Hepatitis A virus (HAV)
is shed in the feces, and peak titersoccur during the 2
weeks before and 1 week after onset of illness. Virus is
also present in serum and saliva during this period,although
in concentrations several orders of magnitude less.
Consequently, the most common mode of transmission is fecal-oral,with the virus being transmitted from person to person or bycontaminated food or water . On the basis of cases of hepatitisA reported in 1992 to the Centers for Disease Control and
Prevention(CDC), the most frequently reported risk factor
was householdor sexual contact with a person with hepatitis
(24%), followedby day-care attendance or employment (15%),
recent internationaltravel (6%), and association with a
suspected food- or water-borneoutbreak (5%). Many persons
with hepatitis A do not identifyrisk factors; their source
of infection may be other infectedpersons who are
Because of the
viremic phase during HAV infection, transfusion-related
hepatitis A occurs occasionally. The source of infection is
usually a blood donor who is incubating the virus at the time
of donation. Predonation interviews regarding hepatitis symptomsas well as screening of blood donations for alanine
aminotransferaseelevations are important safeguards for
preventing blood-borneHAV transmission. Blood-borne HAV
transmission to neonates orother patients has resulted in
nosocomial hepatitis A outbreaksamong hospital personnel.
of HAV transmission to hemophiliacs receivingcontaminated
factor VIII units, described in this issue of theAnnals ,
along with other such outbreaks in Europe, representsfurther
examples of blood-borne HAV transmission. Contamination
presumably occurred from plasma donors who were incubating HAVat the time of donation and was substantial enough that thevirus was purified along with factor VIII during the preparationprocess; the solvent-detergent step used in factor VIII
preparationto inactivate lipid-containing viruses is
ineffective againstHAV. Less likely is the possibility that
contamination occurredsometime during processing.
Transmission of HAV by factor VIIIpreparations has not been
reported in the United States.
Hepatitis B virus
(HBV) is present in high titers in blood andexudates (for
example, from skin lesions) of acutely and chronically
infected persons . Moderate viral titers are found in semen,vaginal secretions, and saliva. Other body fluids that do notcontain blood or serous fluid, such as feces or urine, are nota source of HBV. Therefore, the three principal modes of HBVtransmission are percutaneous (injection drug use, blood orbody-fluid exposures among health care workers, and blood
transfusions),sexual (heterosexual or male homosexual), and
mother-to-infant(through blood exposure at the time of
birth) . Transmissionbetween siblings and other household
contacts readily occurs,through transmission from skin
lesions such as eczema or impetigo,sharing of potentially
blood-contaminated objects such as toothbrushesand razor
blades, and occasionally through bites . Nosocomial
outbreaks, although rare, have occurred due to improper use
or disinfection of medical devices (for example, fingerstick
devices, acupuncture needles) or due to transmission from infectedhealth care workers to patients during invasive procedures [8,9].
The number of
reported cases of hepatitis B has decreased inrecent years
among drug users and homosexual men because ofbehavioral
changes in response to the acquired immunodeficiencysyndrome
(AIDS) epidemic; however, heterosexual transmissionnow
accounts for more cases than any other factor. The most
frequent risk factor among patients with cases reported from
1990 to 1992 in the Sentinel Counties Study, a surveillance
system operated by CDC in four U.S. counties, was heterosexualexposure to a contact with hepatitis or to multiple partners(36%), followed by injection drug use (13%), homosexual activity(11%), household contact (3%), and health care employment (2%).Transmission from blood transfusions is rare because of donordeferral and screening for hepatitis B surface antigen and
antibodyto hepatitis B core antigen (anti-HBc). Perinatal
transmissionand transmission to young children in
households, although notreflected in surveillance data
because acute infection at theseages is largely asymptomatic,
account for a substantial proportionof chronic disease
caused by HBV infection .
virus (HDV) is a defective virus, dependenton HBV for
replication. Hepatitis delta virus is only transmittedas a
co-infection with HBV or as a superinfection to a personwho
is already infected with HBV. An estimated 4% of acute HBV
infections are co-infections with HDV . Seroepidemiologic
studies indicate that in the United States, transmission is
mostly through injection drug use and less commonly through
sexual transmission. The seroprevalence of antibody to HDV amongHBV-infected injection drug users ranges from 20% to 53%.
Hepatitis C virus
(HCV), discovered in the late 1980s, is theagent that most
often causes non-A, non-B hepatitis in the UnitedStates.
Hepatitis C virus circulates in low titers in the bloodof
infected persons and is detected inconsistently in otherbody
fluids [12,13]. The most efficient mode of HCV transmission
is direct percutaneous blood exposure, such as through blood
or blood products or through needle sharing among drug users
or through transfusion of blood or blood products. The risk
for HCV transmission after a needlestick exposure to blood froma source positive for antibody to HCV (anti-HCV) is 3% to 10%. In the Sentinel Counties Study, cases among injectiondrug users account for nearly 40% of acute hepatitis C cases.Donor deferral and screening for surrogate markers (anti-HBcand alanine aminotransferase) and for anti-HCV have made
post-transfusionhepatitis C relatively rare. Follow-up
studies of blood transfusionrecipients indicate that the
risk for acquiring HCV infectionfrom a blood transfusion is
less than 0.5% .
the risk for sexual and perinatal HCV transmissionhave been
limited by small sample size and variable types ofserologic
testing and, in some cases, have produced conflicting
results. Some studies among sexual contacts and spouses of anti-HCV-positivepersons have found HCV infection rates, determined by anti-HCVor detection of HCV by the polymerase chain reaction, as highas 32% [16,17], whereas other studies among similar contactsand among homosexual men have found little or no HCV infection[18,19]. Studies of infants born to HCV-infected women negativefor the human immunodeficiency virus have found the risk fortransmission, determined by persistent anti-HCV positivity,to be from 0% to 13% [20,21,22]. In the Sentinel Counties Study,14% of patients with acute hepatitis C had exposure to a householdor sexual contact with hepatitis or to multiple sexual partners.An additional 42% did not report a source of infection; thesepersons may have denied risk factors or may have had unrecognizedexposures (for example, sexual contact with a person who isasymptomatically infected). Although it appears that sexual,perinatal, and possibly household HCV transmission can occur,further studies are needed to quantify the risk.
In recent years,
hepatitis E virus (HEV), the causative agentof enterically
transmitted non-A, non-B hepatitis, has beenisolated, and
serologic assays have been developed to detectHEV infection
. Hepatitis E occurs in large outbreaks inareas with
extremely poor sanitary conditions, such as refugeecamps in
developing countries. The virus is excreted in feces,and
fecally contaminated drinking water has been the most frequentlydocumented vehicle of transmission; person-to-person transmissionhas not been felt to play a substantial role. Sporadic endemictransmission also occurs in many developing countries, but fewstudies have addressed how such transmission occurs. HepatitisE has only occasionally been reported in the United States;all cases have occurred in recent travelers to HEV endemic areas,and no secondary transmission has been observed .
persons who are infected with one of the hepatitisviruses be
counseled regarding transmission to others? A common
misconception among some patients and providers is that personswith hepatitis should refrain from casual contact (includinghugging and kissing) and from sharing silverware, glassware,or other eating utensils and that they should use separate
bathroomsand wash clothes separately. These are not
recognized routesof transmission for any of the hepatitis
viruses, and thereforesuch precautions are not necessary.
Household articles withthe potential for blood
contamination, such as razor bladesor toothbrushes, should
not be shared. None of the hepatitisviruses are readily
transmitted between children in school settingsor between
employees in the workplace; therefore, persons whoare
infected with any of these viruses can generally returnto
school or work activities without any restrictions as soonas
their medical condition allows. The exceptions are retail
food-handlers who have hepatitis A, for whom most local healthdepartments recommend work restrictions for 1 week after onsetof illness, and HBV-infected health care workers who are hepatitisB e antigen positive and who do invasive procedures, whose
activitiesshould be reviewed by an expert panel to determine
which procedures,if any, they can perform .
On the basis of
the limited available data, the U.S. PublicHealth Service
does not recommend a change in current sexualpractices for
persons with HCV infection who have a steady sexualpartner
. For HCV-infected persons with multiple sexualpartners,
safe sex practices should be followed to prevent transmission
of HCV and other sexually transmitted diseases. No special treatmentsor precautions for HCV-infected pregnant women or their offspringare recommended.
is available to protect contacts of personswith hepatitis A
and B. Household and sexual contacts of personswith
hepatitis A should receive immune globulin within 2 weeksof
last exposure . Children with hepatitis A in day carecan
return to their centers after all other children and employeesreceive immune globulin . Sexual contacts of persons withacute HBV infection and others with direct percutaneous (needlestick,laceration, or bite) or permucosal (ocular or mucous-membrane)exposure to blood of HBV-infected persons should receive hepatitisB immune globulin and hepatitis B vaccine. Household and sexualcontacts of persons who are identified with chronic HBV infectionshould receive hepatitis B vaccine . Available data indicatethat immune globulin does not offer protection against HEV
infection;to prevent transmitting HEV to others, careful
attention shouldbe paid to hand washing and personal
To prevent and
control transmission within populations, effectivevaccines
exist for two of the hepatitis viruses. The challengeis to
develop effective strategies for vaccine delivery. Hepatitis
B vaccine has been available in the United States since the
early 1980s. The failure of vaccination strategies targeting
adult high-risk groups to have a substantial effect on diseaserates has led to recent recommendations for routine childhoodhepatitis B immunization . An inactivated hepatitis A vaccinehas been commercially available in Europe and Asia for severalyears and should be available soon in the United States. Althoughinternational travelers are a relatively accessible group forvaccination, how to use the vaccine in other groups to preventhepatitis A remains to be determined. Vaccines against HCV andHEV, and against HDV to protect HBV carriers, are distant
possibilities.Ultimately, the prevention and control of
transmission of hepatitisviruses will best be achieved
through a combination of modificationof risk behavior,
availability of vaccines, and developmentof successful
strategies for vaccine delivery.
Author and Article Information
Centers for Disease Control and Prevention, Atlanta, GA 30333.
Requests for Reprints: Craig N. Shapiro, MD, Hepatitis Branch, MS G-37,
Centers for Disease Control and Prevention, Atlanta, GA 30333.
Tassopoulos NC, Papaevangelou GJ, Ticehurst JR, Purcell RH. Fecal
excretion of Greek strains of hepatitis A virus in patients with
hepatitis A and in experimentally infected chimpanzees. J Infect Dis.
Cohen JI, Feinstone S, Purcell RH. Hepatitis A virus infection in a
chimpanzee: duration of viremia and detection of virus in saliva and
throat swabs. J Infect Dis. 1989;160:887-90.
Shapiro CN, Shaw FE, Mandel EJ, Hadler SC. Epidemiology of hepatitis A
in the United States. In: Hollinger FB, Lemon SM, Margolis H, eds. Viral
Hepatitis and Liver Disease: Proceedings of the 1990 International
Symposium on Viral Hepatitis and Liver Disease. Baltimore: Williams &
Mannucci PM, Gdovin S, Gringeri A, Colombo M, Mele A, Schinaia N, et al.
Transmission of hepatitis A to hemophilic patients by factor VIII
concentrates treated with organic solvent and detergent to inactivate
viruses. Ann Intern Med. 1994;120:1-7.
Jenison SA, Lemon SM, Baker LN, Newbold JE. Quantitative analysis of
hepatitis B virus DNA in saliva and semen of chronically infected
homosexual men. J Infect Dis. 1987;156:299-307.
Francis DP, Favero MS, Maynard JE. Transmission of hepatitis B virus.
Semin Liver Dis. 1981;1:27-32.
Davis LG, Weber DJ, Lemon SM. Horizontal transmission of hepatitis B
virus. Lancet. 1989;1:889-93.
Polish LB, Shapiro CN, Bauer F, Klotz P, Ginier P, Roberto RR, et al.
Nosocomial transmission of hepatitis B virus associated with the use of
a spring-loaded finger-stick device. N Engl J Med. 1992; 326:721-5.
Recommendations for preventing transmission of human immunodeficiency
virus and hepatitis B virus to patients during exposure-prone invasive
procedures. MMWR Morbid Mortal Wkly Rep. 1991;40:1-9.
Margolis HS, Alter MJ, Hadler SC. Hepatitis B: evolving epidemiology and
implications for control. Semin Liver Dis. 1991;11:84-92.
Alter MJ, Hadler SC. Delta hepatitis and infection in North America. In:
Hadziyannis SJ, Taylor JM, Bonino F, eds. Hepatitis Delta Virus:
Molecular Biology, Pathogenesis, and Clinical Aspects. New York: Wiley-Liss;
Bradley DW, Krawczynski K, Beach MJ, Purdy MA. Non-A, non-B hepatitis:
toward the discovery of hepatitis C and E viruses. Semin Liver Dis.
Fried MW, Shindo M, Fong TL, Fox PC, Hoofnagle JH, Di Bisceglie AM.
Absence of hepatitis C viral RNA from saliva and semen of patients with
chronic hepatitis C. Gastroenterology. 1992;102: 1306-8.
Mitsui T, Iwano K, Masuko K, Yamazaki C, Okamoto H, Tsuda F, et al.
Hepatitis C virus infection in medical personnel after needlestick
accident. Hepatology. 1992;16:1109-14.
Donahue JG, Munoz A, Ness PM, Brown DE Jr, Yawn DH, McAllister HA Jr, et
al. The declining risk of post-transfusion hepatitis C virus infection.
N Engl J Med. 1992;327:369-73.
Osmond DH, Padian NS, Sheppard HW, Glass S, Shiboski SC, Reingold A.
Risk factors for hepatitis C virus seropositivity in heterosexual
couples. JAMA. 1993;269:361-5.
Kao JH, Chen PJ, Yang PM, Lai MY, Sheu JC, Wang TH, et al. Intrafamilial
transmission of hepatitis C virus: the important role of infections
between spouses. J Infect Dis. 1992;166:900-3.
Everhart JE, Di Bisceglie AM, Murray LM, Alter JH, Melpoder JJ, Kuo G,
et al. Risk for non-A, non-B (type C) hepatitis through sexual or
household contact with chronic carriers. Ann Intern Med. 1990;112:544-5.
Osmond DH, Charlebois E, Sheppard HW, Page K, Winkelstein W, Moss AR, et
al. Comparison of risk factors for hepatitis C and hepatitis B virus
infection in homosexual men. J Infect Dis. 1993; 167:66-71.
Lam JP, McOmish F, Burns SM, Yap PL, Mok JY, Simmonds P, et al.
Infrequent vertical transmission of hepatitis C virus. J Infect Dis.
Reinus JF, Leikin EL, Alter HJ, Cheung L, Shindo M, Jett B, et al.
Failure to detect vertical transmission of hepatitis C virus. Ann Intern
Wejstal R, Widell A, Mansson AS, Hermodsson S, Norkrans G.
Mother-to-infant transmission of hepatitis C virus. Ann Intern Med.
Bradley DW. Hepatitis E: epidemiology, aetiology and molecular biology.
Rev Med Virol. 1992;2:19-28.
Hepatitis E among U.S. travelers, 1989-1992. MMWR Morbid Mortal Wkly
Public Health Service inter-agency guidelines for screening donors of
blood, plasma, organs, tissues, and semen for evidence of hepatitis B
and hepatitis C. MMWR Morbid Mortal Wkly Rep. 1991; 40:1-17.
Protection against viral hepatitis. Recommendations of the Immunization
Practices Advisory Committee (ACIP). MMWR Morbid Mortal Wkly Rep.
Hepatitis B virus: a comprehensive strategy for eliminating transmission
in the United States through universal childhood vaccination.
Recommendations of the Immunization Practices Advisory Committee (ACIP).
MMWR Morbid Mortal Wkly Rep. 1991;40:1-25.