https://ojs.wpro.who.int/ 1WPSAR Vol 13, No 1, 2022 | doi: 10.5365/wpsar.2022.13.1.896 Surveillance Report T uberculosis (TB) continues to be a leading cause of death for people living with HIV or AIDS, and HIV remains the strongest known risk factor for progression to active TB disease for persons with latent TB infection.1 In 2019, it was estimated that globally, 8.2% of all people with TB were living with HIV or AIDS.2 Japan has a middle-level, nearly low-level, burden of TB, with 12 739 cases newly notified in 2020, giving a notification rate of 10.1 per 100 000 population.3 In the same year, 750 cases of HIV infection and 345 cases of AIDS were newly reported.4 The number of new cases of TB, HIV and AIDS has continued to decline; however, there have been increases observed in the burden of these diseases among foreign-born persons. Because recent reports on the epidemiology of TB/HIV coinfection in Japan have been limited to regional analy- ses5,6 or hospital-based studies,7 we analysed national TB surveillance data to examine the characteristics and treatment outcomes of people with TB coinfected with HIV in Japan from 2012 to 2020. METHODS This was a cross-sectional study of active TB cases newly notified to the nationwide Japan Tuberculosis Surveillance (JTBS) system between 1 January 2012 and 31 December 2020. Japan Tuberculosis Surveillance system The JTBS system was Japan’s first nationwide computer- ized TB surveillance system, introduced in 1987. As TB is a notifiable disease, new cases are notified to public health centres, which are responsible for collecting and entering case data into the system. The specific data items included in the JTBS system can be found else- a Centre for Japan Pre-Entry Tuberculosis Screening Quality Assessment, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, Japan. b Department of Epidemiology and Clinical Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, Japan. c Department of Global and Community Health, Graduate School of Nursing, Nagoya City University, Nagoya, Japan. d Department of Infectious Diseases and Immunology, Clinical Research Center, Nagoya Medical Center, Nagoya, Japan. Published: 28 March 2022 doi: 10.5365/wpsar.2022.13.1.896 This report examines the characteristics and treatment outcomes of patients with tuberculosis (TB) who are coinfected with HIV in Japan. Active TB cases newly notified to the Japan Tuberculosis Surveillance system during 2012–2020 were analysed retrospectively, during which 379 HIV-positive TB cases were reported. The proportion of HIV-positive cases among those with known HIV status increased, from 1.9% (62/3328) in 2012 to 3.5% (31/877) in 2020. The proportion of those with unknown HIV testing status was consistently high, at approximately 60%, and the proportion of those who did not undergo HIV testing increased significantly, from 21.6% (4601/21 283) in 2012 to 33.7% (4292/12 739) in 2020. The proportion of foreign-born cases more than tripled, from 14.5% (9/62) in 2012 to 45.2% (14/31) in 2020. The TB treatment success rate was higher among HIV-negative than HIV-positive cases (72.7% [3796/5222] versus 60.3% [88/146]), and among Japan-born than foreign-born HIV-positive patients (65.6% [61/93] versus 50.9% [27/53]), owing largely to the high rate of foreign-born cases transferring to care outside Japan. The increasing proportion of HIV positivity among TB cases tested for HIV in this study requires ongoing monitoring, especially among foreign-born persons. However, because the number of reported cases was small, and there was low completeness of reporting of HIV testing data in the TB surveillance system, these results should be interpreted with caution. Encouraging more complete data collection by training public health nurses who complete TB case interviews and ensuring ongoing monitoring of patients with TB/HIV coinfection are recommended. Epidemiology of coinfection with tuberculosis and HIV in Japan, 2012–2020 Lisa Kawatsu,a Kazuhiro Uchimura,b Noriyo Kanekoc and Mayumi Imahashid Correspondence to Lisa Kawatsu (email: kawatsu@jata.or.jp) WPSAR Vol 13, No 1, 2022 | doi: 10.5365/wpsar.2022.13.1.896 https://ojs.wpro.who.int/2 Kawatsu et alTB and HIV coinfection in Japan P values. R version 3.6.3 (R Development Core Team, Vienna, Austria) was used for all statistical analyses. RESULTS General trends, 2012–2020 During the study period, a total of 156 876 TB cases were notified, of which 379 were categorized as HIV-positive, with the number of notifications steadily declining each year (Fig. 1). The proportion of HIV-positive cases among all TB cases was consistent at 0.2–0.3%; however, the pro- portion of HIV-positive cases among those tested for HIV increased significantly, from 1.9% (62/3328) in 2012 to 3.5% (31/877) in 2020 (P < 0.01). The proportion of those with unknown HIV testing status was consist- ently high, at 59.4% in 2020, whereas the proportion of those reported as not being tested for HIV increased significantly, from 21.6% (4601/21 283) in 2012 to 33.7% (4292/12 739) in 2020, although this decrease was not statistically significant (P < 0.01). The propor- tion of foreign-born cases among HIV-positive TB cases more than tripled, from 14.5% (9/62) in 2012 to 45.2% (14/31) in 2020 (Fig. 2). Proportions of cases by HIV status and selected characteristics Among people with TB, 379 were categorized as HIV-positive, 14 339 were HIV-negative, 43 035 were not tested for HIV and 99 123 had unknown HIV testing status (Table 1). The proportion of those tested among the total TB cases was 9.4% (14 718/156 876). The proportion of HIV-positive cases among those tested was significantly higher in males (3.4% [313/9124]) versus 1.2% [66/5594]), highest among those aged 25–64 years old (4.8%; 290/5993) and highest for those whose country of birth was unknown (8.1%; 7/86), followed by those who were foreign-born (7.1%; 107/1505). Among occupational categories, the propor- tion of HIV-positive cases was highest among service industry workers (6.8%; 38/558), followed by tempo- rary workers (5.1%; 34/666) (Table 1). The proportion of those not tested for HIV was significantly higher in females than males (75.7% [17 406/23 000] versus 73.7% [25 269/34 753]), highest in those aged ≥65 years old (78.7%; 29 116/ where.3 The JTBS data are summarized monthly and annually and are made publicly available online (https:// jata-ekigaku.jp/english). Mechanisms to ensure data quality include an automatic verification programme and regular meetings attended by hospital and public health centre staff. HIV status The information regarding a case’s HIV status upon diag- nosis of TB is categorized as HIV-positive, HIV-negative, not tested for HIV and unknown HIV testing status. Entering these data is optional, and they are not cross- referenced with any other clinical database. Country of birth Information regarding country of birth is reported as Japan-born, foreign-born or unknown. Foreign-born cases are defined as people, including Japanese citizens, who were born outside of Japan. Treatment outcomes Prior to 2016, treatment outcomes were evaluated auto- matically using a computerized algorithm available only for pulmonary TB cases treated with a standard regimen. Since 2016, treatment outcomes have been entered directly by public health centres for all cases of active and latent TB. Therefore, this study examined treatment data from 2016 to 2020. Because the numbers of cases with treatment data available were quite small, statistical testing was not conducted to compare the proportions. One case with an unknown country of birth was excluded from the analysis. Data analysis and ethics Trends in the epidemiological and clinical characteristics of TB cases notified in Japan were examined. HIV-pos- itive TB cases, those not tested for HIV and those with unknown HIV testing status were compared. HIV-positive TB cases notified between 2016 and 2019 were ana- lysed by country of birth, and their treatment outcomes were compared with those of HIV-negative TB cases. Trends were tested using the Cochran−Armitage test, and proportions were compared with tests for multiple comparisons, using the Hochberg correction to adjust the https://jata-ekigaku.jp/ https://jata-ekigaku.jp/ WPSAR Vol 13, No 1, 2022 | doi: 10.5365/wpsar.2022.13.1.896https://ojs.wpro.who.int/ 3 TB and HIV coinfection in JapanKawatsu et al Fig. 1. Number of newly notified TB cases by HIV status and proportion that were HIV-positive, by year, Japan, 2012–2020 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 0 5000 10 000 15 000 20 000 25 000 2012 2013 2014 2015 2016 2017 2018 2019 2020 % o f H IV -p os iti ve ca se s N o. o f n ew ly n ot ifi ed T B ca se s Unknown HIV testing status Untested for HIV HIV-negative HIV-positive % HIV-positive among those tested % HIV-positive among all TB cases Fig. 2. Number of newly notified TB cases by country of birth and proportion that were foreign-born, by year, Japan, 2012–2020 0.0 10.0 20.0 30.0 40.0 50.0 60.0 0 10 20 30 40 50 60 70 2012 2013 2014 2015 2016 2017 2018 2019 2020 Japan-born Foreign-born Country of birth unknown % foreign-born % o f f o re ig n -b o rn T B c as es N o. o f n ew ly n o ti �e d H IV -p o si ti ve T B c as es WPSAR Vol 13, No 1, 2022 | doi: 10.5365/wpsar.2022.13.1.896 https://ojs.wpro.who.int/4 Kawatsu et alTB and HIV coinfection in Japan in HIV-positive than HIV-negative cases (65.6% [61/93] versus 72.2% [3288/4557]), despite a larger propor- tion of those who were HIV-negative having died (8.6% [8/93] versus 19.0% [865/4557]). The lower treatment success rate among the HIV-positive cases was largely attributable to the higher proportion of those still on treatment (17.2% [16/93] versus 4.1% [185/4557] of HIV-negative cases still on treatment) (Table 3). Among foreign-born cases, again, the treatment success rate was lower among HIV-positive than HIV-negative cases (50.9% [27/53] versus 76.4% [508/665]). This was largely attributable to higher proportions who were still undergoing treatment (11.3% [6/53] versus 5.6% [37/665]), as well as those who had transferred out (28.3% [15/53] versus 14.4% [96/665]) (Table 3). DISCUSSION Japan has historically had a low HIV prevalence, at less than 0.1 per 1000 population aged 15–49 years,8 with a concentrated epidemic among men who have sex with men (MSM);9 therefore, TB/HIV comorbidity has had less public health importance in Japan compared with other similarly industrialized countries. However, this study has shown an increasing proportion of HIV posi- tivity among TB cases who were tested for HIV, which was 3.5% of those notified in 2020. This positivity rate is higher than in the United Kingdom of Great Britain and Northern Ireland (2.8% in 2018), but lower than in the United States of America (4.7% in 2019).2 The overall increase in HIV positivity in Japan may be due to the increase in the number of foreign-born persons with HIV who are in Japan: HIV positivity in- creased by 46%, from 91 cases in 2000 to 133 cases in 2019.4 There have also been changes in the countries of birth of foreign-born persons with HIV in Japan between 2008 and 2013, with numbers decreasing from coun- tries in the World Health Organization’s South-East Asia Region and increasing from countries in the Western Pacific Region, where the estimated number of people living with HIV has increased in recent years.8,10 Issues associated with diagnosing HIV among foreign-born per- sons in Japan suggest that cases may be underreported. One study estimated that approximately 50% of HIV cases among foreign-born persons in Japan are cur- rently diagnosed,11 as opposed to approximately 80% 36 988) and highest in those whose country of birth was unknown (88.0%; 632/718), followed by those who were born in Japan (74.9%; 39 215/52 342). Among occupational categories, the proportion of those not tested for HIV was highest among children and in- fants (i.e. excluding high school and university students) at 83.0% (225/271), followed by unemployed adults (78.0%; 28 971/37 124) (Table 1). The proportion of those with unknown HIV test- ing status did not significantly differ by sex (63.3% [59 924/94 677] for males versus 63.0% [39 199/62 199] for females); however, it was highest among those aged ≥65 years old (64.2%; 66 295/103 283) and in those whose country of birth was unknown (86.9%; 4752/5470), followed by those who were born in Japan (62.5%; 87 179/139 521). Regarding occupational category, the proportion was highest among those in the category “Other or job unknown”, at 69.0% (4351/6303) (Table 1). Demographic characteristics of HIV-positive TB cases by country of birth The majority of both the Japan-born and foreign-born HIV-positive TB cases were in the two younger age groups (0–24 years and 25–64 years). However, those aged 25–64 years accounted for 85.0% (91/107) of all foreign-born cases compared with 73.6% (195/265) of Japan-born cases. Males comprised 68.2% (73/107) and 88.3% (234/265) of foreign-born and Japan-born cases, respectively. For occupational categories for both Japan-born and foreign-born cases, the highest number of cases was among unemployed adults, followed by other full-time workers, service industry workers and temporary workers. These four occupational categories accounted for 86.8% (230/265) and 80.4% (86/107) of all Japan-born and foreign-born cases, respectively. Among foreign-born cases, high school and university students accounted for another 10.3% (11/107) of cases, but they were not represented in Japan-born cases (Table 2). Treatment outcomes among TB cases by HIV status The overall treatment success rate among HIV-positive TB cases was lower among foreign-born than Japan-born cases (50.9% [27/53] versus 65.6% [61/93]). Among Japan-born cases, the treatment success rate was lower WPSAR Vol 13, No 1, 2022 | doi: 10.5365/wpsar.2022.13.1.896https://ojs.wpro.who.int/ 5 TB and HIV coinfection in JapanKawatsu et al Table 1. Number and proportion of TB cases by selected characteristics and HIV status, Japan, 2012–2020 Characteristic Notified TB cases TOTAL No. HIV- positive No. HIV- negative No. untested for HIV No. HIV testing status unknown % HIV- positive % untested for HIV % HIV testing status unknown Total 156 876 379 14 339 43 035 99 123 2.6 74.5 63.2 Sex Male 94 677 313 8811 25 629 59 924 3.4 73.7 63.3 Female 62 199 66 5528 17 406 39 199 1.2 75.7 63.0 Age group (years) 0–24 7059 17 836 2039 4167 2.0 70.5 59.0 25–64 46 534 290 5703 11 880 28 661 4.8 66.5 61.6 ≥65 103 283 72 7800 29 116 66 295 0.9 78.7 64.2 Country of birth Japan-born 139 521 265 12 862 39 215 87 179 2.0 74.9 62.5 Foreign-born 11 885 107 1398 3188 7192 7.1 67.9 60.5 Unknown 5470 7 79 632 4752 8.1 88.0 86.9 Occupational category Health-care worker 4526 15 478 1259 2774 3.0 71.9 61.3 Service industry worker 3916 38 520 1102 2256 6.8 66.4 57.6 Other full-time worker 22 524 98 2741 5884 13 801 3.5 67.5 61.3 Temporary worker 5256 34 632 1303 3287 5.1 66.2 62.5 Self-employed 6154 20 656 1714 3764 3.0 71.7 61.2 Unemployed Adults 103 310 152 8001 28 971 66 186 1.9 78.0 64.1 High school and university students 4360 11 636 1265 2448 1.7 66.2 56.1 Children and infants 527 1 45 225 256 2.2 83.0 48.6 Other or job unknown 6303 10 630 1312 4351 1.6 67.2 69.0 provided free of charge and anonymously at public health centres, low uptake has been reported in Japan13,14 among younger populations and among MSM, who are considered to be more knowledgeable and conscious about the risk of HIV infection.15 The number of HIV tests conducted at these centres has also gradually decreased, from about 146 000 tests in 2008 to 105 000 tests in 2019.4 The proportion of adult males who have ever had an HIV test in Japan is around 10%,16 much lower than in the United States (41.3%),17 Canada (40.4%)18 and England (32.4%).19 Inconvenience, social stigma against homosexuality and discrimination against MSM and people living with HIV or AIDS are some reasons for the low uptake of testing,9 and these may prevent the active promotion of HIV counselling and testing, even to those considered to be at high risk. It is necessary for public among those born in Japan.9 This estimate, along with delays in seeking HIV care among foreign-born cases8,10 and the findings of this study, suggest that Japan could potentially be facing a large pool of foreign-born persons at risk of TB/HIV coinfection. A low HIV testing rate (9.4%) was observed among TB cases in this study. Although HIV testing is recom- mended for all people with TB in Japan,12 and questions about comorbidities are asked during the TB case inter- view, anecdotal evidence suggests that in practice, public health nurses are reluctant to counsel TB cases about HIV and offer testing. Because approximately 70% of Japan’s TB cases are aged ≥65 years, they are not perceived to be at risk of HIV infection or AIDS. Therefore, the ques- tion may seem unnecessary. Despite HIV testing being WPSAR Vol 13, No 1, 2022 | doi: 10.5365/wpsar.2022.13.1.896 https://ojs.wpro.who.int/6 Kawatsu et alTB and HIV coinfection in Japan health centres to have staff who are adequately trained and have counselling skills to communicate with patients with TB about HIV and AIDS in multiple languages. Treatment success differed by HIV status and country of birth. Treatment success was lower for Japan-born HIV-positive TB cases, at 65.6%, compared with Japan-born HIV-negative cases, at 72.2%, largely due to the high proportion of HIV-positive TB cases who were still undergoing treatment. Since treatment outcomes are entered into the JTBS system after 1 year of surveillance, it is possible that the final treatment outcomes of TB cases with HIV coinfection are not captured, especially as their treatment may have been prolonged due to complications. Among foreign-born patients with TB, treatment success for HIV-positive patients, at 50.9%, was lower than that for HIV-negative cases, at 76.4%. Cases not in the category of treatment success include those still undergoing treatment and those who have transferred out of the system, for example, to return to their home country for treatment. Although there are various public subsidies for antiretroviral therapy in Japan, it is not completely free, and the process of applying for these subsidies can be complicated for people born outside of Japan. Thus the financial burden of antiretroviral therapy, coupled with psychological stress owing to difficulties in communication and cultural differences, Table 2. Demographic characteristics of HIV-positive TB cases, by country of birth, Japan, 2012–2020 (N = 379) Table 3. Treatment outcomes for TB cases by country of birth and HIV status, Japan, 2016–2019 Characteristic Country of birth Japan (n = 265) Foreign country (n = 107) Unknown (n = 7) Sex Male 234 73 6 Female 31 34 1 Age group (years) 0-24 3 14 0 25-64 195 91 4 ≥65 67 2 3 Occupational category Health-care worker 13 2 0 Service industry worker 26 12 0 Other full-time worker 67 29 2 Temporary worker 18 16 0 Self-employed 17 3 0 Unemployed Adults 119 29 4 High school and university students 0 11 0 Children and infants 0 1 0 Other or job unknown 5 4 1 Treatment outcome Country of birth Japan, n (%) Foreign country, n (%) HIV-positive HIV-negative HIV-positive HIV-negative Success 61 (65.6) 3288 (72.2) 27 (50.9) 508 (76.4) Cured 17 (18.3) 815 (17.9) 7 (13.2) 161 (24.2) Treatment completed 44 (47.3) 2473 (54.3) 20 (37.7) 347 (52.2) Died 8 (8.6) 865 (19.0) 3 (5.7) 14 (2.1) Failure 0 (0.0) 4 (0.1) 0 (0.0) 1 (0.2) Lost to follow-up 4 (4.3) 89 (2.0) 1 (1.9) 7 (1.1) Transferred out 2 (2.2) 122 (2.7) 15 (28.3) 96 (14.4) Treatment ongoing 16 (17.2) 185 (4.1) 6 (11.3) 37 (5.6) Unknown 2 (2.2) 4 (0.1) 1 (1.9) 2 (0.3) Total 93 (100.0) 4557 (100.0) 53 (100.0) 665 (100.0) WPSAR Vol 13, No 1, 2022 | doi: 10.5365/wpsar.2022.13.1.896https://ojs.wpro.who.int/ 7 TB and HIV coinfection in JapanKawatsu et al have encouraged people who are HIV-positive, and also prompted physicians to persuade them, to return to their countries of birth to continue treatment.20,21 To prevent disruption of treatment and poor treatment outcomes, social protection measures are urgently required to ensure that foreign-born TB patients receive appropriate care and treatment in Japan; additionally, cross-border referral mechanisms are also needed. Limitations Our study had several limitations. First, entering whether a person is living with HIV into the JTBS system is optional. Therefore, public health nurses who inter- view patients with TB are not obligated to ask for that information. Second, when HIV status is recorded, it is self-reported and not verified or linked to other clinical databases. Therefore, it is possible that the HIV positivity rate reported among TB cases is an underestimation of the true occurrence in Japan. Also, because there are no data in Japan about the uptake of HIV testing stratified by sociodemographic characteristics, it is difficult to assess whether the increase in HIV positivity among those tested was due to a real increase in the number of HIV-positive TB cases or if HIV testing was more focused on high-risk groups.22 CONCLUSIONS The increasing proportion of HIV positivity among TB patients tested for HIV shown in this study requires ongo- ing monitoring, especially among foreign-born persons. However, as the number of reported cases was small, and the data on HIV testing reported in the JTB system were not complete, these results need to be interpreted with caution. Encouraging more complete data collection by training the public health nurses who complete TB case interviews, as well as ensuring there is ongoing monitor- ing of patients with TB/HIV coinfection is recommended. Acknowledgements The authors thank all those involved in collecting and entering data into the Japan Tuberculosis Surveillance system. Conflicts of interest The authors have no conflicts of interest to declare. Ethics statement The study protocol was approved by the Institutional Review Board of the Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association (reference no. RIT/ IRB 2021-5). Informed consent was deemed unneces- sary by the review board, as the surveillance data did not contain personal identifiers. Funding No funding was received to conduct this study. References 1. 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