In mid-September 2019, a teenage Chinese male student and part-time waiter in Tokyo was diagnosed with multidrug-resistant (MDR) sputum smear-positive pulmonary tuberculosis (TB). This study ...describes the outbreak investigation of his friends and colleagues at the restaurant. We investigated 6 friends and 15 colleagues; 5 friends and 13 colleagues underwent interferon-γ release assay (IGRA). Of these, 3 friends (60.0%) and 4 colleagues (30.8%) were IGRA-positive. Each of the friends and colleagues was found to have MDR-TB (20% and 7.7%, respectively). Challenges during the investigation were the unavailability of regimens for latent TB infection (LTBI) for contacts with MDR-TB, budgetary constraints concerning implementing computed tomography (CT) scans for the contacts, frequent address changes of foreign-born patients and contacts, investigation during the coronavirus disease pandemic, and variations of alphabetical expression of the names of the patients and contacts, particularly for those from China. It is recommended that the national government officially adopt prophylaxis regimens for LTBI with MDR-TB, address the budgetary constraints regarding CT scans, and deploy liaison officers for coordinating investigations involving many foreign-born patients and contacts scattered in multiple municipalities. The names of foreign-born persons could more accurately be identified using both the alphabet and Chinese characters.
Abstract
Background
Increased pleural fluid adenosine deaminase (ADA) is useful for diagnosing tuberculous pleurisy (TB), but high ADA levels are associated with other diseases. In this study, we ...compare various disease characteristics in patients with high-ADA pleural effusion.
Methods
We retrospectively collected data for 456 patients with pleural fluid ADA levels of ≥ 40 U/L from January 2012 to October 2021. Cases were classified as TB (n = 203), pleural infection (n = 112), malignant pleural effusion (n = 63), nontuberculous mycobacteria (n = 22), malignant lymphoma (ML) (n = 18), autoimmune diseases (n = 11), and other diseases (n = 27), and data were compared among those diseases. Predictive factors were identified by comparing data for a target disease to those for all other diseases. A diagnostic flowchart for TB was developed based on those factors.
Results
The most frequent disease was TB, though 60.0% of patients were diagnosed with other diseases. Median ADA levels in patients with TB were 83.1 U/L (interquartile range IQR 67.2–104.1), higher than those of patients with pleural infection (median 60.9 IQR 45.3–108.0,
p
= 0.004), malignant pleural effusion (median 54.1 IQR 44.8–66.7,
p
< 0.001), or autoimmune diseases (median 48.5 IQR 45.9–58.2,
p
= 0.008), with no significant difference from NTM (
p
= 1.000) or ML (
p
= 1.000). Pleural fluid lactate dehydrogenase (LDH) levels of < 825 IU/L were beneficial for the diagnosis of TB. Neutrophil predominance or cell degeneration, white blood cell count of ≥ 9200/µL or C-reactive protein levels of ≥ 12 mg/dL helped in diagnosing pleural infection. Pleural fluid amylase levels of ≥ 75 U/L and a pleural fluid ADA/total protein (TP) ratio of < 14 helped in diagnosing malignant pleural effusion. High serum LDH and high serum/pleural fluid eosinophils helped in diagnosing ML and autoimmune diseases, respectively. The flowchart was comprised of the following three factors: pleural fluid LDH < 825 IU/L, pleural fluid ADA/TP of < 14, and neutrophil predominance or cell degeneration, which were decided by a decision tree. The diagnostic accuracy rate, sensitivity, and specificity for the diagnosis of TB were 80.9%, 78.8%, and 82.6%, respectively.
Conclusion
Cases involving high pleural fluid ADA levels should be investigated using several factors to distinguish TB from other diseases.
Nutritional status contributes to the regulation of immune responses against pathogens, and malnutrition has been considered as a risk factor for tuberculosis (TB). Mycobacterium tuberculosis (Mtb), ...the causative agent of TB, can modulate host lipid metabolism and induce lipid accumulation in macrophages, where the bacilli adopt a dormant phenotype. In addition, serum lipid components play dual roles in the regulation of and protection from Mtb infection. We analyzed the relationship between nutritional status and the humoral immune response in TB patients. We found that serum HDL levels are positively correlated with the serum IgA specific for Mtb antigens. Analysis of the relationship between serum nutritional parameters and clinical parameters in TB patients showed that serum albumin and CRP levels were negatively correlated before treatment. We also observed reduced serum LDL levels in TB patients following treatment. These findings may provide insight into the role of serum lipids in host immune responses against Mtb infection. Furthermore, improving the nutritional status may enhance vaccination efficacy.
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Most people infected with
(
) are believed to be in a state of latent tuberculosis (TB) infection (LTBI). Although LTBI is asymptomatic and not infectious, there is a risk of developing active ...disease even decades after infection. Here, to characterize mutations acquired during LTBI, we collected and analyzed
genomes from seven Japanese patient pairs, each pair consisting of two active TB patients whose starting dates of developing active disease were >3 years apart; one had a high suspicion of LTBI before developing active disease, whereas the other did not. Thereafter, we compared these genomes with those of longitudinal sample pairs within a host of chronic active TB infections combined with public data. The bacterial populations in patients with LTBI were genetically more homogeneous and accumulated single nucleotide polymorphisms (SNPs) slower than those from active disease. Moreover, the lower proportion of nonsynonymous SNPs indicated weaker selective pressures during LTBI than active disease. Finally, the different mutation spectrums indicated different mutators between LTBI and active disease. These results suggest that the likelihood of the acquisition of mutations responsible for antibiotic resistance and increased virulence was lower in the
population from LTBI than active disease.IMPORTANCEControlling latent tuberculosis (TB) infection (LTBI) activation is an effective strategy for TB elimination, where understanding
(
) dynamics within the host plays an important role. Previous studies on chronic active disease reported that
accumulated genomic mutations within the host, possibly resulting in acquired drug resistance and increased virulence. However, several reports suggest that fewer mutations accumulate during LTBI than during the active disease, but the associated risk is largely unknown. Here, we analyzed the genomic dynamics of
within the host during LTBI. Our results statistically suggest that
accumulates mutations during LTBI, but most mutations are under low selective pressures, which induce mutations responsible for drug resistance and virulence. Thus, we propose that LTBI acts as a source for new TB disease rather than as a period for in-host genome evolution.
Multidrug resistant-tuberculosis (MDR-TB) is a major global health concern. Its treatment requires toxic medications, is longer and costlier than drug-susceptible TB, and often results in ...productivity losses and poor outcomes. In Japan, a TB middle-burden country, reports on treatment outcome of MDR-TB patients have only been institution-based. We thus sought to shed some light on the nationwide treatment status and outcome of MDR-TB patients in Japan.
Characteristics and treatment status and outcome of MDR-TB patients notified between 2011 and 2013 were evaluated using the data from the Japan TB Surveillance (JTBS) system. Since the treatment outcome from the surveillance data was not directly linked to any clinical records or drug susceptible test results, we also analyzed the treatment duration of MDR-TB cases in an attempt to validate our results.
Between 2011 and 2013, a total of 172 MDR-TB patients had been notified to the JTBS as MDR-TB. 68.6% (118/172) were males and 70.9% (122/172) were Japan-born - however, over the study period, the proportions of foreign-born, of those in the age group 15-64 years old and of new cases have increased. The overall treatment completion rate was 57.0%, however, when restricted to patients aged 64 years old and below, the rate improved to 71.6%. Treatment duration of 29.2% of those patients who had been recorded as "treatment completed" in fact fell short of the 540 days, the minimum duration as recommended by the Japanese guideline.
Increasing proportion of new cases, and of younger age groups among the MDR-TB patients indicate new transmissions. Better strategies for early detection and containment of MDR-TB are urgently needed. The overall treatment completion rate was 57.0% over the three-year study period. However, when restricting the result to those aged 64 years old and below, the rate improved to 71.6%, which was comparable to similarly industrialized countries. Due to the limitations of the JTBS data, a comprehensive survey of all MDR-TB patients may be necessary to provide more concrete evidence for decision-making.
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The Western Pacific Region has one of the fastest-growing populations of older adults (≥ 65 years) globally, among whom tuberculosis (TB) poses a particular concern. This study reports country case ...studies from China, Japan, the Republic of Korea, and Singapore reflecting on their experiences in managing TB among older adults.
Across all four countries, TB case notification and incidence rates were highest among older adults, but clinical and public health guidance focused on this population was limited. Individual country reports illustrated a range of practices and challenges. Passive case finding remains the norm, with limited active case finding (ACF) programs implemented in China, Japan, and the Republic of Korea. Different approaches have been trialled to assist older adults in securing an early diagnosis, as well as adhering to their TB treatment. All countries emphasised the need for person-centred approaches that include the creative application of new technology and tailored incentive programs, as well as reconceptualisation of how we provide treatment support. The use of traditional medicines was found to be culturally entrenched among older adults, with a need for careful consideration of their complementary use. TB infection testing and the provision of TB preventive treatment (TPT) were underutilised with highly variable practice.
Older adults require specific consideration in TB response policies, given the burgeoning aging population and their high TB risk. Policymakers, TB programs and funders must invest in and develop locally contextualised practice guidelines to inform evidence-based TB prevention and care practices for older adults.
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Linezolid (LZD) is classified as a WHO group 5 drug used in the treatment of tuberculosis (TB). Although its efficacy and long-term safety have not yet been established, it is being increasingly used ...in the treatment of multidrug resistant tuberculosis (MDR-TB) and extensive multidrug-resistant tuberculosis (XDR-TB). The current study is a single-center retrospective clinical analysis of hospitalized M/XDR-TB patients in Fukujuji Hospital involving 26 patients (18 men and 8 women) consecutively treated with combinations of anti-TB drugs including LZD from 2009 to 2015. The sputum culture results were negative after using LZD for an average period of 28.0 ± 12.0 (average ± SD) days. LZD was reduced or withdrawn in 11 cases due to adverse effects. Nineteen cases including 3 XDR-TB patients were operated on, and their TB was treated following surgery. The average time from the initiation of LZD therapy to surgery was 87.6 ± 38.7 (average ± SD) days. Favorable clinical outcome was maintained in 23 surviving patients, while 3 patients died during treatment because of end stage cancer and aspiration pneumonia. Our study showed that LZD might be clinically effective in the treatment of M/XDR-TB patients in Japan.
An 84-year-old woman visited our hospital for dyspnea due to right pleural effusion, with lymphocytic dominance and a high adenosine deaminase (ADA) level, that had been noted 1 month earlier. She ...was suspected of having tuberculosis pleurisy; however, anti-tuberculosis treatment yielded no improvements. She was diagnosed with pleural effusion due to primary Sjögren's syndrome (SjS) based on her dry eyes and mouth, positivity for anti-Sjögren's-syndrome-related antigen A/B, and histopathologic findings of a lip biopsy and thoracoscopic pleural biopsy. Her symptoms improved after starting steroid therapy. Cases of pleural effusion due to SjS with a high ADA level may be misdiagnosed as tuberculosis pleurisy.
Abstract
Background
Respiratory symptoms are associated with coronavirus disease 2019 (COVID-19) outcomes. However, the impacts of upper and lower respiratory symptoms on COVID-19 outcomes in the ...same population have not been compared. The objective of this study was to characterize upper and lower respiratory symptoms and compare their impacts on outcomes of hospitalized COVID-19 patients.
Methods
This was a multicenter, retrospective cohort study; the database from the Japan COVID-19 Task Force was used. A total of 3314 COVID-19 patients were included in the study, and the data on respiratory symptoms were collected. The participants were classified according to their respiratory symptoms (Group 1: no respiratory symptoms, Group 2: only upper respiratory symptoms, Group 3: only lower respiratory symptoms, and Group 4: both upper and lower respiratory symptoms). The impacts of upper and lower respiratory symptoms on the clinical outcomes were compared. The primary outcome was the percentage of patients with poor clinical outcomes, including the need for oxygen supplementation via high-flow oxygen therapy, mechanical ventilation, and extracorporeal membrane oxygenation or death.
Results
Of the 3314 COVID-19 patients, 605, 1331, 1229, and 1149 were classified as Group 1, Group 2, Group 3, and Group 4, respectively. In univariate analysis, patients in Group 2 had the best clinical outcomes among all groups (odds ratio OR: 0.21, 95% confidence interval CI: 0.11–0.39), while patients in Group 3 had the worst outcomes (OR: 3.27, 95% CI: 2.43–4.40). Group 3 patients had the highest incidence of pneumonia, other complications due to secondary infections, and thrombosis during the clinical course.
Conclusions
Upper and lower respiratory tract symptoms had vastly different impacts on the clinical outcomes of COVID-19.
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The severity of chest X-ray (CXR) findings is a prognostic factor in patients with coronavirus disease 2019 (COVID-19). We investigated the clinical and genetic characteristics and prognosis of ...patients with worsening CXR findings during early hospitalization. We retrospectively included 1656 consecutive Japanese patients with COVID-19 recruited through the Japan COVID-19 Task Force. Rapid deterioration of CXR findings was defined as increased pulmonary infiltrates in ≥ 50% of the lung fields within 48 h of admission. Rapid deterioration of CXR findings was an independent risk factor for death, most severe illness, tracheal intubation, and intensive care unit admission. The presence of consolidation on CXR, comorbid cardiovascular and chronic obstructive pulmonary diseases, high body temperature, and increased serum aspartate aminotransferase, potassium, and C-reactive protein levels were independent risk factors for rapid deterioration of CXR findings. Risk variant at the ABO locus (rs529565-C) was associated with rapid deterioration of CXR findings in all patients. This study revealed the clinical features, genetic features, and risk factors associated with rapid deterioration of CXR findings, a poor prognostic factor in patients with COVID-19.
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