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.
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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).
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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
|Challenge||Strategy for improvement|
|Low level of clinician awareness of HBV risk||Clinician education|
|Clinician preference may minimize testing in general||Clinician education|
|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||Clinician education|
|Perception that specific travelers have no HBV risk activities||Clinician education|
|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.
Declaration of Interests
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- 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.