The Incidence of HBV and HCV Infection in Australian Travelers to Asia
Corresponding Author: Associate Professor Joseph Torresi, MBBS, PhD, Department of Infectious Diseases, Austin Hospital, Heidelberg, Victoria 3084, Australia. E-mail: email@example.com
We analyzed paired pre- and post-travel sera in a cohort of Australian travelers to Asia and demonstrated the acquisition of hepatitis C virus (HCV) and hepatitis B virus (HBV) infection. The incidence density in nonimmune travelers for HCV infection was calculated as 1.8 infections per 10,000 traveler-days and for HBV infection 2.19 per 10,000 traveler-days.
Worldwide, the number of international travelers has risen dramatically from 435 million in 1990 to 940 million in 2010. Many travelers to highly endemic countries are at risk of acquiring hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
No previous study has quantified the risk of HBV or HCV acquisition in Australian travelers. The estimated monthly incidence of HBV infections for expatriates in endemic countries is 25 per 100,000 for symptomatic infections, and 80 to 420 per 100,000 for both symptomatic and asymptomatic infections. The incidence for short-term travelers is presumed to be lower.[2, 3] A recent study of Danish travelers (62% of cases traveling for less than 4 weeks) demonstrated that the monthly incidence for HBV was 10.2 per 100,000 travelers. Case reports of HCV infection in travelers have been reported following hospitalization abroad.[4, 5] However, the incidence of HCV in travelers is unknown.
To determine the incidence of HBV and HCV in Australian travelers to Asia, we performed a retrospective analysis of a cohort of 361 Australian travelers to Asia.
Australian residents traveling to Asia for more than 7 days were enrolled in a multicenter cohort study over a 32-month period as part of a study to determine the incidence of dengue infection. Blood samples were taken prior to travel and on return. Serological assays were performed using the AxSYM Architect I2000SR analyzer and ARCHITECT anti-HBs, anti-HBc, anti-HBe, HBeAg, HBsAg, and anti-HCV assays (Abbott Diagnostics, Chicago, IL, USA). HBV polymerase chain reaction (PCR) was performed on all samples using forward (5′-GGATGTGTCTGCGGCGTTTTATC-3′) and reverse (5′-CAAATGGCACTAGTAAACTGAGCC-3′) primers from a conserved region of the S gene. HCV RNA was tested by qualitative reverse-transcription PCR (COBAS AMPLICOR, Roche, Sydney, Australia) only on pre- and post-sera of travelers with serological evidence of HCV. Seroconversion was defined as a change from antibody negative (pre-travel specimen) to antibody positive (post-travel specimen).
A pre- and post-travel questionnaire was used to collect data on: gender, birth date, nationality, destination(s), duration, reason for travel, symptoms while abroad, and previous travel. The questionnaires did not collect information associated with blood-borne virus exposure. HBV and HCV infection were calculated as incidence densities representing the number of new infections per 10,000 traveler-days. An informed consent was obtained from all the participants, as indicated by the Human Research Ethics Committees Austin Health HREC H2011/0426.
Of 467 participants enrolled, 361 (77.3%) completed questionnaires and had sufficient paired pre- and post-travel serum for testing; 58 (12.4%) were lost to follow-up; 21 had insufficient blood for testing; and 27 were excluded. There were 214 females (59.3%) and 147 males (40.7%). Pre- and post-travel specimens were collected at a median of 29 days prior to travel (range 0–265 days) and a median of 6 days following return to Australia (range 0–31 days).
The median travel duration was 21 days (range 7–326 days) with 74% <30 days. The major reasons for travel were tourism (73.1%), business (17.7%), and visiting friends and relatives (VFRs, 4.71%). Table 1 shows the demographic data and total traveler-days for the top 10 countries visited.
Table 1. Demographic characteristics of the study cohort
|Age, years ( median)||37 (range 17–78)|
|Hepatitis B immune (HBsAb ≥ 10 mIU/mL)||202 (56%)|
|Volunteer or missionary||19 (5.26%)|
|Research or education||22 (6.09%)|
|Traveler-days for countries visited†|
|Median duration of travel (days)||21 (7–326)|
|Short-term traveler (<30 days)||266 (74%)|
|Born overseas||89 (24.5%)|
|Born in Asia||16 (4.43)|
|Prior trip to Asia||274 (75.9%)|
Four of the 361 travelers (1.1%) demonstrated serological evidence of HCV infection. Two were past infections and two travelers had evidence of seroconversion, representing an incidence density of 1.8 new infections per 10,000 traveler-days (95% CI: 0.22–6.53). Both travelers with seroconversion were asymptomatic, and likely acquired their infection in Vietnam (n = 1) or Thailand (n = 1) during short-term travel (14 days duration each). The traveler to Thailand was a 24-year-old female tourist who visited Koh Samui and Bangkok. The traveler to Vietnam (a 50-year-old male) traveled to the cities of Hanoi and Ho Chi Minh. None of the four HCV seropositive travelers were viremic on testing of either pre- or post-travel sera.
Six of the 361 travelers (1.77%) were anti-HBc antibody positive, consistent with evidence of HBV infection. Five of these infections were present before travel. One traveler showed evidence of seroconversion [pre-travel serum negative for anti-HBc immunoglobulin G (IgG) and IgM, anti-HBs, anti-HBe, HBsAg, and HBV DNA; post-travel anti-HBc IgG positive but IgM negative, anti-HBs positive, HBsAg, HBeAg, anti-HBe, and HBV DNA negative]. The serological profile was consistent with self-limited primary infection. This traveler, a male aged 40, had evidence of seroconversion consistent with acquisition of HBV during his short business trip to China. He had his pre-travel blood collected 31 days prior to departure, traveled through China for 22 days, and had post-travel bloods taken 8 days post return to Australia. HBV PCR testing of sera from the entire cohort was negative; 56% of travelers (202/361) were HBV immune (anti-HBs ≥10 mIU/mL). The incidence density of HBV infection in nonimmune travelers was calculated as 2.19 per 10,000 traveler-days (95% CI: 0.07–12.19).
This retrospective cohort study demonstrates that travelers are at risk of both HBV and HCV infection, and is the first to quantify the risk of HCV infection in travelers. While the number of seroconversions was small the identification of two HCV and one HBV seroconversion is notable and indicates potential exposure to other blood and bodily fluid-borne infections such as HIV.
Previous work suggests travelers commonly undertake activities that place them at risk of HBV and HCV infection, and many have poor knowledge of infectious risks, poor uptake of preventative health measures, and poor adherence to health recommendations.
The two cases of HCV infection occurred in travelers to Vietnam and Thailand on short holiday trips. Screening for HCV in blood products is not universal in many developing countries and reuse of injection equipment without sterilization is common in Southeast Asia. Neither Vietnam nor Thailand has mandatory reporting of HCV infection. Prevalence estimates for Thailand vary from 0.41% to 7.5%. In Vietnam prevalence estimates vary between 2 and 2.9% and up to 21% in studies of blood donors. The one case of HBV infection occurred during a short trip to China, which is known to have an HBV prevalence of greater than 8%.
HCV transmission generally results from parenteral exposure to contaminated blood: travelers who are exposed to contaminated blood or undertake medical procedures while abroad are at risk. Transmission of HBV occurs through percutaneous or mucosal exposure to infected blood or bodily fluids. HBV acquisition in travelers has been associated with: duration of travel, immune status, VFR, casual sex, medical therapy, and the destination HBV prevalence.[2, 3]
Both HBV and HCV may have prolonged incubation periods (up to 6 months). A limitation of our study is the inability to exactly determine the date of HBV or HCV exposure. However, the travel duration together with the time to collection of post-travel serum makes it very likely that these infections were acquired abroad in countries with high endemic rates for both HBV and HCV infection.
Despite limitations of this retrospective study, including inability to elucidate risk behaviors as relevant questions were not included in the traveler questionnaire, quantifying the risk of these infections among travelers is crucial in facilitating informed decision making regarding the importance of vaccination and other preventative strategies. HCV infection prevention requires education and avoidance of high-risk activities. For HBV, the World Health Organization, Centers for Disease Control and Prevention, and Australian Guidelines recommend that HBV vaccination should be considered in nonimmune travelers to countries with a moderate to high prevalence of HBV (HBsAg ≥ 2%).
Allowing sufficient time for pre-travel vaccination is crucial. For hepatitis B, an accelerated HBV vaccine schedule (doses on days 0, 7, 21, and 12 months) is safe and efficacious. In this cohort, 59% (100/159) of travelers with an anti-HBs <10 mIU/mL attended a pre-travel clinic at least 21 days prior to departure to Asia providing sufficient time for HBV vaccination. The traveler diagnosed with HBV seroconversion attended clinic 32 days prior to travel and represents a potentially missed opportunity for vaccination.
The incidence of HCV and HBV in this cohort may be underestimated. Only 4.7% of our travelers were VFRs compared with 27% of travelers overall reported in the United Nations World Tourism Organization data. VFR travelers generally have contact with local populations, a longer duration of travel, use local health facilities, and have greater risks of infections. In addition, we may have underestimated the number of infections given the incubation period of both HBV and HCV can be prolonged. We were unable to perform HCV PCR testing on the entire cohort of travelers and thus some infections in the “window period of testing” may have been missed.
This study nevertheless confirms that travelers to endemic countries are at risk of both HCV and HBV infection. Access to travel advice, HBV vaccination where applicable, and education regarding the modes of HBV and HCV transmission are necessary for travelers to endemic countries.
We acknowledge S. Bowden, Victorian Infectious Diseases Reference Laboratory, North Melbourne, Victoria 3051, Australia for performing the HCV PCRs. This work was supported by an unrestricted research grant by GlaxoSmithKline.
Declaration of Interests
D. F. J., I. R., E. M., L. E. S., D. C., and M. L. G. have no conflict of interest. K. L. and J. T. have received grant funding from GSK for an unrelated project and travel expenses to attend international travel conferences.