Corresponding Author: Lin H. Chen, MD, Director, Travel Medicine Center, Mount Auburn Hospital; Assistant Clinical Professor, Harvard Medical School, 330 Mount Auburn Street, Cambridge, MA 02238 USA. E-mail: email@example.com
Persons born in countries with hepatitis B surface antigen (HBsAg) prevalence ≥2% have increased risk for unrecognized hepatitis B virus (HBV) infection. Testing at pre-travel consultations is a strategy to identify previously undiagnosed HBV infections. Using records of travelers seen at the Boston Area Travel Medicine Network (BATMN) sites, we assessed how these travel clinics currently assess HBV status, describe test results, and describe characteristics of those tested and immunized for HBV.
Demographic data and trip information were collected for all travelers seen at the BATMN sites from June 2008 through July 2010. Proportions of those tested for HBV were determined, and differences between those tested and not tested were analyzed.
Among 13,732 travelers enrolled during the study period, 2,134 (16%) were born in HBV-risk countries (HBsAg prevalence ≥2%); 532/2134 (25%) had previous HBV test results and 230 (11%) had tests performed at the travel clinic visit. Past results showed that 33/453 (7.3%) were HBV-infected (HBsAg+), 252/481 (52.4%) were immune (anti-HBs+, HBsAg–), 164/303 (54.1%) were susceptible (anti-HBs–, HBsAg–, anti-HBc–), and 38/314 (12.1%) had possible HBV exposure (anti-HBc+, HBsAg–, anti-HBs–). Among 230 travelers tested during the travel clinic visit, 7/213 (3.3%) were HBV-infected, 95/218 (43.6%) were immune, 106/179 (59.2%) were susceptible, and 10/182 (5.5%) had possible HBV exposure.
The travel clinic offers an opportunity to capture, identify, and educate infected persons unaware of their infection, educate those with known results, and initiate preventive action (eg, vaccination) for those still susceptible.
Approximately 350 million persons worldwide have chronic hepatitis B virus (HBV) infection, and 620,000 persons die annually from HBV-related liver disease.[1, 2] Chronic HBV infection can lead to chronic liver disease including cirrhosis and hepatocellular carcinoma (HCC). In highly endemic countries (prevalence of HBsAg ≥8%), HBV infection is commonly transmitted vertically or in early childhood, which is the major determinant for chronic infection. Complications (chronic liver disease and HCC) occur in 15%–40% of chronically infected persons, mostly during adulthood but can occur earlier. HCC may develop in asymptomatic infected persons in the absence of cirrhosis. Early screening, monitoring, and treatment can limit transmission and reduce the likelihood of potentially fatal consequences. Diagnosis of HBV infection, immunity, and carrier state is done by serologic testing for hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core antibody (anti-HBc).
As of 2006, more than 50% of new diagnoses of HBV infection in the United States were in foreign-born persons, leading the Centers for Disease Control and Prevention (CDC) to expand testing recommendations for HBV infection to include persons born in countries with HBsAg prevalence of ≥2%. Despite this recommendation, screening for HBV in the foreign-born remains inconsistent, and many individuals from HBV-risk countries have not been screened and are unaware of their status.[6-9] Asians and Pacific Islanders comprise the largest groups of Americans with chronic HBV infection, with a disproportionately high incidence of HCC.[10, 11] The US National Health and Nutrition Examination Survey (1999–2008) found the highest prevalence of chronic HBV (1.97%) in the group called “other race or ethnic groups,” most of whom are Asians. Recent studies confirm that a 2% threshold for prevalence of chronic HBV infection, screening, and vaccinating is cost-effective.[3, 13] Many health care providers, however, lack knowledge about identification, screening, and vaccination in these high-risk populations.[14-17]
In the United States, universal HBV immunization for infants at birth was instituted in 1991. Immunization of risk groups has been advocated for many years, including adults who travel to countries with HBsAg prevalence ≥2%.[4, 18] Although the World Health Organization (WHO) recommended universal HBV vaccination for infants in 1992, many foreign-born individuals living in the United States have not been vaccinated.
We hypothesize that the travel clinic is an underutilized setting for testing and immunization for HBV. Using data collected during a study of the demographics, medical history, and trip characteristics of travelers seen for pre-travel consultation in the Boston area, we describe for travelers born in countries with HBsAg prevalence ≥2% and for those born in the United States, the proportion tested for HBV, their test results, and characteristics associated with testing, infection, and receiving vaccine.
The Boston Area Travel Medicine Network (BATMN) consists of five travel clinics in metropolitan Boston that see approximately 7,500 travelers annually and collaborate on travelers' health research. De-identified demographic data, trip information, HBV serology results, and vaccination status were collected for all travelers at the pre-travel consultations during the study period (June 12, 2008, for four sites and October 21, 2008, for one site through July 31, 2010). Data were entered into a secure database (CS-Pro, US Census Bureau, Washington, DC). IRB approvals were obtained at all sites and the CDC, including waivers of informed consent. Some sites offered optional data fields for clinicians to indicate why a person with unknown HBV status declined testing in a travel clinic including: (1) unclear if insurance covered test, (2) unaware of HBV or risk factors, (3) previously tested but results unknown, (4) patient declined phlebotomy, or (5) get the test from a primary doctor. No guidelines regarding HBV testing were specified for BATMN clinicians.
We collected data on HBV test results for travelers attending these clinics born in countries with HBsAg prevalence ≥2% as defined by the CDC. We assigned travelers to one of the following mutually exclusive categories: (1) HBV-infected (HBsAg+), (2) immune (anti-HBs+, HBsAg–), (3) susceptible (anti-HBs–, HBsAg–, anti-HBc–), and (4) possible exposure to hepatitis B (anti-HBc+, HBsAg–, anti-HBs–). We compared characteristics of travelers who were tested with those who were not. We also collected data on testing and immunization rates of US-born travelers seen at these clinics, and compared these rates by site.
We summarized characteristics of subjects using the median and inter-quartile range (IQR) for continuous variables and frequencies for discrete variables. We compared testing rates by subject characteristics using log-binomial regression to calculate test rate ratios (TRRs) and 95% confidence intervals (CIs). We assessed normality of continuous variables in this model using the normal probability plot and the Shapiro–Wilk test. We constructed a multivariable model of characteristics associated with rate of clinical testing using log-binomial regression and a forward selection technique. The inclusion criterion in the model was a p value <0.20 for a variable or groups of variables based on the likelihood ratio test. All analyses were performed using SAS version 9.13 (SAS Institute Inc., Cary, NC, USA).
Subjects Born in HBV-Risk Countries
The 13,732 participants in the database during the study period included 2,134 (16%) born in countries with HBsAg prevalence ≥2% (Figure 1). Median age of participants born in HBV-risk countries was 39 years; more than half were women; a third reported a non-English primary language. Median trip duration was 21 days and median time to departure was 16 days. Most common regions of birth were Africa (38.0%) and Asia (37.5%), followed by Latin America (8.4%). The most common reason for travel was to visit friends and relatives (VFR) (52.9%), and the most popular accommodations were homes/local residence (57.5%) (Table 1).
Table 1. Demographic data of travelers born in hepatitis B risk countries by test status
Tested previously (n = 518)
Tested in travel clinic (n = 230)
Not tested or test status unknown (n = 584 + 802 = 1,386)
All subjects (n = 2,134)
IQR = inter-quartile range.
Age of traveler
Median age in years (IQR)
Median duration of trip in days (IQR)
Time to departure
Median days to departure (IQR)
Region of birth
Primary language other than English
Type of accommodation at destination
Hotel or hostel
Reason for travel
Visiting friends and relatives
Other purpose of trip
Subjects tested in travel clinics were 50.4% (n = 116) male, with median age of 43.5 years and median time to departure of 29 days; 43.3% (n = 93) reported a primary language other than English, and were most commonly VFR (66.1%, n = 152), staying in home/local residence (59.1%, n = 136), and born in Asia (51.3%, n = 118) or Africa (29.6%, n = 68). Subjects with unknown status and not tested were 45.2% (n = 627) male, with shorter median time to departure (17.5 days) (Table 2).
Table 2. Characteristics with statistically significant differences in the comparison of demographics of subjects from hepatitis B risk countries who were tested versus those who were not tested at all (not tested previously and not tested in clinic)
Percent tested (number tested/ category total)
Univariable predictor TRR (95% CI)
Multivariable model TRR (95% CI)
TRR = test rate ratio.
Age (continuous in years)
Type of accommodation at destination
Hotel or hostel
Reason for travel
Visiting friends and relatives
Other purpose of trip
Region of birth
Hepatitis B immunization
Hep B given at clinic
Hep B not given at clinic
Hepatitis B Testing
Previous HBV test results were obtained from records for 532 travelers (25%) and testing done at the clinic visit for 230 (11%); 14 were tested in both settings, thus results are presented for 748 travelers (Figure 1). Anti-HBs was most commonly ordered (218; 94.7%), followed by HBsAg (213; 92.6%) and anti-HBc (182; 79.1%). Specific tests ordered in the clinics did not follow a protocol, hence denominators for numbers tested varied by test.
Compared with travelers who were not tested in a travel clinic (and without prior testing) in the univariable model, travelers tested in a travel clinic more commonly received HBV immunization in the travel clinic (TRR = 3.5; CI 2.8–4.5) (Table 2). African birth was associated with less testing than Asian birth (TRR 0.6; CI 0.4–0.8). In the multivariable model, travelers tested in a travel clinic were more likely to be male (TRR = 1.3; CI 1.0–1.6), Asian (TRR = 1.7; CI 1.2–2.5), and to speak a non-English primary language (TRR = 1.5; CI 1.1–1.9).
Optional fields regarding reason for lacking HBV testing were completed for 28 travelers with unknown status and not tested during the travel clinic visit. The most common reason was “previously tested but results unknown” (n = 9), “unaware of HBV or their risk factor” (n = 6), “patient declined phlebotomy” (n = 5), “get test from own doctor” (n = 5), “unsure if insurance covered test” (n = 2), and “not determined” (n = 1).
Hepatitis B Test Results
Among 230 travelers tested in the travel clinic, 7/213 (3.3%) were HBV-infected, 95/218 (43.6%) were HBV-immune, 106/179 (59.2%) were susceptible, and 10/182 (5.5%) had possible HBV exposure (Figure 1). Past tests showed that 33/453 (7.3%) were HBV-infected, 252/481 (52.4%) immune, 164/303 (54.1%) susceptible, and 38/314 (12.1%) had possible HBV exposure. Because tests were ordered in numerous combinations, denominators differed between categories and the sum of percentages exceeds 100.
The seven persons newly diagnosed with HBV infection were predominantly male (n = 5) with mean age 42.1 years (range 22–70, including 2 >65 years), mean trip duration 213.8 days (range 6–900), travel to VFR (n = 6), staying in local residence (n = 6), and birth in Asia (n = 3) or Africa (n = 4). Four HBV-infected persons were possibly exposed through sexual infections (one person had a history of sexually transmitted diseases) and one through a close household contact; others were possibly exposed via vertical transmission.
Hepatitis B Immunization History and Hepatitis B Status
Information regarding HBV vaccination was available for 1,762/2,134 travelers from HBV-risk countries; 869/1,762 (49.3%) had received HBV vaccine. Overall 28.6% (504/1,762) reported completing HBV vaccine series. Among 164 travelers whose past tests indicated HBV susceptibility, vaccine was recommended to 32 (19.5%). Among 106 travelers whose travel clinic test found them susceptible, 47 (44.3%) were advised to have HBV vaccination.
Subjects Born in the United States and Other Low-Risk Countries
Hepatitis B Immunization History and Testing
Among 9,559 US-born travelers, 8,346 (87.3%) planned to visit one or more HBV-endemic countries (median age 32 years). Of those visiting HBV-endemic countries with reliable immunization history, 2,295/4,409 (52.1%) had previous HBV immunization, and 114 (1.4%) were previously tested. Rates of HBV testing and vaccination in travel clinics were low, 0.7 and 11.3% respectively; the testing and vaccination rates for all travelers born in low HBV-risk countries were nearly identical.
Sixteen percent of travelers seen at BATMN sites were born in countries with HBsAg prevalence ≥2% and therefore are at risk for HBV infection. Only 25% of these travelers had prior HBV screening, and 11% were tested in clinics. These clinic visits thus represent opportunities to improve testing for at-risk travelers with unknown HBV status. Regarding HBV-susceptible patients, we found that testing in a travel clinic led to a higher rate of hepatitis B immunization than past testing did. Moreover, travel clinic testing showed that 3.3% required further evaluation and monitoring for chronic HBV infection, and 59% were candidates for vaccination, representing unmet health needs in this population. The difference between HBsAg positivity rates in travel clinic tests and past tests (3.3% vs 7.3%) is attributed to the expanded risk definition (testing persons from countries with HBsAg prevalence ≥2% vs ≥8%, respectively).
We found low HBV immunization rates among US-born travelers planning to visit HBV-endemic countries as well as among travelers born in HBV-risk countries. Travel clinics target highest-risk travelers for HBV immunization, such as those planning long stays, close contact with the local population, or activities with possible blood and body fluid exposure despite current recommendation to immunize all such travelers. The low HBV immunization rates indicate that the travel clinic is an underutilized setting for immunizing travelers to HBV-risk countries.
The tests utilized varied widely. HBsAg and anti-HBs were requested more frequently, probably because they establish infection/carrier state and immunity. Anti-HBc was performed least frequently, likely because the multiple possible interpretations of a positive anti-HBc are confusing, and the travel clinics having a single encounter with the patient prefer data that lead to clear action steps. Simple and straightforward guidance on specific tests to be performed should be incorporated into HBV screening recommendations, as highlighted by an Institute of Medicine (IOM) committee report. For simplicity and clarity of interpretation, we advocate HBsAg and anti-HBs as routine tests for individuals born in countries with HBsAg prevalence ≥2%. The addition of anti-HBc is valuable in interpreting serologic tests, as an indicator for possible HBV infection.
These results resonate with other HBV serosurveys on immigrants, where HBV prevalence in foreign-born persons reflected the prevalence in their countries of origin.[7, 20] Likewise, the proportion of travelers born in HBV-risk countries may vary by clinic, depending on the composition of the population in the catchment area. Recommendations derived from our analysis are especially relevant to primary care practices and travel clinics in geographic areas with large immigrant populations. The association of HBV testing in the clinic and advice to immunize suggests an additional benefit of HBV screening in travel clinics.
Akin to an earlier serosurvey in travelers, we found a low rate of HBV screening in the community, and the travel clinics offered opportunities to identify HBV-risk persons and assess their status. While travel clinics only see a small proportion of patients from HBV-risk countries or those who VFRs within the population, they broaden the chronic HBV identification as well as immunization. A pre-departure survey conducted at Boston Logan International Airport found that about 16% of respondents received travel health advice from travel clinics although the proportion was <2% among VFRs. Education of travelers from HBV-risk countries along with their screening and vaccination can lead to dissemination of information to their contacts and communities.
Low clinician awareness of HBV is a major barrier to screening and vaccination in travel clinics. Other possible barriers to screening and vaccination in travel clinics include time to departure and trip length, practice preference for minimal laboratory usage, cost and ability of patients to afford the test, perception that testing would be done elsewhere, clinician time constraints, and sometimes language barriers (Table 3).
Table 3. Challenges identified in HBV testing and immunization, and strategies for improvement
Strategy for improvement
*EthnoMed is the ethnic medicine website of the Harborview Medical Center, University of Washington, available at www.ethnomed.org.
**Global Health Pathway is a program in the Department of Medicine at the University of Minnesota, available at www.globalhealth.umn.edu.
Low level of clinician awareness of HBV risk
Clinician preference may minimize testing in general
Perception that testing might have been done elsewhere or would be done elsewhere
Encourage testing when no reliable results are available
Establish routine collaboration of primary care and travel clinics
Assumption that specific patients from risk countries have lower risk compared to their birth country cohorts
Perception that specific travelers have no HBV risk activities
Low patient awareness
Outreach to patients, especially communities with HBV risk populations
Time constraints: short interval to departure
Encourage testing and immunization regardless of timing
Heath care system
Language barriers associated with lower patient comprehension
Provide translations of materials on HBV risk, identification, treatment, and prevention
Increase provider awareness of the HBV educational materials available in other languages including vaccine information statements and other translations of materials through EthnoMed* and Global Health Pathway**
Lack of data capture for past test results or tests done in the travel clinic
Integrate hepatitis B results into standardized EMRs
Promote routine documentation of test results in health records, and download hepatitis B serology results into EMRs
Lack of immunization records especially in adults
Promote standardized immunization records in EMRs with access to the patients and to treating physicians
Uncertainty about insurance coverage of testing
Support insurance coverage of HBV testing
Cost and ability of patients to pay for the test
Support insurance coverage of HBV testing
Limitations of this analysis include the need to exclude records missing birth country information and data for travelers from HBV-risk countries. Other missing data led to varying denominators throughout the analysis. Another limitation is the data aggregation that leads to generalized interpretation of results, less precise than interpretation of each patient's specific results. Varied approaches to obtaining past test results and testing at travel clinics complicated analysis of serologic results. Some travelers were tested previously and also during the clinic visit, possibly because of the results being unavailable at the time of clinic visit or concern for recent exposure, although the small number (n = 14) unlikely had substantial influence overall. Travelers were included in the database only once even if they had multiple visits for vaccine series, though a small number could have repeat entries if seen for another trip that was not previously addressed. The lower testing rate of women in travel clinics may be attributed to the assumption that women undergo perinatal testing, but the database contained no information to assess this hypothesis. Additionally, health insurance information was unavailable to analyze financial constraints regarding testing and immunization. Speaking a non-English primary language did not seem to deter testing given the higher testing rate in this group than in English speakers, but data were lacking on interpreter usage.
The US CDC's recommendation to screen for chronic HBV in persons born in regions with HBsAg prevalence ≥2% has expanded testing to a larger population. The aforementioned IOM report identified deficiencies in knowledge and awareness, surveillance, immunization, and services for viral hepatitis in the United States, and recommended strategies to optimize prevention and control of hepatitis B and C. The Department of Health and Human Services further supports these strategies. Assessment of persons born in regions with HBsAg prevalence ≥2% is crucial in identifying chronic HBV infection, with multiple benefits through early diagnosis: improved therapeutic response, lower viral loads, halting progression to cirrhosis, and preventing HCC. Non-immune persons at risk for HBV exposure and household members and sexual contacts of HBV-infected individuals should be immunized. It is equally important to determine previous infection status as it is to immunize travelers because of risk of transmission during travel, especially to destinations with high and intermediate HBV prevalence.
Increased awareness of the potential benefits of HBV assessment enables the design of interventions to increase testing/immunization of this traveler population, thus allowing those infected to have earlier access to health care and those who are susceptible to be immunized. Possible interventions (Table 3) include integrating HBV screening, serology queries, and immunizations administered into the templates of electronic health records, educating primary care and travel medicine providers as well as specialists caring for foreign-born persons, and corresponding with primary care physicians regarding the unscreened patients as a reminder to screen their high-risk population. Collaboration between primary care and travel clinics is critical in improving the process. Despite our findings, language is still often a barrier to screening and vaccinating, and providing information on HBV to patients in their primary language remains valuable. Our study shows that travel clinic visits offer an important opportunity to assess HBV status of travelers who may have unrecognized infection or who can benefit from HBV vaccination.
We thank Erika Gleva, Christine Benoit, Rebecca Dufur, Deborah Gannon, and Manveen Bhussar for their assistance with data collection and entry. This research was funded by a cooperative agreement (1 U19CI000508-01) between the CDC and Boston Medical Center. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the CDC.
Declaration of Interests
L. H. C. reports receiving honoraria (Thompson Media Group LLC for serving on the editorial board of Travel Medicine Advisor) and research grant (Xcellerex Inc.), both unrelated to this project. E. D. B. reports financial activities from consultancy (Novartis), expert testimony for malpractice cases, grants (Intercell, Sanofi Pasteur), speakers' bureau (Merck), royalties (Elsevier), and development of educational presentations (PriMed, BMJ Point of Care). The following authors report no conflict of interest: M. E. W., W. B. M., E. A. Y., A. W. K., L. K., W. O., N. B. M., D. H. H. All coauthors had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
This is an Asia-inspired painted wall around a parking lot in the Chinatown area of Boston, where the study by Chen L et al. (pages 29–36) took place. The authors showed that travel clinics offer an opportunity to capture, identify, and educate infected persons unaware of their infections, educate those with known results, and initiate preventive action for those still susceptible. Credit: Eric Caumes (Setting: Boston, 2011)