close contact with a person with TB, TB diagnosis in the last two years or a person living with HIV. Sputum from 1032 participants was tested on the Xpress assay using a swab capture method while residual sputum was tested on the Xpert MTB/RIF Ultra assay for MTBC and rifampicin-resistance detection. Concordance between the Xpress assay and routine SARS-CoV-2 testing was assessed. Results: The Xpress assay detected SARS-CoV-2 in 183/1032 (18%) participants, TB was detected in 35/1032 (3%) participants and 10/1032 (1%) participants were co-infected with TB and COVID-19. The Xpress assay showed substantial agreement with routine testing (Kappa: 0.755). Conclusions: The study findings underscore a substantial identification of TB and rifampicin-resistant TB that would have been missed if bi-disease testing was not performed. In addition, the sputum swab capture method demonstrated reliable performance for SARS-CoV-2 detection. Full article

Background: Treatment outcomes are critical measures of TB treatment success, especially in resource-limited settings where tuberculosis remains a major public health issue. This study evaluated the treatment outcomes of patients with drug-resistant tuberculosis (DR-TB), co-infected with human immunodeficiency virus (HIV), and the impact of nutritional status, as measured by body mass index (BMI), on these outcomes in rural areas of the Olivier Reginald Tambo District Municipality, Eastern Cape, South Africa. Methods: A retrospective review of 360 patient files from four TB clinics and one referral hospital was conducted between January 2018 and December 2020. Data collected included patient demographics, clinical characteristics, BMI (categorized as underweight, normal, overweight, or obese), HIV status, DR-TB type, and treatment outcomes. Statistical analyses assessed the association between BMI categories, HIV status, and treatment outcomes. A scatter plot was used to illustrate BMI trends as a continuous variable in relation to age, enabling an analysis of BMI distribution across different age groups. Additionally, bar charts were utilized to explore categorical relationships and patterns in BMI across these groups. Results: The majority of patients were co-infected with HIV and had DR-TB, with rifampicin-resistant TB (RR-TB) and multidrug-resistant TB (MDR-TB) being the most prevalent forms. Treatment outcomes varied significantly by BMI category. Underweight patients had the lowest cure rates (23.2%), highlighting the adverse impact of malnutrition on DR-TB treatment success. Patients with normal BMI demonstrated higher cure rates (34.7%), while overweight and obese patients had moderate outcomes. HIV co-infection further reduced cure rates, with co-infected individuals showing poorer outcomes than HIV-negative patients. Gender disparities were also observed, with females achieving higher cure rates (39.1%) compared to males (31.4%). Weak trends linked BMI and DR-TB type, such as a higher prevalence of normal BMI among RR-TB cases. Conclusion: This study underscores the significant influence of nutritional status on DR-TB treatment outcomes, particularly among patients co-infected with HIV. Underweight patients face the greatest risk of poor outcomes, emphasizing the need for nutritional support as a critical component of DR-TB management. Comprehensive HIV care and gender-specific interventions are also essential to address disparities in treatment success. Tailored strategies focusing on these aspects can significantly enhance outcomes in high-burden, resource-limited settings. Full article

Background: HIV and tuberculosis (TB) co-infection poses a significant health challenge, particularly when involving the central nervous system (CNS), where it leads to severe morbidity and mortality. Current treatments face challenges such as drug resistance, immune reconstitution inflammatory syndrome (IRIS), and persistent inflammation. Glutathione (GSH) has the therapeutic potential to enhance treatment outcomes by improving antibiotic efficacy, reducing inflammation, and mitigating immune dysfunction. Methods: Relevant studies were identified through systematic searches of PubMed, Elsevier, WHO, and related databases. Inclusion criteria focused on preclinical and clinical research examining GSH or its precursors in HIV, TB, or co-infection, with emphasis on microbial control, immune modulation, and CNS-related outcomes. Results: Preclinical studies showed that GSH improves macrophage antimicrobial function, reduces oxidative stress, and limits Mycobacterium tuberculosis (M.tb) growth. Animal models demonstrated reduced bacterial burden in the lungs, liver, and spleen with GSH supplementation, along with enhanced granuloma stability. Clinical studies highlighted increased TH1 cytokine production, reduced inflammatory markers, and improved CD4+ T cell counts in HIV–M.tb co-infected patients. N-acetylcysteine (NAC), a GSH precursor, was shown to significantly enhance the efficacy of first-line TB antibiotics and mitigate treatment-associated toxicity. Discussion: GSH shows promise as an adjunct therapy for HIV–M.tb co-infection, particularly for cases involving the CNS, where it may improve immune recovery and reduce inflammation. However, evidence is limited by small sample sizes and a lack of randomized trials. Future research should focus on developing CNS-directed GSH formulations and evaluating its integration into current treatment protocols to address the dual burden of HIV and TB, ultimately improving patient outcomes. Full article

Extensive research on tuberculosis (TB) and HIV co-infection reveals the diverse prevalence and co-epidemic patterns across populations, necessitating tailored public health strategies. Co-infection is bidirectional; individuals with HIV are more susceptible to TB, and vice versa. Antiretroviral therapy (ART) and antituberculosis treatment (ATT) are critical for managing these conditions, but pose risks due to drug–pathogen and drug–drug interactions, potentially leading to immune reconstitution inflammatory syndrome (IRIS) in patients with HIV/AIDS. IRIS, often triggered by highly active antiretroviral therapy (HAART), can exacerbate HIV progression, increase drug resistance, and deteriorate patients’ quality of life. Approximately one-third of the global population with HIV is also infected with TB, with extensive drug-resistant (XDR) and multidrug-resistant (MDR) strains posing significant challenges. Latent TB infection (LTBI) further complicates the scenario, as it can progress to active TB, particularly in individuals with both conditions. The global and Indian mortality rates for TB-HIV co-infection remain high, emphasizing the need for new strategies. Additionally, unreported cases and inadequate post-treatment monitoring contribute to the high mortality rate, particularly among patients with LTBI. The complexity of managing HIV-TB co-infection, especially with LTBI, underscores the urgency of addressing these challenges to improve the outcomes for the affected populations. Full article

Drug-resistant tuberculosis (DR-TB) and HIV coinfection present a conundrum to public health globally and the achievement of the global END TB strategy in 2035. A descriptive, retrospective review of medical records of patients, who were diagnosed with DR-TB and received treatment, was conducted. Student’s t-test was performed to assess differences between two means and ANOVA between groups. The Chi-square test with or without trend or Fischer’s exact test was used to test the degree of association of categorical variables. Logistic regression was used to determine predictors of DR-TB treatment outcomes. A decision tree classifier, which is a supervised machine learning algorithm, was also used. Python version 3.8. and R version 4.1.1 software were used for data analysis. A p-value of 0.05 with a 95% confidence interval (CI) was used to determine statistical significance. A total of 456 DR-TB patients were included in the study, with more male patients (n = 256, 56.1%) than female patients (n = 200, 43.9%). The overall treatment success rate was 61.4%. There was a significant decrease in the % of patients cured during the COVID-19 pandemic compared to the pre-pandemic period. Our findings showed that machine learning can be used to predict TB patients’ treatment outcomes. Full article

Background/Objectives: Spinal tuberculosis (STB) is frequently misdiagnosed due to the multitude of symptoms it presents with. This review aimed to investigate the biomarkers that have the potential to accurately diagnose spinal TB in its early stages. Methods: A systematic search was conducted across multiple databases, yielding a diverse range of biomarkers categorized into complete blood count parameters, host inflammatory responses, bacterial antigens, and RNA-based markers. This review included studies on spinal tuberculosis patients, including blood serum biomarkers, while exclusion criteria included pediatric cases, cerebrospinal fluid or imaging biomarkers, co-infection with other bacteria, viruses, comorbidities, tumors, immune diseases, HIV infection, metabolic disorders, animal studies, opinion papers, and biomarkers relevant to health problems outside the disease. QUADAS-2 was used as a quality assessment tool for this review. This review identifies several promising biomarkers with significant diagnostic potential. Results: The neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), IFN-γ, CXCR3, CXCL9, CXCL10, PSMB9, STAT1, TAP1, and specific miRNA combinations demonstrated noteworthy diagnostic accuracy in distinguishing STB from other spinal pathologies. Additionally, these biomarkers offer insights into disease severity and progression. The review also highlighted the importance of combining multiple biomarkers to enhance diagnostic precision. This comprehensive systematic review underscores the potential of biomarkers to revolutionize the diagnosis of spinal tuberculosis. By integrating these markers into clinical practice, healthcare providers can achieve earlier and more accurate diagnosis, leading to improved patient care and outcomes. Conclusions: The combination of multiple biomarkers, including NLR, PSMB9, STAT1, and specific miRNAs, demonstrates promising diagnostic accuracy. Full article

Granuloma is a crucial pathological feature of tuberculosis (TB). The relationship between CD4+ T cells in both peripheral blood and granulomatous tissue, and the integrity of granulomas in Human Immunodeficiency Virus (HIV)–MTB co-infection, remains unexplored. This study collected biopsy specimens from 102 TB patients (53 with HIV-MTB co-infection and 49 only with TB). Hematoxylin and eosin (HE) staining and immunohistochemical staining were performed, followed by microscopic examination of the integrity of tuberculous granulomas. Through statistical analysis of peripheral blood CD4+ T cell counts, tissue CD4+ T cell proportion, and the integrity of granulomas, it was observed that HIV infection leads to poor formation of tuberculous granulomas. Peripheral blood CD4+ T cell counts were positively correlated with granuloma integrity, and there was a similar positive correlation between tissue CD4+ T cell proportions and granuloma integrity. Additionally, a positive correlation was found between peripheral blood CD4+ T cell counts and the proportion of CD4+ T cells in granuloma tissues. Therefore, HIV infection could impact the morphology and structure of tuberculous granulomas, with a reduced proportion of both peripheral blood and tissue CD4+ T lymphocytes. Full article

According to the World Health Organization (WHO), tuberculosis (TB) remains a significant global health challenge, with approximately 10 million new cases and 1.4 million deaths reported in 2020. TB disproportionately affects low- and middle-income countries, where factors such as migrant population, malnutrition, type 2 diabetes, human immunodeficiency virus (HIV) co-infection, and COVID-19 exacerbate its impact. TB also leads to substantial economic losses due to decreased productivity and high healthcare costs. Despite advances in treatments, TB remains a major public health issue, particularly in poorer regions. In Mexico, TB is considered a moderate-incidence disease, with higher prevalence in border states, mainly due to population displacements. Effective TB control requires collaboration between Mexico and the United States of America given the high cross-border human movement, like in the Baja California State that reported predominantly pulmonary TB cases. Effective management of TB involves rapid diagnosis and identification of antibiotic resistance. Techniques such as PCR, high-resolution computed tomography (HRCT), and/or Xpert MTB/RIF have enhanced diagnostic accuracy. Future perspectives about TB management focus on developing new drugs and vaccines to combat drug-resistant strains, and the comorbidities associated, which must be addressed to reinforce of health public programs. Full article

We asked if SARS-CoV-2 seropositivity in HIV/TB co-infected patients plays a role in precipitating active tuberculosis in HIV-infected individuals and alters inflammatory status. A prospective study was conducted on HIV/TB co-infected patients presenting with pulmonary (n = 20) or extrapulmonary (n = 12) tuberculosis. Abbott SARS-CoV-2 IgG kits assessed the presence of anti-nucleoprotein antibodies. Inflammatory markers viz. osteopontin, total and full-length galectin-9, and C-reactive protein were tested at baseline and the end of antituberculosis treatment. The inflammatory score (INS) was assessed based on the percentage of reduction in the inflammatory markers’ levels at the end of the treatment. Anti-SARS-CoV-2 antibodies were detected in five male patients diagnosed with pulmonary (n = 2) and extrapulmonary (n = 3) TB. None of them reported symptomatic COVID-19. Inflammatory marker levels did not differ significantly at baseline compared to those in seronegative patients. However, the INS correlated negatively with SARS-CoV-2 seropositivity (r = −0.386, p = 0.039), indicating persistently raised inflammatory markers in these patients at the end of the treatment compared to seronegative individuals. Among the four markers studied, total galectin-9 levels failed to decrease significantly in these patients (p = 0.030). The majority of HIV/TB co-infected patients enrolled in our study (84.5%) were SARS-CoV-2-seronegative, indicating that SARS-CoV-2 infection might not have played a role in precipitating TB reactivation. Full article

The present study aims to characterise the pharmacokinetics of rifampicin (RIF) in tuberculosis (TB) patients with and without HIV co-infection, considering the formation of 25-O-desacetyl-rifampicin (desRIF). It is hypothesised that the metabolite formation, HIV co-infection and drug formulation may further explain the interindividual variation in the exposure to RIF. Pharmacokinetic, clinical, and demographic data from TB patients with (TB-HIV+ group; n = 18) or without HIV (TB-HIV− group; n = 15) who were receiving RIF as part of a four-drug fixed-dose combination (FDC) regimen (RIF, isoniazid, pyrazinamide, and ethambutol) were analysed, along with the published literature data on the relative bioavailability of different formulations. A population pharmacokinetic model, including the formation of desRIF, was developed and compared to a model based solely on the parent drug. HIV co-infection does not alter the plasma exposure to RIF and the desRIF formation does not contribute to the observed variability in the RIF disposition. The relative bioavailability and RIF plasma exposure were significantly lower than previously reported for the standard regimen with FDC tablets. Furthermore, participants weighting less than 50 kg do not reach the same RIF plasma exposure as compared to those weighting >50 kg. In conclusion, as no covariate was identified other than body weight on CL/F and Vd/F, low systemic exposure to RIF is likely to be caused by the low bioavailability of the formulation. Full article

Tuberculosis (TB), primarily caused by Mycobacterium tuberculosis (M. tb), remains a widespread fatal health issue that becomes significantly detrimental when coupled with HIV. This study explores the host’s innate and adaptive immune system response to TB in HIV immunocompromised patients, highlighting the significant role of CD8+ T cells. While the crucial role of macrophages and cytokines, like TNF-α and IFN-γ, in managing the host’s immune response to M. tb is examined, the emphasis is on the changes that occur as a result of HIV coinfection. With the progression of HIV infection, the primary source of IFN-γ changes from CD4+ to CD8+ T cells, especially when latent TB advances to an active state. This study sheds light on the necessity of developing new preventative measures such as vaccines and new treatment approaches to TB, especially for immunocompromised patients, who are at a higher risk of life-threatening complications due to TB-HIV coinfection. Full article