Intermediate Tuberculosis Burden Research Articles

Features which discriminate between tuberculosis and haematologic malignancy as the cause of pleural effusions with high adenosine deaminase

BackgroundAdenosine deaminase (ADA) is a useful biomarker for the diagnosis of tuberculous pleurisy (TBP). However, pleural effusions with high ADA can also be caused by other diseases, particularly hematologic malignant pleural effusion (hMPE). This study aimed to investigate the features that could differentiate TBP and hMPE in patients with pleural effusion ADA ≥ 40 IU/L.MethodsThis was a retrospective observational study of patients with pleural effusion ADA ≥ 40 IU/L, conducted at a Korean tertiary referral hospital with an intermediate tuberculosis burden between January 2010 and December 2017. Multivariable logistic regression analyses were performed to investigate the features associated with TBP and hMPE, respectively.ResultsAmong 1134 patients with ADA ≥ 40 IU/L, 375 (33.1%) and 85 (7.5%) were diagnosed with TBP and hMPE, respectively. TBP and hMPE accounted for 59% (257/433) and 6% (27/433) in patients with ADA between 70 and 150 IU/L, respectively. However, in patients with ADA ≥ 150 IU/L, they accounted for 7% (9/123) and 19% (23/123), respectively. When ADA between 40 and 70 IU/L was the reference category, ADA between 70 and 150 IU/L was independently associated with TBP (adjusted odds ratio [aOR], 3.11; 95% confidence interval [CI], 1.95–4.95; P < 0.001). ADA ≥ 150 IU/L was negatively associated with TBP (aOR, 0.35; 95% CI, 0.14–0.90; P = 0.029) and positively associated with hMPE (aOR, 13.21; 95% CI, 5.67–30.79; P < 0.001). In addition, TBP was independently associated with lymphocytes ≥ 35% and a lactate dehydrogenase (LD)/ADA ratio < 18 in pleural effusion. hMPE was independently associated with pleural polymorphonuclear neutrophils < 50%, thrombocytopenia, and higher serum LD. A combination of lymphocytes ≥ 35%, LD/ADA < 18, and ADA < 150 IU/L demonstrated a sensitivity of 0.824 and specificity of 0.937 for predicting TBP.ConclusionIn patients with very high levels of pleural effusion ADA, hMPE should be considered. Several features in pleural effusion and serum may help to more effectively differentiate TBP from hMPE.

Incidence of Tuberculosis Among Immigrants in Korea Who Participated in a Latent Tuberculosis Infection Screening Program.

With a rapid decrease in tuberculosis (TB) incidence, the significance of latent tuberculosis infection (LTBI) has been underscored in South Korea. Although South Korea does not have a high proportion of immigrants compared to other countries, there is a growing argument that it should actively embrace immigrants as a solution to address issues of low birth rates and population aging. This study aimed to assess TB incidence among immigrants who participated a pilot LTBI screening program in South Korea. Records of immigrants participated in a pilot LTBI screening program in South Korea between 2018 and 2019 were linked with Korean National TB Surveillance System to determine TB development. Participants underwent interferon-gamma release assay (IGRA) and chest X-rays. Standardized incidence ratios (SIRs) stratified by age, country of origin's TB burden was calculated with a reference group of general South Korean population. Of a total of 9,517 participants, 14 TB cases were identified. Participants with positive IGRA results who did not initiate LTBI treatment showed TB incidence of 312.5 per 100,000 person-years, whereas those with negative results showed TB incidence of 34.4 per 100,000 person-years, resulting in an incidence rate ratio of 9.08 (95% confidence interval [CI], 2.50-32.99). SIR of TB among total participants including those with negative IGRA results was 2.60 (95% CI, 1.54-4.38; P < 0.001), whereas SIR among those with positive IGRA results was 5.86 (95% CI, 3.15-10.89; P < 0.001). In the calculation of SIR among participants with positive IGRA results, those aged under 35 from high TB-burden countries or intermediate TB-burden countries showed a high SIR (18.08; 95% CI, 2.55-128.37; P = 0.004), and 11.30 (95% CI, 2.82-45.16; P < 0.001), respectively). Contrary to previous reports that suggest the majority of elderly population with a positive IGRA result were due to remote infection and had a lower TB risk compared to younger ages, SIR among those aged 65 or over from intermediate TB-burden countries was 6.15 (95% CI, 0.87-43.69; P = 0.069), which was comparable to that in younger participants aged between 35 and 49 (SIR, 4.87; 95% CI, 1.22-19.49; P = 0.025) or those aged between 50 and 64 (SIR, 4.62; 95% CI, 1.73-12.31; P = 0.002). Young immigrants with positive IGRA results from countries with high or intermediate TB burden showed a relatively high TB risk compared to a general South Korea population. In addition, unexpected high TB risk was observed among elderly immigrants with positive IGRA results. In establishing future policies for LTBI in immigrants in South Korea, screenings should primarily focus on younger age group (who aged under 35). Additionally, further research is needed on the high TB risk observed in elderly immigrants.

Effect of a latent tuberculosis infection programme for healthcare workers in a country with an intermediate tuberculosis burden

Management of latent tuberculosis infection (LTBI) among healthcare workers (HCWs) is crucial for the prevention of nosocomial tuberculosis (TB) transmission. We aimed to determine the effect of an LTBI programme for HCWs in a tertiary care hospital in a country with an intermediate TB burden. In 2013, baseline LTBI screening was implemented for newly hired doctors and nurses, along with annual screening of HCWs in high-risk departments. HCWs with LTBI were also provided with treatment. Since 2017, all HCWs without an LTBI test result have been tested for LTBI. We assessed the annual incidence of active TB among HCWs between 2013 and 2020. Additionally, we evaluated the incidence of active TB among HCWs employed at the hospital in 2020, with a specific focus on those who had undergone LTBI tests between 2013 and 2018, considering their LTBI test results and treatment status. The incidence of active TB among HCWs significantly decreased between 2013 and 2020. The average risk reduction for pulmonary TB was 10.2% per year (95% CI, 1.0-19.0; P=0.034). Among HCWs employed at the hospital in 2020, 4354 individuals underwent LTBI tests between 2013 and 2018. Of them, 927 (21.3%) tested positive. Nine (1.5%) of 588 without LTBI treatment developed active TB. Among the 1285 HCWs who underwent follow-up testing, 62 (4.8%) converted, and one (4.3%) of the 23 without treatment developed active TB. None of those who received treatment were diagnosed with active TB. The LTBI programme significantly reduced the incidence of active TB in HCWs. LTBI screening and treatment should be implemented, particularly in countries with a high or intermediate TB burden.

Interferon-γ release assay and mantoux response in infants with tuberculous meningitis in low and intermediate burden countries

AimUntil now, the performance of interferon-γ release assay (IGRA) and Mantoux tests remains unclear in infant tuberculous meningitis (TBM). Therefore, a systematic review is performed to evaluate the sensitivity of IGRA and Mantoux tests for the diagnosis of infant TBM in low and intermediate tuberculosis (TB) burden countries, while following PRISMA.MethodsSeveral databases, including PubMed, EBSCO, Embase, Scopus, Web of Science, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials, were searched. Articles describing the results of IGRA or Mantoux tests among infant TBM were included for analysis. Data, such as age, sex, Mantoux test or IGRA, and cerebrospinal fluid (CSF) microbiological examinations (such as acid-fast bacilli (AFB) smear, TB PCR, and TB culture), were extracted from each study.ResultsA total of 31 articles were enrolled for further analysis, including 48 cases. The mean age was 9.4 ± 5.8 months and boys accounted for 57.1% of infants (24/42). Mantoux test was positive in 57.4% (27/47) of tested infants and IGRA was positive in 77.8% (7/9) of infants. In addition, among the infants with confirmed TB, 18 (52.9%, 18/34) of them have positive Mantoux responses and 7 (20.0%, 7/35) have positive IGRA results.ConclusionsIn low or intermediate TB burden countries, the Mantoux test has a poor performance for diagnosing TBM among infants, and IGRAs appear to have a moderate sensitivity for the diagnosis of infant TBM.

Association of duration of undernutrition with occurrence of tuberculosis

Undernutrition is a risk factor of tuberculosis (TB), but the association between duration of undernutrition and occurrence of TB is inconclusive. The objective of this study was to determine whether there is a difference in occurrence of TB according to the duration of undernutrition expressed as accumulated number of underweight in Republic of Korea, an intermediate TB burden country. The National Health Insurance database was used.Eligible subjects were individuals who received a national health examination between 1 and 2009 and 31 December 2010, and who also had received health examinations for four consecutive years prior to 2009.Finally included individuals in the analysis were followed until 31 December 2017. Accumulated number of underweight was defined as the number of times recorded as underweight over four consecutive years. The outcome of the study was newly diagnosed TB according to accumulated number of underweight. Among a study population of 2,396,434, TB was identified in 9,322 (3.89%) cases. The highest accumulated number of underweight was significantly associated with occurrence of TB (adjusted hazard ratio [aHR] 2.563, 95% CI 2.319–2.833). This association remained consistent after adjusting for demographic factors and underlying diseases (aHR 3.326, 95% CI 3.004–3.84). In stratified analysis based on age, sex, diabetes (DM), hypertension (HTN), and waist circumference (WC) in metabolic syndrome (MS), age and sex were identified as effect modifiers. Occurrence of TB was significantly higher in the group with the highest accumulated number of underweight under 65 years of age.

Risk factors associated with tuberculosis recurrence in South Korea determined using a nationwide cohort study.

ObjectivePrevention of tuberculosis (TB) recurrence is an important issue in TB control. South Korea, a country with a high average income, has been challenged with an intermediate burden of TB. We aimed to estimate the TB recurrence rate after successful completion of the first anti-TB chemotherapy, and to identify the risk factors for the TB recurrence by focusing on co-morbidities and behavioral factors.MethodsThis is a population-based cohort study using data from the National Health Insurance (NHI) database between 2002 and 2013. Newly diagnosed TB patients were identified using the classification of disease codes and prescription records. Final analytical subjects included people who successfully completed the first anti-TB chemotherapy. The primary outcome measure was recurrent TB 6-month after the first treatment completion. A set of associated risk factors, including demographic characteristics, co-morbidities, and health behavior factors were analyzed using Cox regression analysis.ResultsAmong 5,446 TB patients, 2,226 (40.1%) completed the first anti-TB treatment. During the follow-up period, 150 (6.7%) patients had TB recurrence, and the crude recurrent rate was 22.6 per 1000 person-years. The majority of recurrence cases (89%) occurred within the first 2-year period. The major findings show that participants who are male (adjusted HR (aHR) = 1.81, at a 95% CI, range: 1.11–2.94), older in age (aHR = 1.07, at a 95% CI, range: 1.00–1.14), have a lower income (aHR = 1.96, at a 95% CI, range: 1.10–3.48) and who are underweight (aHR = 1.92, at a 95% CI, range 1.15–3.20) were at higher risks for TB recurrence.ConclusionPeople who have risk factors for recurrent TB need to improve treatment compliance through more effective TB management, and follow-up observation for one or two years after the treatment completion.

Clinical relevance of false-negative interferon-gamma release assays in patients with tuberculous pleurisy in an intermediate tuberculosis burden country

BackgroundThere have been few studies to verify factors associated with a false-negative interferon-gamma release assay (IGRA) in patients with tuberculous pleurisy. We investigated the clinical relevance of false-negative results of the blood QuantiFERON-TB Gold In-Tube (QFT-GIT) assay and its risk factors in patients diagnosed with pleural tuberculosis (TB).MethodsMedical records of 650 pleural TB patients in a tertiary hospital between January 2009 and December 2020 were reviewed retrospectively. Patients who underwent the blood QFT-GIT assay and pleural fluid analysis before starting anti-TB medication were included.ResultsOf 199 patients with pleural TB who were performed QFT-GIT assay, 36 (18.1%) were false-negative results. These patients tended to be older than those with a positive result (P=0.060). The QFT-GIT-false-negative group of had significantly more comorbidities such as end-stage renal disease (ESRD), haematological cancer or pneumoconiosis than the QFT-GIT-positive group. Hypoproteinaemia and pH >6 in pleural fluid were associated with a false-negative QFT-GIT. Of the 199 patients, 163 (81.9%) were cured or completed anti-TB treatment; 13 patients (6.5%) died. The QFT-GIT-negative patients had significantly worse outcomes including mortality [unfavourable outcome: 33.3% (12/36 patients) in QFT-GIT-negative groups vs. 14.7% (24/163 patients) in QFT-GIT-positive groups, P<0.017; overall mortality: 16.7% (6/36 patients) vs. 4.3% (7/163 patients), respectively, P<0.015].ConclusionsIn pleural TB, a false-negative QFT-GIT result was 18.1% in a country of intermediate TB incidence. This discordant result in GFT-GIT was associated with ESRD, pneumoconiosis, hypoproteinaemia and a poor outcome. Clinicians should keep in mind the possibility of false-negativity in the blood IGRA test, especially in specific situations and its impact on TB outcome in managing patients with pleural TB.

Prevalence of Latent Tuberculous Infection in Patients With Nontuberculous Mycobacterial Lung Disease and Colonization: A Prospective Study in an Intermediate Tuberculosis Burden Country.

BackgroundControlling latent tuberculosis infection (LTBI) is important in eliminating tuberculosis (TB); however, the prevalence of LTBI has rarely been studied in patients with nontuberculous mycobacterial (NTM) lung disease (LD) and colonization (LC).MethodsWe prospectively recruited subjects with NTM isolated from sputum mycobacterial cultures from December 2011 to June 2019. NTM-LD and NTM-LC were defined according to the American Thoracic Society guidelines. Patients with negative cultures were recruited as controls. Patients with a history of active TB or positive TB cultures were excluded. LTBI was confirmed using a QuantiFERON-TB Gold In-tube test. The prevalence and factors associated with LTBI were analyzed.ResultsA total of 406 participants were enrolled, including 171 in the NTM-LD group, 153 in the NTM-LC group, and 82 in the control group. The prevalence of LTBI was higher in the NTM-LD and NTM-LC groups than in the controls (21.6%, 20.9%, and 6.1%; P = .006). Multivariable analysis showed that old age (adjusted odds ratio [aOR], 1.021, per year increment; P = .042), NTM-LD (aOR, 4.030; P = .005), NTM-LC (aOR, 3.610; P = .011, compared with the controls), and pulmonary cavitary lesions (aOR, 3.393; P = .034) were independently associated with LTBI.ConclusionsThe prevalence of LTBI was higher in the patients with NTM-LD and NTM-LC than in the controls. Old age, pulmonary cavitation, and NTM isolated from sputum were associated with a higher risk of LTBI.

Acute Intrathoracic Tuberculosis in Children and Adolescents with Community-Acquired Pneumonia in an Area with an Intermediate Disease Burden.

Tuberculosis (TB) in the pediatric population is a major challenge. Our objective was to describe the clinical and microbiological characteristics, radiological patterns, and treatment outcomes of children and adolescents (from 1 month to 17 years) with community-acquired pneumonia (CAP) caused by TB. We performed a prospective cohort study of a pediatric population between 1 month and 17 years of age and hospitalized in Medellín, Colombia, with the diagnosis of radiologically confirmed CAP that had ≤ 15 days of symptoms. The mycobacterial culture of induced sputum was used for the bacteriological confirmation; the history of TB contact, a tuberculin skin test, and clinical improvement with treatment were used to identify microbiologically negative TB cases. Among 499 children with CAP, TB was diagnosed in 12 (2.4%), of which 10 had less than 8 days of a cough, 10 had alveolar opacities, 9 were younger than 5 years old, and 2 had close contact with a TB patient. Among the TB cases, 50% (6) had microbiological confirmation, 8 had viral and/or bacterial confirmation, one patient had multidrug-resistant TB, and 10/12 had non-severe pneumonia. In countries with an intermediate TB burden, Mycobacterium tuberculosis should be included in the etiological differential diagnosis (as a cause or coinfection) of both pneumonia and severe CAP in the pediatric population.

The Risk of Tuberculosis in Patients With Inflammatory Bowel Disease Treated With Vedolizumab or Ustekinumab in Korea.

The present study investigated the risk of active tuberculosis in patients with inflammatory bowel disease (IBD) treated with vedolizumab or ustekinumab, in actual clinical settings in a country with an intermediate tuberculosis burden. The medical records of 238 patients with IBD who received vedolizumab or ustekinumab were retrospectively reviewed at a tertiary referral center in South Korea. All patients had ≥ 3 months of follow-up duration and underwent a latent tuberculosis infection screening test before initiation of the administration of these drugs. Of the 238 patients enrolled, 181 had Crohn’s disease, and 57 had ulcerative colitis. During the median 18.7 months of follow-up, active tuberculosis did not develop in any patient treated with vedolizumab or ustekinumab. Therefore, we concluded that the risk of tuberculosis appears to be low in patients with IBD treated with vedolizumab or ustekinumab in South Korea.

The seroconversion rate of QuantiFERON-TB gold in-tube test in psoriatic patients receiving anti-interleukin-23 monoclonal antibodies

Background: Biologic therapies have become the gold standard for the treatment of moderate-to-severe psoriasis and psoriatic arthritis. However, concerns for opportunistic infections exist, especially for tuberculosis (TB) in endemic areas. Previously, tumor necrosis factor inhibitors were reported to carry higher risks of latent TB infection (LTBI) reactivation or new active TB, followed by anti-interleukin (IL)-12/23 and IL-17 agents in Taiwan. Objectives: The objective of the study is to provide real-world clinical rate of seroconversion of serial QuantiFERON-TB gold in-tube (QFT-GIT) tests, for detection of LTBI and newly-acquired TB, in psoriasis patients while receiving IL-23 inhibitors in an intermediate TB burden country. Methods: The local risk management plan required regular monitoring of TB while receiving biologics for psoriasis. This retrospective cohort evaluated consecutive psoriasis patients who received guselkumab or risankizumab between 2015 and 2021 in a tertiary referral center in Taiwan. Results: A total of 144 patients were included, with negative baseline QFT-GIT in 88% and positive in 13%. After receiving at least 6 months of anti-IL-23 drugs, persistently seropositive was found in 15 patients (10%), persistently seronegative in 125 patients (87%), seroconversion in 1 patient (0.6%), and seroreversion in 3 patients (1.9%). The seroconversion rate was 1% (1/127) in individuals under anti-IL-23 medications for at least 12 months. No case of LTBI reactivation was identified. Conclusion: In psoriasis patients under anti-IL-23 therapy, serial interferon-gamma release assays demonstrated a low seroconversion rate (<1%). Anti-IL-23 agents may be a favorable choice for psoriasis patients with a higher risk of TB infection and LTBI reactivation or those who reside in endemic regions.

Pulmonary Tuberculosis and the Incidence of Lung Cancer among Patients with Chronic Obstructive Pulmonary Disease.

Rationale: Although a history of pulmonary tuberculosis (PTB) is a risk factor for developing both chronic obstructive pulmonary disease (COPD) and lung cancer, it remains unclear whether a history of PTB affects lung cancer development in patients with COPD. Objectives: To investigate whether a history of PTB is associated with an increased risk of lung cancer development in a population with COPD. Methods: This cohort study included a nationwide representative sample of 13,165 Korean men and women with COPD, aged between 50 and 84 years. In addition, to assess whether the relationship between PTB and lung cancer risk differs between participants with and without COPD, a matchedcohort without COPD was included. Participants werematched 1:3 for age, sex, smoking history, and PTB status based on the index health screening examination of corresponding participantswith COPD. The two cohorts were followed up for 13 years (January 1, 2003, to December 31, 2015). PTB was diagnosed on the basis of the results of chest radiography, and incident lung cancer was identified from hospitalization and outpatient visit claims (International Classification of Diseases, Tenth Revision diagnosis code C33 or C34). Results: During 370,617 person-years (PY) of follow-up (median follow-up, 7.7 yr) in the COPD group, we observed 430 incident cases of lung cancer in participants without a history of PTB (incidence rate, 524 per 100,000 PY) and 148 cases in those with a history of PTB (incidence rate, 931 per 100,000 PY). Compared with participants without a PTB history, the fully adjusted subdistribution hazard ratio (95% confidence interval [CI]) for lung cancer in those with a history of PTB was 1.24 (1.03-1.50). The association of PTB history and lung cancer development was more evident in never-smokers with COPD. In contrast, among participants without COPD, the corresponding hazard ratio (95% CI) was 0.98 (0.78-1.22). There was no interaction among PTB, smoking status, and COPD. Conclusions: A history of PTB was associated with an increased risk of developing lung cancer among patients with COPD in our country with an intermediate tuberculosis burden. Patients with COPD with a history of PTB, particularly never-smokers, might benefit from periodic screening or assessment for lung cancer development.

PRS27 A Systematic Review on the Impact of Digital Health Technologies in Latent Tuberculosis Infection Management

To date, there is no study that has attempted to focus and summarize the role of digital health technologies in improving latent tuberculosis infection (LTBI) care. This review aims to address this gap and determine the impact of digital health technologies on LTBI screening and treatment outcomes. A systematic literature search was performed on six electronic databases from database inception until November 1, 2020. Studies that assessed the clinical use of digital health technologies in LTBI screening and treatment outcomes were eligible to be reviewed. Two investigators independently evaluated and extracted relevant studies. The Cochrane risk of bias tools were used to evaluate the methodological quality of the included studies. Descriptive data were summarized narratively. The effect of digital health technologies on LTBI treatment completion was estimated using random-effects meta-analysis. A total of 4,723 studies were screened, of which eleven eligible articles describing ten unique studies were included in this review. The use of digital health technologies to improve LTBI care includes voice and/or textual reminders, synchronous video call, tele-education and mobile applications to review tuberculin skin test induration. Improvement in LTBI treatment completion was observed with the use of textual reminders in regions with intermediate and high tuberculosis burden in comparison to regions with low tuberculosis burden [risk ratio (RR): 1.20; 95%CI: 0.99 – 1.46 versus RR: 0.97; 95%CI: 0.90 – 1.04, p = 0.04]. Our findings showed limited improvement in LTBI treatment completion with the use of digital health technologies. Nevertheless, digital interactive tools such as synchronous video call could help establish rapport between health care providers and individuals receiving LTBI treatment. As such, barriers to LTBI management could be addressed efficiently, which could in turn improve the quality of LTBI care among those affected.

The impact of the Xpert MTB/RIF screening among hospitalized patients with pneumonia on timely isolation of patients with pulmonary tuberculosis

In South Korea where the tuberculosis (TB) burden is intermediate, the risk of in-hospital transmission of TB remains high. We conducted a retrospective cohort study of 244 inpatients diagnosed with pulmonary TB (2015–2018) to evaluate the impact of the Xpert MTB/RIF assay (Xpert) screening on timely isolation. TB screening was performed with smear microscopy and a polymerase chain reaction test, and the Xpert was additionally used from November 2016. Among all patients with pulmonary TB, the median time-to-isolation was significantly reduced (22.6 vs. 69.7 h; p < 0.001) and segmented regression analysis adjusting for the time trend showed a reduction in time-to-isolation with the introduction of the Xpert (− 39.3 h; 95% CI − 85.6, 7.0; p = 0.096). Among 213 patients who were timely screened (≤ 72 h after admission), time-to-isolation decreased significantly (− 38.2 h; 95% CI − 70.6, − 5.8; p = 0.021) with the introduction of the Xpert, and its decreasing trend continued. The Xpert provided a shorter turnaround time (4.8 vs. 49.1 h; p < 0.001) and higher sensitivity (76.6% vs. 47.8%; p < 0.001) than smear microscopy. Thus, the Xpert can be a useful screening test for pulmonary TB in real-life hospital settings with an intermediate TB burden.

Distribution of molecular strains of Mycobacterium tuberculosis in an intermediate burden Asia Pacific city.

Hong Kong is an intermediate tuberculosis (TB) burden city in Asia Pacific with slow decline of case notification in the last decade. By 24-loci mycobacterial interspersed repetitive units - variable number of tandem repeats genotyping, we examined 534 Mycobacterium tuberculosis isolates collected from culture-positive hospitalised TB patients in a 1.7 million population geographic region in the city. Overall, 286 (75%) were classified as Beijing genotype, of which 216 (76%) and 59 (21%) belonged to modern and ancient sub-lineage, respectively. Only two cases were genetically clustered while spatial clustering was absent. Male gender, permanent residency in Hong Kong and born in Hong Kong or Mainland China were associated with Beijing genotype. The high prevalence of Beijing modern lineage was similar to that in East Asia, which reflected the pattern resulting from population migration. The paucity of clustering suggested that reactivation accounted for most of the TB disease cases, which was and echoed by observation that half were 60 years old or above, and the presence of co-morbid medical conditions. The predominance of reactivation TB cases in intermediate burden localities implies that the detection and control of latent TB infection would be the major challenge in achieving TB elimination.

Effectiveness of Household Contact Investigation with Preventive Therapy for Infectious Tuberculosis in an Intermediate Tuberculosis Burden Country: A Nationwide Investigation

Background: The effect of nationwide household contact (HHC) investigation with tuberculosis (TB) preventive treatment (TPT), including rifampin-resistant TB (RR-TB), in an intermediate TB burden country has not been well evaluated. Moreover, the coverage of HHC investigation with TPT is limited in low-income countries. Thus, it is important to determine the risk factors to identify the priority population for HHC investigation. Methods: This retrospective cohort study analyzed data of HHC participants registered between January 2015 and December 2018 in a linked database of nationwide TB registry and healthcare administrative claims database of South Korea. The primary outcome measure was incident active TB according to the TPT. As secondary outcome measures, we evaluated the risk factors for co-prevalent TB and latent TB infection (LTBI) among HHCs. Findings: We included 119,233 HHCs. TPT completion indicated a lower risk of active TB (adjusted hazard ratio [aHR], 0·14 [95% CI, 0·09–0·22]). Among HHCs of RR-TB patients, there was no significant difference in the risk of active TB between the LTBI-positive with TPT group and the LTBI-negative group (aHR, 2·27 [95% CI, 0·58-8·83]). Male sex, age ≥76 years, contact with first-degree relatives, comorbid chronic pulmonary disease, comorbid diabetes, and alcohol abuse correlated with a higher risk of co-prevalent TB. Further, male sex, contact with first-degree relatives, and comorbid diabetes correlated with a higher risk of LTBI. Interpretation: Nationwide HHC investigation with TPT may effective in an intermediate-TB burden country. Further, HHC with male sex, first-degree relatives, and comorbid diabetes should be prioritized for HHC investigation. Funding Information: Korea Disease Control and Prevention Agency. Declaration of Interests: We declare no competing interests Ethics Approval Statement: This study was approved by the Institutional Review Board (IRB) of Chung-Ang University (IRB number: 1041078-201801-HR-012-01). Informed consent was waived owing to the use of de-identified data.

Tuberculosis risk with biologics by screening-guided preventive strategy in rheumatoid arthritis under intermediate tuberculosis burden.

We aimed to compare tuberculosis (TB) risk during biologics treatment between patients with RA who did (prophylaxis) and did not (non-prophylaxis) undergo chemoprophylaxis following pre-biologic latent TB screening in Korea of an intermediate TB burden. Using the 2002-16 Korea National Health Insurance database, we conducted a cohort study examining TB risk, defined by International Classification of Diseases Tenth Revision codes plus anti-TB drugs, among RA patients initiating a biologic drug with and without chemoprophylaxis after screening triage for latent TB. To control baseline confounding, we used propensity score-based fine stratification (PSS) and weighting. Cox proportional hazards models estimated hazard ratios and 95% CIs comparing TB risk between the prophylaxis vs non-prophylaxis groups. The PSS-weighted study cohort (mean age 57.0 years; 81.3% female) included 2249 and 7225 RA patients in the prophylaxis and non-prophylaxis groups, respectively. During 2.42 years of biologics treatment, 118 patients developed TB with the incidence rate per 100 person-years of 0.33 in the prophylaxis and 0.63 in the non-prophylaxis groups. The PSS-weighted hazard ratio (95% CI) for TB associated with the prophylaxis was 0.52 (0.32, 0.86). During the follow-up time, the incidence rate of TB remained consistently low in the prophylaxis group but it was highest in the first year, then time-dependently declined in the non-prophylaxis group. This population-based cohort study warns that the current screening-based preventive strategy generates a substantially higher TB risk after biologics initiation among screening-negative patients compared with screening-positive patients receiving chemoprophylaxis, when the background TB burden is not low.

Chest computed tomography scan as an initial diagnostic method for tuberculosis infection detected by mass screening.

Background/AimsWe assessed the diagnostic yield of chest computed tomography (CT) as an initial diagnostic method for patients with a tuberculosis (TB) infection detected by mass screening in a country with an intermediate TB burden.MethodsA retrospective study was conducted on patients with TB infection detected by mass screening performed between January 2015 and March 2018. The patients were classified according to whether they had a chest X-ray (CXR) or CT scan as an initial diagnostic test to exclude active TB.ResultsOf 542 patients with TB infection detected by mass screening, 222 and 320 were initially examined by CXR and CT, respectively; the two modalities showed no significant difference in rate of detection of patients with active TB (0.9% and 2.5%, respectively; p = 0.110). However, chest CT was associated with further invasive tests using bronchoscopy and respiratory specimens, and significantly increased the frequency of hospital visits.ConclusionsChest CT was not supported as an initial diagnostic method to rule out active TB in patients with a TB infection detected by mass screening in a country with an intermediate TB burden.

Chest roentgenography is complementary to interferon-gamma release assay in latent tuberculosis infection screening of rheumatic patients

BackgroundA study of latent tuberculosis infection (LTBI) burden by chest roentgenography (CXR) with reference to interferon-gamma release assay (IGRA) is still lacking in rheumatic patients of an intermediate tuberculosis burden area.MethodsWe retrospectively reviewed clinical data of patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), or psoriatic arthritis (PsA) receiving LTBI screening for biologics from Jan 2013 to April 2014.ResultsA total of 238 rheumatic patients who underwent LTBI screening were included in this study, of whom 46 (19.3%) had positive IGRA tests, 178 (74.8%) had negative results, and 14 (5.9%) had indeterminate results. Radiological findings suggesting healed tuberculosis (CXR-old-TB) were found in 18.1% of all patients, 23.9% in the IGRA -positive patients vs 16.9% in the IGRA-negative patients (OR 1.55 95% CI: 0.71–3.39, p = 0.27). Forty (40/46, 87.0%) IGRA-positive patients received isoniazid prophylaxis and 77.5% of them finished treatment. Six patients developed adverse effects of isoniazid treatment, resulting in an overall number needed to harm (NNH) of 6.7 (40/6). IGRA-non-positive patients with old TB-suggestive CXR comprised 13.4% (32/238) of all our rheumatic patients, and one of them developed pulmonary tuberculosis within one year after screening.ConclusionsLTBI disease burden in rheumatic patients is substantial according to the estimation of CXR and IGRA screening. Correlation between CXR and IGRA is not significant in rheumatic patients, which implies their complementary roles. IGRA-non-positive patients with old TB-suggestive CXR comprise a significant portion in rheumatic patients and merit cautious follow-up by rheumatologists, tuberculosis specialists, and pulmonologists.

Risk of Tuberculosis in Patients With Inflammatory Bowel Disease on Infliximab or Adalimumab Is Dependent on the Local Disease Burden of Tuberculosis: A Systematic Review and Meta-Analysis.

Infliximab (IFX) or adalimumab (ADA) use in patients with inflammatory bowel disease (IBD) leads to increased risk of tuberculosis (TB). This meta-analysis evaluated the factors which determine this risk, with special focus on local TB incidence. All studies until January 31, 2019, which reported the development of TB in patients with IBD on IFX/ADA, were included after searching PubMed and Embase. Data regarding disease type, number of patients on IFX/ADA, number of patients who developed TB, mean age at IFX/ADA initiation, median duration of development of TB, and latent TB (LTB) were extracted. The details on local TB incidence were obtained from the World Health Organization database, and the studies were stratified into low (<10/100,000), intermediate (10-40/100,000), and high TB burden countries (>40/100,000). Random effect meta-analysis was performed to calculate the overall pooled prevalence and prevalence based on local TB burden. Of 130,114 patients (128 studies), 373 developed TB (pooled prevalence: 0.08% [95% confidence interval {CI}: 0.05%-0.10%]). The risk increased with increasing TB burden, pooled prevalence being 0.02% (95% CI: 0.02%-0.03%), 0.21% (95% CI: -0.02% to 0.43%), and 1.59% (95% CI: 1.19%-2.00%) for low, intermediate, and high TB burden countries, respectively. Seventy-three percent of patients who developed TB had no evidence of LTB on screening, the proportion being independent of TB burden. There was no effect of disease or treatment type, study type, gender, age at IFX/ADA initiation, and follow-up duration on TB prevalence. TB risk in patients with IBD on IFX/ADA depends on the local TB burden and is independent of disease/treatment type.