Abstract
Background
Tuberculosis infection (TBI) and chronic hepatitis B virus (HBV) infection disproportionately affect non–US-born persons. Early identification and treatment are critical to reduce transmission, morbidity, and mortality, but little is known about screening in the United States.
Methods
We conducted a cross-sectional study in a large integrated California health system in September 2022 assessing TBI and HBV screening among persons aged ≥18 years who were born in countries with high TB burden (TB disease incidence rates ≥20/100 000 population) and/or HBV burden (hepatitis B surface antigen seroprevalence >2%).
Results
Of 510 361 non–US-born persons born in countries with high TB burden, 322 027 (63.1%) were born in countries with high HBV burden and 188 334 (36.9%) in countries with only high TB burden. Among persons born in countries with high TB and HBV burden, 29.6% were screened for TBI, 64.5% for HBV, and 23.4% for TBI and HBV; 9.9% had TBI and 3.1% had HBV infection. Among persons born in countries with high TB burden only, 27.9% were screened for TBI and 7.5% had TBI.
Conclusions
Among non–US-born persons from countries with high TB and HBV burden, we found low screening rates and elevated prevalence of TBI and chronic HBV infection. Cotesting for TBI and HBV infection in non–US-born persons from countries with high TB and HBV burden might improve outcomes by identifying persons who warrant TBI treatment, HBV treatment, or HBV vaccination. Increased screening is the first step in reducing health inequities and overall disease burden.
Keywords: health disparities, hepatitis B, screening, tuberculosis
Tuberculosis and chronic hepatitis B virus infection can have significant morbidity and mortality, but little is known about screening among non-U.S.–born persons from high burden countries. This study highlights the need to prioritize these persons and consider combined testing
In the United States, an estimated 13 million persons have tuberculosis infection (TBI) and are at risk of progression to tuberculosis (TB) disease if infection remains untreated [1–3]. Nearly 75% of TB cases reported in the United States during 2022 were among non–US-born persons [4]. The US Preventive Services Task Force recommends testing and treatment among populations at higher TBI risk, including non–US-born persons [3]. Despite the efficacy of TBI treatment for preventing morbidity and mortality, prior research has found significant gaps in TBI management, with 72% of persons receiving appropriate screening, 44% receiving a medical evaluation and TBI diagnosis, 31% starting treatment, and only 19% completing treatment [5].
In the United States, up to 2.4 million persons are living with chronic hepatitis B virus (HBV) infection, and of these individuals, 1.47 million are non–US born; approximately 59% emigrated from Asia, 19% from the Americas, and 15% from Africa [6]. The majority of adults who are immunocompetent and infected with HBV have spontaneous clearance of the virus, predominately via the adaptive immune system, but the remainder develop chronic HBV, which, if left undiagnosed and untreated, can progress from asymptomatic infection to cirrhosis and hepatocellular carcinoma [7]. Globally, most chronic HBV infection results from mother-to-child transmission during birth and early childhood [8]. Children with perinatally acquired HBV usually remain hepatitis B e-antigen positive and have high levels of viral replication for prolonged periods [9]; thus, they are at high risk of progression to chronic infection and serious complications. Monitoring, antiviral therapy, and cancer surveillance can decrease morbidity and mortality for persons with chronic HBV. Therefore, early HBV diagnoses among asymptomatic persons can facilitate specific clinical interventions and guidance or behavioral counseling to reduce morbidity and transmission. However, in the United States, only 50% of persons with chronic HBV infection have been diagnosed [10]. Among persons with chronic HBV infection who developed cirrhosis, <40% have received antiviral therapy [11]. Updated 2023 Centers for Disease Control and Prevention (CDC) guidelines recommend onetime universal screening of all adults aged >18 with hepatitis B surface antigen (HbsAg), antibody to hepatitis B surface antigen (HbsAb), and total antibody to hepatitis B core antigen (HbcAb) [12]. Onetime HbsAg screening of adults was estimated to be highly cost-effective and predicted to prevent, for every 100 000 adults screened, an additional 7.4 cases of compensated cirrhosis, 3.3 cases of decompensated cirrhosis, 5.5 cases of hepatocellular carcinoma, 1.9 liver transplants, and 10.3 HBV-related deaths when compared with current screening practices [12]. In addition, HBV infection can be prevented with highly effective and well-tolerated vaccines. In 2022, the CDC Advisory Committee on Immunization Practices switched from a risk-based approach to a universal recommendation for all adults aged 19 to 59 years to receive HBV vaccination [13]. Moreover, previous studies in the US adult population have shown a high prevalence of TBI-HBV coinfection, and a study from California noted that 4% of persons with TB disease were coinfected with HBV [14–16].
Non–US-born persons are disproportionately at risk for TB and HBV; thus, cotesting non–US-born persons for TBI and HBV might present an opportunity to improve screening for both infections. Improved screening is the prerequisite for providing vaccination and treatment, with the ultimate goal to reduce morbidity and mortality of both infections. However, little is known about screening for TBI and HBV among non–US-born persons in the United States. To better understand screening practices, we conducted a cross-sectional study of non–US-born adults in a large integrated health system in California and assessed TBI and HBV screening practices as well as prevalence of diagnosed TBI and HBV infection.
METHODS
Kaiser Permanente Northern California (KPNC) is an integrated health system that provides comprehensive care to 4.6 million members in northern and central California. Most care, including laboratory testing, is conducted in KPNC facilities, including 266 medical offices and 21 hospitals [17].
We conducted a cross-sectional study of non–US-born adult KPNC members from countries that we categorized as having a high TB burden as defined by the CDC (TB disease incidence rates ≥20/100 000 population) [18] with or without high HBV burden (HBsAg seroprevalence >2%) [19]. Individual countries with high TB or HBV burden are shown in Figure 1. We assessed TBI and HBV screening using data obtained from the KPNC electronic health record database (Epic Systems Corporation) on 30 September 2022. The study was approved by the KPNC Institutional Review Board (1838887) with a waiver of the requirement for informed consent as a data-only study based on information collected as a part of routine care.
Figure 1.
Countries categorized as high TB burden with and without high HBV burden. High-burden countries are categorized as a TB disease incidence rate ≥20 per 100 000 population and a hepatitis B surface antigen seroprevalence >2%. Abbreviations: HBV, hepatitis B virus; TB, tuberculosis.
We included all persons aged ≥18 years who had at least 1 year of continuous membership prior to the index date of 30 September 2022 and were born in a country with high TB burden, with and without high HBV burden (documented location of birth in electronic medical records). Persons born in countries with only a high HBV burden were excluded due to small sample sizes. We excluded persons with a history of TB disease prior to 30 September 2022 (based on ICD-9 and ICD-10 codes; Supplemental Table 1), as persons with prior TB disease were ineligible for TBI screening.
We analyzed outcomes for 2 categories based on country of birth: high TB and HBV or high TB burden only. The primary outcomes were as follows:
Percentage of persons screened for TBI: at least 1 interferon gamma release assay (IGRA) or tuberculin skin test (TST) with a valid result before 30 September 2022
Percentage of persons diagnosed with TBI: at least 1 positive IGRA result or TST with induration ≥10 mm before 30 September 2022 (persons with a positive TST result but negative IGRA result were classified as not having TBI)
Percentage of persons screened for HBV: at least 1 HBsAg test completed before 30 September 2022
Percentage of persons with chronic HBV infection: at least 1 HBsAg positive result before 30 September 2022
Percentage of persons with past HBV infection: total HBcAb positive result and HBsAg negative result before 30 September 2022
Percentage of persons with receipt of at least 1 dose of hepatitis B vaccine or evidence of prior immunity based on HbsAb positivity (this excludes persons with HBcAb positivity)
Testing performed outside the KPNC system was not included. Select conditions that increase risk for progression to TB disease were as follows:
HIV infection based on ICD-9 codes 079.53, 042, V08, and 795.71 and ICD-10 codes B20, B97.71, Z21, and O98.7
Solid organ transplantation based on ICD-9 codes V42.0, V42.1, V42.6, V42.7, V42.83, and V42.84 and ICD-10 codes Z94.0 to Z94.4
Leukemia or lymphoma based on ICD-9 codes 200 to 208 and ICD-10 codes C81–C96
Receipt of tumor necrosis α inhibitors based on pharmacy records: adalimumab, certolizumab, etanercept, golimumab, infliximab
Receipt of high-dose corticosteroids defined as ≥20-mg prednisone equivalents of oral or systemic corticosteroids daily for ≥30 days based on pharmacy records
Receipt of other immunosuppressants based on pharmacy records: abatacept, anakinra, auranofin, azathioprine, baricitinib, canakinumab, cyclosporine, fingolimod, guselkumab, leflunomide, mycophenolate mofetil, risankizumab, rituximab, secukinumab, sirolimus, tacrolimus, thalidomide, tofacitinib, tocilizumab, and ustekinumab
Diabetes mellitus based on ICD-9 codes 249 and 250 and ICD-10 codes E08 to E11 and E13
End-stage renal disease based on ICD-9 585.6 code and ICD-10 code N18.6
Other covariates included demographic characteristics (age, sex, race/ethnicity) and Charlson Comorbidity Index score [20].
RESULTS
We identified 510 361 non–US-born persons from countries with a high TB burden, of whom 322 027 (63.1%) were born in countries with high TB and HBV burden and 188 334 (36.9%) were born in countries with high TB burden only (Table 1). Within the medical record, 58.8% of patients had a country of birth listed. Among persons born in countries with high TB and HBV burden, 60.0% were female, as compared with 55.0% female in persons born in countries with a high TB burden only, and the majority of persons were aged >50 years in both groups. Among persons born in countries with high TB and HBV burden, 8726 (2.7%) were of Hispanic ethnicity, as compared with 149 345 (79.3%) persons born in countries with high TB burden only. However, 266 969 (82.9%) persons born in countries with high TB and HBV burden were of Asian race, as compared with 5615 (3.0%) persons born in countries with only a high TB burden. The majority had a Charlson Comorbidity Index score of 0 in persons born in countries with high TB and HBV burden (56.2%) and persons born in countries with only a high TB burden (54.7%). The most prevalent immune compromising condition was diabetes mellitus in persons born in countries with high TB and HBV burden (22.4%) and persons born in countries with only a high TB burden (21.7%). The median time as a Kaiser Permanente member prior to the index date was 7.8 years (IQR, 4.6–11.4).
Table 1.
Characteristics of Persons Born Outside the United States in Countries With High TB Burden, With and Without High HBV Burden: September 2022
| Non–US-Born Persons From Countries With | ||||||
|---|---|---|---|---|---|---|
| High TB With or Without HBV Burden | High TB and HBV Burden | High TB Burden Only | ||||
| No. | % | No. | % | No. | % | |
| Total | 510 361 | 100 | 322 027 | 63.1 | 188 334 | 36.9 |
| Sex | ||||||
| Male | 213 500 | 41.8 | 128 751 | 40.0 | 84 749 | 45.0 |
| Female | 296 861 | 58.2 | 193 276 | 60.0 | 103 585 | 55.0 |
| Age, y | ||||||
| 18–29 | 21 571 | 4.2 | 12 616 | 3.9 | 8955 | 4.8 |
| 30–39 | 70 765 | 13.9 | 44 463 | 13.8 | 26 302 | 14.0 |
| 40–49 | 103 674 | 20.3 | 62 315 | 19.4 | 41 359 | 22.0 |
| 50–59 | 114 700 | 22.5 | 69 220 | 21.5 | 45 480 | 24.1 |
| 60–69 | 98 074 | 19.2 | 64 172 | 19.9 | 33 902 | 18.0 |
| 70–79 | 65 837 | 12.9 | 45 690 | 14.2 | 20 147 | 10.7 |
| ≥80 | 35 740 | 7.0 | 23 551 | 7.3 | 12 189 | 6.5 |
| Race and ethnicity | ||||||
| White | 39 401 | 7.7 | 12 382 | 3.8 | 27 019 | 14.3 |
| Black | 9171 | 1.8 | 8091 | 2.5 | 1080 | 0.6 |
| Hispanic | 158 071 | 31.0 | 8726 | 2.7 | 149 345 | 79.3 |
| Asian | 272 584 | 53.4 | 266 969 | 82.9 | 5615 | 3.0 |
| American Indian/Alaska Native | 1246 | 0.2 | 1092 | 0.3 | 154 | 0.1 |
| Hawaiian/Pacific Islander | 8113 | 1.6 | 7979 | 2.5 | 134 | 0.1 |
| Other/multiple/unknown | 21 775 | 4.3 | 16 788 | 5.2 | 4987 | 2.6 |
| CCI score at index date | ||||||
| 0 | 283 819 | 55.6 | 180 842 | 56.2 | 102 977 | 54.7 |
| 1 | 80 016 | 15.7 | 49 151 | 15.3 | 30 865 | 16.4 |
| 2 | 45 495 | 8.9 | 28 230 | 8.8 | 17 265 | 9.2 |
| ≥3 | 69 377 | 13.6 | 45 463 | 14.1 | 23 914 | 12.7 |
| No visits prior year | 31 654 | 6.2 | 18 341 | 5.7 | 13 313 | 7.1 |
| Immune compromised | ||||||
| HIV infection | 1251 | 0.2 | 568 | 0.2 | 683 | 0.4 |
| Solid organ transplantation | 1872 | 0.4 | 1177 | 0.4 | 695 | 0.4 |
| Diabetes mellitus | 113 098 | 22.2 | 72 254 | 22.4 | 40 844 | 21.7 |
| End stage renal disease | 4128 | 0.8 | 2697 | 0.8 | 1431 | 0.8 |
| Leukemia and lymphoma | 4296 | 0.8 | 2561 | 0.8 | 1735 | 0.9 |
| Receipt of TNF-α inhibitors | 1077 | 0.2 | 588 | 0.2 | 489 | 0.3 |
| Receipt of chronic, high-dose steroids | 11 044 | 2.2 | 6990 | 2.2 | 4054 | 2.2 |
| Receipt of other immunosuppressants | 8267 | 1.6 | 4854 | 1.5 | 3413 | 1.8 |
| Time as member pre–index date, y, median (IQR) | 7.8 | 4.6–11.4 | 7.8 | 4.6–11.4 | 7.8 | 4.6–11.4 |
| Any prior HBV vaccination | 121 837 | 23.9 | 79 662 | 24.7 | 42 175 | 22.4 |
High-burden countries for TB and HBV are categorized as TB disease incidence rates ≥20 per 100 000 population and hepatitis B surface antigen seroprevalence >2%, respectively.
Abbreviations: CCI, Charlson Comorbidity Index; HBV, hepatitis B virus; TB, tuberculosis; TNF-α, tumor necrosis factor α.
Of persons born in countries with high TB and HBV burden, 95 410 (29.6%) were screened for TBI, 207 570 (64.5%) for HBV, and just 75 419 (23.4%) for TBI and HBV (Table 2). Among all persons born in countries with high TB and HBV burden, 31 918 (9.9%) tested positive for TBI (Table 3) and 9949 (3.1%) tested positive for chronic HBV (Table 4). Among persons born in countries with high TB and HBV burden who were tested, 33.5% tested positive for TB and 5.1% tested positive for chronic HBV. Of persons born in countries with only high TB burden, 52 472 (27.9%) were screened for TBI, 14 147 (7.5%) were diagnosed with TBI, 99 465 (52.8%) were screened for HBV, and 340 (0.2%) had been diagnosed with chronic HBV. Among persons born in countries with only high TB burden who were tested, 27% tested positive for TB. In all, 362 479 persons (71.0%) born in countries with high TB burden had not been screened for TBI, and 127 958 persons (39.7%) born in countries with high TB and HBV burden had not been screened for HBV. Among 277 903 persons from countries with high TB and HBV burden who did not have chronic or past HBV infection (ie, currently eligible for HBV vaccination), just 74 241 (26.7%) had prior HBV vaccination (defined as at least 1 dose of the HBV vaccine), and 39.7% had any evidence of HBV immunity (HBsAb positive or received at least 1 dose of HBV vaccine). Among persons born in high TB and HBV countries, only 79 662 (24.7%) had prior HBV vaccination.
Table 2.
Screening for TBI or HBV Infection Among Persons Born Outside the United States From Countries With High TB, With and Without High HBV Burden: September 2022
| Total | Any TBI Screening | Any HBV Screening | Screened for TBI and HBV | No Testing Done | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Region/Country | TB ± HBV | No. | No. | % | No. | % | No. | % | No. | % |
| Born in country with | ||||||||||
| High TB or HBV burden | TB or HBV | 510 361 | 147 882 | 29.0 | 307 035 | 60.2 | 113 607 | 22.3 | 169 051 | 33.1 |
| High TB and HBV burden | TB + HBV | 322 027 | 95 410 | 29.6 | 207 570 | 64.5 | 75 419 | 23.4 | 94 466 | 29.3 |
| High TB burden only | TB only | 188 334 | 52 472 | 27.9 | 99 465 | 52.8 | 38 188 | 20.3 | 74 585 | 39.6 |
| By region | ||||||||||
| Africa | TB + HBV | 11 204 | 4457 | 39.8 | 7162 | 63.9 | 3542 | 31.6 | 3127 | 27.9 |
| TB only | 612 | 184 | 30.1 | 342 | 55.9 | 141 | 23.0 | 227 | 37.1 | |
| Caribbean | TB + HBV | 572 | 206 | 36.0 | 341 | 59.6 | 162 | 28.3 | 187 | 32.7 |
| TB only | 3633 | 1221 | 33.6 | 1982 | 54.6 | 850 | 23.4 | 1280 | 35.2 | |
| South America | TB + HBV | 4177 | 1481 | 35.5 | 2378 | 56.9 | 1076 | 25.8 | 1394 | 33.4 |
| TB only | 8862 | 2989 | 33.7 | 5294 | 59.7 | 2266 | 25.6 | 2845 | 32.1 | |
| Central America | TB only | 141 162 | 39 155 | 27.7 | 74 675 | 52.9 | 28 622 | 20.3 | 55 954 | 39.6 |
| Asia | TB + HBV | 294 005 | 85 311 | 29.0 | 190 570 | 64.8 | 67 578 | 23.0 | 85 702 | 29.1 |
| TB only | 22 082 | 5909 | 26.8 | 11 041 | 50.0 | 4124 | 18.7 | 9256 | 41.9 | |
| Europe | TB + HBV | 1605 | 456 | 28.4 | 820 | 51.1 | 317 | 19.8 | 646 | 40.2 |
| TB only | 11 921 | 2993 | 25.1 | 6083 | 51.0 | 2167 | 18.2 | 5012 | 42.0 | |
| Oceania | TB + HBV | 10 464 | 3499 | 33.4 | 6299 | 60.2 | 2744 | 26.2 | 3410 | 32.6 |
| TB only | 62 | 21 | 33.9 | 48 | 77.4 | 18 | 29.0 | 11 | 17.7 | |
| By country | ||||||||||
| Mexico | TB only | 111 567 | 30 104 | 27.0 | 57 425 | 51.5 | 21 738 | 19.5 | 45 776 | 41.0 |
| Philippines | TB + HBV | 80 850 | 29 322 | 36.3 | 53 720 | 66.4 | 23 544 | 29.1 | 21 352 | 26.4 |
| Chinaa | TB + HBV | 82 870 | 18 977 | 22.9 | 56 670 | 68.4 | 15 231 | 18.4 | 22 454 | 27.1 |
| India | TB + HBV | 49 757 | 16 240 | 32.6 | 27 516 | 55.3 | 12 118 | 24.4 | 18 119 | 36.4 |
| Vietnam | TB + HBV | 33 745 | 7641 | 22.6 | 24 425 | 72.4 | 6505 | 19.3 | 8184 | 24.3 |
| El Salvador | TB only | 15 591 | 4698 | 30.1 | 9115 | 58.5 | 3584 | 23.0 | 5362 | 34.4 |
| Korea | TB + HBV | 10 705 | 2568 | 24.0 | 6271 | 58.6 | 1949 | 18.2 | 3815 | 35.6 |
Abbreviations: HBcAb, hepatitis B core antibody; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; TB, tuberculosis; TBI, tuberculosis infection; IGRA, interferon gamma release assay; TST, tuberculin skin test.
In total, 911 persons with indeterminate HBV testing results are not included. Any TBI screening is defined as at least 1 IGRA or TST with a valid result before 30 September 2022. Screened for HBV is defined as at least 1 HBsAg test completed before 30 September 2022. Mexico, Philippines, China, India, Vietnam, El Salvador, and Korea are the 7 countries with largest non–US-born patient populations in Kaiser Permanente Northern California.
aChina includes Hong Kong, Macau, and Taiwan.
Table 3.
TBI Screening Test Results Among Persons Born Outside the United States in Countries With High TB Burden, With and Without High HBV Burden: September 2022
| Total | Screened for TBI | IGRA or TST Positive (TBI Diagnosis) | All IGRA or TST Negative | No TBI Testing Done | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Region/Country | TB ± HBV | No. | No. | % | No. | % | No. | % | No. | % |
| Born in country with | ||||||||||
| High TB or HBV burden | TB or HBV | 510 361 | 147 882 | 29.0 | 46 065 | 9.0 | 101 817 | 19.9 | 362 479 | 71.0 |
| High TB and HBV burden | TB + HBV | 322 027 | 95 410 | 29.6 | 31 918 | 9.9 | 63 492 | 19.7 | 226 617 | 70.4 |
| High TB burden only | TB only | 188 334 | 52 472 | 27.9 | 14 147 | 7.5 | 38 325 | 20.3 | 135 862 | 72.1 |
| By region | ||||||||||
| Africa | TB + HBV | 11 204 | 4457 | 39.8 | 1861 | 16.6 | 2596 | 23.2 | 6747 | 60.2 |
| TB only | 612 | 184 | 30.1 | 52 | 8.5 | 132 | 21.6 | 428 | 69.9 | |
| Caribbean | TB + HBV | 572 | 206 | 36.0 | 68 | 11.9 | 138 | 24.1 | 366 | 64.0 |
| TB only | 3633 | 1221 | 33.6 | 232 | 6.4 | 989 | 27.2 | 2412 | 66.4 | |
| South America | TB + HBV | 4177 | 1481 | 35.5 | 272 | 6.5 | 1209 | 28.9 | 2696 | 64.5 |
| TB only | 8862 | 2989 | 33.7 | 966 | 10.9 | 2023 | 22.8 | 5873 | 66.3 | |
| Central America | TB only | 141 162 | 39 155 | 27.7 | 10 318 | 7.3 | 28 837 | 20.4 | 102 007 | 72.3 |
| Asia | TB + HBV | 294 005 | 85 311 | 29.0 | 28 137 | 9.6 | 57 174 | 19.4 | 208 694 | 71.0 |
| TB only | 22 082 | 5909 | 26.8 | 1575 | 7.1 | 4334 | 19.6 | 16 173 | 73.2 | |
| Europe | TB + HBV | 1605 | 456 | 28.4 | 117 | 7.3 | 339 | 21.1 | 1149 | 71.6 |
| TB only | 11 921 | 2993 | 25.1 | 1002 | 8.4 | 1991 | 16.7 | 8928 | 74.9 | |
| Oceania | TB + HBV | 10 464 | 3499 | 33.4 | 1463 | 14.0 | 2036 | 19.5 | 6965 | 66.6 |
| TB only | 62 | 21 | 33.9 | 2 | 3.2 | 19 | 30.6 | 41 | 66.1 | |
| By country | ||||||||||
| Mexico | TB only | 111 567 | 30 104 | 27.0 | 7441 | 6.7 | 22 663 | 20.3 | 81 463 | 73.0 |
| Philippines | TB + HBV | 80 850 | 29 322 | 36.3 | 11 308 | 14.0 | 18 014 | 22.3 | 51 528 | 63.7 |
| Chinaa | TB + HBV | 82 870 | 18 977 | 22.9 | 5687 | 6.9 | 13 290 | 16.0 | 63 893 | 77.1 |
| India | TB + HBV | 49 757 | 16 240 | 32.6 | 4776 | 9.6 | 11 464 | 23.0 | 33 517 | 67.4 |
| Vietnam | TB + HBV | 33 745 | 7641 | 22.6 | 2657 | 7.9 | 4984 | 14.8 | 26 104 | 77.4 |
| El Salvador | TB only | 15 591 | 4698 | 30.1 | 1570 | 10.1 | 3128 | 20.1 | 10 893 | 69.9 |
| Korea | TB + HBV | 10 705 | 2568 | 24.0 | 900 | 8.4 | 1668 | 15.6 | 8137 | 76.0 |
Any TBI screening is defined as at least 1 IGRA or TST with a valid result before 30 September 2022. TBI diagnosis is defined as at least 1 positive IGRA result or TST with induration ≥10 mm before 30 September 2022 (persons with a positive TST result but a negative IGRA result were classified as not having TBI). Mexico, Philippines, China, India, Vietnam, El Salvador, and Korea are the 7 countries with largest non–US-born patient populations in Kaiser Permanente Northern California.
Abbreviations: HBV, hepatitis B virus; IGRA, interferon gamma release assay; TB, tuberculosis; TBI, tuberculosis infection; TST, tuberculin skin test.
aChina includes Hong Kong, Macau, and Taiwan.
Table 4.
HBV Screening Among Persons Born Outside the United States in Countries With High TB Burden, With and Without High HBV Burden: September 2022
| Total | Not Screened | Screened for HBV and HBV Negative | Screened and Chronic HBV Infection | Screened and Past HBV Infection | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Region/Country | TB ± HBV | No. | No. | % | No. | % | No. | % | No. | % |
| Born in country with | ||||||||||
| High TB or HBV burden | TB or HBV | 510 361 | 224 242 | 43.9 | 239 014 | 46.8 | 10 289 | 2.0 | 36 451 | 7.1 |
| High TB and HBV burden | TB + HBV | 322 027 | 127 958 | 39.7 | 149 945 | 46.6 | 9949 | 3.1 | 33 826 | 10.5 |
| High TB burden only | TB only | 188 334 | 96 284 | 51.1 | 89 069 | 47.3 | 340 | 0.2 | 2625 | 1.4 |
| By region | ||||||||||
| Africa | TB + HBV | 11 204 | 4682 | 41.8 | 5262 | 47.0 | 204 | 1.8 | 1049 | 9.4 |
| TB only | 612 | 304 | 49.7 | 287 | 46.9 | 1 | 0.2 | 20 | 3.3 | |
| Caribbean | TB + HBV | 572 | 275 | 48.1 | 279 | 48.8 | 0 | 0.0 | 18 | 3.1 |
| TB only | 3633 | 1846 | 50.8 | 1633 | 44.9 | 15 | 0.4 | 137 | 3.8 | |
| South America | TB + HBV | 4177 | 2004 | 48.0 | 2087 | 50.0 | 6 | 0.1 | 80 | 1.9 |
| TB only | 8862 | 3977 | 44.9 | 4680 | 52.8 | 24 | 0.3 | 181 | 2.0 | |
| Central America | TB only | 141 162 | 71 829 | 50.9 | 67 875 | 48.1 | 125 | 0.1 | 1327 | 0.9 |
| Asia | TB + HBV | 294 005 | 115 371 | 39.2 | 136 453 | 46.4 | 9630 | 3.3 | 32 210 | 11.0 |
| TB only | 22 082 | 11 993 | 54.3 | 9381 | 42.5 | 117 | 0.5 | 587 | 2.7 | |
| Europe | TB + HBV | 1605 | 850 | 53.0 | 693 | 43.2 | 16 | 1.0 | 46 | 2.9 |
| TB only | 11 921 | 6319 | 53.0 | 5177 | 43.4 | 55 | 0.5 | 366 | 3.1 | |
| Oceania | TB + HBV | 10 464 | 4776 | 45.6 | 5171 | 49.4 | 93 | 0.9 | 423 | 4.0 |
| TB only | 62 | 16 | 25.8 | 36 | 58.1 | 3 | 4.8 | 7 | 11.3 | |
| By country | ||||||||||
| Mexico | TB only | 111 567 | 58 068 | 52.0 | 52 563 | 47.1 | 83 | 0.1 | 848 | 0.8 |
| Philippines | TB + HBV | 80 850 | 31 718 | 39.2 | 39 656 | 49.0 | 1555 | 1.9 | 7861 | 9.7 |
| Chinaa | TB + HBV | 82 870 | 28 394 | 34.3 | 36 600 | 44.2 | 4364 | 5.3 | 13 359 | 16.1 |
| India | TB + HBV | 49 757 | 24 691 | 49.6 | 24 050 | 48.3 | 177 | 0.4 | 835 | 1.7 |
| Vietnam | TB + HBV | 33 745 | 10 263 | 30.4 | 15 094 | 44.7 | 2317 | 6.9 | 5987 | 17.7 |
| El Salvador | TB only | 15 591 | 7242 | 46.4 | 8064 | 51.7 | 28 | 0.2 | 257 | 1.6 |
| Korea | TB + HBV | 10 705 | 4830 | 45.1 | 4300 | 40.2 | 247 | 2.3 | 1322 | 12.3 |
In total, 911 persons with indeterminate HBV testing results are not included. Chronic HBV infection is defined as at least 1 HBSAg positive result before 30 September 2022. Past HBV infection is defined as HBcAb positive result and HBSAg negative result before 30 September 2022. Mexico, Philippines, China, India, Vietnam, El Salvador, and Korea are the 7 countries with largest non–US-born patient populations in Kaiser Permanente Northern California.
Abbreviations: HBcAb, hepatitis B core antibody; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; TB, tuberculosis.
aChina includes Hong Kong, Macau, and Taiwan.
DISCUSSION
Undiagnosed TBI and HBV infection is often asymptomatic but can lead to TB disease or hepatic fibrosis, cirrhosis, and hepatocellular carcinoma, respectively; screening is the first necessary step to guide appropriate management to reduce morbidity and mortality. In a large health care system in California, less than one-third of non–US-born adults from countries with high TB and high HBV burden were screened for TBI (29.6%), and approximately two-thirds were screened for HBV (64.5%), highlighting the need for increased screening for both infections. These low screening rates may be due to many factors, including inadequate knowledge of guidelines, insufficient time of outpatient visits, and concern for stigma associated with these infections. Despite these low screening rates, a high percentage of non–US-born adults from countries with high TB and HBV burden were diagnosed with TBI (9.9%) or HBV (3.1%), and prevalence rates would be even higher if estimated only among persons who received screening tests (33.5% tested positive for TBI and 5.1% for chronic HBV). Moreover, approximately 1 in 4 persons from countries with high TB and HBV burden who did not have HBV infection had received HBV vaccination. Greater awareness from providers and health systems of the often-unrecognized burden of both diseases in the United States is needed to improve screening and vaccination rates. There were no electronic medical record TB or HBV screening prompts during this study period; thus, ordering these tests depended entirely on providers’ knowledge of current guidelines. Creating a standard electronical medical record prompt may be one solution to increase testing and vaccination.
The CDC 2025 National TB Program Objectives and Performance target to reduce TB disease incidence among non–US-born persons to 8.8 cases per 100 000 will partially rely on increased screening and treatment of TBI in this population [21]. In our large integrated health system, only 29% of all non–US-born persons were ever screened for TBI, which is comparable to screening rates that have been found in other US health care settings [22, 23]; as such, significant improvement in screening is needed to support TB disease elimination in the United States.
Similarly, the US Department of Health and Human Services’ Viral Hepatitis National Strategic Plan set a goal to eliminate the public health threat of viral hepatitis A, B, and C infections in the United States by 2030 [24]. This strategic plan involves the components of prevention, increased surveillance and data usage, improvement in health outcomes, reduction in viral hepatitis–related disparities and health inequities, and coordinated efforts among all partners and stakeholders. In our large health care system, non–US-born persons from countries with high TB and HBV burden had a relatively high prevalence of chronic HBV infection (3.2%), but overall rates of HBV screening and HBV vaccination could be improved substantially. Although there are now expanded recommendations for HBV screening and vaccination, non–US-born persons from endemic regions should initially be prioritized given their high risk for HBV, which also provides an opportunity to concurrently consider TBI testing in this patient population.
Combining screening efforts for TBI and HBV infection in non–US-born persons from countries with high TB and HBV burden has numerous advantages and can broadly support both disease control efforts. First, TBI and HBV screening can be conducted via laboratory testing on blood, and both sets of tests could be offered through the same clinical encounter and conducted as part of the same laboratory visit. Moving away from TST toward IGRA testing can facilitate ease of screening to improve rates. Effectively implementing combined screening may be achieved with prompts for non–US-born patients, as well as bundling TBI and HBV screening with other recommended screening interventions. Second, a recent meta-analysis suggested that persons with chronic HBV are more than twice as likely to have TBI than persons without chronic HBV, highlighting their shared risk factors and the importance testing for both when one is considered [22]. Third, among persons with TBI, screening for HBV infection is important, as underlying chronic HBV infection significantly increases the risk of drug-induced liver injury from potentially hepatotoxic TBI treatment regimens (eg, rifamycins and isoniazid) [25]. Fourth, national strategic plans for TB and HBV control prioritize reducing health disparities. Non–US-born persons from regions with high TB and HBV burden, including Asia, Africa, and Oceania, have increased prevalence of TBI and chronic HBV infection and are thus disproportionately affected. Focused efforts in this population would support overall efforts to reduce the high burden of disease and poor outcomes, thereby reducing health disparities. Fifth, updated HBV screening and testing recommendations include screening all adults aged ≥18 years for hepatitis B at least once in their lifetime via a triple-panel test [26]; accordingly, all persons included in this analysis should be screened for HBV infection. In 2022 California mandated health care facilities to provide HBV screening, as well as hepatitis C screening, in an effort to improve adherence to existing HBV screening guidelines. Similarly, the HBV vaccine is recommended for all adults aged 19 through 59 years and adults aged ≥60 years with risk factors for hepatitis B infection [16].
This study has several strengths and limitations. A key strength is that our analysis is based on a large data set containing 4.5 million members in northern and central California, who receive most of their care within our system; thus, we have robust ascertainment of demographic and clinical characteristics as well as laboratory testing and receipt of vaccinations. In addition, KPNC members have been shown to have similar demographic characteristics to the general population, thereby enabling broader interpretation of results [17]. Moreover, country of birth was available in the medical record for 58.8% of all KPNC members. Many patients are missing the data for country of birth in the medical record, highlighting the importance of collecting social determinants of health data. However, this is still a substantial number, and it is more likely that a non–US-born patient will have country of birth listed; as such, this data set can provide a better understanding of screening practices in this population. A key limitation is the cross-sectional design of this study and inability to delve further into potential drivers of low screening prevalence in our health system.
In summary, TBI and chronic HBV infection can lead to significant morbidity and mortality, and this cross-sectional study of non–US-born persons from countries with high TB and HBV burden highlights the need for increased screening for TBI and chronic HBV infection. Combining screening efforts for TBI and HBV may decrease blood draws and facilitate identification of, and specific clinical interventions to prevent, HBV- and TB-associated mortality.
Supplementary Data
Supplementary materials are available at Open Forum Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.
Supplementary Material
Contributor Information
Jenna M Wick, Internal Medicine Residency Program, Oakland Medical Center, Kaiser Permanente Northern California, Oakland, California, USA.
Yuching Ni, Division of Research, Kaiser Permanente Northern California, Oakland, California, USA.
Nicole Halmer, Division of Research, Kaiser Permanente Northern California, Oakland, California, USA.
Robert J Wong, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, USA; Gastroenterology and Hepatology Section, Veterans Affairs Palo Alto Healthcare System, Palo Alto, California USA.
Amit S Chitnis, Tuberculosis Section, Division of Communicable Disease Control and Prevention, Alameda County Public Health Department, San Leandro, California, USA.
Devan Jaganath, Division of Pediatric Infectious Disease, University of California San Francisco, San Francisco, California, USA.
Amy L Krueger, Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Jacek Skarbinski, Division of Research, Kaiser Permanente Northern California, Oakland, California, USA; Department of Infectious Diseases, Oakland Medical Center, Kaiser Permanente Northern California, Oakland, California, USA; Physician Researcher Program, Kaiser Permanente Northern California, Oakland, California, USA.
Note
Potential conflicts of interest. All authors: No reported conflicts.
References
- 1. Miramontes R, Hill AN, Yelk Woodruff RS, et al. Tuberculosis infection in the United States: prevalence estimates from the National Health and Nutrition Examination Survey, 2011–2012. PLoS One 2015; 10:e0140881. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. Haddad MB, Raz KM, Lash TL, et al. Simple estimates for local prevalence of latent tuberculosis infection, United States, 2011–2015. Emerg Infect Dis 2018; 24:1930–3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Menzies D. Screening for latent tuberculosis infection. JAMA Netw Open 2023; 6:e2312114. [DOI] [PubMed] [Google Scholar]
- 4. Centers for Disease Control and Prevention . Reported tuberculosis in the United States, 2022. Atlanta, GA: US Department of Health and Human Services, 2023. [Google Scholar]
- 5. Alsdurf H, Hill PC, Matteelli A, Getahun H, Menzies D. The cascade of care in diagnosis and treatment of latent tuberculosis infection: a systematic review and meta-analysis. Lancet Infect Dis 2016; 16:1269–78. [DOI] [PubMed] [Google Scholar]
- 6. Wong RJ, Kaufman HW, Niles JK, Meyer WA III, Chitnis AS. Prevalence of hepatitis B virus and latent tuberculosis coinfection in the United States. J Public Health Manag Pract 2022; 28:452–62. [DOI] [PubMed] [Google Scholar]
- 7. Wong RJ, Rupp L, Lu M, et al. Prevalence of hepatitis B virus (HBV) and latent tuberculosis co-infection and risk of drug-induced liver injury across two large HBV cohorts in the United States. J Viral Hepat 2023; 30:512–9. [DOI] [PubMed] [Google Scholar]
- 8. Bertumen JB, Pascopella L, Han E, et al. Epidemiology and treatment outcomes of tuberculosis with chronic hepatitis B infection–California, 2016–2020. Clin Infect Dis 2024; 79:223–32. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. Wong R, Brosgart C, Welch S, et al. An updated assessment of chronic hepatitis B prevalence among foreign-born persons living in the United States. Hepatology 2021; 74:607–26. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. Dusheiko G, Agarwal K, Maini MK. New approaches to chronic hepatitis B. N Engl J Med 2023; 388:55–69. [DOI] [PubMed] [Google Scholar]
- 11. World Health Organization Hepatitis Programme . Hepatitis B vaccination and prevention of mother-to-child transmission. Available at: https://www.who.int/teams/global-hiv-hepatitis-and-stis-programmes/hepatitis/prevention/mother-to-child-transmission-of-hepatitis-b#:∼:text=Hepatitis%20B%20vaccination%20can%20be, HBV%20and%20early%20childhood%20transmission. Accessed 8 March 2024.
- 12. Lok ASF, Lai CL. A longitudinal follow-up of asymptomatic hepatitis B surface antigen–positive Chinese children. Hepatology 1988; 8:1130–3. [DOI] [PubMed] [Google Scholar]
- 13. Bixler D, Barker L, Lewis K, Peretz L, Teshale E. Prevalence and awareness of hepatitis B virus infection in the United States: January 2017–March 2020. Hepatol Commun 2023; 7:e0118. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14. Ogawa E, Yeo YH, Dang N, et al. Diagnosis rates of chronic hepatitis B in privately insured patients in the United States. JAMA Netw Open 2020; 3:e201844. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15. Toy M, Hutton D, Harris AM, Nelson N, Salomon JA, So S. Cost-effectiveness of 1-time universal screening for chronic hepatitis B infection in adults in the United States. Clin Infect Dis 2022; 74:210–7. [DOI] [PubMed] [Google Scholar]
- 16. Weng MK, Doshani M, Khan MA, et al. Universal hepatitis B vaccination in adults aged 19–59 years: updated recommendations of the advisory committee on immunization practices—United States, 2022. MMWR Morb Mortal Wkly Rep 2022; 71:477–83. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17. Davis AC, Voelkel JL, Remmers CL, Adams JL, McGlynn EA. Comparing Kaiser Permanente members to the general population: implications for generalizability of research. Perm J 2023; 27:87–98. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18. Centers for Disease Control . Tuberculosis refugee health domestic guidance. Available at: https://www.cdc.gov/immigrant-refugee-health/hcp/domestic-guidance/tuberculosis.html. Accessed 12 June 2024.
- 19. GBD 2019 Hepatitis B Collaborators . Global, regional, and national burden of hepatitis B, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Gastroenterol Hepatol 2022; 7:796–829. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20. Sundararajan V, Henderson T, Perry C, Muggivan A, Quan H, Ghali WA. New ICD-10 version of the Charlson Comorbidity Index predicted in-hospital mortality. J Clin Epidemiol 2004; 57:1288–94. [DOI] [PubMed] [Google Scholar]
- 21. Division of Tuberculosis Elimination, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention . 2025 national TB program objectives and performance targets. October 2022. Available at: https://www.cdc.gov/tb/programs/evaluation/indicators/default.htm. Accessed 25 March 2023.
- 22. Shapiro AE, Gupta A, Lan K, Kim HN. Latent tuberculosis screening cascade for non–US-born persons in a large health system. Open Forum Infect Dis 2023; 10:ofad303. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23. Vonnahme LA, Raykin J, Jones M, et al. Using electronic health record data to measure the latent tuberculosis infection care cascade in safety-net primary care clinics. AJPM Focus 2023; 2:100148. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24. US Department of Health and Human Services . Viral hepatitis national strategic plan: a roadmap to elimination for the United States (2021–2025). 2020. Available at: https://www.hhs.gov/sites/default/files/Viral-Hepatitis-National-Strategic-Plan-2021-2025.pdf. Accessed 23 May 2023.
- 25. Chen J, Hubbard A, Bagley L, Shiau R, Wong RJ, Chitnis AS. Prevalence of latent tuberculosis infection among persons with chronic hepatitis B virus infection: a systematic review and meta-analysis. Dig Dis Sci 2022; 67:2646–54. [DOI] [PubMed] [Google Scholar]
- 26. Conners EE, Panagiotakppoulos L, Hofmeister MG, et al. Screening and testing for hepatitis B virus infection: CDC recommendations—United States, 2023. MMWR Recomm Rep 2023; 72:1–25. [DOI] [PMC free article] [PubMed] [Google Scholar]
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