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Hepatitis B

Originally known as serum hepatitis, hepatitis B has only been recognized as such since World War II, and has caused current epidemics in parts of Asia and Africa. Hepatitis B is recognized as endemic in China and various other parts of Asia. Over one-third of the world's population has been or is actively infected by hepatitis B virus (acronym HBV). more...

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Molecular biology

The hepatitis B virus is a member of the Hepadnavirus family. It consists of a proteinaceous core particle containing the viral genome in the form of double stranded DNA and an outer lipid-based envelope with embedded proteins. The envelope proteins are involved in viral binding and release into susceptible cells. The inner capsid relocates the DNA genome to the cell's nucleus where viral mRNAs are transcribed. Three subgenomic transcripts encoding the envelope proteins are made, along with a poorly understood transcript encoding the X protein, whose function is still under debate. A fourth pre-genomic RNA is transcribed, which is exported to the cytosol and translates the viral polymerase and core proteins. Polymerase and pre-genomic RNA are encapsidated in assembling core particles, where reverse transcription of the pre-genomic RNA to genomic DNA occurs by the polymerase protein. The mature core particle then exits the cell via normal secretory pathways, acquiring an envelope along the way.

Hepatitis B is one of a few known non-retroviral viruses which employ reverse transcription as part of its replication process. Other viruses which use reverse transcription include HTLV or HIV, the virus that causes AIDS, but HIV and hepatitis B are not related. Hepatitis B's genome is DNA, and reverse transcription is one of the latter steps in making new viral particles, whereas HIV has an RNA genome and reverse transcription is one of the first steps in replication.

Transmission

Hepatitis B is largely transmitted through exposure to bodily fluids containing the virus. This includes unprotected sexual contact, blood transfusions, re-use of contaminated needles and syringes, vertical transmission from mother to child during childbirth, and so on. The primary method of transmission depends on the prevalence of the disease in a given area. In low prevalence areas, such as the continental United States, IV drug abuse and unprotected sex are the primary method. In moderate prevalence areas, the disease is predominantly spread among children. In high prevalence countries, such as China, vertical transmission is most common. Without intervention, a mother who is positive for the hepatitis B surface antigen confers a 20% risk of passing the infection to her offspring at the time of birth. This risk is as high as 90% if the mother is also positive for the hepatitis B e antigen.

Roughly 16-40% of unimmunized sexual partners of individuals with hepatitis B will be infected through sexual contact. The risk of transmission is closely related to the rate of viral replication in the infected individual at the time of exposure.

Clinical consequences and complications

Hepatitis B virus infection may either be acute (self-limited) or chronic (long-standing). Persons with self-limited infection clear the infection spontaneously within weeks to months.

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Transmission of Hepatitis B virus among persons undergoing blood glucose monitoring in long-term-care facilities—Mississippi, North Carolina, and
From Morbidity and Mortality Weekly Report, 3/11/05 by R. Webb

Regular monitoring of blood glucose levels is an important component of routine diabetes care (1). Capillary blood is typically sampled with the use of a fingerstick device and tested with a portable glucometer. Because of outbreaks of hepatitis B virus (HBV) infections associated with glucose monitoring, CDC and the Food and Drug Administration (FDA) have recommended since 1990 that fingerstick devices be restricted to individual use (2,3). This report describes three recent outbreaks of HBV infection among residents in long-term-care (LTC) facilities that were attributed to shared devices and other breaks in infection-control practices related to blood glucose monitoring. Findings from these investigations and previous reports suggest that recommendations concerning standard precautions and the reuse of fingerstick devices have not been adhered to or enforced consistently in LTC settings (2-5). The findings underscore the need for education, training, adherence to standard precautions, and specific infection-control recommendations targeting diabetes-care procedures in LTC settings (4-6) (Box 1).

The three outbreaks described in this report were all reported by state or local health departments to CDC, which provided epidemiologic and laboratory assistance, in each of the three LTC settings, residents were tested for serologic markers for HBV infection. Under the case definitions used in these investigations, residents who tested positive for IgM antibody to hepatitis B core antigen (anti-HBc) were defined as having acute HBV infection. Residents who tested positive for hepatitis B surface antigen (HBsAg) and total anti-HBc, but who tested negative for IgM anti-HBc, were considered to have chronic HBV infection. Residents who tested positive for total anti-HBc, but who tested negative for HBsAg, or those who had antibody to HBsAg (anti-HBs) [greater than or equal to] 10 milli-International Units (mlU) per milliliter were considered immune to HBV infection. Residents were considered susceptible to HBV if they had no HBV markers. A retrospective cohort study was performed as part of each investigation; the study was restricted to acutely infected and susceptible residents to identify risk Factors. In all three investigations, staff members were evaluated; none were identified as sources of infection. Medical records were reviewed and infection-control procedures were assessed through direct observation and by interviews with nursing staff members.

Nursing Home A, Mississippi

During November-December 2003, the Mississippi Department of Health received reports of two fatal cases of acute HBV infection among residents of nursing home A. The first patient with recognized symptoms of HBV infection had received serologic testing for viral hepatitis infection in June 2003 as part of a hospital emergency department evaluation for abdominal pain. Although this patient was found to have a positive test for IgM anti-HBc, indicating acute HBV infection, and the finding was noted in the patient's chart in September 2003, nursing home A did not contact the state health department or initiate an internal investigation. Subsequently, the patient died.

In December 2003, after a second patient with acute HBV infection had died, and after a third with acute HBV infection was reported, serologic testing was performed on specimens from all 158 residents. Test results were available for 160 residents, including the two decedents; 15 (9%) had acute HBV infection, one was chronically infected, 15 (9%) were immune, and 129 (81%) were susceptible. Percutaneous and other possible exposures among residents were evaluated. Among 38 residents who routinely received fingersticks for glucose monitoring, 14 had acute HBV infection, compared with one of 106 residents who did not receive fingersticks (relative risk [RR] = 39.0; 95% confidence interval [CI] = 5.3-290.0).

Glucose monitoring of 14 residents with acute HBV infection and the resident with chronic HBV infection was performed by staff members based at the same nursing station. Reviews of infection-control practices and site inspections indicated that each of the four nursing stations in nursing home A was equipped with one glucometer and one spring-loaded, pen-like fingerstick device. Staff members reported that a new end cap and lancet assembly was used for each fingerstick procedure; however, the spring-loaded barrel and glucometer were not routinely cleaned between patients. investigators also observed that insulin and other multidose medication vials were not labeled with patient names or the dates the vials were opened. In an anonymous survey, several staff members reported observing other workers reuse a needle or lancet or fail to change gloves between patients. No other percutaneous exposures were associated with illness.

Assisted Living Center B, Los Angeles County, California

During January-February 2004, the Los Angeles County Department of Health Services received reports of four residents with diabetes in assisted living center B who had acute HBV infection during November 2003-January 2004. Because these initial reports were among residents with diabetes, serologic testing was performed in January 2004 on residents who had received fingersticks for blood glucose monitoring during May-December 2003. Of 22 residents tested (three declined), eight (36%) had acute HBV infection, including the four residents previously identified; six (27%) were immune (and excluded from the analysis), and none had chronic infection. Reviews of patient records indicated that one of the acutely infected residents had been repeatedly tested at a separate hemodialysis center and had seroconverted to HBsAg-positive in July 2003. Of the nine patients who had daily exposure to fingerstick procedures performed by nursing staff; eight had acute HBV infection, compared with none among the seven residents who performed their own fingersticks (RR = undefined; CI = 2.8-undefined). Although receipt of insulin was also significantly associated with infection, two residents with acute HBV infection had not received insulin. Other percutaneous exposures (e.g., podiatric or dental care) were not associated with HBV infection.

Fingerstick procedures were often performed by nursing staff members in a central living area, with diabetes patients seated at a common table. Although residents had their own fingerstick devices, nurses reported occasionally using a pen-like fingerstick device barrel from their own kits to collect consecutive blood samples; a single glucometer was typically used for all residents. Nurses reported that they were discouraged from wearing gloves to decrease the sense of a clinical environment, and hand hygiene was not performed between procedures.

Nursing Home C, North Carolina

In May 2003, a case of HBV infection in a resident of nursing home C was reported to the North Carolina Department of Health. During June-July 2003, serologic testing was performed on specimens from all 192 residents; 11 (6%) had acute HBV infection, 16 (8%) were immune, and 165 (86%) were susceptible. No resident had chronic HBV infection. Of 45 residents who received fingersticks for glucose monitoring, eight (18%) had acute HBV infection, compared with three (3%) of 117 residents without this exposure (RR = 6.9; CI = 1.9-25.0). After data were controlled for fingerstick exposures, acute HBV infection was not associated with other percutaneous exposures (e.g., insulin injections, podiatry procedures, or phlebotomy). Two diabetes patients at nursing home C who were potential sources of the outbreak were identified retrospectively; one had clinical symptoms of hepatitis B and serologic markers of acute infection during 2002, whereas the other had chronic HBV infection and died in February 2002.

Interviews with staff and direct observation of glucose-monitoring practices revealed that only single-use lancets were used, and insulin vials were not shared among patients. However, on each wing of the facility, a single glucometer was used for all patients receiving fingersticks; glucometers were not routinely cleaned between patients. On some days, a single health-care worker performed approximately 20 fingerstick procedures during a single work shift. In an anonymous survey, nursing staff members indicated that some health-care workers did not always change gloves between patients when performing fingerstick procedures.

Editorial Note: Lack of adherence to standard precautions and failure to implement long-standing recommendations against sharing fingerstick devices place LTC residents at risk for acquiring infections from bloodborne pathogens such as HBV (2,3,7). In nursing home A, the spring-loaded barrel of a fingerstick device was used for multiple patients. Previous outbreaks have been linked to such devices when the platform or barrel supporting the disposable lancet was reused for multiple patients, when used lancets were stored with unused lancets, or when lancet caps were reused (2,3; CDC, unpublished data, 1999). In assisted living center B, nursing staff members routinely administered fingersticks without wearing gloves or performing hand hygiene between patients, and spring-loaded fingerstick devices were also occasionally shared.

In nursing home C, as with other recent outbreaks (8; CDC, unpublished data, 2002), transmission of HBV among residents with diabetes occurred despite use of single-use fingerstick devices or insulin medication vials that were dedicated for individual patient use. In these settings, glucose monitors, insulin vials, or other surfaces contaminated with blood from an HBV-infected person might have resulted in transfer of infectious virus to a health-care worker's gloves and to the fingerstick wound or subcutaneous injection site of a susceptible resident. Similar indirect transmission of HBV in health-care settings through contaminated environmental surfaces or inadequately disinfected equipment has been reported with other health-care procedures, such as dialysis (6,9). HBV is stable at ambient temperatures; infected patients, who often lack clinical symptoms of hepatitis, can have high concentrations of HBV in their blood or body fluids (6). To prevent patient-to-patient transmission of infections through cross-contamination, health-care providers should avoid carrying supplies from resident to resident and avoid sharing devices, including glucometers, among residents.

The risk for patient-to-patient transmission of HBV infection can be reduced by implementing specific prevention measures (Boxes 1 and 2). LTC staff often perform numerous percutaneous procedures; frequent blood glucose monitoring increases opportunities for bloodborne pathogen transmission. The outbreak investigations reported here identified residents with diabetes who received fingersticks from nursing staff members as often as four times per day, according to their physician's routine orders, despite having consistently normal glucose levels. Expert panels have concluded that approximately 8 years are needed before the benefits of glycemic control result in reductions in microvascular complications (1,10). In LTC settings, schedules for fingerstick blood sampling of individual patients should be reviewed regularly to reduce the number of percutaneous procedures to the minimum necessary for their appropriate medical management. In each of the investigations described in this report, implementation of infection-control measures (Boxes 1 and 2) was recommended, along with follow-up serologic testing for markers of HBV.

An estimated 70,000-80,000 HBV infections occur each year in the United States. Most of these infections occur among young adults with behavioral risk factors (i.e., sexual contact and injection-drug use); these adults should receive hepatitis B vaccine. Preventing transmission of HBV among patients in long-term-care settings requires adherence to recommended infection-control practices and prompt response to identified instances of transmission. Routine hepatitis B vaccination or screening of LTC residents is not recommended. In the outbreaks described in this report, initial cases were not identified or investigated in a timely fashion, resulting in missed opportunities to correct deficient practices and interrupt transmission. Evidence of acute viral hepatitis in any LTC resident should prompt a thorough investigation. For a case involving a resident with diabetes, fingerstick blood sampling procedures and insulin administration should receive particular scrutiny. Health departments should encourage reporting of such cases and offer assistance in identifying the source of infection. CDC continues to support investigations in LTC and other health-care settings and is working toward improved implementation of the infection-control recommendations described in this report.

Acknowledgments

The findings in this report are based, in part, on data provided by C Ranck, R Hotchkiss, B Amy, MD, Mississippi Dept of Health. J Rosenberg, MD, Div of Communicable Disease Control, California Dept of Health Svcs. P MacDonald, PhD, Dept of Epidemiology Univ of North Carolina, Chapel Hill; S Smith, P Poole, North Carolina Dept of Health and Human Svcs. M Viray, Epidemiology Program Office, CDC.

References

(1.) American Diabetes Association. Standards of medical care in diabetes. Diabetes Care 2004;27:S15-35.

(2.) CDC. Nosocomial transmission of hepatitis B virus associated with a spring-loaded fingerstick device--California. MMWR 1990;39:610-3.

(3.) CDC. Nosocomial hepatitis B virus infection associated with reusable fingerstick blood sampling devices--Ohio and New York City, 1996. MMWR 1997;46:217-21.

(4.) CDC. Update: universal precautions for prevention of transmission of human immunodeficiency virus, hepatitis B virus, and other bloodborne pathogens in health-care settings. MMWR 1988;37:377-88.

(5.) American Association of Diabetes Educators. Educating providers and persons with diabetes to prevent the transmission of bloodborne infections and avoid injuries from sharps. Chicago, IL: American Association of Diabetes Educators; 1997. Available at http://www. aadenet.org/PublicAffairs/PositionStatements/EducProvidersBlood borneInfetions.pdf.

(6.) Williams IT, Perz JF, Bell BE Viral hepatitis transmission in ambulatory health care settings. Clin Infect Dis 2004;38:1592-8.

(7.) Desenclos JC, Bourdiol-Razes M, Rolin B, et al. Hepatitis C in a ward for cystic fibrosis and diabetic patients: possible transmission by spring-loaded finger-stick devices for self-monitoring of capillary blood glucose. Infect Control Hosp Epidemiol 2001;22:701-7.

(8.) Khan AJ, Cotter SM, Schulz B, et al. Nosocomial transmission of hepatitis B virus infection among residents with diabetes in a skilled nursing facility. Infect Control Hosp Epidemiol 2002;23:313-8.

(9.) CDC. Recommendations for preventing transmission of infections among chronic hemodialysis patients. MMWR 2001;50(No. RR-5).

(10.) Brown AF, Mangione CM, Saliba D, Sarkisian CA; California Healthcare Foundation/American Geriatrics Society Panel on Improving Care for Elders with Diabetes. Guidelines for improving the care of the older person with diabetes mellitus. J Am Geriatr Soc 2003;51: S265-80.

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