|Year : 2022 | Volume
| Issue : 3 | Page : 287-292
Analysis of a tuberculosis outbreak in an office: Hokkaido, Japan, 2019–2020
Satomi Nitta1, Kensaku Terada1, Akemi Kurokawa1, Ryo Yamaguchi2, Munetaka Tateishi3, Masaki Ota4, Yutaka Hoshino4, Tomoko Zama4, Susumu Hirao4
1 Infectious Disease Control Section, Sapporo City Health Office, Sapporo, Hokkaido, Japan
2 Infectious Disease Control Section, Sapporo City Health Office; Sapporo City Institute of Public Health, Sapporo, Hokkaido, Japan
3 Bureau of Health and Welfare, Sapporo City Government, Sapporo, Hokkaido, Japan
4 Division of Technical Assistance to National Tuberculosis Programmes, Research Institute of Tuberculosis, Tokyo, Japan
|Date of Submission||01-Jun-2022|
|Date of Acceptance||10-Aug-2022|
|Date of Web Publication||12-Sep-2022|
No. 3-1-24, Matsuyama, Kiyose City, Tokyo 2048533
Source of Support: None, Conflict of Interest: None
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.
Keywords: Airborne infection, disease outbreak, epidemiology, Japan, tuberculosis
|How to cite this article:|
Nitta S, Terada K, Kurokawa A, Yamaguchi R, Tateishi M, Ota M, Hoshino Y, Zama T, Hirao S. Analysis of a tuberculosis outbreak in an office: Hokkaido, Japan, 2019–2020. Int J Mycobacteriol 2022;11:287-92
|How to cite this URL:|
Nitta S, Terada K, Kurokawa A, Yamaguchi R, Tateishi M, Ota M, Hoshino Y, Zama T, Hirao S. Analysis of a tuberculosis outbreak in an office: Hokkaido, Japan, 2019–2020. Int J Mycobacteriol [serial online] 2022 [cited 2022 Nov 26];11:287-92. Available from: https://www.ijmyco.org/text.asp?2022/11/3/287/355917
| Introduction|| |
Japan has successfully reduced the burden of tuberculosis (TB) in the past seven decades from 590,684 cases (698/100,000 population) in 1951 to 15,590 cases (12.3/100,000 population) in 2018., However, there are still some issues with regard to eliminating TB in Japan, including TB outbreaks occurring in various settings such as hospitals, workplaces, paramilitary training, schools, and casinos and among homeless persons and immigrants,,,,,,,, with about 6000 smear-positive pulmonary TB cases being reported annually. These infectious TB cases pose a public health threat to the community. A review on TB outbreaks that occurred in 1993–2015 found 253 (on average 11.0/year) TB outbreaks involving workplaces affecting on average 5.0 people with active TB.
To detect TB outbreaks as early as possible, local health offices are in charge of conducting contact investigations in Japan. The practice of investigations of TB contacts is similar to that recommended elsewhere. Briefly, once a local health office is notified about a TB case by a physician, a staff member of the health office where the patient lives visits the patient within a couple of days to conduct an interview about his or her contacts., When the case is smear-positive, the health office initiates a contact investigation. Normally, the interferon-γ release assay (IGRA), which was introduced in 2006, rather than tuberculin skin testing, is used to screen for latent TB infection (LTBI) among the contacts because IGRA is more specific without interference caused by Bacillus Calmette–Guérin vaccination.,,,, For an LTBI patient, prophylaxis using isoniazid for 6 to 9 months or rifampicin for 4 to 6 months was normally offered before 2021.
In August 2018, a male computer engineer in his late fifties (Pt1) was diagnosed with smear-positive (WHO grade: 3+) pulmonary TB after abnormal chest X-ray shadows were pointed out in a health checkup. No abnormal shadow was detected in the chest X-ray taken in a health checkup the year before. Since he was a smoker and had occasionally been coughing, the time when his respiratory symptoms started was not clearly determined. The initial contact investigation conducted by the city health office revealed that all of his three family members had also developed active TB. The city health office expanded the contact investigation to staff members in the office he worked in. This study aims to characterize the cases found in the TB outbreak in the office, in terms of time, place, and persons, and share the lessons learnt from the outbreak investigation.
| Methods|| |
Sapporo is a designated major metropolis in Hokkaido, the northern major island of Japan, with a population of almost two million people in 2018, which makes it the largest city north of Tokyo. The city is the commercial and administrative center of Hokkaido. The total area of the city is vast, comprising 1121 km2; however, almost two-thirds of the area is mountainous and not habitable. The TB notification rate for all types of TB in Sapporo was 6.8/100 000 population in 2020, about two-thirds of that of the entire country, with almost three-fourths of the patients being 65-year-old or older.
Pt1 worked for an information technology company with about 80 staff members working in a big room with an area of about 400 m2 that occupied one floor of an 11-story building in the city. He worked normally from 8 am to 6 pm every day, during which time he went to a smoking room on a different floor from the office room almost every hour. The staff members were frequently transferred between offices and from January to August 2018 about 20 staff members left the office.
In our study, a TB case was defined as one in which a patient had (1) bacteriologically positive TB in a sputum sample determined by smear microscopy, culture, or nucleic acid amplification tests, or (2) a patient was determined to have TB by a physician via a chest X-ray and/or chest computed tomography and who had an epidemiological link with Pt1. An LTBI case was defined as one in which a patient had contact with the index patient and tested positive in an IGRA test but had no chest X-ray findings suggestive of TB. A case of TB infection was defined as either a TB case, regardless of the availability of IGRA, or an LTBI case. Those who had a strain of Mycobacterium tuberculosis that was not identical to the other strains determined by variable number tandem repeat (VNTR) tests were excluded from the analysis.
This is a retrospective cohort study. The cohort consisted of the staff members of the company Pt1 worked for and other individuals, including ex-colleagues who had already left the company when the outbreak investigation began and janitors who stayed at least 8 h in the office from December 2017 to August 2018. The risks of the staff members and other individuals who developed TB disease or who were infected with TB were compared among the seating locations and their attributes (ex-colleagues and janitors).
All the IGRA-positive contacts were screened by chest X-ray and those who had abnormal findings were referred to chest physicians who were familiar with TB for further investigation. Those who were IGRA-positive and who agreed to take prophylaxis with isoniazid for 6 or 9 months were treated as such. Those who did not agree to be treated were followed up with semi-annual chest X-ray examinations for 2 years.
The information on Pt1 was obtained from the interview with the patient. The information on the contacts in the office was retrieved from the company records or derived from interviews with company officials. The results of the IGRA and 18 loci VNTR tests were obtained from the Sapporo City Institute of Public Health where those tests were performed. The results of the chest X-ray examinations were obtained from the chest physicians who were consulted. After the line list of the TB and LTBI patients was completed, the identity information, including the name, address, and cellphone number, was removed from the list and the list was analyzed.
Statistical tests, including calculations of 95% confidence intervals (CIs) were conducted using R (Ver. x64 4.0.2. The R Foundation for Statistical Computing, Vienna, Austria). Fisher's exact test was employed for comparison of proportions. The Cochran-Armitage test was used for the trend of proportions among the groups. A P < 0.05 was considered statistically significant.
The ethical review of the study was conducted and waived by the institutional review board of the Research Institute of Tuberculosis (TB), Tokyo, Japan, because the study used secondary data collected by the public health authority based on the Communicable Disease Control Act of 1998 and did not include the patients' identification information and confidential information in the first place (Decision #: 2022-03).
| Results|| |
The city health office conducted an outbreak investigation including TB screening using chest X-rays and IGRA tests for the staff members of the company from October 2018 to October 2020. A total of 116 current and ex-staff members and other individuals [Table 1] of the company were investigated, among whom a total of 13 patients with active TB, including Pt1, the index patient, and 20 with LTBI were found by the end of 2020.
|Table 1: Overall characteristics of the contacts investigated during a tuberculosis outbreak investigation in an office: Hokkaido, Japan, 2018–2019|
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An epidemic curve of the TB patients found during the outbreak investigation is shown in [Figure 1]. About half of active TB patients were diagnosed in October 2018 after they were found to be IGRA-positive and then they underwent chest X-rays that month. Those who were in seating groups 3–9 were tested with IGRA in November 2018 and some of them were diagnosed to have active TB that month after they were found to be IGRA-positive. Pt2 [Figure 1] had occasionally been coughing since July 2018; however, she was diagnosed with active TB after she was found to be IGRA-positive in late November 2018 and to subsequently have pulmonary TB via chest X-ray. Pt3, an ex-staff member, who developed symptoms in September 2018 and was diagnosed with sputum smear-positive pulmonary TB in December 2018, had actually left the office in January 2018 and had never visited the office since then.
|Figure 1: Epidemic curve of tuberculosis cases in an office: Hokkaido, Japan, 2018–2019. The months in which the active tuberculosis patients developed their symptoms are indicated. If the patient did not show any symptoms, the month in which the patient was diagnosed is indicated. The numbers indicated in or around the boxes are the patients' IDs. PCR = Polymerase chain reaction, TB = tuberculosis|
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A schematic map of the office as of September 2018 is shown in [Figure 2]. There were 84 staff members seated in the room and they were arbitrarily divided into nine seating groups: Pt1 belonged to Group 1 located at one end of the room. The numbers of active TB and LTBI cases gradually decreased from 3 of active TB (50.0%) and 2 of LTBI (33.3%) in Group 1 to one of LTBI (12.5%) with no active TB case in Group 9.
|Figure 2: Distribution of staff members with active tuberculosis and latent tuberculosis infection in an office: Hokkaido, Japan, 2018-2019. The seating locations are as of September 2018. Some staff members had already left the office by then|
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[Table 2] shows the risk of TB disease and TB infection (active TB plus LTBI) by the different seating groups or other attributes, and the relative risks of the seating groups or other attributes, with seating groups 7–9 as a reference. Seating groups 1–3 that Pt1 belonged to had the highest risk of TB disease (30.8%, 95% CI: 14.3%–51.8%) and infection (61.5%, 95% CI: 40.6%–79.8%), whereas seating groups 7–9 had the lowest risk of TB disease (0%, 95% CI: 0%–11.6%) and infection (10.0%, 95% CI: 2.1%–26.5%). The staff members in seating groups 1–3 were 6.2 (95% CI: 2.0–18.8) times more likely to acquire TB infection than those in groups 7–9. Cochran-Armitage tests revealed that there were statistically significant trends among seating groups 1–3, 4–6, and 7–9 for active TB disease and TB infection (P = 0.001 and P < 0.0001, respectively).
|Table 2: Risk of tuberculosis disease and latent tuberculosis infection among staff members in a tuberculosis outbreak in an office by different subgroups: Hokkaido, Japan, 2018–2021|
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Among 31 smokers in the office who shared the smoking room with Pt1, five developed TB disease (16.1%, 95% CI: 5.5%–33.7%) and 10 had TB infection (32.3%, 95% CI: 16.7%–51.4%), whereas among 9 nonsmokers, five developed TB disease (55.6%, 95% CI: 21.2–86.3%) and seven had TB infection (77.8%, 95% CI: 40.0%–97.2%). The risks of developing TB disease and infection of the smokers were 0.29 (95% CI: 0.11–0.78) and 0.41 (95% CI: 0.22–0.77) times, respectively, smaller than those for nonsmokers. However, information on the smoking room use was unavailable for half (42 of 84) of the staff members of the office's.
The 18 loci VNTR test results were available for five staff members and all of them had almost identical strains with no or only one difference among each other [Table 3].
|Table 3: The results of variable number tandem repeat (VNTR) tests for five tuberculosis patients who were culture-positive, Hokkaido, Japan, 2018-2019|
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| Discussion|| |
We investigated a large TB outbreak in an office in Hokkaido from 2018 through 2019 and found 13 cases of active TB disease and 20 cases of LTBI as of December 2021. The staff members belonging to seating groups 1–3 in the office were 6.2 times more at risk of TB infection than those in seating groups 7–9 and the trends for the risks of active TB and TB infection among the seating groups increased as the distance from the seat of Pt1 decreased.
The reason why seating groups 1–3 had the highest risks of active TB disease and infection is that Pt1 belonged to the groups and the staff members in the groups were exposed to air containing TB bacilli from Pt1. As the distance from the seat of Pt1 increased, the risk of TB infection decreased because the TB bacilli contained in the air were diluted and thus there was less chance of inhaling them.
The findings of our study summarized above are similar to those of past outbreak investigations. In an office in Melbourne, Australia in 1993, a 23-year-old female was found to have pulmonary TB and the subsequent contact investigation revealed that one more employee developed active TB and approximately one-fourth of the contacts were infected with TB. Those staff members seated close to the index patient were 4.2 times more likely to be infected. In three TB outbreaks in military shipboard environments of the United States, the index patients spread TB to other colleagues working or berthing in adjacent areas; however, the risk of TB infection was much smaller for those who were working or berthing in more remote areas.,, In a TB outbreak in a school in Tokyo, Japan in 2019–2021, the students in the same classroom with the index TB patient were much more likely to acquire TB infection and to develop active TB than those who were on the same floor but in different and more remote classrooms. In two vocational schools in Osaka, Japan, a teacher with sputum-smear positive TB spread the disease to seven of 162 students (4.3%) in a classroom with scarce or no ventilation (0.45–1.0 air change per hour [ACH]) and one of the seven students (0.6%) developed active TB disease, whereas the teacher did not spread the disease to any students in a classroom with better ventilation (3.6–7.0 ACH), indicating that risk of acquiring TB infection is miniscule in well-ventilated rooms. In addition, the risk of TB infection among air passengers seated adjacent to smear-positive TB patients was as low as 1.0%, supporting the idea that risk of acquiring TB infection is miniscule in well-ventilated areas such as commercial airliners.
On the other hand, there is one difference compared with past studies: The number of active TB cases found in our study was much larger than the average number of active TB patients found in 253 TB outbreaks in workplaces in Japan for 23 years. The reasons for this are that Pt1's TB was highly contagious in terms of (1) smear-positivity and (2) intensity of cough, and (3) the long delay, presumably 8 months or longer, for Pt1's diagnosis attested to by the fact that Pt3 had already been infected when he left the office in January 2018, about 8 months before Pt1's diagnosis.
There are several limitations in this study. First, since we did not conduct baseline IGRA tests for the staff members, we were not able to show conversion of IGRA test results, the probable timing of the TB infection of these staff members, or that those who were IGRA-positive were infected by Pt1. However, considering that the presumed duration of the index patient's symptoms before his diagnosis was 8 months or longer, most of the staff members with positive IGRA test results must have already converted to positive when Pt1 was diagnosed. Second, although we discussed the possibility of low ACH in the office that fueled transmission of TB bacilli from Pt1 to other TB and LTBI patients, we did not actually measure ACH in the office and the smoking room. Thus there might possibly have been other factors that influenced the transmission. Third, sputum smear and culture results of some of the staff members were unavailable because they lived outside the city and the detailed information of these staff members was not obtained. However, considering the sequence of the onset of the symptoms or diagnosis, if asymptomatic, of these staff members, it is unlikely that the source of the outbreak was one of these staff members whose sputum status was unavailable. Fourth, this study deals with one TB outbreak in an office setting in a country with a lower-medium burden of TB and the findings might not be generalizable to other countries. However, as we have already discussed above, some of the findings of this study are quite similar to those of TB outbreaks in workplaces, including offices, in other countries and the authors believe the findings of our study are still important to note. Fifth, although the staff members who shared the smoking room with Pt1 were less likely to acquire TB infection and to develop TB disease than those who did not, information on the use of the smoking room was unavailable for half of the staff members of the office and the results may have been biased.
Based on this and the past studies on TB outbreaks in offices and workplaces, we have several recommendations. Local health offices should initiate active case finding using chest X-rays as soon as they are notified of a case of sputum smear-positive TB if the delay of the diagnosis is long (perhaps, longer than 3 months as the incubation period for TB pleuritis is known at shortest as three months) and/or the grade of sputum smear-positivity of the index patient is high (2 + or 3+). The staff members of local health offices should be trained for outbreak investigations to strengthen the preparedness because they will happen in the long-term, although perhaps not very often. The Ministry of Health, Labour, and Welfare should strengthen the capacity for technical assistance in outbreak investigations because there are local health offices that do not have much experience and capacity to respond to outbreaks. Since the number of outbreak investigation reports, particularly those in relation to workplaces, is quite small and the information is limited, local health offices should share the major findings and lessons learnt during the investigations within the public health community. The staff members who conduct an onsite visit to offices, schools, or health facilities where sputum smear-positive patients were studying, working, or hospitalised should seek comprehensive information as much as possible during the first visit in case a large number of contacts needs to be screened and tested such as this investigation.
| Conclusion|| |
A TB outbreak investigation in an office in northern Japan found 13 cases of TB disease and 20 cases of LTBI. The staff members who were seating near the index patient were 6.2 times more at risk of TB infection than those who were seating in the other end of the office room. Local health offices should initiate active case finding using chest X-rays as soon as they are notified of a case of sputum smear-positive TB if the delay of the diagnosis is long.
The ethical review of the study was conducted and waived by the institutional review board of the Research Institute of Tuberculosis, Tokyo, Japan (Decision #: 2022-03).
The authors would like to thank all the staff members of the Bureau of Health and Welfare, Sapporo City Government, who have contributed to the outbreak investigation. Without their help, the investigation would not have successfully been implemented.
Financial support and sponsorship
This study was partially supported by the Japan Agency for Medical Research and Development (Grants #: JP22fk0108127).
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]