Epidemiologic evaluation of pulmonary paragonimiasis in Japan using a Japanese nationwide administrative database.

BACKGROUND: Paragonimiasis is a parasitic disease primarily contracted through consumption of undercooked freshwater crustaceans or wild boar meat. Large-scale nationwide epidemiological data on paragonimiasis are lacking. In this study, we aimed to investigate the nationwide epidemiology of hospitalized patients with paragonimiasis in Japan using a comprehensive nationwide Japanese administrative database. METHODS: We evaluated the Japanese Diagnosis Procedure Combination (DPC) data of patients diagnosed with pulmonary paragonimiasis between April 1, 2012 and March 30, 2020. The patients' address and information, including age, sex, treatment (medication: praziquantel; surgery: open thoracotomy or intracranial mass extirpation), Japan coma scale, comorbidities, and length of hospital stay, were extracted. RESULTS: Of the 49.6 million hospitalized patients, data were extracted on 73 patients with paragonimiasis, of whom 36 were male and 37 were female. The mean age was 49.7 years and the mean length of stay was 12.5 days. The most frequent comorbidity was pleural effusion (31.5 %), followed by pneumothorax (13.7 %). The sites of ectopic paragonimiasis in organs other than the lung included the liver (5.5 %), skin (4.1 %), and brain (2.7 %). Geographically, most patients were from the Kyushu region (54.8 %), followed by the Kanto region (22.0 %). Fukuoka Prefecture had the highest number of patients (22.0 %) by prefecture. During the study period, an average of 9.1 patients/year were hospitalized with lung paragonimiasis in Japan. CONCLUSION: Paragonimiasis has not completely disappeared in Japan; thus, physicians should be aware of paragonimiasis in the Kyushu region, especially in the Fukuoka Prefecture.

Sarcoidosis Associated with Enlarged Mediastinal Lymph Nodes with the Detection of Streptococcus gordonii and Cutibacterium acnes Using a Clone Library Method.

A 77-year-old Japanese woman with mediastinal lymphadenopathy and uveitis was diagnosed with sarcoidosis. The bacterial flora in biopsied samples from mediastinal lymph nodes was analyzed using a clone library method with Sanger sequencing of the 16S rRNA gene, and Streptococcus gordonii (52 of 71 clones) and Cutibacterium acnes (19 of 71 clones) were detected. No previous study has conducted a bacterial floral analysis using the Sanger method for the mediastinal lymph node in sarcoidosis, making this case report the first to document the presence of S. gordonii and C. acnes in the mediastinal lymph node of a patient with sarcoidosis.

A case of idiopathic multicentric Castleman's disease with secondary autoimmune neutropenia.

A 73-year-old Japanese woman with productive cough and dyspnoea on exertion was admitted, and she showed neutropenia and pulmonary reticular opacities and axial and mediastinal lymphadenopathies on chest computed tomography. The clinical findings and surgical lung and lymph node biopsies were diagnostic for idiopathic multicentric Castleman's disease (iMCD) complicated by secondary autoimmune neutropenia (AIN). iMCD is often complicated with hematologic disorders, however, iMCD complicated with AIN has not been reported; therefore, if iMCD is accompanied by neutropenia, the anti-neutrophil antibodies should be measured.

Nationwide surveillance of bacterial respiratory pathogens conducted by the surveillance committee of the Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2019-2020: General view of the pathogens' antibacterial susceptibility.

The trends and prevalence of antimicrobial susceptibility of pathogens vary by country, region, and time. Long-term regular surveillance is required to investigate trends in the antimicrobial resistance of various isolated bacterial pathogens. We report the results of a nationwide surveillance on the antimicrobial susceptibility of bacterial respiratory pathogens in Japan conducted by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology. The isolates were collected from clinical specimens obtained from adult patients who visited a collaborating medical facility between June 2019 and December 2020 and were diagnosed with respiratory tract infections by a physician. Antimicrobial susceptibility testing was performed in a centralized laboratory according to the methods recommended by the Clinical and Laboratory Standards Institute. Susceptibility testing was performed for 932 strains (201 Staphylococcus aureus, 158 Streptococcus pneumoniae, 6 S. pyogenes, 136 Haemophilus influenzae, 127 Moraxella catarrhalis, 141 Klebsiella pneumoniae, and 163 Pseudomonas aeruginosa) collected from 32 facilities in Japan. The proportions of methicillin-resistant S. aureus and penicillin-resistant S. pneumoniae were 35.3% and 0%, respectively. In H. influenzae, 16.2% and 16.9% were ß-lactamase-producing ampicillin resistant and ß-lactamase-negative ampicillin resistant, respectively. Extended-spectrum ß-lactamase-producing K. pneumoniae accounted for 5.0% of all K. pneumoniae infections. Carbapenemase-producing K. pneumoniae and multi-drug-resistant P. aeruginosa with metallo-ß-lactamase were not detected in this study. This surveillance will be a useful reference for treating respiratory infections in Japan and will provide evidence to enhance the appropriate use of antimicrobial agents.

Reduced phagocytic activity of human alveolar macrophages infected with Mycobacterium avium complex.

INTRODUCTION: Co-infection of nontuberculous mycobacteria (NTM) with other bacteria is associated with increased frequency of hospitalization and reduced quality of life. However, the clinical significance of co-infection with NTM and other bacteria remains unclear. Here, we investigated the distribution of alveolar macrophage populations, characterized their phagocytic function in bronchoalveolar lavage fluid (BALF), and assessed the bactericidal function of macrophages infected with NTM using cell lines. METHODS: BALF samples were prospectively obtained from 30 patients with suspected NTM lung disease to evaluate phagocytic activities of macrophages using immunostaining. Bactericidal activities of Staphylococcus aureus (S. aureus) and Mycobacterium intracellulare (M. intracellulare)-infected or -non-infected macrophages were evaluated using macrophage cell lines. RESULTS: Eleven patients with Mycobacterium avium complex (MAC) infection and 19 patients with chronic lower respiratory tract infections except for NTM infection (controls) were enrolled. The percentage of non-polarized (HLA-DR+, CD40-, and CD163-) macrophages in patients infected with MAC was significantly higher than that in controls; non-polarized macrophages demonstrated an impaired ability to phagocytose S. aureus. In vitro experiments revealed higher intracellular S. aureus colony-forming unit counts and proinflammatory cytokine levels in M. intracellulare-infected macrophages than in non-NTM-infected macrophages. Electron microscopy showed morphologically damaged macrophages and M. intracellulare and S. aureus growing in the same phagosome. CONCLUSION: The proportion of alveolar macrophages (HLA-DR+, CD40-, and CD163-) with impaired phagocytosis increased in MAC-infected individuals. M. intracellulare-infected macrophages reduced bactericidal activity in vitro. Dysfunction of alveolar macrophages may contribute to persistent infection by other bacteria, leading to MAC lung disease progression.

Comparative study of bacterial flora in bronchoalveolar lavage fluid of pneumonia patients based on their pneumonia subtypes and comorbidities using 16S ribosomal RNA gene analysis.

INTRODUCTION: The culture method is the gold standard for identifying pathogenic bacteria in patients with pneumonia but often does not reflect the exact bacterial flora in pulmonary lesions of pneumonia, partly owing to easiness or difficulties in culturing certain bacterial species. We aimed to evaluate bacterial flora in bronchoalveolar lavage fluid (BALF) samples directly obtained from pneumonia lesions using 16S ribosomal RNA (rRNA) gene analysis to compare the results of the BALF culture method in each category of pneumonia. METHODS: Bacterial florae were detected by a combination of the culture method, and the clone library method using the 16S rRNA gene sequencing in BALF directly obtained from pneumonia lesions in pneumonia patients from April 2010 to March 2020 at the University of Occupational and Environmental Health, Japan, and affiliated hospitals. Clinical information of these patients was also collected, and lung microbiome was evaluated for each pneumonia category. RESULTS: Among 294 pneumonia patients (120 with community-acquired pneumonia (CAP), 101 with healthcare-associated pneumonia (HCAP), and 73 with hospital-acquired pneumonia (HAP)), significantly higher percentages of obligate anaerobes were detected in CAP than in HCAP and HAP patients by the clone library method. Corynebacterium species were significantly highly detected in HAP patients and patients with cerebrovascular diseases than in patients without, and Streptococcus pneumoniae was frequently detected in patients with diabetes mellitus. CONCLUSION: Obligate anaerobes may be underestimated in patients with CAP. Corynebacterium species should be regarded as the causative bacteria for pneumonia in patients with HAP and cerebrovascular diseases.

Combined Radiographic Features and Age Can Distinguish Mycoplasma pneumoniae Pneumonia from Other Bacterial Pneumonias: Analysis Using the 16S rRNA Gene Sequencing Data.

The study objective was to evaluate chest radiographic features that distinguish Mycoplasma pneumoniae pneumonia (MPP) from other bacterial pneumonias diagnosed based on the bacterial floral analysis with 16S rRNA gene sequencing, using bronchoalveolar lavage fluid samples directly obtained from pneumonia lesions. Patients were grouped according to the dominant bacterial phenotype; among 120 enrolled patients with CAP, chest CT findings were evaluated in 55 patients diagnosed with a mono-bacterial infection (one bacterial phylotype occupies more than 80% of all phylotypes in a sample) by three authorized respiratory physicians. Among this relatively small sample size of 55 patients with CAP, 10 had MPP, and 45 had other bacterial pneumonia and were categorized into four groups according to their predominant bacterial phylotypes. We created a new scoring system to discriminate MPP from other pneumonias, using a combination of significant CT findings that were observed in the M. pneumoniae group, and age (<60 years) (MPP−CTA scoring system). When the cutoff value was set to 1, this scoring system had a sensitivity of 80%, a specificity of 93%, a positive predictive value of 73%, and a negative predictive value of 95%. Among the CT findings, centrilobular nodules were characteristic findings in patients with MPP, and a combination of chest CT findings and age might distinguish MPP from other bacterial pneumonias.

Severe infectious acute respiratory failure mimicking COVID-19 in a healthy adolescent.

A 15-year-old male presented with headache, high fever and respiratory distress. Chest computed tomography showed bilateral pneumonia, and antimicrobial therapy was initiated. However, his respiratory condition deteriorated, and he developed respiratory failure requiring intubation. A multiplex polymerase chain reaction (PCR) test and 16S ribosomal RNA gene analysis were done from his intratracheal secretions to determine the causative pathogens, and Mycoplasma pneumoniae was detected. He was treated with appropriate antimicrobial therapy, systemic corticosteroid therapy and extracorporeal membrane oxygenation. He also presented with pulmonary thromboembolism and was treated with anticoagulants, to which he responded well. This patient demonstrates the similarities between severe M. pneumoniae pneumonia with bilateral pneumonitis and thrombosis, and severe coronavirus disease 2019. Therefore, it is important to identify cases of bilateral pneumonia with severe respiratory dysfunction using multiplex PCR tests to provide appropriate medical management and therapeutic interventions.

Epidemiologic evaluation of pleurisy diagnosed by surgical pleural biopsy using data from a nationwide administrative database.

BACKGROUND: Pleural biopsies for investigating the causes of pleurisy are performed through modalities including needle biopsies, local anesthetic thoracoscopic procedures, and surgery (video-assisted thoracoscopic surgery and open thoracotomy). To date, there have been no large-scale nationwide epidemiological studies regarding pleurisy diagnosed via surgical pleural biopsy. This study examined the epidemiology of pleurisy diagnosed via surgical pleural biopsy in a Japanese nationwide administrative database. METHODS: We evaluated Japanese Diagnosis Procedure Combination data of 24 173 patients who underwent video-assisted thoracoscopic surgery or open thoracotomy and received a diagnosis of pleurisy between April 2014 and March 2020. In addition to pleurisy diagnoses, the patients' clinical information, including age, sex, smoking status (pack-years), dyspnea grade, length of in-hospital stay, and comorbidities, were extracted from the dataset. RESULTS: This study included data from 1699 patients. The most frequent causes of pleurisy were neoplastic diseases (55.9%; malignant mesothelioma 22.5%, lung cancer 15.7%, lymphoma 2.5%), followed by infectious diseases (24.0%; tuberculosis 16.2%, parapneumonic pleural effusion 3.6%, empyema 3.5%, nontuberculous mycobacteriosis 0.5%), collagen vascular diseases (2.8%; rheumatoid arthritis 1.3%, immunoglobulin G4-related diseases 0.7%, systemic lupus erythematosus 0.3%), and paragonimiasis (0.1%). CONCLUSIONS: Neoplastic diseases, including malignant mesothelioma and lung cancer, were frequently and accurately diagnosed as pleurisy via surgical pleural biopsy. The next leading cause was infectious diseases such as mycobacterial infections. Physicians should consider performing surgical biopsy in light of the knowledge regarding the etiology of pleurisy when a definitive diagnosis cannot be made via needle pleural biopsy.

Refinement of microbiota analysis of specimens from patients with respiratory infections using next-generation sequencing.

Next-generation sequencing (NGS) technologies have been applied in bacterial flora analysis. However, there is no standardized protocol, and the optimal clustering threshold for estimating bacterial species in respiratory infection specimens is unknown. This study was conducted to investigate the optimal threshold for clustering 16S ribosomal RNA gene sequences into operational taxonomic units (OTUs) by comparing the results of NGS technology with those of the Sanger method, which has a higher accuracy of sequence per single read than NGS technology. This study included 45 patients with pneumonia with aspiration risks and 35 patients with lung abscess. Compared to Sanger method, the concordance rates of NGS technology (clustered at 100%, 99%, and 97% homology) with the predominant phylotype were 78.8%, 71.3%, and 65.0%, respectively. With respect to the specimens dominated by the Streptococcus mitis group, containing several important causative agents of pneumonia, Bray Curtis dissimilarity revealed that the OTUs obtained at 100% clustering threshold (versus those obtained at 99% and 97% thresholds; medians of 0.35, 0.69, and 0.71, respectively) were more similar to those obtained by the Sanger method, with statistical significance (p < 0.05). Clustering with 100% sequence identity is necessary when analyzing the microbiota of respiratory infections using NGS technology.

Association between obligatory anaerobes and empyema caused by Streptococcus anginosus group bacteria.

Co-infections of Streptococcus anginosus group (SAG) bacteria and obligate anaerobes are observed in patients with empyema; however, their epidemiology and pathology remain unknown. A retrospective study was performed with 44 patients who underwent pleural effusion microbiota evaluation between January 2006 and March 2018, using the clone library method for detecting empyema caused by SAG bacteria. Based on culture analysis of pleural effusion, 12 patients were diagnosed with empyema caused by SAG bacteria. Obligate anaerobe phylotypes were detected in eight patients (66.7%) using the clone library method, whereas anaerobic culture analysis detected anaerobes in only two patients (16.7%). No significant difference was observed between the clinical features of SAG-mediated empyema with and without anaerobes using the clone library method, except for chest computed tomographic data. Co-infection of SAG bacteria and obligate anaerobes may be underestimated if conventional culture methods are used. SAG-mediated empyema with and without anaerobes may present different radiological features; therefore, further studies are required.

A human respiratory tract-associated bacterium with an extremely small genome.

Recent advances in culture-independent microbiological analyses have greatly expanded our understanding of the diversity of unculturable microbes. However, human pathogenic bacteria differing significantly from known taxa have rarely been discovered. Here, we present the complete genome sequence of an uncultured bacterium detected in human respiratory tract named IOLA, which was determined by developing a protocol to selectively amplify extremely AT-rich genomes. The IOLA genome is 303,838 bp in size with a 20.7% GC content, making it the smallest and most AT-rich genome among known human-associated bacterial genomes to our best knowledge and comparable to those of insect endosymbionts. While IOLA belongs to order Rickettsiales (mostly intracellular parasites), the gene content suggests an epicellular parasitic lifestyle. Surveillance of clinical samples provides evidence that IOLA can be predominantly detected in patients with respiratory bacterial infections and can persist for at least 15 months in the respiratory tract, suggesting that IOLA is a human respiratory tract-associated bacterium.

A fatal case of COVID-19-associated invasive pulmonary aspergillosis.

A 79-year-old Japanese man with polymyalgia rheumatica was admitted to hospital with coronavirus disease (COVID-19). On admission, he was treated with ciclesonide inhalation, ivermectin, and meropenem. He was intubated 6 days after admission, and methylprednisolone therapy was initiated (1000 mg/day). Hypoxemia and chest radiographic findings temporarily improved. However, chest computed tomography showed bilateral ground-glass attenuations, multiple nodules, and consolidation. Aspergillus fumigatus was cultured from the tracheal aspirate and he was diagnosed with COVID-19-associated invasive pulmonary aspergillosis (CAPA) and treated with liposomal amphotericin B. However, he died 28 days after admission.

Pseudoaneurysm after total arch replacement mimicking malignant lymphadenopathy.

Pseudoaneurysm should be considered in the differential diagnosis when the computed tomography (CT) findings show a mediastinal mass in patients with a history of cardiovascular surgery even if such surgery occurred over two decades previously.

A Case of Pulmonary Infectious Bulla Caused by Mycobacterium Avium.

A 37-year-old Japanese man presented with a bulla with niveau-like opacity in the right upper lung on chest radiography. Air-fluid level gradually increased despite broad-spectrum antibiotic therapy. Right upper lobectomy was performed, and epithelioid granuloma with mycobacteria was histopathologically observed. Bacterial culture of the fluid was negative, but mycobacterial culture was positive for Mycobacterium avium; therefore, the patient was diagnosed with pulmonary infected bulla caused by Mycobacterium avium. He was further treated with antimycobacterial agents after resection of the infected bulla. To our knowledge, this is the first report of pulmonary infected bulla caused by only Mycobacterium avium in the English literature.

Coinfection With Multiple Nontuberculous Mycobacteria as a Possible Exacerbating Factor in Pulmonary Nontuberculous Mycobacteriosis: Clone Library Analysis Using the 16S Ribosomal RNA Gene.

BACKGROUND: Mycobacterial culture is the gold standard for the diagnosis of nontuberculous Mycobacterium (NTM) infections. However, this method is not suitable for detection of coinfection with different NTMs. RESEARCH QUESTION: The goal of this study was to determine if clone library analysis of BAL fluid (BALF) was useful for detection of NTM phylotypes, including multiple NTM phylotypes, in pulmonary NTM infections. STUDY DESIGN AND METHODS: BALF samples obtained from 120 patients with suspected pulmonary NTM infections were retrospectively evaluated by using the mycobacterial culture and clone library methods between July 2010 and August 2016. RESULTS: In total, 55 (45.8%) patients were diagnosed as NTM positive according to results of mycobacterial culture, and 52 patients were NTM positive as determined by using the clone library method. Furthermore, 45 (86.5%) and seven (13.5%) patients exhibited a single phylotype (mono-phylotype group) and multiple phylotypes of NTM (multi-phylotype group), respectively. Compared with the mono-phylotype group, the multi-phylotype group had a significantly higher incidence of adverse chest CT findings (P = .048). In addition, 11 patients who were NTM negative according to results of BALF mycobacterial culture were determined to be NTM positive according to the clone library method. Six of these 11 patients were eventually diagnosed as NTM positive by using mycobacterial culture results within 6.2 ± 2.1 months following the initial sample collection. INTERPRETATION: Coinfection multiple phylotypes could be associated with adverse clinical findings. In addition, patients who test positive for NTM genes but negative for mycobacterial culture may be diagnosed with NTM lung infection within 1 year of the initial sample collection. Further follow-up of these patients may facilitate early detection of NTM species.

Poor oral hygiene is associated with the detection of obligate anaerobes in pneumonia.

BACKGROUND: Oral cavity is a reservoir of various respiratory pathogens, and poor oral hygiene is associated with an increase in anaerobic bacteria in oral cavity. In addition, it positively relates higher risk of developing pneumonia and increased pneumonia-related mortality. However, the association between poor oral hygiene and increase in obligate anaerobes in the lungs of pneumonia patients is unclear. METHODS: A total of 39 patients with pneumonia in whom bronchoscopic examination and oral hygiene evaluation were performed were prospectively enrolled. The microbiota of the bronchoalveolar lavage fluid (BALF) directly obtained from the pneumonia lesion was analysed by the clone library analysis. In addition, oral hygiene evaluations were performed using oral hygiene index (OHI), tongue coating score, oral dryness, and community periodontal index of treatment needs (CPITN). The association between the detection of oral streptococci and obligate anaerobes and oral hygiene status was evaluated. RESULTS: Using the clone library analysis of BALF, the phylotypes of oral streptococci and obligate anaerobes were detected in 31 (79.5%) and 26 (66.7%) patients, respectively. Increased oral dryness, OHI, and CPITN, but not the tongue coating score, significantly correlated with higher rate of detection of obligate anaerobes, although no significant associations between the detection of oral streptococci in the lungs and each oral hygiene evaluation were observed. Significantly higher number of obligate anaerobes were detected in the lungs in patients with total oral hygiene score of ≥ 5 (P = 0.008). CONCLUSION: Poor oral hygiene is associated with increased obligate anaerobes in the lungs of patients with pneumonia.

Pulmonary Mycobacterium parascrofulaceum Infection in a Patient with Chronic Progressive Pulmonary Aspergillosis: A Case Report and Literature Review.

A 67-year-old man with a pulmonary cavity was admitted to our hospital. Mycobacterial culture of the bronchoalveolar lavage fluid sample obtained from the right upper pulmonary lesion tested positive for mycobacterium, and sequencing of the 16S rRNA genes, hsp65, and rpoB revealed that the cultured mycobacterium was Mycobacterium parascrofulaceum. Treatment with antimycobacterial agents was ineffective, and repeated culturing of bronchoscopic specimens revealed that the specimens were positive for Aspergillus fumigatus. Combination treatment of antimycobacterial agents and voriconazole improved the lung lesion. This is the first report of a patient with pulmonary M. parascrofulaceum infection complicated with chronic progressive pulmonary aspergillosis.

[Evaluation of the Influence of the Experience and Training of EBUS-TBNA on Diagnostic Rate and Safety].

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been widely used in Japan. The guidelines of the American College of Chest Physicians has recommended that EBUS-TBNA should be performed by well-trained operators who can perform highly accurate procedures, but the indicators of the degree of experience and training are unclear. In our department, physicians who do not have enough experience perform EBUS-TBNA under the supervision of bronchoscopic instructors who have EBUS-TBNA techniques (Board Certified Member of the Japan Society for Respiratory Endoscopy) after guidance and training in EBUS-TBNA using a simulator as an operator and helper. In order to evaluate the influence of the experience and training of EBUS-TBNA on diagnostic accuracy and safety, we retrospectively compared the diagnostic accuracy and safety of EBUS-TBNA performed by physicians within one year of experience of EBUS-TBNA and those performed by physicians with more than one year of experience. A total of 111 cases (148 lesions) who were eventually diagnosed as having primary lung cancer and underwent EBUS-TBNA in our department between April 2014 and January 2016 were divided into two groups. Group A (43 cases, 57 lesions) was examined by third-year doctors within one year of experience of EBUS-TBNA, and group B (68 cases, 91 lesions) was examined by doctors with four or more years of experience and with more than one year of experience of EBUS-TBNA. Diagnostic rate, examination time, and complications were evaluated. There were no significant differences between the two groups in the diagnostic rate (A, 89.5% vs. B, 90.1%, P = 1.0) or examination time (A, 27 min vs. B, 23 min, P = 0.149), and no complications were observed in either group. This study suggests that even less-experienced physicians may safely perform EBUS-TBNA as well as moderately-experienced physicians with more than 1 year experience of EBUS-TBNA with similar diagnostic rates when proper training and supervision are supplied.