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BMC Infectious Diseases May 2024Screening for tuberculosis (TB) and providing TB preventive treatment (TPT) along with antiretroviral therapy is key components of human immune deficiency virus (HIV)...
BACKGROUND
Screening for tuberculosis (TB) and providing TB preventive treatment (TPT) along with antiretroviral therapy is key components of human immune deficiency virus (HIV) care. The uptake of TPT during the coronavirus disease 2019 (COVID-19) period has not been adequately assessed in Addis Ababa City Administration. This study aimed at assessing TPT uptake status among People living with HIV (PLHIV) newly initiated on antiretroviral therapy during the COVID-19 period at all public hospitals of Addis Ababa City Administration, Ethiopia.
METHODS
A retrospective data review was conducted from April-July 2022. Routine District Health Information System 2 database was reviewed for the period from April 2020-March 2022. Proportion and mean with standard deviation were computed. Logistic regression analysis was conducted to assess factors associated with TPT completion. A p-value of < 0.05 was considered statistically significant.
RESULTS
A total of 1,069 PLHIV, aged 18 years and above were newly initiated on antiretroviral therapy, and of these 1,059 (99.1%) underwent screening for TB symptoms. Nine hundred twelve (86.1%) were negative for TB symptoms. Overall, 78.8% (719) of cases who were negative for TB symptoms were initiated on TPT, and of these 70.5% and 22.8% were completed and discontinued TPT, respectively. Of 719 cases who were initiated on TPT, 334 (46.5%) and 385 (53.5%) were initiated on isoniazid plus rifapentine weekly for three months and Isoniazid preventive therapy daily for six months, respectively. PLHIV who were initiated on isoniazid plus rifapentine weekly for three months were more likely to complete TPT (adjusted odds ratio [AOR],1.68; 95% confidence interval [CI], 1.01, 2.79) compared to those who were initiated on Isoniazid preventive therapy daily for six months.
CONCLUSION
While the proportion of PLHIV screened for TB was high, TPT uptake was low and far below the national target of achieving 90% TPT coverage. Overall a considerable proportion of cases discontinued TPT in this study. Further strengthening of the programmatic management of latent TB infection among PLHIV is needed. Therefore, efforts should be made by the Addis Ababa City Administration Health Bureau authorities and program managers to strengthen the initiation and completion of TPT among PLHIV in public hospitals.
Topics: Humans; Retrospective Studies; Ethiopia; Adult; HIV Infections; Female; Male; Tuberculosis; Middle Aged; COVID-19; Antitubercular Agents; Young Adult; Adolescent; Isoniazid; SARS-CoV-2; Mass Screening
PubMed: 38760665
DOI: 10.1186/s12879-024-09403-z -
Breathe (Sheffield, England) Mar 2024Responding to a surge in new tuberculosis (TB) cases among migrants from high-incidence countries, low-incidence European nations have heeded World Health Organization... (Review)
Review
Responding to a surge in new tuberculosis (TB) cases among migrants from high-incidence countries, low-incidence European nations have heeded World Health Organization recommendations by implementing TB screening in this population. This review aims to synthesise evidence on current screening strategies for active TB and latent tuberculosis infection (LTBI) in European high-income countries, and their main barriers and interventions. PubMed, Web of Science and Scopus were searched from March to April 2023, including articles in English, published in the last decade, pertaining to screening strategies for active TB or LTBI in Europe focused on migrants, excluding those exclusively composed of refugees, asylum seekers or other migrant populations. 32 studies fit the criteria. Screening in migrants varies between countries regarding timing, population, screening location and diagnosis. Furthermore, some barriers prevent migrants from benefiting from screening, namely physical, cultural and professional barriers. Additional research is needed to determine the patterns through which regular migrants adhere to current screening strategies in European countries.
PubMed: 38746905
DOI: 10.1183/20734735.0357-2023 -
Frontiers in Cellular and Infection... 2024The influencing factors of the process from latent tuberculosis infection (LTBI) to the onset of active tuberculosis (TB) remain unknown among different population...
BACKGROUND
The influencing factors of the process from latent tuberculosis infection (LTBI) to the onset of active tuberculosis (TB) remain unknown among different population groups, especially among older individuals in high-incidence areas. This study aimed to investigate the development of active TB among older adults with LTBI and identify groups in greatest need of improved prevention and control strategies for TB.
METHODS
In 2021, we implemented an investigation among older individuals (≥ 65 years old) in two towns in Zhejiang Province with the highest incidence of TB. All participants underwent assessment using standardized questionnaires, physical examinations, interferon-gamma release assays, and chest radiography. All the participants with suspected TB based on the clinical symptoms or abnormal chest radiography results, as well as those with LTBI, were referred for diagnostic investigation in accordance with the national guidelines. Those with an initial diagnosis of TB were then excluded, whereas those with LTBI were included in a follow-up at baseline. Incident patients with active TB were identified from the Chinese Tuberculosis Management Information System, and a multivariate Cox regression model was used to estimate the incidence and risk of TB among those with LTBI.
RESULTS
In total, 667 participants with LTBI were followed up for 1,315.3 person-years, revealing a disease density of 1,292.5 individuals/100,000 person-years (17/1,315.3). For those with LTBI, chest radiograph abnormalities had adjusted hazard ratios for active TB of 4.9 (1.6-15.3).
CONCLUSIONS
The presence of abnormal chest radiography findings increased the risk of active TB among older individuals with LTBI in high-epidemic sites in eastern China.
Topics: Humans; Latent Tuberculosis; China; Aged; Incidence; Male; Female; Risk Factors; Cohort Studies; Aged, 80 and over; Tuberculosis; Interferon-gamma Release Tests; Epidemics
PubMed: 38741890
DOI: 10.3389/fcimb.2024.1332211 -
Open Forum Infectious Diseases May 2024The persistence of tuberculosis today and its global disparity send a powerful message that effective tuberculosis control must respond to its regional epidemiology....
BACKGROUND
The persistence of tuberculosis today and its global disparity send a powerful message that effective tuberculosis control must respond to its regional epidemiology. Active case finding through contact investigation is a standard protocol used for tuberculosis control, but its effectiveness has not been established, especially in endemic areas.
METHODS
To quantify the potential effectiveness of contact investigation in Kampala, Uganda, we used a cross-sectional design to evaluate the social networks of 123 tuberculosis index cases and 124 controls without tuberculosis.
RESULTS
Tuberculous infection was present in 515 of 989 tuberculosis case contacts (52.1%) and 396 of 1026 control contacts (38.6%; adjusted prevalence ratio, 1.4; 95% CI, 1.3-1.6). The proportion of infected participants with known exposure within the social network of the tuberculosis case was 35%. The population-attributable fraction was 11.1% for any known exposure, with 7.3% attributable to household exposure and 3.4% attributable to extrahousehold exposure.
CONCLUSIONS
This low population-attributable fraction indicates that contact tracing in the social networks of index cases will have only a modest effect in reducing tuberculous infection in a community. New approaches to community-level active case finding are needed.
PubMed: 38737427
DOI: 10.1093/ofid/ofae200 -
New Microbes and New Infections Jun 2024The paper presents epidemiological process modeling, with a focus on tuberculosis utilizing multi-agent system.
INTRODUCTION
The paper presents epidemiological process modeling, with a focus on tuberculosis utilizing multi-agent system.
MATERIAL AND METHODS
This study involves the development of an algorithm that harnesses the potential of artificial intelligence to create a geospatial model that highlights the different pathways of TB transmission. The modeling process itself is characterized by a series of key stages, including initialization of the city, calibration of health parameters, simulation of the working day, propagation of the spread of infection, the evolution of disease trajectories, rigorous statistical calculations and transition to the following day. A comprehensive description of the course of active tuberculosis is presented, following the official hypothesis recommended by the World Health Organization. A comprehensive simulation, illustrating the propagation of tuberculosis in an entirely healthy environment devoid of any preventive or therapeutic measures, is presented. To ascertain the adequacy of the model and its sensitivity to the principal parameters governing the course of tuberculosis, a series of experiments were meticulously conducted, employing three distinct approximations, namely: the basic model, the model incorporating mortality factors, and the comprehensive model, encompassing all relevant aspects.
CONCLUSIONS
The model's results exhibit stability and lack of significant fluctuations. The statistical values obtained for infected, latent, and recovered individuals align well with known medical data, confirming the model's adequacy.
PubMed: 38737327
DOI: 10.1016/j.nmni.2024.101417 -
The presence of cytotoxic CD4 and exhausted-like CD8+ T-cells is a signature of active tuberculosis.Biochimica Et Biophysica Acta.... May 2024Chronic infections induce CD4+ T-cells with cytotoxic functions (CD4 CTLs); at present, it is still unknown whether latent tuberculosis (LTB) and active tuberculosis...
Chronic infections induce CD4+ T-cells with cytotoxic functions (CD4 CTLs); at present, it is still unknown whether latent tuberculosis (LTB) and active tuberculosis (ATB) induce CD4 CTLs. Plasma and cells from four patient groups-uninfected contact (UC), LTB, and ATB (divided as sensitive [DS-TB]- or resistant [DR-TB]-drug)-were evaluated by flow cytometry, q-PCR, and proteomics. The data showed that ATB patients had an increased frequency of CD4+ T-cells and a decreased frequency of CD8+ T-cells. The latter displays an exhausted-like profile characterized by CD39, CD279, and TIM-3 expression. ATB had a high frequency of CD4 + perforin+ cells, suggesting a CD4 CTL profile. The expression (at the transcriptional level) of granzyme A, granzyme B, granulysin, and perforin, as well as the genes T-bet (Tbx21) and NKG2D (Klrk1), in enriched CD4+ T-cells, confirmed the cytotoxic signature of CD4+ T-cells during ATB (which was stronger in DS-TB than in DR-TB). Moreover, proteomic analysis revealed the presence of HSP70 (in DS-TB) and annexin A5 (in DR-TB), which are molecules that have been associated with favoring the CD4 CTL profile. Finally, we found that lipids from Mycobacterium tuberculosis increased the presence of CD4 CTLs in DR-TB patients. Our data suggest that ATB is characterized by exhausted-like CD8+ T-cells, which, together with a specific microenvironment, favor the presence of CD4 CTLs.
PubMed: 38734321
DOI: 10.1016/j.bbadis.2024.167219 -
Journal of Infection and Public Health Apr 2024The risk of infection including tuberculosis (TB) infection or reactivation during biological therapy with the current various clinical application is a major concern....
BACKGROUND
The risk of infection including tuberculosis (TB) infection or reactivation during biological therapy with the current various clinical application is a major concern. This risk may be higher in countries endemic to TB. Our aim of this study is to determine the risk of TB infection in patients receiving 3 biological treatments, Adalimumab, Etanercept and Tocilizumab.
METHODS
A retrospective cohort study extending over 2 years follow-up for all patients receiving Adalimumab, Etanercept and Tocilizumab for various clinical indications in a tertiary care center in Saudi Arabia.
RESULT
Over the period of 2015-2019, A total of 410 patients received Adalimumab, 271 received Etanercept and 58 patients received Tocilizumab. Rheumatoid arthritis was the most common indication for therapy in all groups and for Adalimumab the most common indication was inflammatory bowel disease, for Etanercept was psoriatic arthritis and for Tocilizumab was juvenile idiopathic arthritis. After a mean follow up period of 36 ± 8.9 months for patients receiving Adalimumab, 21.5 ± 8.4 months for patients receiving Etanercept and 21 ± 2.5 months for patients receiving Tocilizumab there were no reported cases of TB infection in all groups. Only one patient was diagnosed with latent TB 7 months later after starting Adalimumab and tow patients after starting Etanercept. The overall Interferon Gamma Release Assays (IGRA) positivity rate was 9.7%. There was significant association between IGRA positivity rate and patient age. The cutoff age in which IGRA positivity has significantly increased was 53.20 years.
CONCLUSION
In our study, patients receiving Etanercept, Adalimumab and Tocilizumab had no increased risk of TB infection. Only 0.3% of patients treated with Adalimumab and 0.9% of patients treated with Etanercept converted to a positive IGRA during therapy.
PubMed: 38728834
DOI: 10.1016/j.jiph.2024.04.016 -
Clinical Case Reports May 2024This report highlights the risk of latent tuberculosis (TB) reactivation after treatment with Polatuzumab Vedotin (PV), Rituximab, and Bendamustine (PBR protocol)...
This report highlights the risk of latent tuberculosis (TB) reactivation after treatment with Polatuzumab Vedotin (PV), Rituximab, and Bendamustine (PBR protocol) despite appropriate chemoprophylaxis. A 48-year-old male with refractory Burkitt's lymphoma (BKL) was treated with PBR protocol. At baseline, the patient had a negative QuantiFERON test result, which turned out to be positive prior to starting PBR. He received chemoprophylaxis for 9 months and was compliant with treatment. One year later, he was admitted with COVID-19 pneumonia and was treated according to the protocol. His symptoms persisted for 1 month. Investigations yielded disseminated TB-infiltrated bone marrow and pleura. Downstream B-cell and T-cell depletion secondary to CD20 and CD79b antagonism may potentially explain the increased risk of TB reactivation associated with the combination of PV and rituximab. Further research is necessary to monitor the risk of TB reactivation among patients receiving a combination of PV and rituximab, especially in endemic areas with high prevalence and incidence of TB.
PubMed: 38721565
DOI: 10.1002/ccr3.8838 -
JCI Insight May 2024T cells are required for protective immunity against Mycobacterium tuberculosis. We recently described a cohort of Ugandan household contacts of tuberculosis cases who...
T cells are required for protective immunity against Mycobacterium tuberculosis. We recently described a cohort of Ugandan household contacts of tuberculosis cases who appear to "resist" M. tuberculosis infection (resisters; RSTRs) and showed that these individuals harbor IFN-γ-independent T cell responses to M. tuberculosis-specific peptide antigens. However, T cells also recognize nonprotein antigens via antigen-presenting systems that are independent of genetic background, known as donor-unrestricted T cells (DURTs). We used tetramer staining and flow cytometry to characterize the association between DURTs and "resistance" to M. tuberculosis infection. Peripheral blood frequencies of most DURT subsets were comparable between RSTRs and latently infected controls (LTBIs). However, we observed a 1.65-fold increase in frequency of MR1-restricted T (MR1T) cells among RSTRs in comparison with LTBIs. Single-cell RNA sequencing of 18,251 MR1T cells sorted from 8 donors revealed 5,150 clonotypes that expressed a common transcriptional program, the majority of which were private. Sequencing of the T cell receptor α/T cell receptor δ (TCRα/δ) repertoire revealed several DURT clonotypes were expanded among RSTRs, including 2 MR1T clonotypes that recognized mycobacteria-infected cells in a TCR-dependent manner. Overall, our data reveal unexpected donor-specific diversity in the TCR repertoire of human MR1T cells as well as associations between mycobacteria-reactive MR1T clonotypes and resistance to M. tuberculosis infection.
Topics: Humans; Mycobacterium tuberculosis; Uganda; Adult; Male; Minor Histocompatibility Antigens; Female; Tuberculosis; T-Lymphocytes; Latent Tuberculosis; Clone Cells; Disease Resistance; Young Adult; Histocompatibility Antigens Class I
PubMed: 38716731
DOI: 10.1172/jci.insight.166505 -
European Journal of Case Reports in... 2024Although there is no specific therapy for COVID-19, it is recommended that patients with severe SARS-CoV-2 infection are treated with corticosteroids and anti-IL-6...
BACKGROUND
Although there is no specific therapy for COVID-19, it is recommended that patients with severe SARS-CoV-2 infection are treated with corticosteroids and anti-IL-6 receptor monoclonal antibodies. Both COVID-19 itself and the treatment modalities mentioned above have suppressive effects on the immune system which may lead to an increased susceptibility to other infections. In patients with latent tuberculosis (TB) reactivation of TB infection after recovery from severe COVID-19 has been described. Most of these cases have occurred in parts of the world where tuberculosis is endemic.
CASE DESCRIPTION
The patient is a female in her 70s who was born and raised in Southeast Asia and has lived in the Netherlands for more than 30 years. She was treated for a severe COVID-19 requiring mechanical ventilation for several weeks and pharmaceutical treatment with corticosteroids and anti-IL-6 receptor monoclonal antibodies (Sarilumab). She recovered well. Two years later she was readmitted with symptoms of a serious pulmonary infection and meningitis. Her condition deteriorated in a short time. An active TB infection was diagnosed. Despite adequate antibiotic treatment and supportive therapy her condition worsened and four days after admission to the ICU she deceased.
DISCUSSION
Reactivation of latent TB after recovery from a severe COVID-19 has been described several times and may occur several months after the SARS-CoV-2 infection. In this case the reactivation presented two years after COVID-19. This case illustrates that long-term follow-up of patients with latent TB that recover from a severe COVID-19 may be indicated.
LEARNING POINTS
Reactivation of latent tuberculosis infection in patients treated for a severe COVID-19 may occur even two years after recovery from SARS-CoV-2 infection.Most cases of reactivation of tuberculosis after COVID-19 are described in regions where tuberculosis is endemic. However, it may also occur in countries with a relatively low prevalence of tuberculosis infection. The exact incidence of tuberculosis reactivation after COVID-19 is unknown and probably underestimated.A long-term follow-up of patients after severe COVID-19 treated with corticosteroids and/or anti-IL-6 receptor monoclonal antibodies with a history of tuberculosis or patients migrated from countries where tuberculosis is endemic seems to be important.
PubMed: 38715882
DOI: 10.12890/2024_004406