Intermediate Burden Country Research Articles

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.

Incidence of Tuberculosis in Systemic Necrotizing Vasculitides: A Population-Based Study From an Intermediate-Burden Country.

Objective: Tuberculosis (TB) has a significant impact on public health; however, its incidence in patients with systemic necrotizing vasculitides (SNV) remains unknown. Therefore, we evaluated the incidence of TB in patients with SNV using a nationwide claims database.Methods: The Health Insurance and Review Agency database was used to identify patients diagnosed with SNV between 2010 and 2018. The standardized incidence ratio (SIR) was calculated to compared the risk of TB between patients and the general population, based on the 2016 annual national TB report. The incidence of TB after SNV diagnosis was compared by estimating age- and sex- adjusted incidence rate ratio (IRR). A time-dependent Cox regression analysis was performed to estimate factors associated with TB.Results: Among the included 2,660 patients, 51 (1.9%) developed TB during the follow-up period. The risk of TB was significantly higher in patients with SNV [SIR 6.09, 95% confidence interval (CI) 4.53–8.00], both in men (SIR 5.95) and women (SIR 6.26), than in the general population; this increased risk was consistent in all disease subtypes, except eosinophilic granulomatosis with polyangiitis. Additionally, the incidence of TB was the highest in patients with SNV within the first 3 months after diagnosis (adjusted IRR: 8.90 compared to TB ≥ 12 months). In Cox regression analysis, the diagnosis of microscopic polyangiitis [hazard ratio (HR) 3.22, 95% CI 1.04–9.99], granulomatosis with polyangiitis (HR 4.63, 95% CI 1.53–14.02), and polyarteritis nodosa (HR 3.51, 95% CI 1.13–10.88) were independent factors associated with TB.Conclusion: Even when considering the high incidence of TB in the geographic region, the risk of TB increased in patients with SNV, with a difference based on disease subtypes. Moreover, taking into account of the high incidence of TB in SNV, vigilant monitoring for TB is required especially during the early disease period.

Delayed diagnosis of extrapulmonary tuberculosis presenting as fever of unknown origin in an intermediate-burden country

BackgroundTuberculosis (TB), especially extrapulmonary tuberculosis (EPTB), is an important cause of fever of unknown origin (FUO) in TB-burdened areas. Little information is known about patients with EPTB with clinical features presenting as FUO and about the factor of delaying the diagnosis.MethodsWe retrospectively analyzed EPTB patients who were referred with FUO at 3 university-affiliated hospitals over 8 years (2010–2017). The subjects were assigned to groups of early diagnosis and delayed diagnosis within 3 days of an initial comprehensive evaluation from the referral. Clinical and laboratory variables were compared between the groups.ResultsA total of 95 patients with febrile EPTB were included. Localizing symptoms and/or signs suggestive of anatomy were identified in 62.1% of the patients. Concurrent lung involvement by TB was presented by 49.5% (47/95) of the patients, and only 23.4% of them showed typical findings of pulmonary TB on simple chest X-ray. Most of the patients showed abnormal lesions on cross-sectional CT (98.9%) and MRI (100%). The clinical variables and blood test results of patients were not significantly different between the two groups. The less typical imaging finding of EPTB on CT (38.5% vs. 79.0%) and MRI (37.5% vs. 79.0%) in the delayed diagnosis group was a risk factor for delayed diagnosis.ConclusionFebrile EPTB referred as FUO showed nonspecific clinical manifestations. The active application of cross-sectional imaging tests according to clinical clues or randomly in the absence of local manifestations, combined with invasive diagnostic approaches even for atypical presentations may lead to an earlier diagnosis of febrile EPTB.

Lessons learned from continued TB outbreaks in a high school.

We investigated the aftereffects of confirmatory QuantiFERON testing (QFT) added to a positive tuberculin skin test (TST). We reviewed the pre and post course of sequential tuberculosis (TB) outbreaks in a high school where massive 43 active TB cases had been found within one year before delayed contact investigation. And we investigated the TB development in relation to initial TST and QFT during mean follow-up of 3.9 ± 0.9 years. After delayed contact investigation for two subsequent TB outbreaks, 925 contacts were divided into the following 3 groups: TST- (n = 632), TST+/QFT+ (n = 24), TST+/QFT- (n = 258). QFT- was more prevalent than QFT+ in contacts with 10mm ≤ TST <15mm (158, 61.2%) compared with TST ≥15mm (100, 38.8%) among the TST+ reactors (P < 0.001). Among the 258 TST+/QFT- subjects, 256 received no latent TB infection (LTBI) treatment, but 7 contacts developed TB during follow-up. Among these 7 patients, 4 had initial TST ≥15mm and 3 had 10mm ≤ TST <15mm. In conclusion, the delayed contact investigation for LTBI in a high school resulted in continued TB developments. False-negative QFT performed late among the TST+ reactors should not be considered criteria for LTBI treatment. Additionally, the contacts only with TST ≥15mm should be considered for LTBI treatment in congregate settings of intermediate-burden countries.

Clinical Study of Extrapulmonary Head and Neck Tuberculosis: A Single-Institute 10-year Experience.

Introduction Although the incidence of tuberculosis (TB) in Japan has been decreasing yearly, Japan remains ranked as an intermediate-burden country for TB. Objective This study aims to investigate the current situation of head and neck extrapulmonary TB (EPTB) diagnosed in our department. Methods We retrospectively reviewed the clinical records of 47 patients diagnosed with EPTB in the head and neck in our department between January 2005 and December 2014. The extracted data included sex and age distribution, development site, chief complaint, presence or absence of concomitant active pulmonary TB (PTB) or history of TB, tuberculin skin test (TST) results, interferon-gamma release assay (IGRA) results, and duration from the first visit to the final diagnosis of EPTB. Results The subjects consisted of 20 men and 27 women, and age ranged from 6 to 84 years. The most common site was the cervical lymph nodes (30 patients), with the supraclavicular nodes being the most commonly affected (60%). Histopathological examination was performed on 28 patients. TST was positive in 9 out of 9 patients and the IGRA was positive in 18 out of 19 patients. We observed concomitant PTB in 15 out of the 47 patients. Mean duration from the first visit to the final diagnosis of EPTB was 56 days. Conclusion The clinical symptoms of TB, especially those in the head and neck region, are varied. Otolaryngologists should be especially aware of the extrapulmonary manifestations of TB to ensure early diagnosis and treatment from the public health viewpoint.

Setting the Gray Zone of Near-Cutoff Values in a Real-Time PCR Test for the Detection of Mycobacterium tuberculosis in an Intermediate Burden Country.

Recently, molecular detection of Mycobacterium tuberculosis in a respiratory specimens is accepted as one of the standard procedures for diagnosis of tuberculosis in Korea. When detecting tuberculosis using a real-time polymerase chain reaction (PCR), results showed the repeated near-cutoff values in a specimen make it difficult for the laboratory to give definitive reports as positive or negative. We retrospectively evaluated clinical state of ninety-eight patients who were not currently taking antituberculosis medications and had near-cutoff values of respiratory specimens using a real-time PCR test. Sixty-eight percent of the patients had clinical tuberculosis. In subgroup analysis, patients less than the age of 50, 94.3% had tuberculosis while only 55.6% of the patients with the age of equal and over 50 had tuberculosis (p < 0.001). Setting a gray zone for real-time PCR result and give additional tailored information onto the interpretative report would be suggested for the clinical practice in an intermediate burden of tuberculosis country.

A Study on the Relapse Rate of Tuberculosis and Related Factors in Korea Using Nationwide Tuberculosis Notification Data

ObjectivesFrom the perspective of public health, tuberculosis (TB) remains an important issue that threatens health. Korea is an intermediate burden country with a TB incidence of 97/100,000 individuals. Among many TB control measures, a relapse rate of TB is one indicator that can be used to indirectly assess the level of TB control in countries and in communities. Relapse TB has an approximately 12% yearly incidence in Korea. This study aims to estimate the relapse rate of TB and to investigate the associated factors by using nationwide TB notification data in Korea. MethodsThe nationwide TB notification data in 2005 was used with the exclusion criteria of duplicated reporting, foreign-born patients, outcome–died, and outcome–diagnosis changed. The data were double-checked as to whether they were reported again during 2006–2010 and the estimated relapse rate of TB. Associated factors were analyzed by multivariate logistic regression with the variables of age, sex, registration type, results of sputum smear test, medication, and outcome of treatment. ResultsAmong 45,434 TB patients in 2005, 4,371 patients were again reported as TB patients from 2006 to 2010. Five hundred and sixty-four patients were reported more than twice and the cumulative number of relapses was 5,072 cases. The 5-year relapse rate was estimated as 9.62%. The relapse rate decreased yearly: 4.8% in 2006, 2.4% in 2007, 1.6% in 2008, 1.4% in 2009, and 1.0% in 2010. Age, sex, registration type, tuberculosis type, and medication were independently associated with a relapse of TB. In the multivariate logistic regression analysis, the following factors were related: male sex, 40–49 years old; registration type, relapse, treatment after failure, treatment after default, transfer in, and other, the sputum smear-positive pulmonary TB, and medications (including individuals taking 2–5 drugs). ConclusionThis study has estimated a 5-year relapse rate of TB in Korea that is slightly lower than the rate of relapse TB in the annual reports. This study could be conducted and cross-checked with data from the National Health Insurance in the future.

Risk of tuberculosis among healthcare workers in an intermediate-burden country: A nationwide population study

The potential association between healthcare workers (HCWs) and the risk of clinically active tuberculosis (TB) in countries with intermediate TB burdens remains unclear. A nationwide, population-based cohort study was performed by using Taiwan National Health Insurance Database during 2000-2010. We included HCWs and non-HCWs without history of tuberculosis matched at a 1:1 ratio according to age, sex, monthly income, underlying comorbidities, and concomitant medications. All subjects were followed from the date of enrollment until TB occurrence, death, or 31 December 2010. The study population comprised 11,811 healthcare workers and 11,811 matched subjects. 62 HCWs and 38 control subjects developed TB during a median follow-up period of 9.4 years. The incidence of TB was higher among HCWs than among matched subjects (61.08 vs. 37.81 per 100,000 person-years). The risk of TB was also greater among HCWs (adjusted hazard ratio [aHR], 1.62; 95% confidence interval [CI], 1.08-2.43), particularly for pulmonary TB in comparison with extrapulmonary TB (aHR, 1.56; 95% CI, 1.02-2.39). Among different job categories of HCWs, we found that only nurses had a significantly increased risk of developing TB (aHR, 2.55; 95% CI, 1.37-4.72) compared to the matched cohort. HCWs are associated independently with a higher risk of developing TB in this intermediate-burden country. Therefore, the importance of TB surveillance among HCWs should be emphasized.

GenoType® MTBDR&lt;I&gt;plus&lt;/I&gt; assay detection of drug-resistant tuberculosis in routine practice in Korea

Korea is an intermediate-burden country with high rates of tuberculosis (TB) drug resistance. To evaluate the performance of the GenoType® MTBDRplus (MTBDR) assay in diagnosing drug-resistant TB in routine practice in Korea. The MTBDR assay was performed on 428 samples, and the results were retrospectively compared with the results of conventional drug susceptibility testing (DST). The interval between treatment and diagnosis of drug resistance was also compared. The sensitivity, specificity and positive and negative predictive values of the MTBDR assay were respectively 96.6%, 98.9%, 93.4% and 99.5% for the detection of rifampicin (RMP) resistance; 93.8%, 98.3%, 92.7% and 98.6% for isoniazid (INH) resistance; and 91.1%, 99.2%, 99.4% and 98.7% for multidrug-resistant TB (MDR-TB). The median interval between the start of anti-tuberculosis chemotherapy and the reporting of results was 88.9 days for conventional DST and 19.8 days for MTBDR using clinical specimens. The specificity of the MTBDR assay in detecting MDR-TB was very high, although the sensitivity in detecting INH resistance and MDR-TB was not optimal (<95%). Although the turnaround time in detecting drug resistance was dramatically reduced with MTBDR compared to conventional DST, more effort is needed to shorten the turnaround time.

High time to tackle childhood tuberculosis

When Robert Koch published his groundbreaking paper on the aetiology of tuberculosis (TB) in 1882, he reported that about a third of the working population died of TB [1]. World TB Day today should remind us not only about the first identification of the tubercle bacillus but also that the main burden of the TB epidemic has shifted from Europe to other regions in the world. The 329,391 reported TB cases in the WHO European Region in 2009 contribute only 5.6% of all newly detected TB cases and relapses in the world, according to the latest report Tuberculosis surveillance in Europe 2009, jointly published by the European Centre for Disease Prevention and Control (ECDC) and the WHO Regional Office for Europe [2]. Furthermore a sustained decline in TB can be noted with a mean annual reduction of 3.8% between 2005 and 2009, mainly attributable to the highand intermediate-burden countries in the European Union (EU) and European Economic Area (EAA).

Utility of QuantiFERON-TB In-Tube Test for Differentiating Active Tuberculosis from Latent Tuberculosis Infection in an Intermediate Burden Country

Utility of QuantiFERON-TB In-Tube Test for Differentiating Active Tuberculosis from Latent Tuberculosis Infection in an Intermediate Burden Country