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Original Research |

Hepatitis B Virus in the United States: Infection, Exposure, and Immunity Rates in a Nationally Representative Survey

George N. Ioannou, BMBCh, MS
[+] Article and Author Information

From Veterans Affairs Puget Sound Health Care System and University of Washington, Seattle, Washington.


Disclaimer: Dr. Ioannou had full access to all of the data in the study and takes responsibility for the integrity and the accuracy of the data analysis. Dr. Ioannou was responsible for study concept and design, acquisition of data, analysis and interpretation of the data, and drafting of the manuscript.

Grant Support: By the Veterans Affairs Research Enhancement Award Program.

Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M10-1301.

Reproducible Research Statement:Study protocol, statistical code, and data set: Not available.

Corresponding Author: George N. Ioannou, BMBCh, MS, Veterans Affairs Puget Sound Health Care System, Gastroenterology, S-111-Gastro, 1660 South Columbian Way, Seattle, WA 98108; e-mail, georgei@medicine.washington.edu.

Author Contributions: Conception and design: G.N. Ioannou.

Analysis and interpretation of the data: G.N. Ioannou.

Drafting of the article: G.N. Ioannou.

Critical revision of the article for important intellectual content: G.N. Ioannou.

Final approval of the article: G.N. Ioannou.

Statistical expertise: G.N. Ioannou.

Obtaining of funding: G.N. Ioannou.

Collection and assembly of data: G.N. Ioannou.


Ann Intern Med. 2011;154(5):319-328. doi:10.7326/0003-4819-154-5-201103010-00006
Text Size: A A A

Background: Up-to-date estimates of the prevalence of hepatitis B virus (HBV) infection, exposure, and immunity are necessary to assess the effectiveness of ongoing programs aimed at preventing HBV transmission.

Objective: To determine the prevalence and associations of chronic HBV infection, past exposure, and immunity in the United States from 1999 to 2008.

Design: Nationally representative, cross-sectional household survey.

Setting: U.S. civilian, noninstitutionalized population.

Participants: 39 787 participants in the National Health and Nutrition Examination Survey (1999 to 2008) aged 2 years or older.

Measurements: Chronic HBV infection was defined by presence of serum HBV surface antigen and past exposure by serum antibody to hepatitis B core antigen among persons aged 6 years or older. Infant immunity was defined by presence of serum antibody to hepatitis B surface antigen among children aged 2 years.

Results: Among persons aged 6 years or older, 0.27% (95% CI, 0.20% to 0.34%) had chronic HBV infection (corresponding to approximately 704 000 persons nationwide), and 4.6% (CI, 4.1% to 5.0%) had been exposed to HBV (approximately 11 993 000 persons). These estimates are lower (P < 0.001) than estimates of HBV infection (0.42%) and exposure (5.1%) in the United States reported from 1988 to 1994. Infection and past exposure were very uncommon among persons aged 6 to 19 years. Children aged 2 years have high rates of immunity (68.6% [CI, 64.1% to 73.2%]). Adults, including those at high risk for infection, have much lower rates of immunity.

Limitations: Incarcerated and homeless persons were not sampled. Categorization of race or ethnicity did not identify high-risk groups, such as persons of Asian and Pacific Islander descent.

Conclusion: A cohort of children and adolescents is growing up in the United States with high rates of immunity against HBV and very low rates of infection. Vaccination of high-risk adults should continue to be emphasized.

Primary Funding Source: The Veterans Affairs Research Enhancement Award Program.

Figures

Grahic Jump Location
Figure 1.
Prevalence of anti-HBc in the U.S. population, by age and race or ethnicity.

anti-HBc = antibody to hepatitis B core antigen.

Grahic Jump Location
Grahic Jump Location
Figure 2.
Prevalence of anti-HBc, by age and birthplace.

anti-HBc = antibody to hepatitis B core antigen.

Grahic Jump Location

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Universal HBV vaccination program make Hepatitis B virus infection decline in China
Posted on March 3, 2011
Shaohua Chen
The First Affiliated Hospital, College of Medicine, Zhejiang University
Conflict of Interest: None Declared

Hepatitis B virus (HBV) infection is a global public health problem. We read with great interest the recent article by Ioannou GN, et al in which they determined the prevalence and associations of chronic HBV infection, past exposure, and immunity in the United States from 1999 to 2008. The authors also provided important information that the cohort of children and adolescents is growing up in the United States with high rates of immunity against HBV and very low rates of infection. Vaccination of high-risk adults should continue to be emphasized. Currently, an estimated two billion people have been infected with HBV, and more than 350 million have chronic liver infections worldwide1. HBV infection is one of the leading causes of illness and death in China. According to the nationalwide epidemiological survey in China in 1992 and 2006, the HBsAg carrier rate declined from 9.75% in 1992 to 7.18% in 2006 in the overall population2,3. The universal HBV vaccination program made great contribution to the decline of HBV infection, especially in the children. A HBV vaccine has been available in China since 1982 and was first recommended for routine vaccination of newborns in China in 1992, with the first dose to be administered within 24 h of birth and subsequent doses at 1 and 6 months4,5. According to the investigation, the HBsAb positive rate increased from 15.75% in 1992 to 72.25% in 2006 in the 1-4 year-old children. Implementation of HBV vaccination was highly successful to uninfected people.

Shaohua Chen and Youming Li* The First Affiliated Hospital, College of Medicine, Zhejiang University,China.

*Corresponding author: Youming Li, The First Affiliated Hospital, College of Medicine, Zhejiang University. Address: No.79, Qingchun Road,Hangzhou city, 310003, P.R.China Email:li-youming@hotmail.com

References:

1. http://www.who.int/mediacentre/factsheets/fs204/en/index.html

2. Xia GL, Liu CB, Cao HL. Prevalence of hepatitis B and C virus infections in the general Chinese population. Results from a nationwide cross-sectional seroepidemologic study of hepatitis A, B, C, D, and E virus infections in China, 1992. International Hepatology Communications 1996; 5: 62-73.

3. Liang X, Bi S, Yang W, Wang L, Cui G, Cui F, et al. Epidemiological serosurvey of hepatitis B in China - declining HBV prevalence due to hepatitis B vaccination. Vaccine 2009; 27: 6550-6557.

4. CDC. Progress in hepatitis B prevention through universal infant vaccination-China, 1997-2006. Morbidity and Mortality Weekly Report 2007; 56: 441-445.

5. Shen LP, Zhang Y, Wang F, Zhang S, Yang JY, Fang KX, et al. Epidemiological changes in hepatitis B prevalence in an entire population after 20 years of the universal HBV vaccination programme. Epidemiol Infect. 2010 Dec 15:1-7. [Epub ahead of print]

Conflict of Interest:

None declared

Hepatitis B, comparing us (France) to the US
Posted on March 16, 2011
Alain braillon
none
Conflict of Interest: None Declared

Ioannnou provides us a survey on the evolution of the burden of Hepatitis B in the United States and shows the beneficial results of public health measures, including the universal childhood vaccination implemented in 1992 as a federal program(1). This confirms a 1984 wise position paper in the Journal(2).

In France, no representative survey has ever been published in a peer reviewed journal. The Institut National de Veille Sanitaire (INVS, the French Center for Disease Control) reported positive serum AgHBs in 0.65 % (IC95 % : 0.45-0.93) of a low risk population (18-80 years, continental Europe, medically insured with the national mandatory fund), more than twice higher than in the US.(http://www.invs.sante.fr/publications/2006/prevalence_b_c/vhb_france_2004.pdf) AgHBs is far more frequent in those living in non-European French territories, the needy and the immigrates who constitute an increasing population in France.

The INVS recently reported a slight increase in the percentage of immunized 1-year-olds (BEH, 27 July 2010, p. 330) However, the population was seriously biased (compliance to post-natal visits which means roughly only 60% of those insured) and the presence of only one shot on the record was counted as a full schedule. However, in 2006, the percentage of 1-year -olds immunized with three doses of hepatitis B was 29% (vs. 86% in Germany, a comparable country), ie. lower than in almost all the very poor countries in the world(3).

Since 2006, the French National Cancer Institute (INCA) have no longer reported data on the prevalence of hepatocellular cancer mortality, stating that the data have a too low quality.(http://www.e- cancer.fr/component/docman/doc_download/5986-dynamique-devolution-des-taux -de-mortalitedes-principaux-cancers-en-france-novembre-2010 p3). In the US, the National Cancer Institute's Registry allows for sound clinical research for the fifth most common cancer in men, which exhibits an alarming rise in incidence(4). Meanwhile, several French public bodies funded a research which recently claimed, even in a pre-publication public media campaign, that 'Engerix B vaccine appeared to increase the risk of demyelinating neurological disorders in childhood', despite serious methodological flaws(3). On one point France and the US were similar, as they both forgot that in 1976, Philippe Maupas published in the Lancet the first clinical trial of vaccination against hepatitis B in humans, at Tours (France). However, the JAMA has recently acknowledged this error(4).

References

1 Ioannou GN. Hepatitis B virus in the United States: infection, exposure, and immunity rates in a nationally representative survey. Ann Intern Med. 2011;154:319-28.

2 Health and public policy committee. Hepatitis B Vaccine. Ann Intern Med, 1984 100:149-150. 3 Braillon A. A new French paradox: HBV vaccination. J Hepatol 2009;51:597 -8.

4 Mathur AK, Osborne NH, Lynch RJ, Ghaferi AA, Dimick JB, Sonnenday CJ. Racial/Ethnic disparities in access to care and survival for patients with early-stage hepatocellular carcinoma. Arch Surg 2010;145:1158-63.

5 Braillon A. Developers of the hepatitis B vaccine. JAMA 2009;302:2552.

Conflict of Interest:

None declared

Prevalence of Hepatitis B Virus Infection in the U.S.: An Under-estimation
Posted on March 29, 2011
Alison A. Evans
Hepatitis B Foundation; Drexel University School of Public Health
Conflict of Interest: None Declared

Dear Editors:

We were encouraged to see the publication of the paper by Ioannou in the March 1 issue of Annals, using NHANES data to estimate prevalence of infection, exposure, and immunity to hepatitis B virus (HBV) (1). The data as presented are useful as a snapshot of the portion of the US population adequately sampled in NHANES. We are concerned, however, that readers will have come away with a false sense of security regarding the prevalence of chronic infection. NHANES, by design, does not sample that portion of the US population most at risk.

The recent Institute of Medicine (IOM) report on viral hepatitis in the US has reported on the significant limitations of NHANES for estimating chronic HBV prevalence in particular (2). In short, the undercounting of Asian Americans, particularly recent immigrants for whom native language versions of the NHANES questionnaire instruments are not available, and the exclusion of institutionalized, incarcerated, military, homeless and undocumented immigrant populations has excluded those at highest risk. In a 2008 publication in the Journal of Viral Hepatitis (15:1, 12-13), we attempted to enumerate those missed by NHANES estimates by reviewing other sources of data on prevalence in these populations (3). We believe that as many as 800-900,000 additional chronically infected persons remain uncounted by NHANES, making the total more than double that estimated by Ioannou. We therefore urge that the results in the Ioannou paper be interpreted with caution. While they appear to be an accurate reflection of the HBV infection prevalence in the NHANES survey population, they greatly underestimate the burden of disease in the US as a whole.

References

1. Ioannou, GN. Hepatitis B virus in the United States; infection, exposure, and immunity rates in a nationally representative survey. Annals of Internal Medicine 2011; 154: 319-328.

2. Institute of Medicine. Hepatitis and Liver Cancer: A National Strategy for the Prevention and Control of Hepatitis B and C. Washington, D.C: The National Academies Press, 2010.

3. Cohen C, Evans A, London WT, Block J, Conti M, Block T. Underestimation of chronic hepatitis B virus infection in the United States of America. J Viral Hepat 2008; 15(1): 12-13.

Conflict of Interest:

None declared

Chronic Hepatitis B Estimates: Better Sampling of Asian & Pacific Islanders Needed
Posted on March 30, 2011
Su H. Wang
Charles B. Wang Community Health Center, New York, New York
Conflict of Interest: None Declared

Accurate estimates of hepatitis B infection and immunity are important for targeting disease prevention and treatment efforts. Because Asians and Pacific Islanders (API) account for more than half of chronic hepatitis B (CHB) infection cases in the US, their underrepresentation in Ionnaou's study should not be downplayed. We believe that the undersampling of APIs in NHANES data leads to significant underestimates of HBV nationally.

CDC estimates of people in the US with CHB are higher at 800,000-1.4 million compared to 700,000 calculated by Ionnaou. Their estimates utilized similar NHANES data but addressed deficiencies by applying country-specific prevalence rates to the foreign-born groups. The Institute of Medicine concludes that NHANES has severe limitations when addressing viral hepatitis and recommends enhanced surveillance of HBV in at-risk populations. Our community health center and numerous partners have found consistently high rates of HBV in the API population in community screenings. From 2004-2008, the Asian American Hepatitis B Program screened almost 8,900 APIs in New York City and found a 12% HBV infected rate, with an even higher rate (22%) in the Chinese subgroup. At our community health center which serves mostly APIs, HBV screening is incorporated into routine care for all patients. Even in this primary care setting, where estimates may be less affected by self-selection bias of HBV screening events, we found 11.5% of 3,700 patients screened in 2010 had CHB.

Low national prevalence estimates may lead physicians to conclude that CHB is of waning concern in this era of HBV vaccination. Yet it remains a significant health risk for certain groups, and many infected persons are unaware of their diagnosis. Physicians should be vigilant about screening at-risk patients and remember that CHB can progress to cirrhosis and hepatocellular cancer (HCC). In fact, HCC rates in the US are increasing, but early care and treatment of CHB can reduce mortality and be cost-effective. While we agree with Ioannou that more screening is needed to identify high risk susceptible adults who should receive the HBV vaccine, it is equally important to identify and provide care to those infected.

Over the years, NHANES has oversampled certain groups, such as low- income persons, elderly, Mexicans and Black Americans, to provide reliable statistics for groups of interest. As of 2011, NHANES will begin oversampling APIs, so we anticipate better epidemiological data on the burden of hepatitis B in the future.

References

1. Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR 2008;57:RR8. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5708a1.htm

2. IOM (Institute of Medicine). 2010. Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C. Washington, DC: The National Academies Press; (pp 61-62). http://www.iom.edu/Reports/2010/Hepatitis-and-Liver-Cancer-A-National- Strategy-for-Prevention-and-Control-of-Hepatitis-B-and-C.aspx

3. The Dawn of a New Era: Transforming our Domestic Response to Hepatitis B and C. Session Nine: Transforming strategies to provide access to care. Edited by Lok, A, and Schiff, E. Supplement to The Journal of Family Practice, Vol 59, No 1, S59-S64. http://www.jfponline.com/pages.asp?AID=8553

4. Hepatocellular Carcinoma --- United States, 2001--2006. MMWR May 7, 2010 / 59(17);517-520. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5917a3.htm

5. Post S, et al A Simulation Shows That Early Treatment Of Chronic Hepatitis B Infection Can Cut Deaths And Be Cost-Effective.Health Affairs, 30, no.2 (2011):340-348

Conflict of Interest:

None declared

Iatrogenic exposures are an important risk factor for HBV (and HCV) infection
Posted on April 8, 2011
James Craner
University of Nevada, Las Vegas School of Medicine
Conflict of Interest: None Declared

Ioannou's analysis of the prevalence of hepatitis B virus (HBV) infection and exposure in the U.S. (1) postulates that regulations governing needle-using practices are expected to reduce the incidence of new HBV infection.

The risk patient-to-patient (PTP) transmission of both HBV and hepatitis C virus (HCV) from unsafe injection practices in outpatient medical facilities is actually on the rise. At least 33 outbreak investigations of acute HBV outbreaks involving PTP transmission in 471 newly infected individuals occurred between 1992 and 2007 (2). There is a similarly "disturbing trend" of new cases of acute HCV infections resulting from PTP outbreaks involving hundreds of new cases (3). A significant proportion have involved multi-dose vials of propofol, heparin, and saline.

The largest population ever exposed to PTP transmission occurred between 2004 and 2008 at a Las Vegas, Nevada endoscopy clinic (4). An outbreak investigation linked a cluster of acute HCV infections to unsafe injection practices of propofol dispensed from multi-dose medication vials. Nearly 63,000 former patients received a public health advisory to undergo laboratory testing for HBV, HCV, and HIV infection.

The true incidence of health care-associated HBV and HCV infections is significantly underestimated (3, 5). Among the thousands of newly diagnosed cases of HBV and HCV infection in the US each year that have no identifiable, well characterized demographic, behavioral or occupational risk factors, some may be attributable to iatrogenic, PTP transmission from prior medical procedures or treatments.

No concerted public health effort to collect longitudinal data from any acute outbreak investigations has been initiated to determine the incidence of attributable chronic HBV or HCV infection, including hundreds of former Las Vegas endoscopy center patients who have subsequently tested positive for HBV and HCV. Advocacy of cancer screening procedures such as flexible sigmoidoscopies and colonoscopies that has spurred the proliferation of such high-volume, specialty procedure clinics may paradoxically put even more susceptible and healthy people--including those in higher income and educational strata than prevalence studies otherwise identify (1)--unknowingly at risk of exposure to infection.

A history of a medical procedure involving injectable medication should be included as a risk factor or predictor of HBV and HCV in NHANES surveys and clinical practice guidelines. Public health initiatives are needed to measure the incidence and distribution of iatrogenic chronic hepatitis infection from PTP transmission in order to effectively control this entirely preventable source of infectious disease in our population.

References

1. Ioannou GN. Hepatitis B virus in the United States: infection, exposure, and immunity rates in a nationally representative survey. Ann Intern Med. 2011;154(5):319-28.

2. Lanini S, Puro V, Lauria F, Fusco F, Nisii C, Ippolito G. Patient to patient transmission of hepatitis B virus: a systematic review of reports on outbreaks between 1992 and 2007. BMC Medicine. 2009;7(1):15.

3. Perz JF, Thompson ND, Schaefer MK, Patel PR. US outbreak investigations highlight the need for safe injection practices and basic infection control. Clin Liver Dis. 2010;14(1):137-51.

4. Centers for Disease Control. Acute hepatitis C virus infections attributed to unsafe injection practices at an endoscopy clinic--Nevada, 2007. MMWR Morb Mortal Wkly Rep. 2008;57(19):513-7.

5. Thompson ND, Perz JF, Moorman AC, Holmberg SD. Nonhospital health care-associated hepatitis B and C virus transmission: United States, 1998- 2008. Ann Intern Med. 2009;150(1):33-9.

Conflict of Interest:

The author has served as a consultant in litigation involving HBV and HCV transmission at Endoscopy Center of Southern Nevada.

Author's Reply
Posted on April 18, 2011
George Ioannou
University of Washington
Conflict of Interest: None Declared

Dear Editors,

I would like to thank Drs. Evans and Wang for their thoughtful comments.

Certain racial/ethnic groups (such as Hispanics and non-Hispanic Blacks) were deliberately oversampled in NHANES, whereas Asians were not oversampled. It is well-documented that the prevalence of chronic HBV infection in the United States is much higher among Asians than other racial/ethnic groups, such as Hispanics. However, these facts alone do not lead to an underestimation of the national prevalence of HBV in my analyses because weights are provided by the NHANES investigators to account for oversampling. Weights also account for non-response while a final post-stratification adjustment is made to match the year 2000 US census population. All analyses presented in the manuscript have used sample weights (as well as the complex sampling variables for primary sampling units and strata) such that my estimates are representative of the US population and are not affected by the deliberate oversampling or undersampling of certain ethnic/racial groups. The introduction of oversampling of Asians and Pacific Islanders by NHANES in 2011, mentioned by Dr. Wang, will allow more accurate estimates of the prevalence of HBV infection/exposure among these racial groups but should not be expected to "lead" directly to higher NHANES-derived estimates of the absolute number of persons infected with HBV in the US, for the reasons described above.

Unauthorized or non-English-speaking aliens are less likely to be represented in NHANES and this non-deliberate, under-representation may not have been accounted for completely by the NHANES sampling and weighting methods. This may lead to an underestimation of the absolute number of HBV-infected persons. However, the vast majority of unauthorized or non-English-speaking aliens in the United States are Hispanics, primarily from Mexico, who actually have the lowest prevalence of HBV infection/exposure of any major racial/ethnic group in the United States. Thus, the under-representation of unauthorized or non-English-speaking aliens in NHANES would not be expected to lead to underestimation of the prevalence of HBV infection or exposure in the United States.

The estimate of 800,000-1,400,000 persons chronically infected with HBV in the US, quoted by Drs. Evans and Wang, was derived by attempting to estimate the number of HBV-infected, foreign-born US residents by multiplying the estimated number of such foreign-born residents from each region/country of the world by the estimated prevalence of chronic HBV infection in that region/country of the world (1-2). This method requires accurate estimates of the prevalence of HBV in each region/country of the world, which are not available, and which have been changing (mostly declining) over the last 20 years due to immunization. The method lumps together large regions of the world (e.g. the whole of Africa) leading to inaccuracy. Finally, the method assumes that the prevalence of HBV in an immigrant group in the US is the same as the prevalence of HBV in the entire region/country of origin of that immigrant group. This assumption is likely incorrect. For these reasons, I suspect that the estimate derived solely from the NHANES data is more accurate.

I agree with Dr. Wang that decisions on the appropriateness of screening for HBV should be made based on the local prevalence of HBV, not the national prevalence.

References

1. Weinbaum CM, Mast EE, Ward JW. Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. Hepatology 2009;49:S35-44.

2. Weinbaum CM, Williams I, Mast EE, Wang SA, Finelli L, Wasley A, Neitzel SM, Ward JW. Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Recomm Rep 2008;57:1-20.

Conflict of Interest:

None declared

Population-Based Prevalence Reports May Mask the Prevalence of HBV in High Risk Groups and Contribute to Liver Disease and Liver Cancer
Posted on May 18, 2011
Corinna Dan
Association of Asian Pacific Community Health Organizations (AAPCHO)
Conflict of Interest: None Declared

While we agree that oversampling of Asian Americans (AA) in the NHANES may not significantly change the estimation of the national prevalence of HBV, it may help generate a more accurate estimate for AAs. The oversampling coupled with proposed strategies to provide language assistance to foreign-born Asians with limited English proficiency will generate a more unbiased AA sample and will increase the participation of foreign-born AAs among whom a higher prevalence of HBV infection is expected.

Given the clearly identified high-risk groups and their relatively small proportions of the entire U.S. population, the very effort to generate national estimates of HBV or HCV infection using national health surveys may be of limited utility. Instead, it may be more effective to improve hepatitis surveillance and screening, particularly for these high risk groups.

As the Institute of Medicine determined, the viral hepatitis system in the United States is highly-fragmented, underfunded, and poorly- developed (1). Reporting of surveillance data to CDC by state and territorial health departments is voluntary, and little federal funding is provided for HBV and HCV surveillance (2) despite high volume of reports and personnel required. Unlike those for HIV/AIDS, CDC's viral hepatitis cooperative agreements with health departments do not include surveillance. As IOM recommends, the capacity of local and state health departments to conduct standard disease surveillance on HBV and HCV infections needs to be enhanced. Additionally, targeted surveillance on specific populations including foreign-born AAs, Native Hawaiians, and Pacific Islanders, close contacts and sex partners with chronic HBV infection, men who have sex with men, injection drug-users, and HIV- positive persons, not fully represented in the collection of core surveillance data, also needs to be strengthened (1,3,4).

Accurate tests to screen for HBV and a safe and effective vaccine to eliminate HBV exist, but the surveillance data to effectively target or support increases in resources are inadequate. Diagnosis rates remain very low, the IOM report estimated that only 35% of people with chronic HBV have been diagnosed (1,5). Population-based prevalence reports may mask the prevalence of HBV in high risk communities and contribute to the low levels of awareness among the public, policy-makers, and health care providers, potentially leading to missed opportunities for testing, vaccination, and treatment and thus unnecessary disability and death from liver disease and liver cancer caused by hepatitis B.

References:

1. Institute of Medicine (IOM). 2011. Hepatitis and Liver Cancer.

2. Klein et al. 2008. Wanted: An effective public health response to hepatitis C virus in the U.S. J of Public Health Management and Practice 14(5): 471-475

3. CDC. 2008. Recommendations for Identification and Public Health Management of Persons with Chronic Hepatitis B Virus Infection

4. CDC. 2009. Viral Hepatitis Statistics & Surveillance. http://www.cdc.gov/hepatitis/Statistics/index.htm

5. Thacker SB. 2000. Historical development. In: Principles and Practice of Public Health Surveillance, edited by Teutsh S and Churchill RE. Oxford, UK: Oxford University Press.

Conflict of Interest:

None declared

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