Hepatitis Viruses
Adelisa L. Panlilio
Melissa K. Schaefer
Nicola D. Thompson
Three hepatitis viruses are of clinical significance in healthcare settings in the United States because of healthcare-related transmission: hepatitis A virus (HAV), hepatitis B virus (HBV), and hepatitis C virus (HCV). This chapter discusses the epidemiology, clinical presentation, diagnosis, and prevention of transmission of these viruses, focusing on transmission from patient to patient in healthcare settings. Transmissions from patient to patient in dialysis settings, through transfusion or transplantation, and to and from healthcare personnel are covered elsewhere.
Patient-to-patient transmission of HAV, HBV, and HCV has been detected in a variety of healthcare settings, both in developed and less developed countries (1,2, 3, 4, 5, 6, 7 and 8). Such transmission generally occurs indirectly through lapses in infection control practices of caregivers, and almost all of the transmissions reported were preventable through adherence to recommended practices for infection control.
Worldwide, exposures associated with healthcare delivery account for many HBV and HCV infections. Therapeutic injections, which are commonly overused and administered in an unsafe manner in developing and transitional countries, are estimated to account for over 21 million new HBV infections and 2 million new HCV infections each year (9). Historically, in the United States, surveillance data have suggested that healthcare-associated HBV and HCV transmission was unusual; however, mounting data compiled from public health outbreak investigations suggest that transmission of viral hepatitis related to healthcare procedures is more common than previously recognized (8,10,11).
HEPATITIS A
Epidemiology
Hepatitis A is caused by HAV, an RNA virus, classified as a picornavirus (12). HAV infection can cause both acute disease and asymptomatic infection, does not cause chronic infection, and confers lifelong immunity from future HAV infection (13). HAV is transmitted primarily by the fecaloral route, by either person-to-person contact or ingestion of contaminated food or water (12).
While hepatitis A occurs worldwide, major geographic differences exist in its endemicity and resulting epidemiologic features. The degree of endemicity is closely related to sanitary and living conditions and other indicators of the level of development. Historically, most US cases have resulted from person-to-person transmission, and infection often occurred in the context of community-wide and child daycare center outbreaks (12,14). In a majority of reported cases, risk factors for infection have not been identified (10,14,15).
The national incidence rate of hepatitis A has declined steadily since the introduction of licensed hepatitis A vaccines in the United States in 1995 and the issuance of the first public health recommendations for the use of vaccine to prevent transmission of HAV in 1996 (16). In 2007, a total of 2,979 acute symptomatic cases of hepatitis A were reported; the national incidence (1.0 case per 100,000 population) was the lowest ever recorded (10). The most frequently reported risk factors for hepatitis A were international travel (18%), and sexual and household (8%) or other (9%) contact with another person with hepatitis A. (Risk factors are not mutually exclusive.) The majority of cases have no risk factor data available. After asymptomatic infection and underreporting were taken into account, an estimated 25,000 new infections occurred in 2007 (10,17).
Rarely, HAV infection has been transmitted by transfusion of blood or blood products collected from donors during the viremic phase of their infection, before they are symptomatic or jaundiced (1,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28 and 29). Transmission has not been reported to occur after inadvertent needlesticks or other contact with blood, although transmission of HAV among injection drug users (IDUs) may be through both percutaneous and fecal-oral routes (12,30).
Depending on conditions, HAV can be stable in the environment for months (31). Heating foods at temperatures >185°F (85°C) for 1 minute or disinfecting surfaces with a 1:100 dilution of sodium hypochlorite (i.e., household bleach) in tap water is necessary to inactivate HAV (32). Laboratory studies have demonstrated that HAV can survive on human hands for up to 4 hours and that the quantity of HAV transferred from hands to animate and inanimate surfaces can be increased by the application of pressure and friction (33). This study suggests that human hands and environmental surfaces may serve as sources of HAV dissemination.
Clinical Illness
The average incubation period for hepatitis A is 28 days (range 15-50 days) (34). Typically, acute hepatitis A starts abruptly with symptoms that can include fever, malaise, anorexia, nausea, abdominal discomfort, dark urine, and jaundice. The severity of clinical disease associated with HAV infection increases with age. In children <6 years of age, most (70%) infections are asymptomatic; if illness does occur, it is usually anicteric (35). Among older children and adults, infection is usually symptomatic, with jaundice occurring in >70% of patients (36). Signs and symptoms usually last <2 months, although 10% to 15% of symptomatic persons have prolonged or relapsing disease lasting up to 6 months (37).
Fulminant hepatitis is a rare complication of hepatitis A; the case-fatality rate for all ages is 0.3% to 0.6%, but reaches 1.8% among adults >50 years (10). Persons with chronic liver disease who acquire hepatitis A are at increased risk for acute liver failure and death (10,38). Other complications include cholestatic hepatitis, with very high bilirubin levels that can persist for months, and relapsing hepatitis, in which exacerbations can occur weeks to months after apparent recovery. Chronic infection does not occur following HAV infection (12).
In infected persons, HAV replicates in the liver, is excreted in bile, and is shed in the stool. Feces can contain up to 108 infectious virions per milliliter and are the primary source of HAV (39,40). Fecal excretion of HAV and, hence, peak infectivity are greatest during the incubation period of disease before the onset of jaundice or elevation of liver enzymes (39,40). The concentration of virus in stool declines after jaundice appears; once disease is clinically obvious, the risk of transmitting infection is decreased. However, some patients admitted to the hospital with HAV, particularly immunocompromised patients, may still be shedding virus because of prolonged or relapsing disease, and such patients are potentially infectious (41). Fecal shedding of HAV, formerly believed to continue only as long as 2 weeks after the onset of dark urine, has been shown to occur as late as 6 months after diagnosis of infection in premature infants (who are more likely to be anicteric). Children and infants can shed HAV for longer periods than do adults, up to several months after the onset of clinical illness (28). Viremia occurs soon after infection and persists through the period of liver enzyme elevation (42,43). The amount of virus in the blood is several orders of magnitude lower than that in stool (42, 43 and 44). Although virus has also been found in saliva during the incubation period in experimentally infected animals, transmission by saliva has not been reported (44).
Diagnosis
Hepatitis A cannot be differentiated from other types of viral hepatitis on the basis of clinical or epidemiologic features alone. The diagnosis of acute HAV infection is confirmed during the acute or early convalescent phase of infection by the presence of immunoglobulin M (IgM) anti-HAV. In most persons, IgM anti-HAV becomes detectable 5 to 10 days before the onset of symptoms and can persist for up to 6 months after infection (43,45). Immunoglobulin G (IgG) anti-HAV, which also appears early in the course of infection, remains detectable for the lifetime of the individual and confers lifelong protection against infection (13). Although commercial tests are available for the detection of IgM and total (IgM and IgG) anti-HAV in serum, IgM HAV testing should be limited to persons with evidence of clinical hepatitis or to those who have had recent exposure to an HAV-infected person to avoid the possibility of falsepositive test results (46).
HAV RNA can be detected in the blood and stool of most persons during the acute phase of infection by using nucleic acid amplification methods, and nucleic acid sequencing has been used to determine the relatedness of HAV isolates (47). However, these methods are available in only a limited number of research laboratories and generally are not used for diagnostic purposes.
HAV Transmission in Healthcare Settings
Transmission of HAV from patient to patient in healthcare settings has been reported infrequently, usually occurring when the source patient had unrecognized hepatitis and was fecally incontinent or had diarrhea (1). Other risk factors for HAV transmission include activities that increase the risk of fecal–oral contamination, such as eating or drinking in patient-care areas, inadequate hand hygiene after handling an infected patient and/or the patient-care environment, and sharing food, beverages, or cigarettes with patients, their families, or other staff members. Healthcare-associated hepatitis A outbreaks are summarized in Table 46-1 in chronological order of the date they were reported. The table shows the number of patients, staff, and family contacts infected, the country and healthcare setting in which each outbreak occurred, and factors contributing to transmission such as asymptomatic viral shedding, gross fecal environmental contamination, and hospitalization during the prodrome of hepatitis A (18,20,22,23,25, 26, 27, 28 and 29,48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60 and 61). The majority of reports are from the 1980s, with the last published report from 2002. Two illustrative outbreaks will be described in greater detail.
Several outbreaks have occurred in neonatal intensive care units (NICUs), often involving transfusion of neonates with infected blood and subsequent transmission of HAV infection to other infants and staff (22,23,26, 27, 28 and 29,48). The first such reported outbreak resulted from exchange transfusion of blood from a donor in the prodrome of hepatitis A (18). (The donor became ill 4 weeks after donation.) The infant had received an exchange transfusion at birth for Rh incompatibility and developed subclinical HAV infection. She was subsequently nursed on a surgical ward for treatment of Staphylococcus aureus osteitis for 4 weeks, during which period she had to be turned every hour. Transmission to her mother, to nine staff who provided care to the index patient, and to one other patient on the same ward as the index case was documented.
In many of the NICU outbreaks, lapses in infection control practices, including smoking, eating, and drinking in patient-care areas, not wearing gloves as appropriate when providing patient care, and inadequate hand hygiene, facilitated transmission of HAV from patient to patient and from patient to staff, contributing to propagation of the outbreaks (22,23,26, 27, 28 and 29,48). NICUs provide a setting that has been conducive to further spread of HAV once it
is introduced. The combination of frequent contact with soiled diapers, asymptomatic infection in neonates, and prolonged HAV excretion among preterm infants may facilitate HAV transmission.
is introduced. The combination of frequent contact with soiled diapers, asymptomatic infection in neonates, and prolonged HAV excretion among preterm infants may facilitate HAV transmission.
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Most patients hospitalized for symptomatic hepatitis A are admitted after onset of jaundice, when they are beyond the point of peak infectivity (1,62). Consequently, most source patients for outbreaks of hepatitis A outside of NICUs were usually admitted for diagnoses other than hepatitis A, were incubating hepatitis A, and developed subclinical or symptomatic hepatitis after hospitalization (20,25,49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60 and 61). Patient-to-healthcare personnel and patient-to-patient transmission of HAV in such situations was usually associated with fecal incontinence and/or gross environmental contamination with feces (20,25,49, 50, 51, 52, 53 and 54,56, 57 and 58,61). One such outbreak involved an adult hospitalized for elective cholecystectomy who developed fever, abdominal pain, vomiting, and diarrhea postoperatively (51). She had several episodes of fecal incontinence with gross contamination of her bed linen and floor. Despite developing jaundice, she was discharged without a specific diagnosis. However, on readmission for further diagnostic evaluation of her jaundice, she was confirmed to have acute hepatitis A. Five nurses who were exposed to the patient during her first admission became clinically ill with laboratory- confirmed hepatitis A. As part of a serologic survey of exposed personnel, a sixth nurse was found to have asymptomatic infection. The index patient’s hospital roommate, who had assisted the index patient in the bathroom postoperatively, also developed clinical illness.
Other healthcare-associated outbreaks of hepatitis A had features similar to the outbreak just described (25,50,52, 53, 54, 55, 56, 57, 58, 59, 60 and 61). In many of these outbreaks, the index patient was admitted for a condition other than hepatitis, for example, malaria, amebic hepatic abscess, burns, or cardiac surgery. When the index patient developed symptoms consistent with hepatitis A, the diagnosis was often not suspected until after his or her contacts, usually personnel, developed symptomatic hepatitis A.
Prevention of Healthcare-Related HAV Transmission
The primary means of preventing HAV transmission in healthcare settings is by observing Contact Precautions with patients with acute hepatitis A who are in diapers and/or incontinent and by avoiding fecal–oral contact (63). Continent patients can be managed with Standard Precautions alone (63). Meticulous hand hygiene after touching the patient, the patient’s feces, or the environment around the patient (64) and not eating, drinking, or smoking in patientcare areas are essential to preventing HAV transmission in healthcare settings (63). In addition, cleaning and disinfection of all patient-care areas is important for frequently touched surfaces, especially those closest to the patient, which are most likely to be contaminated (e.g., bedrails, bedside tables, commodes, doorknobs, sinks, surfaces, and equipment in close proximity to the patient) (63). The frequency or intensity of cleaning may need to change based on the patient’s level of hygiene and the degree of environmental contamination (63). An Environmental Protection Agency (EPA)—approved hospital disinfectant/detergent designed for general housekeeping surfaces is preferred (65).
Inactivated hepatitis A vaccines are available for prevention of hepatitis A (12,66, 67 and 68). The vaccines containing HAV antigen that are currently licensed in the United States are the single-antigen vaccines HAVRIX (manufactured by GlaxoSmithKline, Rixensart, Belgium) and VAQTA (manufactured by Merck & Co., Inc., Whitehouse Station, NJ) and the combination vaccine TWINRIX (containing both HAV and HBV antigens; manufactured by GlaxoSmithKline). These vaccines are highly immunogenic as well as highly effective in the prevention of clinical hepatitis A (67,68). With universal childhood immunization with hepatitis A vaccine, catch-up vaccination of older children in geographic regions with historically high incidence, and broader vaccination coverage of at-risk groups, the overall population level of immunity will continue to rise. Already, increased vaccination coverage for hepatitis A among children has led to the lowest rates of hepatitis A in the United States, consistent with herd immunity (69). Healthcare-associated hepatitis A transmission is likely to remain a rare event.
Because serologic surveys among healthcare personnel have not shown greater prevalence of HAV infection than in control populations, healthcare personnel are not considered at increased risk for acquiring HAV infection, and routine administration of vaccine in healthcare personnel is not recommended (12,70,71). Vaccine is recommended for some persons because of occupational risk, including those who handle HAV-infected primates or are exposed to HAV in a research laboratory (12). Hepatitis A vaccine is also recommended for all children at age 1 year (12-23 months), for persons at increased risk of infection, such as those traveling or working in countries with high or intermediate endemicity of infection, men who have sex with men, injection and noninjection illicit-drug users, persons with clotting factor disorder, and for persons with chronic liver disease who are at increased risk for severe complications from hepatitis A (12).
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