Tuberculosis and Hiv Infection - So Many Questions Pending

Since the early days of HIV infection, back in the eighties, TB - particularly extrapulmonary TB emerged as one of the opportunistic infections affecting these patients, specifically as a reactivation of latent TB infections. A diagnosis of TB in the context of HIV infection was then considered as an 'AIDS defining condition' according to classification systems used at that time. It has been recognized for a long time that there are many interactions between HIV and Mycobacterium tuberculosis, which lead to further immune deterioration and to worsening of both conditions due to complex biological and mechanistic interactions between these two agents. Many methods and techniques have been proposed in order to improve diagnosis of TB in HIV-infected subjects, knowing that TB is the most frequent opportunistic infection;and, if not treated in a timely fashion, it may easily take the lives of affected patients. It is not easy to have a diagnosis of TB in HIV-infected subjects, because of the difficulties for obtaining adequate sputum samples, or because of lack of adequate facilities for making a timely diagnosis, particularly in the so-called developing world. On the other hand, extrapulmonary TB is most frequently found in HIV-infected individuals compared to non-infected subjects, and its diagnosis poses significant difficulties, since so many times invasive procedures must be performed in order to obtain an adequate tissue sample and then be able to identify the pathological characteristics of tuberculous disease. In the first days of HIV infection when no antiretroviral therapy was available, a diagnosis of TB was made on clinical grounds, considering a history of contact or some characteristics of the disease, and those of us who are old (or experienced) enough offered antituberculosis therapy for these subjects, obtaining an adequate response many times, but in all cases, the natural history of HIV infection took place, and ultimately these patients died because of the occurrence of another opportunistic infection (or malignancy). With the advent of antiretroviral therapy in the late nineties, another problem occurred. The possibility of drug-drug interactions, taking into account hepatic metabolism of rifampin and the alterations of antiretroviral drug blood - or tissue - concentrations. On top of this, the occurrence of IRIS became another problem, and strategies and protocols have been designed in order to establish the adequate timing of antituberculosis therapy and sometime later antiretroviral therapy. A last point to be considered is the COVID-19 pandemic. The question to be asked is what the influence of the pandemic has been for affecting TB and HIV diagnosis and therapy strategies and programs, particularly in the developing world, knowing that health systems in these countries have many limitations, and that - scant - resources had to be dedicated for the fight against the pandemic.Copyright © 2023

Real-World Single-Centre Experience of Jak Inhibitor Use in Ra

Background/Aims The use of Janus Kinase Inhibitors (JAKi) has been gradually increasing overtime in the management of rheumatoid arthritis (RA) and other inflammatory arthritis and these appeal to patients. being oral agents. Nevertheless, rheumatologists have become cautious about their use since recent trials have shown safety concerns about VTEs, MACE and malignancies. Methods We decided to study use of JAKi at our centre in Princess of Wales Hospital Bridgend. The aim was to assess whether appropriate patients were selected (considering cautions about MACE, VTEs and malignancies). We also wanted to see whether all patients had required pretreatment safety testing and post-treatment monitoring performed. Results These were 70 patients;59 were females and 11 were males. All of them were diagnosed as RA. Average age was 61.1 years (20-85), average duration of disease 129.9 months (16-340) and average duration of treatment was 58.1 weeks. The most common JAKi being used was baricitinib (84%) followed by tofacitinib (12%) and upadacitinib (4%). 50% patient were on concomitant csDMARDs among whom two-thirds were on methotrexate. Looking at previous biologic use, 9 patients were biologic naive, 22 had one biologic, 15 had two biologics used in the past. All patients were appropriately selected (severe RA and no significant risk factors for MACE, VTEs and malignancies). All patients had pre-treatment Hepatitis B, Hepatitis C, latent TB, FBC and LFTs checked. All patients had FBC and LFTs monitored post treatment. No patient developed VTE, MACE or cancer on treatment. 84.2% patients had lipids tested before starting JAKi. 22.8% patients had abnormal lipids before Rx initiation and 62.5% of these were on lipid lowering Rx. All patients had lipids tested post treatment, but the timing was quite variable and only 62.5% of patients had lipids tested on the recommended time. There were 2 deaths recorded in this cohort. One of those was an 80-year-old RA patient on baricitinib 2mg OD, who died due to chest infection on the background of ILD. He was not on steroids or csDMARDs. The second patient was 63 years' old (on baricitinib 4mg OD), and died due to respiratory sepsis, and was also on azathioprine. She had RA with advanced ILD. The reasons for discontinuing JAKi were inefficacy (46%), side effects (39%) and both inefficacy and side effects (15%). 41.4%of patient experienced side effects due to JAKi. These included infection 28%, deranged lipids 17%, cytopenia 14%, deranged LFTs 14%, GI side effects 10%, skin rash 7% and varicella zoster 3%. Conclusion There has been steady increase in the use of tsDMARDs for RA and other rheumatic conditions. Due to short half-life, these drugs became a popular choice during COVID-19 pandemic but on the other hand safety monitoring became extremely challenging during this time.

Knowledge About Preventive Health Guidelines for Inflammatory Bowel Diseases in Patients: A Quality Improvement Project

Introduction: Preventive care guidelines for patients with Inflammatory Bowel Disease (IBD) emphasize the need for a patient-centered interdisciplinary approach, with assessment and management of the patient's physical and mental health as well as the IBD. There is no data about compliance with current IBD preventive care guidelines in Puerto Rico. This study aims to evaluate current IBD preventive care in the clinic, and knowledge among patients and gastroenterologists about the preventive care guidelines. The 3-phase study includes retrospective medical record review, an anonymous online survey of gastroenterologists, and an anonymous survey of patients. We report the results of the patient survey. Method(s): Adult patients with an established diagnosis of at least 6 months of ulcerative colitis (UC), Crohn's disease (CD) or indeterminate colitis (IC), were recruited from the IBD Clinics and through IBDrelated social media. Questionnaires were filled in the clinic and online using Google forms. Statistical analysis was performed using descriptive statistics. Comparisons of proportions and means between groups was based on Fisher's exact and chi square tests. The study was approved by the MSC IRB. Result(s): 83 patients completed the survey, 42 from the clinics and 41 through social media. 60% had CD, 47.4% were diagnosed more than 10 years ago, 57.9% were younger than 38 years old and 68% were on immunosuppressants/biologics. 83.13% and 60.24% of patients knew that COVID and Influenza vaccines were indicated, respectively. However only 42.17%, 36.14%, 32.53% and 31.33% of patients knew about indications for HPV, pneumococcal, varicella and zoster vaccines, respectively. There was a significant difference about knowledge regarding screening for latent TB (p=0.019), anxiety and depression (p= 0.03) and smoking status (p=0.033) between CD and UC/IC patients, as shown in Table. Conclusion(s): Our study showed a significant lack of knowledge about IBD preventive care in patients. Strategies to improve patient education are needed. The results of the review of records from the clinic as well as the knowledge of gastroenterologists will point out other deficiencies in the healthcare system and help design methods to improve patient care. Another aspect that needs to be explored is access to preventive measures such as vaccines. (Table Presented).

Research Roundup

George Winter provides an overview of recently published articles that are of interest to practice nurses. Should you wish to look at any of the papers in more detail, a full reference is provided.

The latent tuberculosis infection cascade of care during the COVID-19 pandemic response in a Mid-Sized US city.

Background: The COVID-19 pandemic response may unintentionally disrupt multiple public health services, including tuberculosis control programs. We aimed to assess differences in the cascade of care for latent tuberculosis infection (LTBI) in a Midwest U.S. city during the COVID-19 pandemic response. Methods: We conducted a retrospective cohort study of adult patients who presented for LTBI evaluation at the Hamilton County Public Health Tuberculosis Clinic in Ohio between 2019 and 2020. The pre-COVID-19 response period was defined as 01/2019 to 02/2020, and the COVID-19 pandemic response period (first wave) was defined as 04/2020 to 12/2020. We reviewed electronic medical records to extract sociodemographic information, medical history, follow-up and treatment data to define steps within the LTBI cascade of care. Logistic regressions were used to assess factors associated with LTBI treatment acceptance and completion, adjusted by potential confounders and COVID-19 period. Results: Data from 312 patients were included. There was a significant decrease in the number of monthly LTBI referrals (median, 18 vs. 8, p = 0.02) and LTBI evaluations (median, 17.5 vs. 7, p < 0.01) during the first wave of COVID-19. The proportion for whom immigration was listed as the indication for LTBI testing also declined (30% vs. 9%; p < 0.01) during COVID-19. More LTBI diagnoses were based on interferon-gamma release assay (IGRA; 30% vs. 49%; p < 0.01) during the COVID-19 response period. The proportion of people in the clinic for whom treatment for LTBI was recommended was similar before and during COVID-19 (76% vs. 81%, p = 0.41), as was LTBI treatment acceptance rates (56% vs. 64%, p = 0.28), and completion rates (65% vs. 63%, p = 0.85). In multivariate analysis, LTBI treatment acceptance was associated with Hispanic ethnicity, younger age, male sex, IGRA being used for diagnosis, and non-healthcare occupation, independent of COVID-19 period. LTBI treatment completion was associated with taking a rifamycin-containing regimen, independent of COVID-19 period. Conclusion: We observed a significant decline in the number of monthly LTBI referrals and evaluations during the first wave of COVID-19, revealing an unintended negative impact of the COVID-19 response in our region. However, LTBI treatment acceptance and completion rates were not affected during COVID-19.

Scaling Up TB Screening and TB Preventive Treatment Globally: Key Actions and Healthcare Service Costs.

The 2018 United Nations High-Level Meeting on Tuberculosis (UNHLM) set targets for case detection and TB preventive treatment (TPT) by 2022. However, by the start of 2022, about 13.7 million TB patients still needed to be detected and treated, and 21.8 million household contacts needed to be given TPT globally. To inform future target setting, we examined how the 2018 UNHLM targets could have been achieved using WHO-recommended interventions for TB detection and TPT in 33 high-TB burden countries in the final year of the period covered by the UNHLM targets. We used OneHealth-TIME model outputs combined with the unit cost of interventions to derive the total costs of health services. Our model estimated that, in order to achieve UNHLM targets, >45 million people attending health facilities with symptoms would have needed to be evaluated for TB. An additional 23.1 million people with HIV, 19.4 million household TB contacts, and 303 million individuals from high-risk groups would have required systematic screening for TB. The estimated total costs amounted to ~USD 6.7 billion, of which ~15% was required for passive case finding, ~10% for screening people with HIV, ~4% for screening household contacts, ~65% for screening other risk groups, and ~6% for providing TPT to household contacts. Significant mobilization of additional domestic and international investments in TB healthcare services will be needed to reach such targets in the future.

Tuberculosis Preventive Therapy among Persons Living with HIV, Uganda, 2016-2022.

During October 2016-March 2022, Uganda increased tuberculosis (TB) preventive therapy coverage among persons living with HIV from 0.6% to 88.8%. TB notification rates increased from 881.1 to 972.5 per 100,000 persons living with HIV. Timely TB screening, diagnosis, and earlier treatment should remain high priorities for TB/HIV prevention programming.

Prevalence of Latent Tuberculosis Infection among Patients Undergoing Regular Hemodialysis in Disenfranchised Communities: A Multicenter Study during COVID-19 Pandemic.

Background and Objectives: Due to their weakened immune response, hemodialysis (HD) patients with latent tuberculosis infection (LTBI) are at higher risk for active tuberculosis (TB) disease and are more subject to patient-to-patient transmission within dialysis units. Consequently, current guidelines advocate screening these patients for LTBI. To our knowledge, the epidemiology of LTBI in HD patients has never been examined before in Lebanon. In this context, this study aimed to determine LTBI prevalence among patients undergoing regular HD in Northern Lebanon and to identify potential factors associated with this infection. Notably, the study was conducted during the COVID-19 pandemic, which is likely to have catastrophic effects on TB and increase the risk of mortality and hospitalization in HD patients. Materials and Methods: A multicenter cross-sectional study was carried out in three hospital dialysis units in Tripoli, North Lebanon. Blood samples and sociodemographic and clinical data were collected from 93 HD patients. To screen for LTBI, all patient samples underwent the fourth-generation QuantiFERON-TB Gold Plus assay (QFT-Plus). Multivariable logistic regression analysis was used to identify the predictors of LTBI status in HD patients. Results: Overall, 51 men and 42 women were enrolled. The mean age of the study population was 58.3 ± 12.4 years. Nine HD patients had indeterminate QFT-Plus results and were therefore excluded from subsequent statistical analysis. Among the remaining 84 participants with valid results, QFT-Plus was positive in 16 patients, showing a positivity prevalence of 19% (95% interval for p: 11.3%, 29.1%). Multivariable logistic regression analysis showed that LTBI was significantly associated with age [OR = 1.06; 95% CI = 1.01 to 1.13; p = 0.03] and a low-income level [OR = 9.29; 95% CI = 1.62 to 178; p = 0.04]. Conclusion: LTBI was found to be prevalent in one in five HD patients examined in our study. Therefore, effective TB control measures need to be implemented in this vulnerable population, with special attention to elderly patients with low socioeconomic status.

COVID-19 and Tuberculosis: Two Knives in a Sheath

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) has caused a global human outbreak, making it a more serious threat to human health than any other infectious disease. Coronavirus infectious disease 2019 (COVID-19) has severely affected the lifestyles of people around the world and caused high mortality throughout the world. In both pandemic and seasonal influenza, co-infection of COVID-19 with other diseases has been linked to worse outcomes. The literature revealed that it is char-acteristically associated with comorbidities such as hypertension, blood pressure, obesity, cardiovascular diseases, and other microbial infections. Furthermore, microbial coinfections worsen respiratory viral infections and are a common cause of death in influenza pandemics. Deplorably, Tuberculosis (TB) is also a dreadful lung infection and attains cytokine equilibrium with host cells to maintain the latent stage. Studies showed that human coronaviruses (hCoV) activate latent TB to an active state due to unregulated cytokine production, called a cytokine storm. The present review concisely discusses the reason and status of co-infection of COVID-19 with TB based on previous case reports, cohorts, and scientific studies. COVID-19 patients are prone to be infected with TB and vice-versa in TB-prone areas. The therapeutic opportunities for overcoming the COVID-19 induced cytokine storm have also been emphasized by the present clinical trial candidates. In conclusion, we recommend categorizing the patients based on their medical history and cured or latent TB patients should be particularly closely monitored. They should be tested for Interferon Gamma Release Assay (IGRA) regularly on and after COVID-19 infection.Copyright © 2022 Bentham Science Publishers.

METABOLIC BIOLOGICAL MARKERS FOR DIAGNOSING AND MONITORING THE COURSE OF TUBERCULOSIS.

The international biomedical community has been currently facing a need to find a simple and most accessible type of analysis that helps to diagnose tuberculosis (TB) with the maximum reliability even before the onset of clinical manifestations. Tuberculosis results in more deaths than any other pathogen, second only to pneumonia caused by the SARS-CoV-2 virus, but the majority of infected people remain asymptomatic. In addition, it is important to develop methods to distinguish various forms of tuberculosis infection course at early stages and to reliably stratify patients into appropriate groups (persons with a rapidly progressing infection, chronic course, latent infection carriers). Immunometabolism investigates a relationship between bioenergetic pathways and specific functions of immune cells that has recently become increasingly important in scientific research. The host anti-mycobacteria immune response in tuberculosis is regulated by a number of metabolic networks that can interact both cooperatively and antagonistically, influencing an outcome of the disease. The balance between inflammatory and immune reactions limits the spread of mycobacteria in vivo and protects from developing tuberculosis. Cytokines are essential for host defense, but if uncontrolled, some mediators may contribute to developing disease and pathology. Differences in plasma levels of metabolites between individuals with advanced infection, LTBI and healthy individuals can be detected long before the onset of the major related clinical signs. Changes in amino acid and cortisol level may be detected as early as 12 months before the onset of the disease and become more prominent at verifying clinical diagnosis. Assessing serum level of certain amino acids and their ratios may be used as additional diagnostic markers of active pulmonary TB. Metabolites, including serum fatty acids, amino acids and lipids may contribute to detecting active TB. Metabolic profiles indicate about increased indolamine 2.3-di-oxygenase 1 (IDO1) activity, decreased phospholipase activity, increased adenosine metabolite level, and fibrous lesions in active vs. latent infection. TB treatment can be adjusted based on individual patient metabolism and biomarker profiles. Thus, exploring immunometabolism in tuberculosis is necessary for development of new therapeutic strategies. Copyright © 2022 Saint Petersburg Pasteur Institute. All rights reserved.

Impact of COVID-19 Pandemic on Tuberculosis Preventive Services and Their Post-Pandemic Recovery Strategies: A Rapid Review of Literature.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic has disrupted tuberculosis (TB) care and prevention around the world. The aim of this study is to review literature on the impact of COVID-19 on TB preventive services and discuss their policy options during and after the pandemic. METHODS: We conducted a rapid review of scientific literature on the impact of COVID-19 on TB preventive services and their recovery strategies. After conducting a line-by-line open coding, their codes were applied in the descriptive theme building process, which was guided by the End TB strategy. TB preventive measures were selected and classified into five analytical categories: 1) vaccination against TB, 2) detection and treatment of latent TB infection (LTBI), 3) screening and diagnostics, 4) active case finding and contact tracing, and 5) surveillance. RESULTS: We identified 93 articles, of which 65 were research articles. During the pandemic, we observed decrease in Bacillus Calmette-Guérin (BCG) coverage, TB diagnostic services, case finding activities, and LTBI management. TB case detection was declined, which was not resumed to the pre-pandemic level after loosening the lock-down. Several recommendations were highlighted: 1) secure BCG stocks and its supply chains, 2) consider catch-up activities of routine immunization and LTBI screening, 3) maintain minimal TB health services, infection prevention and control, and surveillance, 4) leverage laboratory capacity and contact tracing mechanisms, 5) consider simultaneous testing for TB and COVID-19, and 6) Incorporate digital health technologies. CONCLUSIONS: Our findings and lessons learnt from the pandemic can aid in the development of future national TB control program.

Investigation of Increased Latent Tuberculosis Infection Rates During the COVID-19 Pandemic Among International Students at a U.S. University Campus

Background. The COVID-19 pandemic has caused dramatic changes in the epidemiology of many diseases globally due to various changes in exposure to different pathogens, social restrictions, and demographic shifts. A university student health center located in the U.S. Midwest detected an increase in latent tuberculosis infection (LTBI) rate among its incoming international students (INTS) from 5.7% to 8.1% in the fall semesters of 2019 and 2021, respectively. We describe our approach to investigating the increase in LTBI rate at a university campus in a low-endemicity area. Methods. Factors that may affect LTBI rates were evaluated. LTBI testing policy and methods were reviewed. Medical and lab staff were interviewed regarding the consistency of specimen collection, transport, and processing. LTBI risks in the general population such as older age, male gender, and country of origin (COO) were also considered. Factors that were expected to be uncommon in the INTS (homelessness, incarceration, and illicit drug abuse) were not evaluated. Results. No changes in the INTS screening policy were noted. All incoming INTS were screened for LTBI during initial health screening, regardless of COO. The same manufacturer's QuantiFERON-TB Plus test was utilized. Compared to previous years, no inconsistencies in the testing logistics were reported. A total of 1,016 INTS were screened in 2019 and 1,179 in 2021. There were no significant differences in average age in years (23.1 vs. 23.3) or male gender (59.6% vs. 56.8%) between 2019 and 2021, respectively. Most INTS came from two countries (A and B). Country A was COO of 21.6% of INTS in 2019, which dropped to 8.4% in 2021. Country B was COO of 44.8% of INTS in 2019, which increased to 57.6% in 2021 (p< 0.001;Figure 1). Although LTBI rates within each country (A and B) remained similar before and during the COVID-19 pandemic (Figure 2), country B had consistently higher rates than country A (p< 0.001), which contributed to the overall increased rate of LTBI in 2021. (Table Presented) Conclusion. Evaluating changes in COO of INTS is essential in investigating trends in LTBI rates at otherwise low-endemicity universities. In our investigation, demographic changes in university admissions over two years relative to COVID-19 pandemic restrictions contributed to an increase in the overall LTBI rate.

Longitudinal Evaluation of the QuantiFERON-TB Gold Plus Assay in Hospitalized COVID-19 Patients with a First Indeterminate Result: Resolution of Inflammation and Restoration T-lymphocyte Counts and Interferon-gamma Production

Background. Several studies reported an increased rate of indeterminate QuantiFERON-TB Gold Plus (QFT-P) assay results in patients with severe Coronavirus Disease (COVID)-19. Methods. Aim of the study was to longitudinally evaluate QFT-P responses in patients who survived COVID-19, with a previous indeterminate result. Results. We observed 223 patients with an indeterminate QFT-P assay among 949 patients hospitalized because of COVID-19 (23,5%) during 2020 and 2021. 36 patients among those with an indeterminate QFT-P assay were enrolled for reassessing the test. In 12 patients peripheral blood lymphocyte subsets were also reassessed. Considering disease severity, 30 were classified as severe and 6 as non-severe. Median age was 57,5 (interquartile range [IQR]: 49,5-63,8), with a prevalence of male sex (M/F: 24/12);median Charlson Comorbidity Index was 2 (IQR: 1-3). The second QFT-P assay was performed after at least 1 month from the first assay (median time 7 months, IQR: 5-12 months). All QFT-P assays gave a determined result: 2 positive (5.5%) and 34 negatives (94,4%). A statistically significant difference was observed after comparing the laboratory parameters at the time of the first and the second QFT-P assay: the absolute counts of total lymphocyte, total CD3+, CD4+ and CD8+ T-lymphocytes were significantly increased (p< 0.001) while neutrophil absolute counts, neutrophil to lymphocyte (N/L) ratio, D-dimer,fibrinogen, ferritin, C-reactive protein (CRP) were significantly reduced (p< 0.0001). Concerning the QFT-P assay, interferon gamma (INF-gamma) production in the Mitogen-Nil, TB1-Nil and TB2-Nil conditions were significantly increased (p< 0.0001;p=0.0019;p=0.0205, respectively) (Table 1 and Figure 1). Conclusion. Once the acute phase of COVID-19 is resolved, inflammatory markers and peripheral blood leucocyte counts tend to normalize with an effective INF-gamma production after specific and nonspecific stimulation. All the 36 QFT-P showed a determinate result. Moreover, we observed 2 positive QFT-P assay, supporting the importance of retesting patients with indeterminate result to identify latent tuberculosis infection and monitor patients for possible reactivation because of the immunesuppression associated with COVID-19.

A low risk of nosocomial transmission of subclinical tuberculosis to neonates in a postpartum care center under COVID-19 control measures.

We report the results of investigating and managing a tuberculosis (TB) exposure in apostpartum care center. Among the contacts exposed to a nursing assistant with subclinical TB,5 of 44 neonates (11.4%) had positive tuberculin skin tests (TSTs) at 3 months of age, and all theTST-positive neonates received the Bacille Calmette-Guérin vaccination. Seven of 28 healthcareworkers (25.0%) and 1 of 3 household contacts (33.3%) were positive in the initial or repeatedinterferon-gamma release assay. None of the contacts developed TB disease during the studyperiod. Annual TB examinations of healthcare personnel at a postpartum care center under theTuberculosis Prevention Act in South Korea enabled the early detection of subclinical TB, whichreduced the risk of transmission to neonates under strict coronavirus disease 2019 preventionmeasures.

A Case of Pleural Tuberculosis vs Latent Tuberculosis Reactivation as a Result of COVID-19 Infection and Treatment.

The reactivation of latent tuberculosis occurs when a patient living with Mycobacterium tuberculosis enters a state where the immune system is suppressed. Since early 2021, the standard of care has been to provide corticosteroids in patients with COVID-19 infection in hospitalized patients receiving supplemental oxygen or mechanical ventilation. The immunomodulatory effects of corticosteroids are potentially detrimental for patients with latent vs active tuberculosis, with concomitant SARS-CoV2 infection. We present one of the first few cases in the literature detailing a case of reactivation of latent tuberculosis vs. pleural tuberculosis as a consequence of COVID-19, and who underwent subsequent corticosteroid treatment.

Baffling Case of a Patient With History of Lupus in a COVID-19 Pandemic.

Systemic lupus erythematosus (SLE) is an autoimmune disease with a myriad of clinical presentations and periodic flares. We present a case of a young lady with a history of SLE who presented with constitutional symptoms 1 week after starting Isoniazid and Rifampin for treatment of latent TB. Her presentation shared similarities with several diseases including TB lymphadenitis, SLE flare, Kikuchi-Fujimoto Disease (KFD) and hemophagocytic lymphohistiocytosis (HLH) posing a diagnostic dilemma. Additionally, she presented not long after the onset of the global COVID-19 pandemic, further expanding the differential diagnosis. She was ultimately diagnosed with a severe SLE flare caused by rifampin induced suppression of the CYP3A4 system, thereby reducing the therapeutic efficacy of steroids. This case highlights the deadly potential of drug-drug interactions, especially in patients with autoimmune conditions.

Profiles of Plasminogen Activator Inhibitor-1 Levels in Healthcare Workers with Latent Tuberculosis and Non-Latent Tuberculosis Infections (Healthy Control)

BACKGROUND: Mycobacterium tuberculosis infection causes the release of pro-inflammatory cytokines affecting hemostasis. Although the plasminogen activator inhibitor-1 (PAI-1) has a vital role in the fibrinolysis system, little is known about its profile among people with latent tuberculosis (TB). METHODS: This is a cross-sectional study that involves 80 healthcare workers. The study was conducted in two academic medical centers of Makassar city, Indonesia, from September to October 2021. PAI-1 levels were measured using the enzyme-linked immunosorbent assay technique. The statistical test results were significant if p < 0.05. RESULTS: Although there was no statistically significant difference (p > 0.05) in PAI-1 levels, PAI-1 level among participants in the latent TB infection (LTBI) group was found to be lower (4.9 ng/mL) than in the healthy control group (6.0 ng/mL). In addition, participants in the LTBI group with a history of being infected (9.6 ng/mL) with the COVID-19 had higher PAI-1 levels than those who had never been infected (2.3 ng/mL), which is statistically significant (p = 0.004). Although there was no statistically significant difference (p > 0.05) in PAI-1 levels among participants in the healthy control group, those with a history of being infected (6.7 ng/mL) demonstrated higher PAI-1 levels than those who had never been infected (4.8 ng/mL). CONCLUSIONS: PAI-1 levels were lower in LTBI participants, which potentially is due to more participants in the healthy control group having a history of COVID-19 infection.