IGRA Test Research Articles

Cellular and Humoral Immune Responses to SARS-CoV-2 Vaccination in Inflammatory Bowel Disease Patients.

Background and AimsKnowledge on the immunogenicity of anti-SARS-CoV-2 vaccines in inflammatory bowel disease (IBD) patients is limited. Therefore, SARS-CoV-2-specific T-cell response and antibodies were analyzed in 60 IBD vaccine recipients and 30 controls.MethodsSARS-CoV-2 IgG antibodies against the viral spike protein were measured at baseline and at 8 and 26 weeks after the second vaccine dose. SARS-CoV-2 IgG antibodies against the nucleocapsid antigens were measured at week 26. SARS-CoV-2 interferon-gamma released assay (IGRA) was performed in all vaccinees at week 26.ResultsAt weeks 0 and 8, no differences were found in anti-spike antibodies between cohorts. At week 26, the decrease in antibody levels was more significant in the IBD cohort compared to the healthy cohort, and anti-nucleocapsid antibodies were not detected in either group. At week 26, 16 of 90 (18 %) vaccinated individuals had a negative IGRA test result, 7 of 90 (8 %) were borderline, and 67 (74 %) had a positive IGRA result; 22 of the 23 individuals with negative or borderline IGRA results belonged to the IBD cohort. However,the overall functional ability of T-lymphocytes to produce interferon-gamma after the unspecific mitogen stimulation was lower in IBD patients. In vaccinees with low or borderline IGRA, treatment with TNF-alpha inhibitors was the most frequent. In individuals with a significant drop in anti-spike antibody levels, plasmatic interferon-gamma concentrations after the specific SARS-CoV-2 stimulation were also insufficient.ConclusionsSimple humoral and cellular post-vaccination monitoring is advisable in IBD patients so that repeated vaccine doses may be scheduled.

Effectiveness of nationwide programmatic testing and treatment for latent tuberculosis infection in migrants in England: a retrospective, population-based cohort study

SummaryBackgroundIn low-incidence countries, tuberculosis mainly affects migrants, mostly resulting from reactivation of latent tuberculosis infection (LTBI) acquired in high-incidence countries before migration. A nationwide primary care-based LTBI testing and treatment programme for migrants from high-incidence countries was therefore established in high tuberculosis incidence areas in England. We aimed to assess the effectiveness of this programme.MethodsWe did a retrospective, population-based cohort study of migrants who registered in primary care between Jan 1, 2011, and Dec 31, 2018, in 55 high-burden areas with programmatic LTBI testing and treatment. Eligible individuals were aged 16–35 years, born in a high-incidence country, and had entered England in the past 5 years. Individuals who tested interferon-γ release assay (IGRA)-negative were advised about symptoms of tuberculosis, whereas those who tested IGRA-positive were clinically assessed to rule out active tuberculosis and offered preventive therapy. The primary outcome was incident tuberculosis notified to the national Enhanced Tuberculosis Surveillance system.FindingsOur cohort comprised 368 097 eligible individuals who had registered in primary care, of whom 37 268 (10·1%) were tested by the programme. 1446 incident cases of tuberculosis were identified: 166 cases in individuals who had IGRA testing (incidence 204 cases [95% CI 176–238] per 100 000 person-years) and 1280 in individuals without IGRA testing (82 cases [77–86] per 100 000 person-years). Overall, in our primary analysis including all diagnosed tuberculosis cases, a time-varying association was identified between LTBI testing and treatment and lower risk of incident tuberculosis (hazard ratio [HR] 0·76 [95% CI 0·63–0·91]) when compared with no testing. In stratified analysis by follow-up period, the intervention was associated with higher risk of tuberculosis diagnosis during the first 6 months of follow-up (9·93 [7·63–12·9) and a lower risk after 6 months (0·57 [0·41–0·79]). IGRA-positive individuals had higher risk of tuberculosis diagnosis than IGRA-negative individuals (31·9 [20·4–49·8]). Of 37 268 migrants who were tested, 6640 (17·8%) were IGRA-positive, of whom 1740 (26·2%) started preventive treatment. LTBI treatment lowered the risk of tuberculosis: of 135 incident cases in the IGRA-positive cohort, seven cases were diagnosed in the treated group (1·87 cases [95% CI 0·89–3·93] per 1000 person-years) and 128 cases were diagnosed in the untreated group (10·9 cases [9·16–12·9] per 1000 person-years; HR 0·14 [95% CI 0·06–0·32]).InterpretationA low proportion of eligible migrants were tested by the programme and a small proportion of those testing positive started treatment. Despite this, programmatic LTBI testing and treatment of individuals migrating to a low-incidence region is effective at diagnosing active tuberculosis earlier and lowers the long-term risk of progression to tuberculosis. Increasing programme participation and treatment rates for those testing positive could substantially impact national tuberculosis incidence.FundingNational Institute for Health Research Health Protection Research Unit in Respiratory Infections.

Determinants of latent tuberculosis infection among nurses at public health centers in Indonesia.

The incidence of latent tuberculosis among healthcare workers, especially nurses, at public health centers in Indonesia has been increased. Therefore, factors related to the tuberculosis incidence need to be further investigated. This study aimed to identify the determinants of latent tuberculosis infection among nurses at public health centers in Indonesia. This non-experimental, cross-sectional study included 98 nurses. Data on the determinants of latent tuberculosis infection were collected using validated questionnaires, and the infection status was confirmed by Interferon Gamma Release Assay or IGRA test. Logistic regression was used for statistical analysis, with a significance level of p < 0.05. Health facilities for tuberculosis transmission prevention were available in all public health centers (100%). Protocols for preventing tuberculosis transmission including occupational health and safety training (OR = 13.24, 95% CI [2.29-58.55]; p = 0.001), handwashing after contact with patients or specimens (OR = 20.55, 95% CI [4.23-99.93]; p = 0.000), and wearing of medical masks (OR = 9.56, 95% CI [1.99-45.69]; p = 0.005) were found to be significant determinants of latent tuberculosis infection among nurses. The availability of protective equipment and implementation of health protocols among nurses at public health centers are the main determinants of latent tuberculosis infection. Hence, they should be maintained by all nurses to prevent the spread of tuberculosis.

QuantiFERON-TB Gold Plus evaluation for latent tuberculosis infection among Italian healthcare workers: a cross-sectional study

&#x0D; Background: healthcare workers (HCWs) are at higher risk of being exposed to tuberculosis (TB). The aim of this study was to estimate LTBI prevalence and evaluate associated risk factors among Italian HCWs using a new generation IGRA test, Quantiferon Plus (QTF-Plus), providing also an analytical evaluation of this test.&#x0D; Methods: this cross-sectional study was conducted during the annual health surveillance program performed in 2017, evaluating 1470 HCWs of a teaching hospital in Rome, tested with QTF-Plus. A standardized questionnaire was collected for multivariate risk analysis. The independent variables associated with a higher frequency of LTBI were tested in a multivariate logistic regression model.&#x0D; Results: LTBI was diagnosed in 50 out of 1470 (3.4%) of HCWs. The male gender and age&gt;40 years were significantly associated with the risk of LTBI. The levels of interferon-γ were significantly lower in subjects with a recent conversion than in those with an older positivity. Moreover, interferon-γ values exceeding 8 IU/ml were recorded in 8 out of 35 remote subjects but in no recent subjects. The concordance between TB1 and TB2 results was 88%, while in 6 out of 50 subjects we found a discrepancy.&#x0D; Conclusion: the LTBI condition among Italian HCWs was very low. In subjects with discordant outcomes between TB1 and TB2, especially when the test values are close to the cut-off, is recommended a repetition of the test to confirm its positivity.&#x0D; Key words: tuberculosis, latent tuberculosis infection, interferon-gamma release assay, quantiferon plus, healthcare workers&#x0D;

US Postarrival Evaluation of Immigrant and Refugee Children with Latent Tuberculosis Infection Diagnosed Overseas, 2007-2019

To assess outcomes from the US postarrival evaluation of newly arrived immigrant and refugee children aged 2-14years who were diagnosed with latent tuberculosis infection (LTBI) during a required overseas medical examination. We compared overseas and US interferon-γ release assay (IGRA)/tuberculin skin test (TST) results and LTBI diagnosis; assessed postarrival LTBI treatment initiation and completion; and evaluated the impact of switching from TST to IGRA to detect Mycobacterium tuberculosis infection overseas. In total, 73 014 children were diagnosed with LTBI overseas and arrived in the US during 2007-2019. In the US, 45 939 (62.9%) completed, and 1985 (2.7%) initiated but did not complete a postarrival evaluation. Among these 47 924 children, 30 360 (63.4%) were retested for M tuberculosis infection. For 17 996 children with a positive overseas TST, 73.8% were negative when retested by IGRA. For 1051 children with a positive overseas IGRA, 58.0% were negative when retested by IGRA. Overall, among children who completed a postarrival evaluation, 18 544 (40.4%) were evaluated as having no evidence of TB infection, and 25 919 (56.4%) had their overseas LTBI diagnosis confirmed. Among the latter, 17 229 (66.5%) initiated and 9185 (35.4%) completed LTBI treatment. Requiring IGRA testing overseas could more effectively identify children who will benefit from LTBI treatment. However, IGRA reversions may occur, highlighting the need for individualized assessment for risk of infection, progression, and poor outcome when making diagnostic and treatment decisions. Strategies are needed to increase the proportions receiving a postarrival evaluation and completing LTBI treatment.

Comparison of Tuberculin Skin Test and QuantiFERON-TB Gold Test in Children

Objective: Interferon-γ release tests (IGRAs) and tuberculin skin testing (TST) are important helpful tests for diagnosing tuberculosis (TB) disease in children. It was aimed to compare the sensitivity and compatibility of QuantiFERON-TB Gold In-tube test (QFT) and TST used in children with TB and Latent tuberculosis infection (LTBI). Material and Methods: A total of 118 patients between September 2018 and January 2020 were included in the study prospectively to determine the case characteristics related to the performance of the tests, and to measure the sensitivity of these tests. Results : A total of 118 patients were included in the study; and 13 (11%) patients presented with pneumonia symptoms and 7 (6%) patients were diagnosed with TB in active TB Contact Screening. TB diagnosis was made 20% microbiologically. Mycobacterium tuberculosis culture positivity was found to be 10%. None of the patients had acid-resistant bacilli positivity. The male / female rate was 74/44 in our study (p = 0.006). The median age was found to be 14 (1.17-19.2 years) in males, and 12 (0.33 -17.9 years) in females. The mean age of the LTBI Group was higher than the TB Group at significant levels (p <0.05), and was similar to the non-infected group (p>0.05). A total of 53.5% of the patients had a history of meeting someone with tuberculosis, and 97 children were vaccinated with BCG (82.2%). TST and QFT positivities were 19.5% and 22%, respectively. The most common radiological finding that was detected was consolidation areas. While there was moderate compliance between TST and IGRA test in patients with TB diagnosis (kappa =0.50, p=0.025), no compliance was found between tests in LTBI patients. In patients who were diagnosed with TB and LTBI, the sensitivity of TST was found to be 51.1%, and the sensitivity of QFT was found to be 60.4%. Conclusion: TST seems to continue as the most preferred method of diagnosis in rural areas with limited resources and poor laboratory infrastructure due to the costs and technical considerations.

Različiti oblici infekcije mikobakterijama kod bolesnika na anti-TNF terapiji - prikazi bolesnika

Biological agents, including TNF-alpha antagonists, have been used in treatment of autoimmune diseases for over 20 years. Due to impaired T-cell immunity and blocked effects of TNF-alpha mediator, patients receiving this therapy have increased risk of developing tuberculosis or other non-tuberculous mycobacterial infections. Both tuberculosis and other mycobacterial infections may occur anytime in patients who have ever used these medicines, even after the first injection. Most often we see activation of latent tuberculosis confirmed by screening tests. IGRA tests (QuantiFERON and T-SPOT.TB) are significantly more sensitive and specific for testing population of immunosuppressed patients, in comparison to tuberculosis skin test. There are contemporary recommendations for diagnosing, monitoring, chemoprophylaxis and treatment of latent and active tuberculosis in adults and children in case of planning administration of TNF-alpha antagonists or in cases when these drugs have already been used. Prevention of active tuberculosis via diagnosing LTBI and use of chemoprophylaxis is the crucial component of the strategy of World Health Organization for elimination of TB (End TB Strategy).

Latentna tuberkuloza - najčešće dileme ili ko je tražio quantiferon?

Due to the increasing use of immunosuppressants, particularly biological therapy, as well as HIV epidemics, latent tuberculosis (LTBI) is being activated, and this disease, which had been rather forgotten in the Western world, is becoming a topical issue in the recent years. Numerous categories of patients should be tested for latent tuberculosis, using PPD or IGRA tests. Interpreting test results is a very touchy issue, since it is the way to determine therapy of latent TB, that is, to decide on chemoprophylaxis. For the last two years, during the Covid-19 pandemics, large percentage of patients received high doses of corticosteroid and other types of immunosuppressant therapies, and it is therefore necessary to consider the potential risks for these patients, in terms of contracting tuberculosis and perhaps testing them for LTBI.

S2456 TB or Not TB? Miliary Tuberculosis in a QuantiFERON-Indeterminate Patient on Infliximab Therapy

Introduction: Miliary tuberculosis results from massive hematogenous dissemination of tuberculosis (TB) typically to the lung, bone, and less commonly to the gastrointestinal tract. It accounts for 2% of TB cases which may present as a life-threatening septic shock in the setting immunosuppression. Case Description/Methods: A 53-year-old Cuban male physician with moderate to severe ileocolic Crohn's disease and a history of travel to Cuba was recently initiated on Infliximab due to the failure of conventional therapy. Pretreatment Interferon-γ Release Assay (IGRA) QuantiFERON-TB Gold In-Tube, and tuberculin skin test were negative. Fourteen weeks later, he reported fever, emesis, and unintentional weight loss. Colonoscopy revealed severely inflamed mucosa of the right hemi-colon promoting escalation of infliximab dose with steroids for a presumed CD flare. Biopsy subsequently revealed numerous acid-fast bacilli. Therapy was immediately aborted, and he was then advised to initiate TB treatment. He returned eight days later with shock progressing to multiorgan failure. During emergent exploratory laparotomy, the small bowel and omentum were studded with white granulomatous nodules. He expired n the first postoperative day. Sputum, omentum, and abdominal wall cultures were all positive for Mycobacterium tuberculosis, and repeat IGRA was indeterminate. Discussion: Crohn’s disease (CD) is a chronic granulomatous inflammatory and destructive disease which follows a relapsing and remitting course. Infliximab therapy is initiated in moderate to severe stages however it carries with it an increased risk of reactivation of latent TB. IGRA testing before and during treatment is important during treatment with infliximab. It is difficult to surmise whether the subsequent hospital visits post infliximab initiation were due to worsening CD, or a manifestation of intestinal TB given the striking similarities. This patient’s insidious weight loss and rapid decline concomitant with the escalation of Infliximab and corticosteroid use points towards intestinal TB as the etiology of the symptoms. Despite the high sensitivity of IGRA testing, this patient’s travel history in an endemic area decreases the negative predictive value of the test. Diagnosis of miliary TB is challenging given its nonspecific presentation and limited diagnostic modalities. Therefore, patients continually exposed to endemic areas should prompt more frequent diagnostic re-evaluation prior to Infliximab escalation.

LATENT MYCOBACTERIUM TB REACTIVATION IN TWO PATIENTS WITH COVID-19 PNEUMONIA

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Since December 2019, the world has been suffering from the pandemic of the new coronavirus (COVID-19) with a significant mortality rate. It mainly affects the respiratory system with a wide severity range from being asymptomatic to causing severe acute respiratory distress syndrome (ARDS). Few case reports have reported pulmonary tuberculosis co-infection or reactivation in COVID-19 pneumonia patients(1-2). We present two cases of COVID-19 pneumonia who presented, after the resolution of the acute symptoms, with shortness of breath and were found to have pulmonary cavities, suspicious for tuberculosis (TB). CASE PRESENTATION: Case 1: 76-year-old Brazilian male with multiple comorbidities including COPD on home oxygen, who received the monoclonal antibody infusion (Bamlanivimab) a month ago for mild COVID-19 pneumonia, presented with generalized weakness associated with fever and cough. CT chest showed extensive peribronchiolar and centrilobular patchy and nodular opacities with internal cavities (Figure 1 Right). A previous chest x-ray showed left basal lung scarring (Figure 1 left). Case 2: 71-year-old Columbian male with a history of diabetes mellitus and COVID-19 pneumonia treated with dexamethasone and remdesivir for 10 days, presented 3 months later with dyspnea, fever, and productive cough. X-ray and CT chest showed diffuse nodular opacities with dense consolidation in both upper lobes associated with areas of cavitations (Figure 2 Right). A previous chest x-ray did not show any evidence of prior lung pathologies (Figure 2 Left). Bronchial washing PCR was positive for mycobacterium tuberculosis in both cases. DISCUSSION: Cavitary lung lesions are usually caused by mycobacterial, fungal, neoplastic, or autoimmune pathologies. Viral pneumonia, including SARS-CoV and MERS-CoV, is not a common cause of lung cavities even in severe viral infections (3). Although few case reports have reported cavitary lesions as sequelae of COVID-19 pneumonia, common causes should be excluded first. The two most common CT chest findings in COVID-19 patients are ground-glass opacities and bilateral patchy shadowing (4). The presence of lung cavities in such patients should raise the suspicion of TB, especially in high-risk patients. Whether or not the immune system reaction to the COVID-19; including leukopenia, lymphopenia, and an inflammatory cytokine storm can lead to latent TB reactivation is not fully understood yet. However, treatment of COVID-19 with immunosuppressant drugs such as corticosteroids could be a risk factor for TB reactivation. Both of our patients had new lung cavitary lesions with confirmed mycobacterial infection. CONCLUSIONS: Pulmonary cavities in COVID-19 pneumonia patients should raise the suspicion of other pathologies such as tuberculosis, especially in high-risk patients. REFERENCE #1: 1.Tham, S.M., et al., Four Patients with COVID-19 and Tuberculosis, Singapore, April-May 2020.Emerg Infect Dis, 2020. 26(11): p. 2764-2766.10.1056/NEJMoa2002032. REFERENCE #2: 2. Torre, A., et al., Preliminary observations on IGRA testing for TB infection in patients with severe COVID-19 eligible for immunosuppressive therapy. Respir Med, 2020. 175: p. 106204. REFERENCE #3: 3. Zoumot Z, et al. Pulmonary cavitation: an under-recognized late complication of severe COVID-19 lung disease. BMC Pulm Med 21, 24 (2021). https://doi.org/10.1186/s12890-020-01379-14. Guan WJ, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med 2020; 382:1708-1720. DOI: 10.1056/NEJMoa2002032. DISCLOSURES: No relevant relationships by Sherif Elkattawy, source=Web Response No relevant relationships by Muhammad Atif Noori, source=Web Response No relevant relationships by onyeka Nwachukwu, source=Web Response No relevant relationships by John Viechweg, source=Web Response No relevant relationships by Islam Younes, source=Web Response

Assessment of humoral and cellular immunity induced by the BNT162b2 SARS-CoV-2 vaccine in healthcare workers, elderly people, and immunosuppressed patients with autoimmune disease.

The development of vaccines to prevent SARS-CoV-2 infection has mainly relied on the induction of neutralizing antibodies (nAbs) to the Spike protein of SARS-CoV-2, but there is growing evidence that T cell immune response can contribute to protection as well. In this study, an anti-receptor binding domain (RBD) antibody assay and an INFγ-release assay (IGRA) were used to detect humoral and cellular responses to the Pfizer-BioNTech BNT162b2 vaccine in three separate cohorts of COVID-19-naïve patients: 108 healthcare workers (HCWs), 15 elderly people, and 5 autoimmune patients treated with immunosuppressive agents. After the second dose of vaccine, the mean values of anti-RBD antibodies (Abs) and INFγ were 123.33 U/mL (range 27.55–464) and 1513 mIU/mL (range 145–2500) in HCWs and 210.7 U/mL (range 3–500) and 1167 mIU/mL (range 83–2500) in elderly people. No correlations between age and immune status were observed. On the contrary, a weak but significant positive correlation was found between INFγ and anti-RBD Abs values (rho = 0.354, p = 0.003). As to the autoimmune cohort, anti-RBD Abs were not detected in the two patients with absent peripheral CD19+B cells, despite high INFγ levels being observed in all 5 patients after vaccination. Even though the clinical relevance of T cell response has not yet been established as a correlate of vaccine-induced protection, IGRA testing has showed optimal sensitivity and specificity to define vaccine responders, even in patients lacking a cognate antibody response to the vaccine.

WITHDRAWN: Diagnosis of tuberculous infection in immunosuppressed patients and/or candidates for biologics using a combination of 2 IGRA tests: T-SPOT.TB/QuantiFERON TB Gold In-Tube vs. T-SPOT.TB/QuantiFERON TB Gold Plus

The Publisher regrets that this article is an accidental duplication of an article that has already been published, https://doi.org/10.1016/j.arbres.2020.04.026 . The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal

German S3-Guideline on the treatment of Psoriasis vulgaris, adapted from EuroGuiDerm - Part 2: Treatment monitoring and specific clinical or comorbid situations.

German S3-Guideline on the treatment of Psoriasis vulgaris, adapted from EuroGuiDerm - Part 2: Treatment monitoring and specific clinical or comorbid situations.

Prevalence of latent tuberculosis before biotherapy initiation in rheumatoid arthritis and spondyloarthritis: data from the Moroccan biotherapy registry.

Before the initiation of biotherapy in the treatment of rheumatic diseases, it is highly recommended for the patients to be screened for latent tuberculosis infection (LTBI). The objective of this study is to identify the prevalence of LTBI among patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA) before the initiation of biologic therapy in the Moroccan biotherapy registry (RBSMR). A cross sectional study was conducted using the baseline data of the Moroccan biotherapy registry. Tuberculin skin test or IGRA test or both tests were done before starting anti-TNF treatment for screening LTBI. The comparisons between positive and negative LTBI patients according to rheumatic disease were examined using categorical comparisons. 259 patients were included in this study.94 patients had RA and 165 had SpA. The mean age of the RA patients was 50.49 ± 11.82years with a majority of females (84%). The mean age for the SpA patients was 36 ± 13.7years with a majority of males (67.3%). The prevalence of LTBI in the RBSMR was 21.6%. This prevalence was at 24.8% in SpA patients, while it was at 15.9% for RA patients. After the comparison between positive and negative LTBI patients according to rheumatic disease, no demographic, clinical, or therapeutic characteristics were statistically associated with LTBI. This study found that in an endemic TB country like Morocco, a high prevalence of patients with SpA and RA had LTBI, and that RA patients had a lower prevalence than SpA patients.

Isolated spleen tuberculosis in an immunocompetent patient, a rare case report.

IntroductionTuberculosis (TB), as a major public health concern, is affecting almost 10 million people globally. At present, diagnostic and screening efforts mainly focus on positive smear results. Therefore, the number of extra pulmonary and negative sputum TB is rising and hampering the diagnosis and treatment process due to the large number of false negatives. Rare cases such as solitary splenic TB are usually seen in patients with splenic abnormalities, spleen trauma, immunosuppression, sickle cell disease, pyogenic infections, etc.Presentation of caseA 40-year-old female with no comorbidity came with chief complaint of early satiety every mealtime and epigastric pain in the last 6 months prior to admission. There was no significant positive examination except for positive IGRA test and enlargement of spleen with multiple cystic lesions on abdominal CT. We performed laparotomy with splenectomy followed by a histopathology examination which showed features of primary tubercular abscess.DiscussionIn the immunocompromised patient, the visceral abdomen is usually involved and a part of miliary TB. However, this case revealed the rare possibility of a healthy person with primary isolated tubercular splenic abscess while being immunocompetent and lacking any comorbidity.ConclusionSplenic TB diagnosis is difficult in patients lacking pulmonary involvement and without specific symptoms. Thorough examinations and clinical expertise are needed to provide accurate diagnosis and treat uncommon forms of TB and cases with negative smear results in consideration of rising prevalence and difficult disease control.

Screening for TB in Hospitalised Patients with Inflammatory Bowel Disease before Anti-TNF Therapy: Is QuantiFERON® Gold Testing Useful?

Background—Tumour necrosis factor alpha (TNFα) plays an important role in the pathogenesis of inflammatory bowel disease (IBD) and in immunity to Mycobacterium tuberculosis. Patients should be tested for latent tuberculosis infection using interferon-gamma release assays (IGRA/QF) prior to anti-TNFα therapy. Indeterminate QF results can delay anti-TNFα therapy. We sought to investigate factors associated with indeterminate QF results. Method—Retrospective study of all IGRA tests requested for gastroenterology patients in 2017. We compared inpatients and outpatients and investigated factors potentially associated with QF usefulness (steroid exposure, C-reactive protein (CRP), hypoalbuminaemia, thrombophilia). Results—We included 286 outpatients and 74 inpatients with IBD. Significantly more inpatients had an indeterminate IGRA (52.7% vs. 3.14% in outpatients; p < 0.0001). Laboratory parameters reflecting inflammation (high CRP, low albumin, low haemoglobin and high platelets) were also associated with an indeterminate QF (p < 0.0001). Exposure to steroids was more common in patients with an indeterminate QF (p < 0.0001). A binary logistic regression analysis revealed inpatient status and steroid exposure to be independently predictive of an indeterminate QF (p < 0.0001). Conclusion—There is a high chance of indeterminate QF results in inpatients. QF testing should ideally be performed in the outpatient setting at diagnosis.

ТУБЕРКУЛЕЗ В УСЛОВИЯХ НОВОЙ КОРОНАВИРУСНОЙ ИНФЕКЦИИ

Tuberculosis (TB) remains an important medical and social problem up to today. In recent years, great strides have been made in the fight against tuberculosis infection (TI) in reducing TB morbidity and mortality, especially in the Russian Federation. Emergence of new COVID-19 infection in the world has led to the need for long-term isolation of the population, on the one hand, and the need to resort to personal protective equipment, on the other. The spread of COVID-19 may have an impact on the increase in TB morbidity, despite the decrease in the incidence rate, which is related to objective difficulties in detecting TB and complexity of the structure of clinical manifestations of the disease against the background of coronavirus infection and severe complications after COVID-19. The use of immunosuppressive therapy in the treatment of COVID-19 may cause immunosuppression, which will affect the results of TI immunodiagnostics using skin tests. At the same time, IGRA tests can be useful in these conditions, since they are of great diagnostic value. Equally important is the reduction of patient visits to treatment facilities in the context of a pandemic or a high incidence of COVID-19.

#54: Tuberculosis in South African Children with Cancer

Abstract Background Children with cancer are immunocompromised, with increased susceptibility to infections including infections with Mycobacterium tuberculosis. Method This prospective study, enrolled children one-19 years old hospitalized for cancer treatment. Screening for M. tuberculosis infection was undertaken by tuberculin skin testing (Mantoux method), and ELISPOT (T-SPOT®.TB) (T-spot) on whole blood. Sputum/gastric-washings were investigated for microscopy and culture; and the diagnosis of probable TB was based on existing guidelines. We evaluated the burden of TB in South African children in a setting of high TB-HIV prevalence. Results We enrolled 169 children, 82 (42.5%) with hematological malignancy (HM) and 87 (51.5%) with solid tumors (ST), median age 68.5 months, 10.7% HIV-infected. The majority had severe malnutrition, 78.3% using mid-upper arm circumference and 57.8% using arm muscle anthropometry. Five (2.9%) children with a reactive TST at enrollment, were empirically treated for TB, and were excluded from further analyses. The T-Spot yielded indeterminate/negative results in the first 100 children (including 2.9% who had a reactive TST), and further IGRA testing was terminated. Thirty-four (20.7%) children were diagnosed with TB, (70.6% with HM and 29.4% with ST). At the screening, 14 had indeterminate and 7 negative T-Spot results. Twelve (35.3%) of the 34 TB cases were culture-confirmed. The mean time from initiation of cancer treatment to TB diagnosis was 5.5 months and the time to TB diagnosis from presentation of malignant disease was 6.6 and 4.9 months for culture-confirmed and probable TB, respectively. The spectrum of cancer was acute lymphoblastic leukemia (ALL) (n = 12/32, 37.5%), followed by non-Hodgkin Lymphoma (n = 8/19, 42.1%; seven with HIV infection). The overall incidence (per 100 child-years) of TB was 7.6 (95% CI: 5.3–10.7), 11.3 (95% CI: 7.2–16.8) with HM and 4.3 (95% CI: 2.1–7.9) with ST. HIV-infected children had a higher rate of TB (19.3; 95% CI: 8.3–38) than those not (6.4; 95% CI: 4.2–9.4). Cancer type, HIV-status nor nutritional status was independently associated with risk of TB. Children who developed TB had a higher exposure period to high-dose corticosteroid courses (350 per 100 child-years) than those who did not (29.4 per 100 child-years; P &amp;lt; 0.001). Children with TB compared with those who remained TB-free were more likely to have been treated for septic episodes (SE) associated with profound neutropenia (322.2 vs. 31.3; P &amp;lt; 0.001), profound lymphopenia (288.9 vs. 27.2; P &amp;lt; 0.001) and profound monocytopenia (416.7 vs. 43.0; P &amp;lt; 0.001) prior to the diagnosis of TB. There were 26 deaths (76.5%) in the 34 children with TB and 39/83 (50.0%; P = 0.004) in those who did not develop TB. Eleven had ALL, eight NHL (seven living with HIV), 3 had acute myeloid leukemia, and one each had HIV-related Kaposi Sarcoma, Nephroblastoma, osteosarcoma, and adrenocortical-carcinoma. At the time of death, multiple pathogens were isolated (multi-drug-resistant bacteria, fungi, and respiratory viruses). Conclusion Screening of children undergoing cancer treatment for MTB infection in a setting of high HIV and TB prevalence, was of limited value. The high rate of TB, and poor outcomes, emphasize the need for a high index of suspicion to diagnose TB and consideration for routine prophylaxis.

МЕСТО IGRA-ТЕСТОВ (ТЕСТЫ НА ОПРЕДЕЛЕНИЕ ИНТЕРФЕРОНА-ГАММА) В ДИАГНОСТИКЕ ТУБЕРКУЛЕЗНОЙ ИНФЕКЦИИ

The review presents scientific data available to date on the concept of the emergence and spread of latent tuberculosis infection (TI) in the current tuberculosis epidemic situation in society. Information on modern immunological tests for TI diagnosis is presented and the significant role of IGRA tests in the diagnostic tactics of detecting latent TI in various population groups is determined.

Changes in the lungs of a child with Gaucher disease: differential diagnosis with disseminated tuberculosis

The article describes a clinical case of a rare combination of hereditary pathology – Gaucher disease and latent tuberculosis infection in an 8-y ea r-o ld child. The child was examined for tuberculosis due to disseminated small foci and calcination in the lung tissue detected by chest computed tomography. The particular parameter of latent tuberculosis infection of this case was the positive results of IGRA tests ( T- S POT TB and Quanti FERON ) with a negative response to the intradermal test with recombinant tuberculosis allergen. According to the examination results, the disseminated tuberculosis was not confirmed, diffuse lung damage was regarded as a manifestation of Gaucher disease, which was a rare sign of this pathology according to the published data.