Abstract [Background] Infectious disease caused by Mycobacterium avium shows diverse pathological and clinical manifestations. This is possibly due to both host factors and bacterial factors, but many questions remain answered regarding these manifestations. [Methods] To assess the relationship between the different pathological and clinical manifestations of M.avium disease and bacterial factors, we performed comparative genome analysis using clinical isolates from patients with various symptoms. [Results] We determined the complete genome sequence of the previously unreported M.avium strain TH135 isolated from a patient with pulmonary M.avium disease, and further demonstrated the presence of a novel plasmid, pMAH135, encoding proteins involved in the pathogenicity and antimicrobial resistance of mycobacteria. Our analysis also showed that M.avium strains, which cause pulmonary and disseminated disease, have genetically distinct features, and isolates from patients with pulmonary disease were more resistant to seven antibiotics, including clarithromycin, than isolates from patients with disseminated disease. Comparative genome analysis of 79 M. avium strains comprising four subspecies revealed the presence of genetic elements speciﬁ c to each lineage, which are thought to be acquired via horizontal gene transfer during the evolutionary process. More-over, the analysis identiﬁ ed potential genetic determinants associated with not only the progression of pulmo-nary disease but also the host range characteristics of M.avium. Notably, this analysis indicated an association between the progression of pulmonary M.avium disease and several virulence genes including pMAH135. [Conclusion] These results suggest that bacterial factors play an important role in the diverse pathological and clinical manifestations of M.avium disease.
Key words: Mycobacterium avium disease, Pathological manifestation, Clinical manifestation, Bacterial factors, Genome analysis
Department of Microbiology, Faculty of Pharmacy, Meijo University Correspondence to : Kei-ichi Uchiya, Department of Microbiology, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya-shi, Aichi 468_8503 Japan.
(E-mail: email@example.com) (Received 1 Aug. 2019) Kekkaku Vol.94, No.11_12: 519_526, 2019
−−−−−−−−Memorial Lecture by the Imamura Award Winner−−−−−−−−
ANALYSIS OF BACTERIAL FACTORS ASSOCIATED WITH
PATHOLOGICAL OR CLINICAL MANIFESTATIONS OF
DISEASE BASED ON GENOME ANALYSIS
Nontuberculous mycobacteria (NTM) are ubiquitous in the environment, including natural water, soil, and household dust1) 2), and can cause signiﬁ cant disease in humans and animals3). The incidence of NTM infection is increasing annually in many countries, including the United States and Japan4)_7). In Japan, the causative NTM strain for pulmonary disease with the highest incidence is Mycobacterium avium (approximately 60％), followed by M.intracellulare, M. kansasii, and M.abscessus, and the incidence per 100,000 population has increased remarkably from 5.7 in 2007 to 14.7 in 20146) 8).
Among NTM species, M.avium is the most clinically signiﬁ cant species in humans and animals and comprises
four subspecies that have speciﬁ c pathogenic and host range characteristics as follows: M.avium subsp. avium (MAA) and M.avium subsp. silvaticum (MAS) are avian pathogens; M.avium subsp. paratuberculosis (MAP) causes John s disease in ruminants; and M.avium subsp. hominissuis (MAH) infects mainly pigs and humans9)_11). MAH is the causative pathogen of two main types of disease in humans: disseminated disease in immunocompromised hosts such as individuals infected with human immunodeﬁ ciency virus (HIV), and pulmonary disease in individuals without sys-temic immunosuppression3). However, the genetic differences among the four subspecies are still unknown.
Pulmonary disease caused by NTM, which is both intrac-table and infectious, has variable clinical manifestations. Although some patients remain stable without treatment,
Prospects of the Medical Care System / S. Kato 533
Abstract The incidence of tuberculosis (TB) in Japan has markedly decreased owing to various efforts based on the Tuberculosis Prevention Law. The introduction of a short regimen of rifampicin and pyrazinamide has shortened hospitalization periods. As a result, the required number of TB beds has decreased, and many hospitals removed TB beds altogether. This has caused poor accessibility of TB medical services in many areas. However, the bed occupancy rate for TB is low, and enormous differences can be seen among prefectures.
We estimated the necessary number of hospital beds for TB patients by prefecture using the data from 2017 surveil-lance data along with the following assumptions: All sputum smear-positive patients are hospitalized. Among sputum smear-negative patients, 30 percent of those aged over 70 years old and 5% of the remaining patients are hospitalized. The ﬁ nal estimate was obtained by multiplying 1.6, as a seasonable variable, to adjust for ﬂ uctuations in the number of TB patients based on the time when the above number was calculated.
TB medical care creates a ﬁ nancial deﬁ cit in most TB hospitals due to poor bed occupancy rates, unreasonable reimbursement from public health insurance, and additional costs for infection control. As the number of TB patients decreases, it is becoming difﬁ cult for hospitals to secure physicians who are experienced with TB medical care, especially in low incidence areas. The medical care system for TB, which is in a critical situation in many prefectures, needs to be restructured.
The following proposals should be implemented for the medical care system in low incidence situations, to improve patient-centered medical care for TB: 1) secure hospital beds for TB patients, 2) shorten hospitalization periods, 3) recon-sider the applications of TB beds, model beds, and infectious disease beds for TB patients, 4) maintain the quality of TB medical services, 5) establish a collaboration mechanism for TB work in respective areas.
In order to secure an adequate number of hospital beds, ﬁ nancial deﬁ cits need to be resolved by adjusting bed occupancy rates and improving the related income. As the incidence of TB is expected to decrease, the area set up with-in a ward for TB patients needs to be ﬂ exible. Consequently, beds for TB should be in isolation rooms complete with a pre-admittance room. In this way, the room can be used for infectious diseases other than TB. In order to shorten
hos-pitalization periods, a policy amendment should be imple-mented to facilitate the smooth transfer of non-infectious TB patients to general hospitals or geriatric facilities, and new technology should be developed to evaluate the contagious-ness of the patients so that they can be transferred as soon as possible. As needs and social resources for the medical service of TB patients become increasingly diverse, the ap-plication of TB beds, model beds, and infectious disease beds for TB patients should be reconsidered. To maintain the quality of medical service, it is necessary to provide train-ing for health care workers and opportunities for interns to experience medical care for TB patients through the collabo-ration of governments, medical facilities, and educational organizations. It is also important to establish a consulting system for medical service providers at the prefectural level; however, a national-level center may be required in the future as it may be difﬁ cult to maintain it at the prefectural level. In order to tackle the above-mentioned challenges, a regional collaboration mechanism should be established. In some prefectures, holding collaboration meetings among hospitals that have TB beds or model beds, university hospitals, core hospitals for infection control, and the government is func-tioning well and facilitating mutual understanding.
In conclusion, the provision of medical services for TB patients is facing critical situations in many areas. It is necessary to establish a medical service system for TB pa-tients in low incidence situations. In order to realize patient-centered medical care, which requires a sufﬁ cient number of hospital beds for various needs of medical care alongside quality service, it is necessary to resolve ﬁ nancial deﬁ cits, shorten hospitalization periods, utilize hospital beds beyond their current demarcation, and establish a medical service collaboration mechanism at the regional level.
Key words: Tuberculosis, Hospital beds, Low incidence, Medical care system, Regional collaboration
Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association
Correspondence to: Seiya Kato, Research Institute of Tuber-culosis, Japan Anti-Tuberculosis Association, 3_1_24, Matsuyama, Kiyose-shi, Tokyo 204_8533 Japan.
(E-mail: firstname.lastname@example.org) −−−−−−−−Review Article−−−−−−−−
PROSPECTS OF THE MEDICAL CARE SYSTEM FOR TUBERCULOSIS IN JAPAN
Tuberculous Pathogenesis / A. Kurashima 539
Abstract Today, research papers on tuberculosis have been developed internationally on an unprecedented scale and depths. Although it is important to clinicians, many of these have not been introduced in a way that clinicians can grasp easily in Japan today. Here, I present the historical overview of the pathogenesis of tuberculosis from the personal appreciation of a physician who is pursuing mycobacterial disease. And I am going to introduce a result of modern tuberculosis research.
Experimental tuberculosis has mainly used rabbits and guinea pigs as animals that can reproduce the pathogenesis of tuberculosis of man that has led to the formation of TB cavities. Today, new methodologies with cutting-edge tech-niques, such as zebraﬁ sh, new pure mice, cynomolgus mon-keys, DNA-labeled TB bacilli and PET/CT evaluation etc. are opening up a fundamental understanding of tuberculosis immunity that has not been fully elucidated for example, the
Koch phenomenon .
This article is a review that focuses on the pathogenesis of tuberculosis among the special lectures reported at the 94th Annual Meeting of the Japanese Society for Tuberculosis. Key words: Primary complex, Koch phenomenon, Epitu-berculosis, Delayed type hypersensitivity, Cell mediated immunity, Concurrent infection with tuberculosis
Clinical Research Advisor, Fukujuji Hospital, Japan Anti-Tuberculosis Association
Correspondence to: Atsuyuki Kurashima, Fukujuji Hospital, Japan Anti-Tuberculosis Association, 3_1_24, Matsuyama, Kiyose-shi, Tokyo 204_8522 Japan.
(E-mail: email@example.com) −−−−−−−−Review Article−−−−−−−−
HISTORY IN TUBERCULOUS PATHOGENESIS FROM A VIEWPOINT OF PHYSICIAN
13） Dannenberg Jr. AM: Pathogenesus of Human Pulmonary Tuberculosis. ASM press, Washington DC, 2006.
14） Hunter RL, Jagannath C, Actor JK: Pathology of postprimary tuberculosis in humans and mice: Contradiction of long-held beliefs. Tuberculosis. 2007 ; 87 : 267 278.
15） Leong FJ, Datoris V, Dick T, ed.: A Color Atlas of Comparative Pathology of Tuberculosis. CRC Press Tayloe
& Francis group, New York, 2011.
16） Cadena AM, Hopkins F, Flynn J, et al.: Concurrent infection with Mycobacterium tuberculosis confers robust protection against secondary infection in macaques. PLOS Pathogens. https://doi.org/10.1371/journal.ppat.1007305 (October 12, 2018).
結核 第 94 巻 第 11_12号 2019年11_12月
Abstract The percentage of foreign-born TB patients in Japan is gradually increasing and reached to 10.7％ in 2018. There are various demanding factors such as difﬁ culty of communication, drug resistance, instability of social infra-structure, transfer out, returning home country, etc. To complete their treatment domestically take the top priority. Treatment support for them is involved in many aspects, especially we should make patients centered, and there is a greater need for early detection, prevention of infection spread, and completion of treatment. Well-trained medical interpreters have supported our treatment for many years at Center for Health Check and Promotion of Japan Anti-Tuberculosis Association. We have held DOTS meetings for foreigners with staff members of public health center
regularly since 2006 and have various ideas and materials to prevent interruptions of the treatment. We show some tips in treating TB outpatients through our experience.
Key words: Tuberculosis, Foreign nationals, Outpatient Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association
Correspondence to: Kiyoko Takayanagi, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, 3_1_ 24, Matsuyama, Kiyose-shi, Tokyo 204_8533 Japan. (E-mail: firstname.lastname@example.org)
CURRENT SITUATION OF FOREIGN-BORN TUBERCULOSIS PATIENTS IN JAPAN
― How It Is and How It Should Be on Treating Especially Outpatients ―Kiyoko TAKAYANAGI
15） 東京都福祉保健局：結核対策多言語動画. http://www.fuku shihoken.metro.tokyo.jp/iryo/kansen/kekkaku/videomaterial.
結核 第 94 巻 第 11_12号 2019年11_12月
Abstract The epidemiologists of tuberculosis are able to obtain huge amount of genotypic information at one time due to the innovation of new sequencing technology. The new technology, whole genome sequencing (WGS), possesses higher ability of analyzing the cluster and linkage associa-tions among the clinical isolates of tuberculosis (TB) than traditional methods like genotyping, RFLP, VNTR and spoligotyping. Furthermore, the WGS analysis is also able to predict drug susceptibility of the isolate against anti-TB drugs. I here review the role of the WGS analysis in epi-demiological investigations of tuberculosis.
Key words: Tuberculosis, Molecular epidemiology, Whole genome analysis
1Department of Mycobacteriology, Research Institute of Tu-berculosis, Japan Anti-Tuberculosis Association, 2Graduated School of Pharmaceutical Sciences, Nagoya City University Correspondence to: Takemasa Takii, Department of Myco-bacteriology, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, 3_1_24, Matsuyama, Kikyose-shi, Tokyo 204_8533 Japan. (E-mail: email@example.com)
WHOLE GENOME SEQUENCING AS A PROMISING TOOL FOR
EPIDEMIOLOGICAL INVESTIGATIONS OF TUBERCULOSIS
1, 2Takemasa TAKII
Japan. BMC Infect Dis. 2009 ; 9 : 138.
16） Nguyen D, Brassard P, Menzies D, et al.: Genomic characterization of an endemic Mycobacterium tuberculosis strain: evolutionary and epidemiologic implications. J Clin Microbiol. 2004 ; 42 : 2573 2580.
17） Wyllie DH, Robinson E, Peto T, et al.: Identifying Mixed
Mycobacterium tuberculosis Infection and Laboratory Cross-Contamination during Mycobacterial Sequencing Programs. J Clin Microbiol. 2018 ; 56.
18） Auld SC, Shah NS, Mathema B, et al.: Extensively drug-resistant tuberculosis in South Africa: genomic evidence supporting transmission in communities. The Eur Respir J. 2018 ; 52.
19） van der Werf MJ, Kodmon C: Whole-Genome Sequencing as Tool for Investigating International Tuberculosis Out-breaks: A Systematic Review. Front Public Health. 2019 ; 7 : 87.
20） Walker TM, Merker M, Knoblauch AM, et al.: A cluster of multidrug-resistant Mycobacterium tuberculosis among patients arriving in Europe from the Horn of Africa: a molecular epidemiological study. Lancet Infect Dis. 2018 ; 18 : 431 440.
21） Fiebig L, Kohl TA, Popovici O, et al.: A joint cross-border investigation of a cluster of multidrug-resistant tuberculosis in Austria, Romania and Germany in 2014 using classic, genotyping and whole genome sequencing methods: lessons learnt. Euro Surveill. 2017 ; 22 : 30439.
22） Benjak A, Sala C, Hartkoorn RC: Whole-genome sequencing
for comparative genomics and de novo genome assembly. Methods Mol Biol. 2015 ; 1285 : 1 16.
23） Dixit A, Freschi L, Vargas R, et al.: Whole genome sequencing identiﬁ es bacterial factors affecting transmission of multidrug-resistant tuberculosis in a high-prevalence setting. Sci Rep. 2019 ; 9 : 5602.
24） Bainomugisa A, Duarte T, Lavu E, et al.: A complete high-quality MinION nanopore assembly of an extensively drug-resistant Mycobacterium tuberculosis Beijing lineage strain identiﬁ es novel variation in repetitive PE/PPE gene regions. Microb Genom. 2018 ; 4.
25） Colman RE, Mace A, Seifert M, et al.: Whole-genome and targeted sequencing of drug-resistant Mycobacterium
tuberculosis on the iSeq100 and MiSeq: A performance, ease-of-use, and cost evaluation. PLoS Med. 2019 ; 16 : e1002794.
26） Phelan JE, O Sullivan DM, Machado D, et al.: Integrating informatics tools and portable sequencing technology for rapid detection of resistance to anti-tuberculous drugs. Genome Med. 2019 ; 11 : 41.
27） Pullen MF, Boulware DR, Sreevatsan S, et al.: Tuberculosis at the animal-human interface in the Ugandan cattle corri-dor using a third-generation sequencing platform: a cross-sectional analysis study. BMJ Open. 2019 ; 9 : e024221. 28） Doyle RM, Burgess C, Williams R, et al.: Direct
Whole-Genome Sequencing of Sputum Accurately Identiﬁ es Drug-Resistant Mycobacterium tuberculosis Faster than MGIT Culture Sequencing. J Clin Microbiol. 2018 ; 56 : e00666 18.
TB Surveillance/K. Matsumoto 561
Abstract To clarify the present status and problems of tuberculosis surveillance in tuberculosis control, TB analysis and assessment meeting (TB meeting), which evaluates tuberculosis surveillance in Osaka City, analyzed the degree of contribution to tuberculosis control . The purpose of this meeting is to share problems and evaluate tuberculosis control activities. Concerning methods, data on tuberculosis are collected and analyzed, accurate evaluation is performed, and effective measures are taken. The TB meeting consisted of 4 external members specializing in tuberculosis and epidemiology, members of Division of Microbiology, Osaka Institute of Public Health, and physicians and public health nurses in Public Health Ofﬁ ce and Public Health and Welfare Centers in 24 wards and others. The major evaluation contents were: 1) Changes in the incidence of tuberculosis: Changes in newly registered tuberculosis cases were evaluated in the entire Osaka City and each of the 24 wards. 2) Topics: Analy-sis and evaluation of tuberculoAnaly-sis control activities were performed, and advanced topics were provided. 3) Evaluation of newly registered cases: Patient control is performed in the 24 wards. Whether the diagnosis and treatment of each case,
and contact examination were appropriately performed in each ward was determined. Based on changes in the incidence of tuberculosis, the characteristics of each jurisdiction district were clariﬁ ed, and the direction of control activities was determined. The provision of topics was useful for the plan-ning, evaluation, and revisions of control measures. The case study allowed the evaluation of the consistency of control activities. These results showed the importance of the use of tuberculosis surveillance for tuberculosis control.
Key words: TB control, Surveillance, Evaluation, Evidence, Analysis and assessment meeting
1Osaka City Public Health Ofﬁ ce, 2Nishinari Ward Ofﬁ ce, Osaka City
Correspondence to: Kenji Matsumoto, Osaka City Public Health Ofﬁ ce, 1_2_7_1000, Asahimachi, Abeno-ku, Osaka-shi, Osaka 545_0051 Japan.
(E-mail: firstname.lastname@example.org) −−−−−−−−Review Article−−−−−−−−
PRESENT STATUS AND PROBLEMS OF TUBERCULOSIS SURVEILLANCE
結核 第 94 巻 第 11_12号 2019年11_12月
Abstract Reported poor prognostic factors of Mycobacte-rium avium complex lung disease (MAC-LD) include radio-graphic ﬁ ndings, undernutrition, anemia and high inﬂ amma-tion test values. To clarify the pathophysiology of MAC-LD, we investigated cytokine proﬁ les in patients with MAC-LD. We analyzed 27 patients with MAC-LD, 6 with the ﬁ bro-cavitary form and 21 with the nodular bronchiectatic form. Serum C-X-C motif ligand 10 (CXCL-10) concentration was signiﬁ cantly elevated in patients with the ﬁ brocavitary form. CXCL-10 levels correlated with body mass index, serum albumin concentration and high-resolution CT scores. Serum CXCL-10 levels probably reﬂ ect the severity of MAC-LD. Key words: Non-tuberculous mycobacterial pulmonary
disease, Mycobacterium avium complex pulmonary disease, Fibrocavitary disease, Nodular bronchiectatic disease, CXCL-10
Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences
Correspondence to: Hiroshi Moro, Department of Respira-tory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, 757 Ichibancho, Asahimachidori, Chuo-ku, Niigata-shi, Niigata 951_8510 Japan. (E-mail: email@example.com) −−−−−−−−Review Article−−−−−−−−
CHARACTERISTICS OF TWO DIFFERENT FORMS OF MYCOBACTERIUM
COMPLEX PULMONARY DISEASE; FIBROCAVITARY
AND NODULAR BRONCHIECTATIC DISEASE
Preventing TB Infection in Healthcare Settings / N. Suzuki et al. 573
Abstract In Japan, in recent years, we have a serious prob-lem of Doctor s Delay of elderly people s diagnosis of tuberculosis (TB), related to the aging of patients receiving emergency medical care. The prevalence of TB in Japanese healthcare workers (HCWs) is generally about twice the same age. National hospital organization, the A hospital is in the central part of Japan and is a national acute hospital with no TB disease bed (600 beds), which is often associated with this issue and latent tuberculosis infection (LTBI) occurs in HCW. Therefore, we analyzed cases of the Doctor s Delay, which occurred in elderly TB and examined the risk of LTBI of HCWs and countermeasures.
We targeted the case (Doctor s Delay) where elderly people aged 65 and over were hospitalized without suspecting TB and subsequently diagnosed with TB, in the acute care hos-pital from 2016_2017. The subject cases were 15 cases, the average age was 82.7 years old, and the male was 10 cases (67％). The main symptoms of hospitalization were weight loss, body movement difﬁ culty, dizziness, falls, malaise, he-matemesis, decreased appetite, lower extremity edema, cough, runny nose, fever, dyspnea, etc. Seven patients were admitted through the emergency department. Six patients used nursing care services before hospitalization. The average number of days in a Doctor s Delay was 35.7 days. In each case, 22 to 92 HCWs were involved in and a total of 800 HCWs were screened for TB contact. There were 236 nurses, 61 physicians, 67 radiologists, 50 therapists and 58 other healthcare profes-sionals. There were two cases showing LTBI was contracted. Three HCWs: an occupational therapist, a nurse, and a pharmacist were diagnosed with LTBI.
The symptoms of elderly tuberculosis patients were not
typical and not always accompanied by fever and prolonged cough symptoms. Furthermore, in the beginning, there were many cases where they were admitted to the emergency ﬁ rst-aid clinic due to falls or sudden weight loss. In acute phase hospitals, it is difﬁ cult for all elderly patients to be treated with tuberculosis at an early stage, even if they see respiratory disease specialists. Therefore, it is considered that delays in diagnosis have occurred. More importantly, these elderly people are using nursing care, so there is concern that tuber-culosis infection may have occurred in facility users and care workers at nursing homes without physicians.
To prevent tuberculosis infection in medical staff caused by the onset of tuberculosis in the elderly, it is necessary to share information and educate on how to control infection early in the onset of tuberculosis in these elderly people and the risk of infection to medical personnel. The key to prevent-ing LTBI and TB is to consider the possibility of TB in high-risk groups, and make the diagnosis as quickly as possible. Key words: Tuberculosis nosocomial infection, Tuberculosis infection control, Elderly tuberculosis
Medical Safety Division, National Hospital Organization Higashiowari National Hospital
Correspondence to: Naoko Suzuki, Medical Safety Division, National Hospital Organization Higashiowari National Hospital, 2_1301, Omori-kita, Moriyama-ku, Nagoya-shi, Aichi 463_ 0802 Japan.
(E-mail: firstname.lastname@example.org) −−−−−−−−Review Article−−−−−−−−
PREVENTING TUBERCULOSIS INFECTION IN HEALTHCARE SETTINGS
結核 第 94 巻 第 11_12号 2019年11_12月
Abstract [Objective] To assess the epidemiological validity of the concept of tuberculosis danger group .
[Methods] Smear positive index patients aged between 20 to 64 years old, who were notiﬁ ed to Osaka City Public Health Center, and their contacts were investigated to calcu-late the number and rate of secondary index patients by job category. Multiple regression analysis was also conducted to identify potential risk factors for secondary transmission. [Results] Secondary infection rate was the highest for con-struction workers (28.2％), followed by physicians and nurses (26.7％). Number of secondary patient per index case was the largest for trainees (1.3), followed by construction work-ers (1.0).
[Conclusions] Secondary infection rate of jobs such as healthcare workers and service industry workers, which have traditionally been regarded as danger groups was not signiﬁ cantly higher than other jobs, while that of
construc-tion workers was higher. Appropriateness of the use of the term danger group in prioritizing TB policies should be reconsidered.
Key words: Tuberculosis, Danger group , Contact inves-tigation
1Department of Epidemiology and Clinical Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association; 2Osaka City Public Health Center
Correspondence to: Lisa Kawatsu, Department of Epide-miology and Clinical Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, 3_1_24, Matsuyama, Kiyose-shi, Tokyo 204_8533 Japan.
(E-mail: email@example.com) −−−−−−−−Original Article−−−−−−−−
EPIDEMIOLOGICAL EVALUATION OF
THE TERM TUBERCULOSIS DANGER GROUP POPULATION
― A Case Study from Osaka City, Japan ―
1Lisa KAWATSU, 1Kazuhiro UCHIMURA, 1Akihiro OHKADO, 2Jun KOMUKAI, 2Kenji MATSUMOTO, 2Yoshimi YONEDA, and 2Hideki YOSHIDA
受診の遅れ. https://jata.or.jp/research.php#jump0（2019 年 5 月アクセス） 13） 山内祐子, 永田容子, 小林典子, 他：近年の日本にお ける女性看護師・男性医師の結核感染・発病のリスク の検討. 結核. 2017 ; 92 : 5 10. 14） 大森正子, 星野斉之, 山内祐子, 他：職場の結核の疫 学 的 動 向 ︱ 看 護 師 の 結 核 発 病 リ ス ク の 検 討. 結 核. 2007 ; 82 : 85 93. 15） 猪狩英俊, 前原亜矢乃, 鈴木公典, 他：千葉市におけ る飯場の労働者の結核と都市結核の課題. 結核. 2009 ; 84 : 701 707. 16） 木村友子, 鈴木公典, 矢部 勤, 他：飯場における結 核検診の検討. 結核. 2002 ; 77 : 597 603. 17） 飯降聖子, 藤田次郎, 矢島宏泰, 他：結核の集団発生 事例の検討 ︱ 保健面・医療面・福祉面・労働面からの 連携の必要性. 結核. 2001 ; 76 : 691 698. 18） 倉澤卓也, 佐藤敦夫, 中谷光一, 他：再感染発病が示 唆された建設作業宿舎内の結核集団発症. 結核 . 2000 ; 75 : 389 394. 19） 松本健二, 有馬和代, 小向 潤, 他：大阪市における 結核患者と喫煙. 結核. 2012 ; 87 : 541 547.
Pulmonary M. xenopi / H. Machii et al. 585
randomised trial of treatments for pulmonary disease caused by M.avium intracellulare, M.malmoense, and M.xenopi in HIV negative patients: rifampicin, ethambutol, and isoniazid versus rifampicin and ethambutol. Thorax. 2001 ; 56 : 167 172.
11） Jenkins PA, Campbell IA and Research Committee of the British Thoracic Society: Pulmonary disease caused by
Mycobacterium xenopi in HIV-negative patients: ﬁ ve year follow-up of patients receiving standard treatment. Respi-ratory Medicine. 2003 ; 97 : 439 444.
12） Jenkins PA, Campbell IA, Banks J et al.: Clarithromycin vs ciproﬂ oxacin as adjuncts to rifampicin and ethambutol in treating opportunist mycobacterial lung diseases and an assessment of Mycobacterium vaccae immunotherapy. Thorax. 2008 ; 63 : 627 634.
13） Haworth CS, Banks J, Capstick T, et al.: British Thoracic
Society guidelines for the management of non-tuberculous mycobacterial pulmonary disease. Thorax. 2017 ; 72 : iii1-ii64.
14） Grifﬁ th DE, Aksamit T, Brown-Elliott BA, et al.: An Ofﬁ cial ATS/IDSA Statement: Diagnosis, Treatment, and Prevention of Nontuberculous Mycobacterial Diseases. Am J Respir Crit Care Med. 2007 ; 175 : 367 416. 15） 日本結核病学会非結核性抗酸菌症対策委員会：肺非結 核性抗酸菌症に対する外科治療の指針. 結核. 2008 ; 83 : 527 528. 16） 小松弘明, 泉 信博, 水口真二郎, 他：Mycobacterium xenopi肺感染症の2切除例. 日呼外会誌. 2015 ; 29 : 745 750. 17） 村上裕亮, 小山孝彦, 加藤良一, 他：肺癌との鑑別が困 難であった排非結核性抗酸菌症（Mycobacterium xenopi の1切除例. 日呼外会誌. 2018 ; 32 : 697 702.
Abstract A 68-year-old man was referred to our hospital to undergo surgery for an abdominal aortic aneurysm. Pre-operative computed tomography (CT) revealed a cavitary lesion with an irregularly thick wall in the left upper lung. When we were consulted 3 weeks later, a second CT revealed a new thin-walled cavitary lesion in the right upper lung. Another week later, the cavity had changed to a nodule as revealed by high-level uptake of ﬂ uoro-deoxy-glucose by positron emission tomography (PET). The bronchial lavage ﬂ uid obtained via bronchoscopy exhibited smear positivity for acid-fast bacteria but the results of polymerase chain reaction for both Mycobacterium tuberculosis and Myco-bacterium avium complex were negative. Two months after the PET study, the nodule in the right lung became a cavity with a thick wall resembling the original lesion in the left upper lung. Subsequently, the acid-fast bacterial culture was positive and identiﬁ ed as Mycobacterium xenopi by DNA-DNA hybridization method. Furthermore, M.xenopi was also isolated in the patient s sputum specimen, and the patient
was ultimately diagnosed with a pulmonary M.xenopi infection. Chemotherapy with rifampicin, ethambutol, and clarithromycin was initiated and levoﬂ oxacin was added 10 months later because of an indelible cavitary lesion. The wall thicknesses of both right and left lesions became markedly thinner after 2 years of continuous treatment. The patient subsequently survived successfully without a relapse of the infection for 4 years.
Key words : Pulmonary nontuberculous mycobacteriosis, Mycobacterium xenopi, Imaging ﬁ ndings, Chemotherapy Department of Respiratory Medicine, Japanese Red Cross Nagoya Daiichi Hospital
Corresondence to: Haruka Machii, Department of Respiratory Medicine, Japanese Red Cross Nagoya Daiichi Hospital, 3_ 35, Michishita-cho, Nakamura-ku, Nagoya-shi, Aichi 453_ 8511 Japan. (E-mail: firstname.lastname@example.org) −−−−−−−−Case Report−−−−−−−−
A CASE OF PULMONARY MYCOBACTERIUM XENOPI INFECTION
PRESENTING INTERESTING IMAGING CHANGES
Haruka MACHII, Toshihiko YOKOYAMA, Masayasu INAGAKI, Mari TANAKA, Mitsuki TANIMOTO, Yuiko YOKOYAMA, Takashi KOHNOH, Daisuke AOYAMA,