|Year : 2020 | Volume
| Issue : 1 | Page : 53-57
Positivity of interferon-gamma release assay among foreign-born individuals, Tokyo, Japan, 2015–2017
Satoshi Miyake1, Masayuki Endo1, Keiko Ikedo1, Aya Kayebeta1, Ikumi Takahashi1, Masaki Ota2
1 Shinjuku City Health Office, Tokyo, Japan
2 Research Institute of Tuberculosis, Tokyo, Japan
|Date of Submission||13-Nov-2019|
|Date of Acceptance||23-Nov-2019|
|Date of Web Publication||6-Mar-2020|
Research Institute of Tuberculosis, 3-1-24 Matsuyama, Kiyose City, Tokyo 204-8533
Source of Support: None, Conflict of Interest: None
Background: The aim of this study is to analyze interferon-gamma release assay (IGRA) data of foreign-born individuals in Japan derived from tuberculosis (TB) contact investigations. Methods: A contact with a TB patient was considered to have occurred when an individual had contact with a TB patient for more than 8 h indoors. This is a retrospective cohort study, and all the TB contacts tested with IGRA during the contact investigations conducted by the Shinjuku city Health Office from 2015 through 2017 were enrolled. Results: A total of 880 foreign-born contacts were investigated. The IGRA positivity of the contacts from China and Viet Nam were both 5.1% (95% confidence intervals [CIs]: 3.2%–7.8% and 2.4%–9.5%, respectively), whereas that from Nepal and Myanmar were 24.4% (95% CI: 16.0%–34.6%) and 23.3% (95% CI: 9.9%–42.3%), respectively. Multiple logistic regression analysis showed that the risk factors were smear status of the index patient (1+: adjusted odds ratio [aOR]: 6.2, 95% CI: 1.2–30.5, smear status 3+: aOR: 14.3, 95% CI: 1.7–118.2), age of the contact (aOR: 1.1, 95% CI: 1.0–1.1 for 1 year increment), and being born in Nepal (aOR: 5.6, 95% CI: 2.8–11.2) and Myanmar (aOR: 4.3, 95% CI: 1.4–13.0), compared with China as reference. Conclusions: In contact investigations involving foreign-born individuals, local health offices should carefully consider the composition of the TB contacts and expand the focus of the investigation, if deemed necessary.
Keywords: Contact investigation, epidemiology, interferon-gamma release assay, tuberculosis
|How to cite this article:|
Miyake S, Endo M, Ikedo K, Kayebeta A, Takahashi I, Ota M. Positivity of interferon-gamma release assay among foreign-born individuals, Tokyo, Japan, 2015–2017. Int J Mycobacteriol 2020;9:53-7
|How to cite this URL:|
Miyake S, Endo M, Ikedo K, Kayebeta A, Takahashi I, Ota M. Positivity of interferon-gamma release assay among foreign-born individuals, Tokyo, Japan, 2015–2017. Int J Mycobacteriol [serial online] 2020 [cited 2020 Jul 8];9:53-7. Available from: http://www.ijmyco.org/text.asp?2020/9/1/53/280137
| Introduction|| |
In Japan, the tuberculosis (TB) notification rate has decreased in the past six decades from 698.4/100,000 population in 1951 to 17.7/100,000 population in 2011. However, nearly 8000 smear-positive TB cases are still reported annually, and these infectious TB cases pose a public health threat to the community. Imported TB from immigrants is becoming a challenge in eliminating TB in Japan. The proportion of immigrants among all TB cases in Japan has steadily increased from 2.4% in 2000 to 9.1% in 2017. Immigrants accounted for two-thirds of the TB cases among those aged 20–24 years in 2017. TB outbreaks involving hospitals, workplaces, schools and sometimes homeless people have also been reported,,,,,, and recently, ones involving immigrants at Japanese language schools are becoming more frequent.,,
The practice of contact investigations of TB contacts in Japan,,, is similar to that recommended elsewhere. Briefly, once a TB case is reported to a local health office by a physician, a public health nurse of the health office where the patient lives visits the patient to conduct an interview about contacts, including his or her household, school, workplace, or whether congregate settings are involved. When the case is smear-positive, the health office initiates a contact investigation. Since 2006 when quantiFERON TB Gold was introduced in Japan, health screening usually involves interferon-gamma release assay (IGRA), to screen for latent TB infection (LTBI),,, rather than tuberculin skin testing. The reason is because IGRA is more specific and can avoid interference caused by Bacillus Calmette–Guérin (BCG) vaccination and in Japan coverage of BCG vaccination is quite high (90%–95%). A baseline and a second IGRA tests may be conducted for each contact to see a conversion. A chest X-ray may be used to rapidly screen for cases with TB disease among the contacts in case an outbreak of TB is suspected.
One of the challenges in conducting contact investigations involving foreign-born individuals is the scarcity of IGRA-positivity data as a sort of the baseline for them, particularly those from countries with a high-burden of TB. This leads to difficulty deciding whether IGRA positivity among a group of certain contacts with a smear-positive TB patient is higher than expected and subsequently whether the scope of contact investigation should further be expanded.
Shinjuku City Health Office in Tokyo has annually conducted contact investigations for 1200–1600 TB contacts with IGRA, including 200–300 foreign-born individuals, and the IGRA data for the foreign individuals could be used for surrogate indicators for baseline IGRA positivity for them.
This study aims to analyze IGRA data of foreign-born individuals derived from contact investigations conducted in Shinjuku, Tokyo, Japan.
| Methods|| |
Shinjuku is a special ward in Tokyo, Japan. It is a major commercial and administrative center, housing the northern half of the busiest railway station in the world (Shinjuku Station) and the Tokyo Metropolitan Government Building, the administrative center for the government of Tokyo. In 2015, the ward had an estimated population of 338,000, and a population density of 18,500 people/km2. The total area is 18 km2. Since the end of the Second World War, Shinjuku has been a major secondary center of Tokyo. Historically, it has had Korean and then Chinese communities in the Okubo area and now has 43 thousand foreign residents, making up 12.4% of the total population. It also has over 50 Japanese language schools within its jurisdiction and there are sometimes TB outbreaks related to the schools., TB notification rate for all types of TB of Shinjuku was 33.7/100,000 population in 2016, which has been 2.4 times as high as that of the entire country with two peaks in young (66.5/100,000 population in those aged 20–29 years) and in elderly (68.0/100,000 population in those aged 80 years or older). Meanwhile, treatment outcomes were relatively good (88.2% for treatment success for all types of TB for 2015 cohort) with its intensive directly observed treatment, short-course program.
In our study, a TB case was defined as an individual who had bacteriologically positive TB in a sputum sample determined by smear microscopy, culture, or nucleic acid amplification with confirmation of Mycobacterium tuberculosis, or was determined to have TB by a physician via a chest X-ray, histological or pathological tests, or clinically. A contact with a TB patient was defined as an individual who had contact with a TB patient for more than 8 h indoors. An LTBI case was defined as an individual who tested positive in an IGRA test. A TB outbreak in our study was arbitrarily determined as an event in which at least one smear-positive TB case was found and more than 40% of his or her contacts investigated were IGRA positive. Normally, in contact investigations, the contacts were interviewed, blood specimens were withdrawn by a staff member of the Shinjuku City Health Office and the specimens were sent to the Tokyo Metropolitan Institute of Public Health for QuantiFeron Gold-in-tube (Qiagen, Hilden, Germany).
This is a retrospective cohort study and all the contacts tested for IGRA during the contact investigations conducted from 2015 to 2017 were enrolled; however, the contacts of the TB outbreaks were excluded from the analysis because the expected IGRA positivity among the contacts was too high. The data for all the foreign-born contacts with TB cases who were screened with IGRA during the study period were retrieved from the data of the contact investigations conducted by the Shinjuku City Health Office. The individual contact information for each contact investigation was normally stored in Excel (Microsoft Corp., Seattle, WA, USA), and the authors merged the data for our study. Information collected during the contact investigations normally consisted of the name, address, cell phone number, age and sex, the country of birth, other members in the household, and the IGRA result. For the analysis, we detached the identification information from the data and analyzed only the anonymized data. The estimated TB incidence rates of countries were retrieved from the World Health Organization.
IGRA positivity was calculated as a whole and by country of birth. Pearson's correlation analysis was conducted between the IGRA positivity of the contacts and the estimated incidence rate by country. The countries chosen for the Pearson's correlation analysis were the most common countries of birth of foreign-born contacts, namely China, Myanmar, Nepal, South Korea, Sri Lanka, Taiwan (China), and Viet Nam. We also conducted multiple logistic regression analysis with backward stepwise method with Akaike information criterion as an estimator to explore which variables were associated to IGRA positivity. Independent variables included in the multiple logistic regression analysis were age, sex, country of birth with China as reference, other members in the household, smear status of the index patient, and whether the index patient had cavities in the lungs. A 95% confidence interval (CI) was calculated, and correlation and multiple logistic regression analysis was conducted with R (Version 3.6.0. The R Foundation for Statistical Computing, Vienna, Austria). P < 0.05 was considered as statistically significant.
This investigation was conducted in accordance with the Infectious Disease Control Act of 1998 of Japan. We also obtained a waiver of the ethical review for the study from the Institutional Review Board of the Research Institute of TB because this study was retrospective, the secondary use of the data that had already been collected by the local health office based on the statute law, and it did not involve confidential information (RIT/IRB: 30-21).
| Results|| |
From January 2015 to December 2017, 72 TB cases involving contacts born outside Japan were reported, of which 4 cases with 79 foreign-born contacts were considered to be the source cases of TB outbreaks with over 40% of their contacts being IGRA positive. Remaining 68 TB cases had 880 contacts born outside Japan. The overview of the index cases in terms of the grade of smear positivity and existence of cavity in the lung is shown in [Table 1]. Of these 880 contacts, 515 (58.5%) were males and the average age was 23.7 years old (standard deviation: ± 6.0 years) [Table 2]. Three hundred and eighty-nine (44.2%) were born in China, 175 (19.9%) in Viet Nam and 90 (10.2%) in Nepal.
|Table 1: Overview of the index tuberculosis cases whose foreign-born contacts were investigated, Tokyo, Japan, 2015-2017|
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|Table 2: Overview of foreign-born individuals investigated, Tokyo, Japan, 2015-2017|
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[Table 3] shows IGRA-positivity results by countries of birth of the contacts. The positivity of the contacts born in China was 5.1% (95% CI: 3.2%–7.8%), for Viet Nam 5.1%, (95% CI: 2.4–9.5), Nepal 24.4% (95% CI: 16.0%–34.6%). Although the sample size is quite small (n = 30), the positivity of the contacts born in Myanmar is also high (23.3%, 95% CI: 9.9%–42.3%). Pearson's correlation analysis found that there is a statistically significant association between IGRA positivity of the contacts and the estimated incidence rate by the country (r = 0.79, 95% CI: 0.10–0.97). Multiple logistic regression analysis revealed that the risk factors related to the IGRA positivity were the smear status of the index patient's (smear status 1+: adjusted odds ratio [aOR]: 6.2, 95% CI: 1.2–30.5, smear status 3+: aOR: 14.3, 95% CI: 1.7–118.2), age of the contact (aOR: 1.1, 95% CI: 1.0–1.1 for 1 year increment) and being born in Nepal (aOR: 5.6, 95% CI: 2.8–11.2) and Myanmar (aOR: 4.3, 95% CI: 1.4–13.0), compared with China as reference [Table 4].
|Table 3: Interferon-gamma release assay - positivity of foreign-born individuals by country of birth, Tokyo, Japan, 2015-2017|
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|Table 4: Risk factors for interferon-gamma release assay - positivities among foreign-born individuals, Tokyo, Japan, 2015-2017|
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| Discussion|| |
We analyzed IGRA data of foreign-born individuals derived from contact investigations conducted in Shinjuku and found that the IGRA-positivity rates of those from China and Viet Nam were both 5.1%, whereas those from Nepal and Myanmar were 24.4% and 23.3%, respectively, much higher than for China and Viet Nam. Multiple logistic regression analysis also supported that being born in Nepal and Myanmar is independent risk factors besides the age of the contacts and the smear status of the index patient: those born in the two countries are four to five times more likely to be IGRA positive than born in China.
The reason why the IGRA positivity of individuals from Nepal and Myanmar was much higher than that of China and Viet Nam is that the incidence rates of TB of the former are higher than the latter and the individuals from Nepal and Myanmar may have been infected with TB before they have arrived in Japan as supported by the Pearson's correlation analysis.
There are many reports on IGRA positivity in the clinical setting among Chinese; however, there are not many population-based studies or studies on the general Chinese population. In one population-based study in rural China, IGRA positivity ranged from 15% to 24%, but was from 5% to 17% in the participants aged 10–29 years. In Jiangsu Province in eastern China, IGRA-positivity ranged from 0.4% to 2.2% in those aged 10–29 years. In another study in Jiangsu, it ranged from 6.5% to 15%. In Shenzhen, southern China, IGRA positivity ranged from 4.7% to 12.8% in individuals aged 10–29 years. Thus, our IGRA positivity of the Chinese-born contacts (5.1%) was almost within the ranges of young mainland Chinese. The IGRA positivity of the Viet Nam-born contacts was much lower than that of the visa applicants from Viet Nam bound for United States, which ranged from 22% to 28%., One of the reasons is that in our study, most contacts were young, whereas the visa applicants were middle aged, and age is one of the risk factors of IGRA positivity. On the other hand, available IGRA positivity data for Nepalese are quite limited and variable; 4.8% of Nepalese military recruits were IGRA positive, whereas 48% of children in Kathmandu, Nepal, were,, and the data are not comparable with our findings.
One of our study's limitations is that our data derived from contact investigations conducted by the local health office and the IGRA positivity among foreign-born contacts may be overestimated as those who had contact with higher degree of smear status were more likely to be IGRA positive; however, as the logistic regression analysis showed, the degrees of smear status, the age of the contacts, and the countries of birth, particularly being born in the certain countries, are mutually independent risk factors. Furthermore, IGRA positivity for Chinese- and Viet Nam-born individuals were still low (5.1%). Thus, the degree of overestimation may not be large. Another limitation is the representativeness of the foreign-born contacts in our study and they do not represent their whole countries. However, for countries with a medium burden of TB and with large immigrant populations from China, Viet Nam, and Nepal, the results could be of importance.
| Conclusions|| |
Positivity of IGRA among foreign-born individuals in Japan is quite variable depending on his or her age and country of birth. In contact investigations involving foreign-born individuals, local health offices should carefully consider the composition of the TB contacts, particularly their countries of birth and expand the focus of contact investigation, if deemed necessary.
The authors would like to thank the public health staff members of the Shinjuku City Government for their essential contributions to contact investigations. We also greatly appreciate the efforts made by the staff members of Tokyo Metropolitan Institute of Public Health for the IGRA examination, without which our findings would not have been possible. This study was partially supported by the Japan Agency for Medical Research and Development (Grant #: JP18fk0108041).
Financial support and sponsorship
This study was financially supported by Agency for Medical Research and Development (Grant #: JP18fk0108041).
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]