Applicability of artificial intelligence-based computer-aided detection (AI-CAD) for pulmonary tuberculosis to community-based active case finding.

BACKGROUND: Artificial intelligence-based computer-aided detection (AI-CAD) for tuberculosis (TB) has become commercially available and several studies have been conducted to evaluate the performance of AI-CAD for pulmonary tuberculosis (TB) in clinical settings. However, little is known about its applicability to community-based active case-finding (ACF) for TB. METHODS: We analysed an anonymized data set obtained from a community-based ACF in Cambodia, targeting persons aged 55 years or over, persons with any TB symptoms, such as chronic cough, and persons at risk of TB, including household contacts. All of the participants in the ACF were screened by chest radiography (CXR) by Cambodian doctors, followed by Xpert test when they were eligible for sputum examination. Interpretation by an experienced chest physician and abnormality scoring by a newly developed AI-CAD were retrospectively conducted for the CXR images. With a reference of Xpert-positive TB or human interpretations, receiver operating characteristic (ROC) curves were drawn to evaluate the AI-CAD performance by area under the ROC curve (AUROC). In addition, its applicability to community-based ACFs in Cambodia was examined. RESULTS: TB scores of the AI-CAD were significantly associated with the CXR classifications as indicated by the severity of TB disease, and its AUROC as the bacteriological reference was 0.86 (95% confidence interval 0.83-0.89). Using a threshold for triage purposes, the human reading and bacteriological examination needed fell to 21% and 15%, respectively, detecting 95% of Xpert-positive TB in ACF. For screening purposes, we could detect 98% of Xpert-positive TB cases. CONCLUSIONS: AI-CAD is applicable to community-based ACF in high TB burden settings, where experienced human readers for CXR images are scarce. The use of AI-CAD in developing countries has the potential to expand CXR screening in community-based ACFs, with a substantial decrease in the workload on human readers and laboratory labour. Further studies are needed to generalize the results to other countries by increasing the sample size and comparing the AI-CAD performance with that of more human readers.

Age-period-cohort analysis on tuberculosis cases in Japan, 1953-2022.

Background: Age-period-cohort (APC) analysis has been employed to differentiate long-term trends in the incidences of communicable diseases, including tuberculosis (TB), into the effects of age, birth year, and calendar period. However, no such study was hitherto conducted for Japan, which has 70 years of surveillance data. Therefore, we conducted APC analysis for TB in Japan. Methods: The national TB data for 1953-2022 were analyzed using the log-transformed linear model of APC analysis. Results: Annual age-and sex-standardized notification rates of TB peaked at 599.0 per 100 000 population in 1955 and fell by 99% to 4.5 in 2022. Adjusting for the effects of the birth cohort and period, the relative age-effect risk of TB peaked at 20-29 years and went down toward 60-69 years. Regarding the birth cohort effect, the TB risk showed a turning point in approximately 1913 for the central years of birth. Another change appeared in 1963 when the decline of the risk slightly stagnated; then, it started declining again at a rate as fast as in 1923-1953. Period effects showed a hump in the late 1950s and early 1960s, then sharply declined to the late 1970s, and reached a near plateau level until 2022. Conclusion: Our results highlight the continuing peak in TB disease risk for young adults and sharp decrease in disease risk in the 1960s and 70s. The introduction of anti-TB drugs in the 1950s and early 1970s had the most important impact on the epidemiology of TB in Japan.

Epidemiology of the koch phenomenon of infants after bacillus calmette-Guerin vaccination by interferon-γ release assay status, Japan, 2013-2019.

Background: The epidemiology of infants who exhibited the Koch-like phenomenon after Bacillus Calmette-Guérin vaccination and who subsequently tested positive in interferon-γ release assay (IGRA) was compared to that of those who tested negative. The reports of pediatricians on the phenomenon to the health authorities of Japan were retrieved and analyzed. Methods: In 2013-2019, 790 infants with such events were reported with IGRA test results available, of whom 81 (10.3%) tested positive and 709 (89.7%) negative. Results: The infants who were IGRA positive did not show an increasing trend (P = 0.06, P = 0.60), whereas those who were IGRA negative showed a significantly increasing trend (P = 0.42, P = 0.0002). The infants who were IGRA positive did not exhibit seasonality, whereas those who were IGRA negative had a higher number of cases in winter than in summer. The rates of infants who were IGRA positive per 10 million live births showed a significant correlation with the tuberculosis (TB) notification rates by prefecture (P = 0.41, P = 0.004), whereas those who were IGRA negative did not (P = 0.04, P = 0.78). Conclusion: The IGRA-positive infants were distributed quite differently from those who were IGRA negative and appeared more likely to be infected with TB. Reports of pediatricians on the Koch-like phenomenon should continuously be collected as the reports reflect a risk of TB infection including TB outbreaks among infants in Japan. The reports should include IGRA test results as IGRA is more specific than tuberculin skin testing. Infants with IGRA-positive results should be followed up for 2-3 years to determine their final outcomes.

Analysis of a tuberculosis outbreak in an office: Hokkaido, Japan, 2019-2020.

Background: In August 2018, a male worker (Pt1) in an office was diagnosed with smear-positive pulmonary tuberculosis (TB). This study aims to characterize the cases found in the TB outbreak in the office. Methods: The risks of TB disease or infection were compared among the staff members by seating locations. Results: A total of 116 current and ex-staff members were investigated, among whom 13 patients with active TB, including Pt1, and 20 with latent TB infection were found by the end of 2020. One-third of the seating groups located at one end of the office that Pt1 belonged to had the highest risk of TB disease (30.8%, 95% confidence interval [CI]: 14.3%-51.8%) and infection (61.5%, 95% CI: 40.6%-79.8%) with a high relative risk of TB infection (6.2, 95% CI: 2.0-18.8) compared to another one-third of the seating groups at the other end of the office that had the lowest risk of active TB (0%, 95% CI: 0%-11.6%) and TB infection (10.0%, 95% CI: 2.1%-26.5%). Conclusion: The seating groups that Pt1 belonged to had the highest risk of TB disease and infection because the staff members in the groups were exposed to the air containing TB bacilli from Pt1. Local health offices should initiate active case finding using chest X-rays as soon as they are notified of a sputum smear-positive TB case if the delay of the diagnosis is longer than three months.

Multidrug-Resistant Tuberculosis Outbreak among Immigrants in Tokyo, Japan, 2019-2021.

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.

Turnaround times of the sputum sample courier system at tuberculosis treatment centers in Lusaka, Zambia, 2021.

Background: Health facilities which do not have capacity to diagnose tuberculosis (TB) depend on other facilities. This involves the courier of specimen such as sputum to diagnostic centers. This study was aimed at determining the turnaround time of sputum examinations for TB patients involving a courier system between the treatment and diagnostic centers. Methods: The study tracked the sputum samples between TB treatment and diagnostic centers. Sputum samples for both diagnosis and follow-up reasons were purposely and serially tracked from the time they were sent to the laboratory to the time results were received at the treatment centers. Results: Of the 65 sputum samples tracked at Chazanga, results were available for 49 (75.4%), 6 (9.2%) were unaccounted for, 4 (6.2%) were rejected by the laboratory, 4 (6.2%) had "error" results, and 2 (3.1%) were declared "missing" because it took more than a month to return the results. The turnaround time ranged from 2 days to 18 days with an average of 5.8 days (95% confidence interval [CI]: 4.5-7.1 days). At Kaunda Square, of the 49 samples tracked, results were available for 44 (89.8%), 2 (4.1%) were unaccounted for, 2 (4.1%) were rejected, and 1 (2.0%) was declared "missing." The turnaround time ranged from 2 to 25 days with an average of 6.3 days (95% CI: 5.3-7.4 days). Conclusion: The turnaround times of sputum examinations of the two treatment centers were long. The courier system should be closely monitored to determine if it is performing well because the system is still necessary for facilities without laboratories.

A diffused community tuberculosis outbreak that could be detected earlier using surveillance data, Japan, 2012-2014.

Background: Early detection of an outbreak is a role of disease surveillance systems; however, tuberculosis (TB) surveillance systems were underutilized to detect the outbreaks. In mid-2015, a local health office of central Japan noticed the number of TB cases of city in 2012-2014 were well above the expected numbers. This study was conducted to determine whether and when a community TB outbreak could be detected and characterize the cases using the national surveillance data. Method: The surveillance data of the A city and surrounding areas were retrospectively reviewed and analyzed for 2006-2018. Results: The TB notification rates of the A city from 2012 to 2014 were 28.0 (95% confidence interval [CI]: 20.3-38.4), 26.0 (95%CI: 18.6-36.0), 28.2 (95%CI: 20.3-38.4) per 100,000 population, respectively, higher than that of the entire prefecture (13.6, 13.0, 13.3, respectively). Similarly, in the neighboring B city, the rates of 2012 and 2014 were 51.0 (95%CI: 27.2-87.2) and 51.2 (95%CI: 27.3-87.5), respectively, higher than that of its parent prefecture (13.4 and 12.7, respectively). By the end of July 2012 (A city) or August 2012 (B city), the accumulated numbers of TB cases exceeded the previous annual TB cases. The average TB notification rates of A and B cities for 2012-2014 were higher than the surrounding areas. Conclusion: A community TB outbreak without well-defined setting could be detected by monitoring TB surveillance data.

A multidrug-resistant tuberculosis outbreak in a language school: Tokyo, Japan, 2019-2020.

Background: Japan has successfully reduced the burden of tuberculosis (TB) in the past seven decades; however, there are still some issues in eliminating TB. Its presence in immigrants, particularly multidrug-resistant (MDR) TB, is one of them. In mid-September 2019, a teenage Chinese male student in a morning class of a Japanese language school in Tokyo, Japan, was diagnosed with sputum smear-positive pulmonary MDR-TB. Method: The outbreak cases were analyzed in a cohort study. Results: We investigated 138 students and 18 teachers, of whom 81 (51.9%) were male, 115 (73.7%) were aged from 20 to 29 years, and 124 (76.9%) were from China. Four other students in the same classroom and another in a different classroom from the index patient in the morning classes were also diagnosed with MDR-TB disease by the end of November 2020. In addition, 31 cases of latent TB infection (LTBI) were detected among the students and teachers. Students in the same classroom had the highest risk of TB infection (78.9%, 95% confidence interval [CI]: 54.4%-93.9%) with a relative risk of 8.6 (95% CI: 3.9-19.0), followed by students in the other classrooms of the morning classes (25.9%, 95% CI: 15.0%-39.7%) with a relative risk of 2.8 (95% CI: 1.2-6.8), compared with the afternoon class students (9.2%, 95% CI: 3.5-19.0) who had minimal contact with the index patient. Conclusion: National TB programs should adopt prophylaxis regimens for MDR-TB LTBI cases and provide prophylaxis to them, particularly if related to an outbreak. The Japanese government should screen immigrants for TB, particularly those from TB-endemic areas.

Where, when, and how many tuberculosis patients are lost from presumption until treatment initiation? A step by step assessment in a rural district in Zimbabwe.

OBJECTIVES: To describe the pre-diagnosis and pre-treatment loss to follow-up (LTFU) in the tuberculosis (TB) care cascade in Guruve (2015-16), a rural district in Zimbabwe. DESIGN: Guruve has 19 rural health centres (RHCs) and one district hospital. In this cohort study, persons ≥15 years of age with presumptive pulmonary TB were tracked from the facility presumptive TB registers to the laboratory registers; if laboratory diagnosed, they were tracked to the district TB register (contains details of all TB patients registered for treatment). Each patient was tracked for 90days after registration as presumptive TB and for 90days after laboratory diagnosis. Environmental health technicians transported sputum specimens from the health facilities to the laboratories (n=3). RESULTS: Of 2974 persons with presumptive TB, pre-diagnosis LTFU occurred in 575 (19%, 95% confidence interval 18-21%). Associated factors included registration at a RHC, at a facility more than 2km from the laboratory, and absence of an environmental health technician. Of 162 laboratory diagnosed pulmonary TB patients, pre-treatment LTFU occurred in 19 (12%, 95% confidence interval 8-18%). CONCLUSIONS: The presumptive TB register was helpful to assess the pre-diagnosis gaps beginning from presumption. Pre-diagnosis LTFU can be reduced by placement of an environmental health technician at all facilities.

Novel aspects on the pathogenesis of Mycoplasma pneumoniae pneumonia and therapeutic implications.

Mycoplasma pneumoniae (Mp) is a leading cause of community acquired pneumonia. Knowledge regarding Mp pneumonia obtained from animal models or human subjects has been discussed in many different reports. Accumulated expertise concerning this critical issue has been hard to apply clinically, and potential problems may remain undiscovered. Therefore, our multidisciplinary team extensively reviewed the literature regarding Mp pneumonia, and compared findings from animal models with those from human subjects. In human beings, the characteristic pathological features of Mp pneumonia have been reported as alveolar infiltration with neutrophils and lymphocytes and lymphocyte/plasma cell infiltrates in the peri-bronchovascular area. Herein, we demonstrated the novel aspects of Mp pneumonia that the severity of the Mp pneumonia seemed to depend on the host innate immunity to the Mp, which might be accelerated by antecedent Mp exposure (re-exposure or latent respiratory infection) through up-regulation of Toll-like receptor 2 expression on bronchial epithelial cells and alveolar macrophages. The macrolides therapy might be beneficial for the patients with macrolide-resistant Mp pneumonia via not bacteriological but immunomodulative effects. This exhaustive review focuses on pathogenesis and extends to some therapeutic implications such as clarithromycin, and discusses the various diverse aspects of Mp pneumonia. It is our hope that this might lead to new insights into this common respiratory disease.

Kinetics of c-reactive protein (CRP) and serum amyloid A protein (SAA) in patients with community-acquired pneumonia (CAP), as presented with biologic half-life times.

Context: In management of community-acquired pneumonia (CAP), excellent biomarkers for inflammation would be helpful in our practice. Objectives: Kinetics of c-reactive protein (CRP) and serum amyloid A (SAA) was characterized, using their biologic half-life times. Materials and methods: Time course of CRP and SAA levels in the successfully treated 36 CAP patients were investigated and their half-life times were determined and compared. Results & Discussions: SAA and CRP declined in an exponential mean and the biologic half-life times of SAA levels was 34.9 ± 28.7 h, significantly shorter than that of CRP, 46.4 ± 21.7 h (p = 0.0014). Conclusion: The kinetic evidence, presented as biologic half-life times of CRP and SAA, helps us make a clinical assessment of CAP patients.

Inflammation provoked by Mycoplasma pneumoniae extract: implications for combination treatment with clarithromycin and dexamethasone.

Recently, combination treatment with a macrolide and a steroid for Mycoplasma pneumoniae (Mp) pneumonia has been reported to be effective. Thus, the effect of this combination on a mouse model of lung inflammation associated with Mp extract (the LIMEX mouse) was studied. Interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) were induced in Mp extract-treated RAW264.7 cells, and this induction was inhibited by dexamethasone, parthenolide, SB203580 or LY294002. This suggested that Mp extract activates nuclear factor κB-, p38- and PI-3K-linked pro-inflammatory signals. The LIMEX mice were then either treated with or without clarithromycin and/or dexamethasone. Clarithromycin administration enhanced the production of IL-6, TNF-α, macrophage inflammatory protein-1α, monocyte chemotactic protein-1 and RANTES, while their production was perfectly suppressed by the combination of clarithromycin and dexamethasone. IL-17, IL-23, keratinocyte-derived chemokine (KC) and interferon-γ levels were not affected by clarithromycin treatment, but they were significantly suppressed by the combination of dexamethasone and clarithromycin. Collectively, some components of Mp extract provoked an inflammatory reaction in the RAW 264.7 cell line and LIMEX mice. Whereas the lung reaction in LIMEX mice was further exacerbated by clarithromycin treatment, it was resolved by the combinational treatment with clarithromycin and dexamethasone.

Front-loading sputum microscopy services: an opportunity to optimise smear-based case detection of tuberculosis in high prevalence countries.

Setting. Ethiopia, Nepal, Nigeria, and Yemen. Objective. To reduce the time to complete sputum microscopy. Design. Cross-sectional surveys enrolling 923 patients with chronic cough in the 4 countries and using similar protocols. Spot-morning-spot sputum specimens were collected. An additional sputum specimen (Xspot) was collected one hour after the first, and the yields of the first two or the three specimens collected as spot-morning-spot or spot-Xspot-morning were compared. Results. 216 patients had >/= one positive smear. 210 (97%) were identified by the spot-morning-spot, and 210 (97%) were identified by the spot-Xspot-morning specimens, with 203 and 200 identified by the first 2 specimens of each approach, respectively. Neither difference was significant. Conclusions. The time to complete smear microscopy could be reduced.