Transmission dynamics variability of lineage 2 Mycobacterium tuberculosis strains in Kobe, Japan, determined using population-based whole-genome sequencing analysis.

Currently, tuberculosis (TB) in Japan is highly prevalent among elderly patients who were born during a time when TB was highly prevalent. Mycobacterium tuberculosis (Mtb) lineage 2 (L2) is the predominant strain in the country. Moreover, the proportion of foreign-born patients with TB has been increasing. This epidemiological situation in Japan motivated us to explore the heterogeneity in transmission dynamics among the sublineages of Mtb L2 within this aging population. For this purpose, we conducted a population-based whole genome sequencing analysis of 550 Mtb strains in Kobe, Japan, and employed pairwise single nucleotide polymorphism (SNP) distance clustering and terminal branch length (TBL) distribution analysis to assess Mtb transmission. The genomic clustering rate with a threshold of ≤5 SNPs was significantly lower in elderly patients aged 70 years or higher than in non-elderly patients. The elderly patient group showed significantly longer TBL than the non-elderly group. These results supported the notion that reactivation of distant infection is a major driving force for the high incidence of TB in elderly individuals. The age group distribution and frequency of lineages/sublineages were found to significantly differ between foreign-born and Japan-born patients. The increased proportion of foreign-born patients might have resulted in more strain diversity in Japan. The L2.2.A sublineage demonstrated a significant association with elderly patients and exhibited lower transmission rates, which indicate to be prone to reactivate from long-term latency. In contrast, L2.2.Modern, showed a strong association with younger and foreign-born patients. This sublineage showed a high genomic cluster rate, suggesting its high transmissibility. The other three major sublineages, namely L2.2.AA2, L2.2.AA3.1, and L2.2.AA3.2, exhibited a consistent increase in cluster rates across varying SNP thresholds, indicating their relatively recent emergence as endemic sublineages in Japan. In conclusion, this study highlights distinct differences in the transmission dynamics of L2 sublineages within an aging society.

Clinical outcomes of COVID-19 caused by the Alpha variant compared with one by wild type in Kobe, Japan. A multi-center nested case-control study.

OBJECTIVES: The emergence of the Alpha variant of novel coronavirus 2019 (SARS-CoV-2) is a concerning issue but their clinical implications have not been investigated fully. METHODS: We conducted a nested case-control study to compare severity and mortality caused by the Alpha variant (B.1.1.7) with the one caused by the wild type as a control from December 2020 to March 2021, using whole-genome sequencing. 28-day mortality and other clinically important outcomes were evaluated. RESULTS: Infections caused by the Alpha variant were associated with an increase in the use of oxygen (43.4% vs 26.3%. p = 0.017), high flow nasal cannula (21.2% vs 4.0%, p = 0.0007), mechanical ventilation (16.2% vs 6.1%, p = 0.049), ICU care (30.3% vs 14.1%, p = 0.01) and the length of hospital stay (17 vs 10 days, p = 0.031). More patients with the Alpha variant received medications such as dexamethasone. However, the duration of each modality did not differ between the 2 groups. Likewise, there was no difference in 28-day mortality between the 2 groups (12% vs 8%, p = 0.48), even after multiple sensitivity analyses, including propensity score analysis. CONCLUSION: The Alpha variant was associated with a severe form of COVID-19, compared with the non-Alpha wild type, but might not be associated with higher mortality.

[Evaluation of the flu call center and medical system data on pandemic (H1N1) 2009 influenza. Comparison of cases in Kobe city and Ibaraki prefecture].

OBJECTIVES: To make recommendations on the revision of the Pandemic Influenza National Action Plan and Guidelines, we reviewed the data from the flu call center and medical institutions in Kobe city and compared them with data from Ibaraki prefecture. METHODS: The overall duration of study from May 2009 to December 2009 was divided into 4 periods; we analyzed details of the calls received by the call center and examined the correlation between them and cases who were seen at medical institutions in Kobe. We used a mathematical model to approximate the cumulative growth curve of the number of calls received by the call center and the number of cases attending fever clinics in Kobe. We compared the above data with data from Ibaraki because the total number of confirmed cases of pandemic (H1N1) 2009 influenza was similar: Kobe identified the first confirmed case of the influenza in Japan, while Ibaraki reported their first case 1 month later. RESULTS: Following the report of the initial domestic case, the Kobe call center received 30,067 calls in a month. A "delayed sigmoid curve" fitted well for both the rise in the number of calls at the call center and of cases attending the fever clinics. "Feeling sick despite no overseas travel history" was the most common reason for call. More than 2,000 calls/day were received, and the responses to such calls were instructions to consult a general medical institution (40%), instructions to refer to a fever clinic (8%), guidance on home care or how to manage underlying disorders, and listening to callers' anxieties and complaints. The numbers of calls decreased towards the end ofJuly; the number of calls increased again when outbreaks were reported in schools and a death due to influenza was confirmed. After November, on an average, 500 calls/day were received; most were complaints regarding vaccination. Unlike Kobe, Ibaraki did not experience a surge in the number of calls to the call center or consultations to fever clinics within a short period of time. CONCLUSION: The outbreak of pandemic (H1N1) 2009 influenza showed different call patterns and medical consultations in different regions. The time of disease outbreak and the availability of medical resources differ among regions; hence, each municipality should act practically and flexibly according to the situation in their locality.

[Comparison of conventional tuberculin skin test and QFT-2G, a new method for diagnosis of tuberculosis infection, with the use of the contact score].

BACKGROUND: QuantiFERON TB-Gold (QFT) has recently been developed as a new method for diagnosing tuberculosis (TB) infection. To evaluate the usefulness of QFT, we analyzed the relationship between QFT and the closeness of contact with a source of infection, in comparison with that of the tuberculin skin test (TST). METHODS: Male (n=322) and female (n=340) subjects (4-75 years old) who had contact with an index case received QFT and TST. The diagnostic criterion for TB infection with TST was defined as a test with an erythema diameter of > or = 30 mm. The closeness of contact with an index case was quantified in the "contact score," based on the information obtained with a questionnaire. RESULTS: There was a significant positive correlation between the contact score and QFT-positive rate, while there was no such relationship for TST positivity. The odds ratios for positive QFT rate for the subjects in the 3rd and 4th quartile groups of contact score (taking the QFT-positive rate in the lowest score quartile as unity) were 3.40 (95% confidence interval: 1.07-10.76, p<0.05) and 7.62 (95% confidence interval: 2.60-22.37, p<0.01), respectively. These odds ratios were also significantly greater than unity after adjustment for age, sex, history of BCG vaccination and history of health care-related jobs. There was a wide difference in the QFT-positive rates between the 2nd and 3rd quartiles of contact score (3.5% vs. 11.9%). The borderline value of the contact score between these two quartiles corresponded to 200, which could be a cutoff value for defining a high-risk contact. CONCLUSION: The QFT-positive rates correlated well with closeness of contact, while TST showed a poor correlation. Thus, QFT is considered more useful than TST for diagnosing tuberculosis infection.

Population structure dynamics of Mycobacterium tuberculosis Beijing strains during past decades in Japan.

We used 909 strains to compare the population structures of the Mycobacterium tuberculosis Beijing family between different birth-year cohorts in Japan. The results revealed that the spread of a modern sublineage that has high transmissibility is currently increasing, while the spread of an ancient sublineage, STK, has significantly decreased in younger generations.

Hypervariable loci that enhance the discriminatory ability of newly proposed 15-loci and 24-loci variable-number tandem repeat typing method on Mycobacterium tuberculosis strains predominated by the Beijing family.

The newly proposed 15- and 24-loci mycobacterial interspersed repetitive unit (MIRU)-variable-number tandem repeat (VNTR) typing method was evaluated for its ability to differentiate 181 Mycobacterium tuberculosis Beijing family strains. Compared with the original 12-loci MIRU-VNTR typing method, the 15-loci system dramatically improved the discriminatory power for Beijing strains; however, large clusters that could be further differentiated by IS6110 restriction fragment length polymorphism (RFLP) were still obtained. The clonal stability and allelic diversity of a total of 31 VNTR loci were evaluated. VNTRs 3232, 3820, and 4120 were identified as the effective hypervariable VNTR set for the second-line typing of clustered strains following the 15-loci based scheme. Consequently, the discriminatory power of the new scheme (18 loci) equaled that of IS6110 RFLP.

Aortico-pulmonary paraganglioma: case report and Japanese review.

Aortico-pulmonary paraganglioma (APPG) is a rare middle mediastinal tumor. We experienced a case of APPG in a 52-year-old man. Chest computed tomography and magnetic resonance imaging revealed a multi-cystic mass in the subaortic area. A left thoracotomy was performed without definitive preoperative diagnosis. The tumor was strongly adherent to the pericardium and the surrounding large vessels, but a complete resection was undertaken. Histological and immunohistochemical examination revealed that it was a malignant paraganglioma with a microscopically positive surgical margin. After radiotherapy of 50 Gy for the mediastinum, the patient almost recovered from his hoarseness by thyroplasty. We also reviewed nine Japanese cases of APPG reported previously. Though APPG is rare, we must consider that a middle mediastinal tumor may be APPG, and preoperative examination and preoperative planning are necessary to prevent massive bleeding and microscopic residual tumor.

[Clinical analysis of 10 cases of chest wall tuberculosis].

AIM/METHODS: A series of 10 cases of chest wall tuberculosis (man/woman=7/3, average age 62 +/- 17 years old) during past seven years were reviewed. RESULTS: Acid-fast bacillus was detected from an abscess in 60% by smear, 30% by culture, and 75% by polymerase chain reaction (PCR). It was characteristic that enhanced CT of abscess revealed a low density mass with peripheral enhancement, 'rim enhancement findings', in all cases. CT also showed ipsilateral pleural thickening in all cases, suggesting lymphogenous pathogenesis of chest wall lesions from tuberculous pleurisy. As for the treatment, antituberculosis chemotherapies were done in all cases. In addition, open drainage was done in 8 cases and curettage of abscess was performed in 5 cases. None of these ten cases had relapsed during the follow-up periods for 12 to 77 months. CONCLUSIONS: Chest wall tuberculosis is still important as a disorder of a chest wall mass requiring differential diagnosis. Contrasting CT is thought to be useful for the diagnosis. It should be emphasized that 50% of the cases had good outcome without curettage.

[Problems about the management of active pulmonary tuberculosis patients undergoing haemodialysis--our experiences and nation-wide questionnaire survey].

UNLABELLED: End-stage renal failure patients on chronic dialysis are high risk groups of tuberculosis due to attenuated cellular immunity. Patients receiving haemodialysis stay prolonged time inside the health-care facilities, thereby increased risk of tuberculosis transmission if a patient has active disease. So management of active pulmonary tuberculosis undergoing haemodialysis is important, however, the number of hospitals which are capable of taking care of such patients is estimated to be few in Japan. METHODS: From August 1994 through July 2002, 1059 active pulmonary tuberculosis patients (mean age; 57 +/- 19, male/female = 773/286) were admitted to Nishi-Kobe Medical Center, a 500-bed teaching hospital. Out of them, patients undergoing haemodialysis were retrospectively studied to describe the clinical characteristics of such cases. Then we conducted a questionnaire survey regarding the management of active pulmonary tuberculosis patients undergoing haemodialysis for 86 self-governing bodies in Japan. RESULTS: (1) Clinical characteristics of active pulmonary tuberculosis undergoing haemodialysis. We encountered 14 cases (mean age; 65 +/- 11, male/female = 7/7) of pulmonary tuberculosis undergoing haemodialysis during 8 years. In addition to pulmonary involvement, 3 pleural, one knee joint and one lymph node involvement was detected. Primary renal disease included diabetic nephropathy (n = 3), chronic glomerulonephritis (n = 3), congenital anomaly (n = 1), and unknown (n = 7). Nine cases were referred to our hospital from health-care facilities located out of city or prefecture. In five cases it took more than three months from the onset or detection of abnormal chest X-ray findings to the admission to our hospital. Five cases developed pulmonary tuberculosis within the first year after the initiation of dialysis. None of the patients had a past history of tuberculosis. Cavitary lesion on chest X-ray was observed in only one case. Triple antituberculosis therapy was used in 9 patients, and 4 antituberculosis drugs were used in 5 patients. Antituberculosis therapy was successfully done in all cases except two patients who died of apoplexy and cerebral infarction. (2) The nation-wide questionnaire survey. Of the 86 self-governing bodies we mailed, 66 self-governing bodies replied. Of them, 31% reported that they have experienced difficulties in the management of active pulmonary tuberculosis patients undergoing haemodialysis, and 25% reported the lack of health-care facilities to take care of such cases in their territory. They have referred such patients to hospitals located in the nearby prefectures or they have recommended antituberculosis therapy visiting a local haemodialysis facility. CONCLUSION: There are sometimes difficulties to manage active pulmonary tuberculosis patients undergoing haemodialysis in Japan. Health-care facilities to take care of such patients should be arranged and the formation of the network is necessarily.

[A case of Japanese summer-type hypersensitivity pneumonitis: monitoring with serum KL-6 and examination of the phenotype of HLA].

A 55-year-old woman was admitted with a cough and fever in August. A diagnosis of Japanese summer-type hypersensitivity pneumonitis was made on the basis of radiological, serological and pathological findings, in addition to positive returning home provocation. Serum KL-6 was monitored during the clinical course. Although KL-6 fluctuated slowly in comparison with the clinical symptoms and HRCT findings, it was considered useful for confirming the effects of treatment. Serum anti-Trichosporon antibody and the phenotype of HLA were studied in both the patient and her asymptomatic roommate, with whom she had no blood relationship. Though both were sensitized immunologically, HLA-DQ 3, which was reported to be associated with Japanese summer-type hypersensitivity pneumonitis, was detected in the patient but not in her roommate. It was suggested that HLA plays a role in the development of this disease.