Unnoticed Adverse Effect of Isoniazid during Childhood Tuberculosis Preventive Treatment: Hyperuricemia

2021 ◽  
Author(s):  
Bahar Kandemir ◽  
Ipek Duman ◽  
Yasemin Durduran ◽  
Ozge Metin Akcan ◽  
Muhammed Burak Selver ◽  
...  
Keyword(s):  
Uric Acid ◽  
Median Duration ◽  
Preventive Treatment ◽  
Serum Levels ◽  
Positive Tuberculin Skin Test ◽  
University Hospital ◽  
Latent Tb ◽  
Latent Tb Infection ◽  
Elevated Transaminases

Abstract Objective Isoniazid for 6 to 9 months is the most widely used form of tuberculosis (TB) preventive treatment. We aimed to assess the adverse effects of isoniazid by using the serum levels of aspartate transaminase (AST), alanine transaminase (ALT), and uric acid (SUA) in children and adolescents receiving long-term isoniazid for latent TB infection. Methods The study included children ≤18 years of age who underwent TB preventive treatment with isoniazid (IPT) between 2015 and 2019 at a university hospital. Serum transaminase, SUA, urea, and creatinine levels of patients were measured before the initiation of IPT, 15th day, and once a month during treatment. Patients with ALT, AST, or SUA results above cut-off levels during treatment were evaluated. The final values in follow-up were included in the data analysis. Results A total of 141 children who underwent IPT were included. In total, 70 children had family members with confirmed TB disease, and 71 children had a positive tuberculin skin test. SUA increased above cut-off values in 16 children (11.3%), and half of them had uric acid levels over 7 mg/dL. The median duration of the development of hyperuricemia was 4.0 months. ALT or AST increased above cut-off values in 23 children (16.3%). ALT was above cut-off values in seven patients, AST was high in 20 patients. The median duration to the development of AST and/or ALT levels above cut-off was 4.0 months. Two patients had hepatotoxic transaminase levels. Three patients had both elevated transaminases and SUA levels. Conclusion Isoniazid may also cause hyperuricemia besides elevation in transaminases in children.

scholarly journals Age-Related Immunoreactivity Profiles to Diverse Mycobacterial Antigens in BCG-Vaccinated Chinese Population

2021 ◽  
Vol 11 ◽  
Author(s):  
Qing-yuan Yang ◽  
Yu-tong Zhang ◽  
Jia-ni Xiao ◽  
Yu-shuo Liang ◽  
Ping Ji ◽  
...  
Keyword(s):  
Elispot Assay ◽  
Vaccine Development ◽  
Age Related ◽  
Healthy Donors ◽  
Latent Tb ◽  
Latent Tb Infection ◽  
Mycobacterial Antigens ◽  
Selection Of

Long-term immunoreactivity to mycobacterial antigens in Bovis Calmette-Guérin (BCG)-vaccinated population is not well investigated. Herein, 361 volunteer healthy donors (HDs) with neonatal BCG vaccination from Shanghai region (China) were enrolled. They were subdivided into ESAT-6/CFP10- (E6C10-) and ESAT-6/CFP10+ (E6C10+) groups based on gamma-interferon release assays (IGRAs). Three mycobacterial antigens, including Rv0934, Rv3006, and Rv3841, were subjected to the determination of immunoreactivity by ELISPOT assay. The immunoreactivities to three mycobacterial antigens were firstly compared among TB patients (N=39), E6C10+ HDs (N=78, 21.61% of HDs) and E6C10- HDs (N=283, 78.39% of HDs). It was revealed that Rv3006 was dominant upon M.tb infection, while Rv3841 was likely to be more responsive upon latent TB infection. In E6C10- population, the immunoreactivity to Rv3841 maintained along with aging, whereas those to Rv3006 and Rv0934 attenuated in E6C10- HDs older than 45 years old. Our study implies the shift of dominant antigens at different infection statuses, providing the clues for the selection of mycobacterial antigens in vaccine development and precision revaccination in the future.

scholarly journals Heme Oxygenase-1 and Neopterin Plasma/Serum Levels and their role in Diagnosing Active and Latent TB among HIV/TB Co-Infected Patients

2019 ◽  
Author(s):  
Uwimaana Esther ◽  
Bernard S Bagaya ◽  
Barbara Castelnuovo ◽  
David P Kateete ◽  
Anguzu Godwin ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Heme Oxygenase ◽  
Area Under The Curve ◽  
Serum Levels ◽  
Diagnostic Tools ◽  
Heme Oxygenase 1 ◽  
Hiv Patients ◽  
Receiver Operating Characteristic Curves ◽  
Latent Tb ◽  
Latent Tb Infection

Abstract Background: Tuberculosis(TB) diagnosis in the presence of HIV co-infection remains challenging. Heme oxygenase 1(HO-1) and neopterin have been validated as potential biomarkers for TB diagnosis. Infection of macrophages with Mycobacterium tuberculosis (M .tb ) causes the production of HO-1 and neopterin and previous studies have shown these to be markers of immune activation. This study was conducted to determine the levels of HO-1 and neopterin and their utility in the diagnosis of TB among individuals enrolled in the Community Health and Social Network of Tuberculosis(COHSONET) study and the Kampala TB Drug Resistance Survey(KDRS). Methods: A total of 210 participants were enrolled in a study of a diagnostic method aimed at determining the levels of HO-1 and neopterin and determine their diagnostic accuracy as biomarkers in TB diagnosis from March to May 2019. M. tb culture was performed on sputum to confirm active TB(ATB) and QuantiFERON TB gold test to confirm latent TB infection(LTBI). ELISAs were performed to determine the levels of HO-1 and neopterin. Data analysis was done using Kruskal Wallis and Receiver Operating Characteristic curves to determine the diagnostic accuracy. Results: HO-1 levels among ATB/HIV patients, LTBI/HIV patients and TB negative individuals were 10.7ng/ml (IQR: 7.3-12.7ng/ml), 7.5ng/ml (IQR: 5.4-14.1ng/ml), 3.3ng/ml (IQR: 2.0-7.1ng/ml) respectively. Neopterin levels among ATB/HIV patients, LTBI/HIV patients and TB negative individuals were 11.7ng/ml (IQR: 5.219.4ng/ml), 8.8ng/ml (IQR: 2.4-19.8ng/ml), and 5.9ng/ml (IQR: 3.410.2ng/ml) respectively. HO-1 showed a sensitivity of 78.57% and a specificity of 71.43% with area under the curve(AUC) of 0.839 when used to diagnose ATB. HO-1 showed AUC of 0.79, sensitivity of 70% and specificity 70% when used to diagnose LTB. Neopterin showed a sensitivity of 61.43% and a specificity of 74.29% with AUC 0.71 when used to diagnose ATB. Neopterin as a biomarker in LTB diagnosis showed AUC of 0.56 which was not significant. Conclusion: HO-1 and neopterin are valuable diagnostic biomarkers for ATB and LTB which could be further utilized to develop less costly rapid diagnostic tools to overcome current TB diagnostic challenges.

Long-term survival outcomes with immune checkpoint inhibitors (ICI) in metastatic uveal melanoma (MUM).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21585-e21585
Author(s):  
Cha Len Lee ◽  
Naomi Walsh ◽  
Fergus Keane ◽  
Emer Lynch ◽  
Tadhg Reddan ◽  
...  
Keyword(s):  
Median Duration ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Response Rates ◽  
University Hospital ◽  
Phase Ii Trials ◽  
Term Survival ◽  
Long Term Survival

e21585 Background: The treatment of MUM remains highly unsatisfactory. Single agent ICI produce low response rates. Two recent phase II trials of combination Ipilimumab and Nivolumab yielded response rates of 12% and 18%. We report the long-term survival results of MUM patients (pts) treated with ICI in our institution. Methods: We conducted a retrospective analysis of all pts with a diagnosis of MUM in St Vincent’s University Hospital. Overall survival (OS) was calculated from time of first systemic relapse to death or latest follow-up. One-way ANOVA is used with p < 0.05 considered statistically significant. Results: Out of 244 pts with UM registered in our clinics between April 2008 to October 2020, 52 developed MUM. Median age at initial diagnosis 63 years. 26(50%) are females. Median duration of follow-up of the MUM pts is 35.1 months [2.71-123.2]. Median duration of follow-up from initiation of ICI therapy is 9.1 months [1.6-84.2]. First sites of metastases: liver only 71%, liver plus extrahepatic 17%, and extrahepatic only 12%. Fifteen pts (29%) underwent radical metastasectomy as initial treatment. Thirty-seven (71%) had non-resectable MUM and received systemic treatment (23 total: ICI = 18, chemotherapy = 4, BRAF inhibitors = 1), non-surgical locoregional therapies (5 total: chemosaturation = 3, radiofrequency ablation = 2) or supportive/palliative care (9) as first-line. An additional 22 pts received ICI as second or subsequent treatment, for a total of 40 treated with ICI. Of these, 17 received single agents ICI (Ipilimumab = 11, Pembrolizumab = 6), 13 received sequential Ipilimumab and anti-PD1, and 10 received combination Ipilimumab /Nivolumab. At the time of analysis on 31st October 2020, 9 out of 52 pts (17%) are alive at 2.6, 5.0,5.4,8.9,17.3, 54.7, 77.5, 83.1 and 121.7 months (the 6 longest all had ICI). The median OS is 14.3 months [0.6-121.7]. Pts treated with ICI demonstrated longer OS than pts who did not receive ICI [15.0 months, 5.0-121.7 vs 7.2 months, 0.6-34.6; p = 0.089]. The median OS is 24.9 months (sequential Ipilimumab and anti-PD1) vs 15.0 months (combination Ipilimumab/Nivolumab) vs 13.4 months (single agents). Of the three pts remain alive > 5 years, one is currently disease-free. Conclusions: Prolonged survival beyond five years is achieved by a minority of pts with MUM who receive ICI during their treatment history, although durable initial ICI-induced remission is very rare. Our data suggest that pts who receive two ICI drugs during their illness may have longer survival compared to those who receive only a single ICI.

scholarly journals Quantitative Analysis of Gamma Interferon Release Assay Response in Children with Latent and Active Tuberculosis

2017 ◽  
Vol 56 (2) ◽  
Author(s):  
Giulia Lombardi ◽  
Roberta Petrucci ◽  
Ilaria Corsini ◽  
Maria Letizia Bacchi Reggiani ◽  
Francesca Visciotti ◽  
...  
Keyword(s):  
Immune Response ◽  
Pediatric Population ◽  
Active Tuberculosis ◽  
University Hospital ◽  
Content Type ◽  
Release Assay ◽  
Latent Tb ◽  
Specific Antigens ◽  
Ifn Γ ◽  
Latent Tb Infection

ABSTRACT The use of interferon gamma (IFN-γ) release assays (IGRAs) for the diagnosis of tuberculosis (TB) infection in children is still under debate because of concerns about the immature immune response in children. The aim of this study was to investigate quantitative values of the QuantiFERON-TB Gold In-Tube (QFT-IT) test, a commercially available IGRA, in a large cohort of children screened for TB infection. A retrospective analysis was conducted on samples from 517 children aged 0 to 14 years old at the Pediatric Unit of S. Orsola-Malpighi University Hospital of Bologna (Italy); quantitative responses to QFT-IT stimuli were analyzed according to diagnosis and age. Elevated IFN-γ values in the QFT-IT nil (background) tube were statistically associated with diagnosis of active TB. Quantitative IFN-γ response to Mycobacterium tuberculosis-specific antigens (TB Ag) was not significantly different in children with active TB compared to those with latent TB infection (LTBI), even though the median values were higher in the first group. When children were grouped by age, those less than 5 years old produced significantly higher levels of IFN-γ in response to TB Ag if they had active TB (median 10 IU/ml) than those with LTBI (median 1.96 IU/ml). IFN-γ response to mitogen increased with age. The overall rate of indeterminate results was low (3.9%), and no indeterminate QFT-IT values were observed in active or latent TB patients. In conclusion, quantitative QFT-IT values could provide further information to clinicians to manage TB in children, and these observations could be transferred to the new version of the test, QuantiFERON-TB Gold Plus, which to date lacks data from the pediatric population.

Tuberculin Testing and Treatment of Latent TB Infection Among Long–term Jail Inmates

2004 ◽  
Vol 11 (1) ◽  
pp. 99-117
Author(s):  
Christopher H. Hayden ◽  
Bonita T. Mangura ◽  
Ileen Channer ◽  
G. Elaine Patterson ◽  
Marian R. Passannante ◽  
...  
Keyword(s):  
Jail Inmates ◽  
Latent Tb ◽  
Tuberculin Testing ◽  
Latent Tb Infection

scholarly journals Effect of Isoniazid Therapy for Latent TB Infection on QuantiFERON-TB Gold In-Tube Responses in Adults With Positive Tuberculin Skin Test Results in a High TB Incidence Area

CHEST Journal ◽  
2014 ◽  
Vol 145 (3) ◽  
pp. 612-617 ◽  
Author(s):  
John L. Johnson ◽  
Hendrik Geldenhuys ◽  
Bonnie A. Thiel ◽  
Asma Toefy ◽  
Sara Suliman ◽  
...  
Keyword(s):  
Tuberculin Skin Test ◽  
Skin Test ◽  
Positive Tuberculin Skin Test ◽  
Test Results ◽  
Latent Tb ◽  
Latent Tb Infection

scholarly journals Experiences with latent TB cascade of care strengthening for household contacts in Calgary, Canada

2021 ◽  
Vol 11 (3) ◽  
pp. 126-131
Author(s):  
N. Bedingfield ◽  
L. Barss ◽  
O. Oxlade ◽  
D. Menzies ◽  
D. Fisher
Keyword(s):  
Treatment Recommendation ◽  
Foreign Born ◽  
Ltbi Treatment ◽  
Household Contacts ◽  
Care Workers ◽  
Assessment And Treatment ◽  
Cascade Of Care ◽  
Latent Tb ◽  
Latent Tb Infection

SETTING: Identification, assessment, and treatment of latent TB infection (LTBI), collectively known as the LTBI cascade of care, is critical for TB prevention.OBJECTIVE: The objective of this research, conducted within the ACT4 trial, was to assess and strengthen the LTBI cascade of care for household contacts at Calgary TB Services, a clinic serving a predominately foreign-born population in Western Canada.DESIGN: Baseline assessment consisted of a retrospective LTBI cascade analysis of 32 contact investigations, and questionnaires administered to patients and health care workers. Four solutions were implemented in response to identified gaps. Solution impact was measured for 6 months using descriptive statistics.RESULTS: Pre-implementation, 56% of household contacts initiated treatment. Most contacts were lost to care because the tuberculin skin test (TST) was not initiated, or physicians did not recommend treatment. Evening clinics, a patient education pamphlet, a nursing workshop, and treatment recommendation guidelines were implemented. Post-implementation, losses due to LTBI treatment non-recommendation were reduced; however, the overall proportion of household contacts initiating treatment did not increase.CONCLUSION: Close engagement between researchers and TB programmes can reduce losses in the LTBI cascade. To see sustained improvement in overall outcomes, long-term engagement and data collection for ongoing problem-solving are required.

scholarly journals Peculiarities of tuberculosis in the COVID‑19 pandemic

2020 ◽  
pp. 27-34
Author(s):  
L. D. Todoriko ◽  
I. O. Semianiv
Keyword(s):  
Health Care ◽  
Full Text ◽  
Comprehensive Analysis ◽  
Long Term Results ◽  
Short Term ◽  
Tb Control ◽  
Number Of Patients ◽  
Latent Tb ◽  
Latent Tb Infection

OBJECTIVE. The purpose of our comprehensive analysis is to assess the prospects for the effects of the interaction between coronavirus disease 2019 (COVID‑19) and tuberculosis (TB) and to strategize the risks of spreading TB infection in a coronavirus pandemic. MATERIALS AND METHODS. Test access to full-text and abstract databases was used. RESULTS AND DISCUSSION. An analysis of the available literature has shown that a 3-month lockdown and a long 10-month recovery worldwide could lead to an additional 6.3 million TB cases and another 1.4 million TB deaths between 2020 and 2025. On average, the detection of TB in Ukraine decreased by 27.4 %, and the incidence of TB among children decreased by 34.5 %. This is an alarming figure because we know very well that within 6 months the number of patients with TB has not decreased, they simply stopped being detected. In addition, COVID‑19 may accelerate the activation of latent TB infection and thus increase the number of active cases. CONCLUSIONS. The overall incidence of TB in 2021 will increase to the level that was last observed between 2013 and 2016. The epidemiological indicators of TB control are expected to deteriorate for at least 5-8 years due to the COVID‑19 pandemic. Long-term results can be strongly affected by the rate of short-term recovery. Priority should be given to all governments, during a pandemic, to ensure the continuity of basic health care, including the implementation of national TB programs.

Immune parameters and level of cortisol in patients with opiate addiction during withdrawal syndrome

2017 ◽  
pp. 38-45
Author(s):  
Т.П. Ветлугина ◽  
Е.В. Матафонова ◽  
Н.А. Бохан ◽  
В.Б. Никитина ◽  
А.И. Мандель ◽  
...  
Keyword(s):  
Cortisol Level ◽  
Withdrawal Syndrome ◽  
Physical Dependence ◽  
Serum Levels ◽  
Opiate Withdrawal ◽  
Opiate Addiction ◽  
Laboratory Methods ◽  
Immune Parameters ◽  
Opiate Withdrawal Syndrome

Цель исследования: изучение динамики показателей иммунитета и уровня кортизола у больных опийной наркоманией в процессе терапии синдрома отмены. Методика. В исследование включено 136 больных опийной наркоманией (инъекции экстракта опия) с сформировавшейся физической зависимостью. Пациенты получали в стационаре стандартную терапию с полной отменой наркотика. Исследование проводилось на следующих этапах: при поступлении в стационар (опийный абстинентный синдром - ОАС); на 5-7-е сут. терапии (переход в постабстинентное состояние - ПАС); на 25-28-е сут. лечения (становление терапевтической ремиссии - СТР). Лабораторные методы включали определение количества лимфоцитов с рецепторами CD3, CD4, CD8, СD16, с рецепторами к дофамину (D-RFC); содержание иммуноглобулинов М, G, А, уровня кортизола и циркулирующих иммунных комплексов (ЦИК) в сыворотке крови. Результаты. Основной иммуноэндокринный паттерн на всех этапах терапии синдрома отмены характеризуется дефицитом субпопуляций Т-лимфоцитов CD3, CD4, СD8; увеличением числа лимфоцитов с рецепторами к дофамину (D-RFC); активацией гуморальных факторов иммунитета (IgM, IgG, ЦИК); высокой концентрацией кортизола. На этапе ОАС и ПАС эти изменения были наиболее выражены; на 25-28-е сут. лечения отмечена позитивная динамика Т-лимфоцитов СD3 и цитотоксических Т-лимфоцитов (СD8); хелперы/индукторы CD4 оставались устойчиво сниженными; D-RFC лимфоциты, параметры гуморального иммунитета и концентрация кортизола - повышенными. Длительный срок наркотизации при употреблении высоких доз наркотика связан с большей выраженностью нарушений. Заключение. Установленная дизрегуляция параметров иммуноэндокринной системы у больных опийной наркоманией на всех этапах терапии синдрома отмены в наблюдаемые сроки (25-28 сут.) свидетельствует о неустойчивости достигнутой терапевтической ремиссии и необходимости проведения дальнейших реабилитационных мероприятий. The purpose: investigate changes in immunity parameters and cortisol level in subjects with opiate addiction during the treatment of opiate withdrawal syndrome. Methods. The study enrolled 136 subjects with opiate addiction with physical dependence receiving injections of opium extract. Patients received conventional therapy with complete opiate withdrawal. The study was performed at the following stages: at admission to the hospital (acute withdrawal syndrome (AWS); on days 5-7 of therapy (transition into post-withdrawal state - PWS); on days 25-28 of therapy (formation of therapeutic remission - FTR). Laboratory methods included determination count of lymphocytes with receptors CD3, CD4, CD8, СD16, with receptors to dopamine (D-RFC); the serum levels of IgМ, IgG, IgА, cortisol, circulating immune complexes (CIC). Results. The principal immunoendocrine pattern for all stages of withdrawal syndrome therapy is characterized in comparison to the reference normal values quantitative deficit of CD3, CD4, СD8 Т-lymphocyte subpopulations, increased count of lymphocytes with receptors to dopamine, activation of humoral immunity factors (IgM, IgG, CIC), high cortisol level. At AWS and PAS stages such changes are most pronounced; on days 25-28 of therapy positive changes in cytotoxic Т-lymphocytes (СD8) and Т-lymphocytes СD3 was revealed. CD4 count remained steadily reduced, count of lymphocytes with receptors to dopamine and cortisol level were elevated. Clinical and immunological analysis demonstrated that consumption of high opiate doses, long-term narcotization are associated with higher intensity of disorders detected. Conclusion. Dysregulation of immunoendocrine parameters was revealed in subjects with opiate addiction at all stages of withdrawal syndrome therapy within the term observed evidencing instability of therapeutic remission achieved and necessity in further rehabilitation events.

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