Risk and Management of Blood-Borne Infections in
Health Care Workers
Elise M. Beltrami,1,* Ian T. Williams,2 Craig N. Shapiro,2 and Mary E.
Clinical Microbiology Reviews, July 2000, p. 385-407, Vol. 13, No. 3
HIV Infections Branch, Hospital Infections Program,1 and Hepatitis
Branch, Division of Viral and Rickettsial Diseases,2 National Center for
Infectious Diseases, Centers for Disease Control and Prevention, Public
Health Service, U.S. Department of Health and Human Services, Atlanta,
Exposure to blood-borne pathogens poses a serious risk to health care
workers (HCWs). We review the risk and management of human
immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C
virus (HCV) infections in HCWs and also discuss current methods for
preventing exposures and recommendations for postexposure prophylaxis.
In the health care setting, blood-borne pathogen transmission occurs
predominantly by percutaneous or mucosal exposure of workers to the
blood or body fluids of infected patients. Prospective studies of HCWs
have estimated that the average risk for HIV transmission after a
percutaneous exposure is approximately 0.3%, the risk of HBV
transmission is 6 to 30%, and the risk of HCV transmission is
approximately 1.8%. To minimize the risk of blood-borne pathogen
transmission from HCWs to patients, all HCWs should adhere to standard
precautions, including the appropriate use of hand washing, protective
barriers, and care in the use and disposal of needles and other sharp
instruments. Employers should have in place a system that includes
written protocols for prompt reporting, evaluation, counseling,
treatment, and follow-up of occupational exposures that may place a
worker at risk of blood-borne pathogen infection. A sustained commitment
to the occupational health of all HCWs will ensure maximum protection
for HCWs and patients and the availability of optimal medical care for
all who need it.
Exposure to blood-borne pathogens poses a serious risk to health care
workers (HCWs). Transmission of at least 20 different pathogens by
needlestick and sharps injuries has been reported (79). Despite improved
methods of preventing exposure, occupational exposures will continue to
Assessment of the risk of blood-borne pathogen transmission in the
health care setting requires information derived from various sources,
including surveillance data, studies of the frequency and preventability
of blood contacts, seroprevalence studies among patients and HCWs, and
prospective studies that assess the risk of seroconversion after an
exposure to infected blood. Factors influencing the risk to an
individual HCW over a lifetime career include the number and types of
blood contact experienced by the worker, the prevalence of blood-borne
pathogen infection among patients treated by the worker, and the risk of
transmission of infection after a single blood contact.
In this article, we review the risk and management of the three
blood-borne viruses most commonly involved in occupational transmission:
human immunodeficiency virus (HIV), hepatitis B virus (HBV), and
hepatitis C virus (HCV). We also will discuss current methods of
preventing exposure, including standard precautions and the use of
safety devices in the health care setting, as well as recommendations
for postexposure prophylaxis.
TRANSMISSION OF BLOOD-BORNE PATHOGENS IN THE HEALTH CARE SETTING
Modes of Blood-Borne Pathogen Transmission
In the health care setting, blood-borne pathogen transmission occurs
predominantly by percutaneous or mucosal exposure of workers to the
blood or body fluids of infected patients. Occupational exposures that
may result in HIV, HBV, or HCV transmission include needlestick and
other sharps injuries; direct inoculation of virus into cutaneous
scratches, skin lesions, abrasions, or burns; and inoculation of virus
onto mucosal surfaces of the eyes, nose, or mouth through accidental
splashes. HIV, HBV, and HCV do not spontaneously penetrate intact skin,
and airborne transmission of these viruses does not occur.
Epidemiology of Blood Contact
To understand the nature, frequency, and prevention of percutaneous
injuries and mucocutaneous blood contacts among HCWs, prospective
observational studies have been performed in different patient care
settings (Table 1). The percentage of procedures with at least one blood
contact of any type ranged from 3% of procedures performed by invasive
radiology personnel in a study in Dallas, Tex. (130), to 50% of
procedures performed by surgeons in a study in Milwaukee, Wisc. (224).
The percentage of procedures with at least one injury caused by a sharp
instrument also varied widely, from 0.1 to 15%. These differences may be
related to variations in study methods, procedures observed, and
precautions used by the workers performing the procedures.
Several of these studies assessed specific risk factors for injury or
exposure. For example, of the 99 percutaneous injuries observed by
Tokars et al. during 1,382 operations in five different surgical
specialties (general, orthopedic, gynecologic, trauma, and cardiac),
most (73%) were related to suturing (256). Rates were highest (10%)
during gynecologic surgeries (256). Panlilio et al. found in their study
of blood contacts during surgery that risk factors for blood contacts by
surgeons included performing an emergency procedure, patient blood loss
greater than 250 ml, and surgery duration greater than 1 h (208). In
their study of dental procedures, Cleveland et al. found that most
percutaneous injuries sustained by dental residents occurred extraorally
and were associated with denture impression procedures (77).
Retrospective studies and surveys have also shown high rates of blood
contact among HCWs in different patient care settings. Tokars et al.
found that among 3,420 participants at the American Academy of
Orthopaedic Surgeons annual meeting, 87.4% of surgeons surveyed reported
a blood-skin contact and 39.2% reported a percutaneous blood contact in
the previous month (258). In a retrospective survey by O'Briain in
1991 (202), 56% of 36 resident and staff pathologists reported that they
had sustained a cut or needlestick injury in the preceding year. In this
study, pathologists reported 72 injuries, corresponding to a rate of one
injury for every 37 autopsies performed and one injury for every
2,629 surgical specimens handled (202). An anonymous national survey of
certified nurse-midwives by Willy et al. found that 74% had soiled their
hands with blood, 51% had splashed blood or amniotic fluid in their
faces, and 24% had sustained one or more needlestick injuries in the
preceding 6 months (281). Among 550 medical students and residents in
Los Angeles, Calif., who were surveyed anonymously by O'Neill et al.,
71% reported exposures to patients' blood and body fluids during the
preceding year (204). In a recent study of third- and fourth-year
medical students in San Francisco, Calif., by Osborn et al., 12%
reported an exposure to infectious body substances over the 7-year study
period, from 1990 to 1996 (205). There is evidence among some groups of
HCWs, such as dentists, that rates of exposure are decreasing over time,
temporally associated with increased awareness and compliance with the
practice of standard precautions (76).
DETECTION AND DIAGNOSIS OF BLOOD-BORNE PATHOGEN INFECTIONS
An understanding of the detection and diagnosis of HIV, HBV, and HCV
infection is vital for the appropriate management and care of HCWs
exposed to or infected with bloodborne viruses.
Detection and Diagnosis of HIV Infection
After initial primary infection with HIV, there is a window period prior
to the development of detectable antibody. In persons with known
exposure dates, the estimated median time from initial infection to the
development of detectable antibody is 2.4 months; 95% of individuals
develop antibodies within 6 months of infection (34). Among HCWs with a
documented seroconversion to HIV, 5% tested negative for HIV antibodies
at >6 months after their occupational exposure but were seropositive
within 12 months (73). The two antibody tests commonly used to detect
HIV are the enzyme immunoassay (EIA) and the Western blot. An HIV test
result is reported as negative when the EIA result is negative. The
result is reported as positive when the EIA result is repeatedly
reactive and when the result of a more specific, supplemental
confirmatory test, such as the Western blot, is also positive. Once an
individual develops an antibody response, it usually remains detectable
for life. HIV infection for longer than 6 months without detectable
antibody is uncommon (73, 226).
Direct virus assays (e.g., PCR for HIV RNA) are sensitive methods for
the detection of HIV infection. However, problems with laboratory
contamination, false-positive rates, and increased costs limit their
routine use. While PCR for HIV RNA is approved for use in established
HIV infection, its reliability in detecting very early infection has not
been determined (34). At present, the false-positive and false-negative
rates of PCR are too high to warrant a broader role for it in routine
postexposure management (207).
Detection and Diagnosis of HBV Infection
The incubation period for acute hepatitis B ranges from 45 to 160 days,
with an average of 120 days. Exposure to HBV can lead to an acute
infection which may result in a chronic infection. Acute hepatitis B
resembles other forms of viral hepatitis and cannot be distinguished
based on history, physical examination, or serum biochemical tests.
The diagnosis of acute HBV infection is confirmed by the demonstration
in serum of hepatitis B surface antigen (HBsAg), which appears well
before onset of symptoms and before development of antibody to hepatitis
B core antigen (anti-HBc), and immunoglobulin M (IgM) antibody to HBc,
which appear at approximately the same time as symptoms (143). The
presence of IgM anti-HBc indicates recent HBV infection, usually within
the preceding 4 to 6 months. The presence of hepatitis B e antigen (HBeAg)
in serum correlates with HBV replication, high titers of HBV, and
infectivity. Persons who are positive for HBeAg typically have 108 to
109 HBV particles per ml of blood (243). In persons who resolve acute
HBV infection, antibody to HBsAg (anti-HBs) develops and indicates
immunity. The persistence of HBsAg for 6 months after the diagnosis of
acute HBV is indicative of progression to chronic HBV infection.
HBV serologic markers in different stages of infection and convalescence
are summarized in Table 2. Anti-HBc indicates prior infection and lasts
indefinitely. In persons who respond to the hepatitis B vaccine, anti-HBs
is the only antibody that is elicited. Persons with chronic infection
who have mutations in the precore region of the HBV genome that prevent
the expression of HBeAg but allow the expression of infectious virus
have been described (40, 260). High titers of HBsAg can be observed in
these persons even though they are HBeAg negative. The prevalence of
these precore mutations in persons in the United States is unknown. The
prevalence may be relatively high in certain parts of the world (41,
124, 171, 173, 197).
Detection and Diagnosis of HCV Infection
The incubation period for acute HCV infection ranges from 2 to 24 weeks,
with an average of 6 to 7 weeks (166, 179; L. B. Seef, Letter, Ann.
Intern. Med. 115:411, 1991). Because different types of viral hepatitis
are indistinguishable based on clinical symptoms alone, serologic
testing (Table 3) is necessary to establish a specific diagnosis of
hepatitis C (121). Screening EIA and supplemental immunoblot assays are
licensed and commercially available to detect antibodies to HCV (anti-HCV)
(283). Because the rate of false positivity for the screening EIA is
high in many populations, including HCWs, supplemental immunoblot assays
must be used to judge the validity of repeatedly reactive EIA results.
Anti-HCV may be detected within 5 to 6 weeks after the onset of
infection and remains detectable long after the primary infection. In
general, the interpretation of serologic tests for anti-HCV is limited
by the following factors: (i) assays for anti-HCV do not distinguish
between acute, chronic, or past infection; (ii) in acute infection there
may be a prolonged interval between onset of illness and anti-HCV
seroconversion (though most infected individuals seroconvert within
3 months of exposure); and (iii) the detection of anti-HCV does not
necessarily indicate active HCV replication (8).
HCV RNA can be detected in serum or plasma within 1 to 2 weeks of
exposure to the virus and several weeks before onset of alanine
aminotransferase (ALT) elevations or the appearance of anti-HCV (103).
In patients with chronic HCV infection, HCV RNA levels may remain
relatively stable or can fluctuate over 1,000,000-fold. Fluctuations in
HCV RNA may or may not correlate with elevations in transaminase levels.
Rarely, the detection of HCV RNA may be the only evidence of HCV
PCR techniques to amplify reverse-transcribed cDNA are currently the
most sensitive methods for detecting HCV RNA. Both qualitative (122) and
quantitative (87, 229) methods can be used to detect HCV RNA.
Quantitative assays are less sensitive than qualitative assays and
should not be used as a primary test to confirm or exclude the diagnosis
of HCV infection (212). Currently, testing for HCV RNA is available on a
research basis and no tests have been approved by the U.S. Food and Drug
Administration. Because of assay variability, results of HCV RNA testing
should be interpreted cautiously.
There are at least six different genotypes and more than 90 subtypes of
HCV (33). About 70% of HCV-infected persons in the United States are
infected with genotype 1; subtype 1a predominates over subtype 1b.
Several different nucleic acid detection methods are commercially
available to group isolates of HCV based on genotypes and subtypes
RISK OF OCCUPATIONAL TRANSMISSION OF HIV FROM PATIENTS TO WORKERS
Risk of HIV Infection Postexposure
Prospective studies of HCWs have estimated that the average risk for HIV
transmission after a percutaneous exposure to HIV-infected blood is
approximately 0.3% (95% confidence interval = 0.2 to 0.5%) (23) and that
after a mucous membrane exposure it is 0.09% (95% confidence
interval = 0.006 to 0.5%) (147). The risk after a cutaneous exposure is
less but has not been well quantified since no HCW enrolled in a
prospective study has seroconverted after an isolated skin exposure.
There are insufficient data to quantify the risk of transmission after
occupational exposure to potentially infectious tissues or fluids other
than blood. However, in a study by Fahey et al., none of
559 participants reporting cutaneous exposures to blood, sputum, urine,
feces, or other body substances from patients presumed infected with HIV
acquired HIV infection (102). There is also no evidence of a risk for
HIV transmission by the aerosol route. Transmission of HIV by aerosol
would require the generation of aerosolized particles of blood, the
presence of infective HIV in these aerosolized particles, and the
deposition of a sufficient number of infective particles in the
respiratory tract or on the mucous membranes of a susceptible host to
cause infection. Biological or epidemiologic evidence that HIV can be
transmitted by aerosols via the respiratory route currently does not
exist (22). Although not specifically designed to assess the possibility
of aerosol transmission of HIV, the 1991 seroprevalence survey of
attendees of the annual meeting of the American Academy of Orthopaedic
Surgeons addressed this concern indirectly (258). There were 1,201 study
participants without nonoccupational risk factors who had participated
in procedures on patients with HIV infection or AIDS and had never used
a "space suit" or other device to prevent inhalation of aerosols. Since
power instruments are used frequently in orthopedic procedures, many of
these participants may have been exposed to blood or tissue aerosols
produced by these instruments; all were HIV seronegative (258).
The risk of HIV transmission after a percutaneous exposure appears to be
influenced by several factors. To assess possible risk factors, the
Centers for Disease Control and Prevention (CDC), in collaboration with
international public health authorities, conducted a retrospective
case-control study using data reported to national surveillance systems
in the United States, France, Italy, and the United Kingdom. Based on
logistic regression analysis, factors associated with HIV transmission
after percutaneous exposure included a deep injury, a device visibly
contaminated with the source patient's blood, procedures involving a
needle placed directly in the patient's vein or artery, and a source
patient who died from AIDS within 60 days of the exposure (39). The
findings of the case-control study suggest that the risk for HIV
infection likely exceeds 0.3% for percutaneous injuries involving a
larger volume of blood and/or higher titer of HIV in the blood. Several
laboratory studies support these findings. In vitro models have shown
that increasing needle size and penetration depth are associated with
increased blood transfer volume (182), that hollow-bore needles transfer
greater volumes of blood than solid suture needles, and that gloves
reduce the amount of blood transferred (26). Studies also have shown
that the level of infectious HIV present in the blood of most patients
with symptomatic AIDS is significantly higher than the level present in
patients with asymptomatic HIV infection (141). An additional finding of
the case-control study was that postexposure use of zidovudine (ZDV) by
HCWs was associated with a lower risk for HIV transmission (39). (This
issue will be discussed in more detail in the section Postexposure
Chemoprophylaxis for HIV [below]). It is also possible that host defense
mechanisms influence the risk of HIV transmission. One study
demonstrated an HIV-specific T-helper cellular immune response when
peripheral blood mononuclear cells from a small number of HCWs exposed
to HIV were stimulated in vitro by HIV. None of the HCWs seroconverted.
One possible explanation for these observations is that host immune
responses prevented establishment of HIV infection after exposure (75).
Similar cytotoxic T-lymphocyte responses have been observed in other
populations with repeated HIV exposure without resulting infection (70,
74, 160, 170, 225).
HIV Seroprevalence among Patients
In the United States, HIV seroprevalence rates vary widely by geographic
area and patients' demographic characteristics. The CDC's Sentinel
Hospital Surveillance System tested 195,829 anonymous patient blood
samples at 20 hospitals in 15 cities between September 1989 and October
1991. The HIV seroprevalence at these institutions ranged from 0.2 to
14.2% and was highest among men aged 25 to 44 years and patients with
infectious conditions (excluding symptomatic HIV infection) and
drug-related conditions (153).
Similarly, seroprevalence data for unselected hospital admissions and
for patients presenting to emergency departments, operating rooms, and
obstetrical units have demonstrated considerable variation (Table 4).
The lowest seroprevalence rates have been reported in rural and suburban
areas: 0.15% among trauma patients in Wichita, Kans. (190), and 0.4%
among elective surgery patients in suburban Baltimore, Md. (68). The
highest seroprevalence rates have been reported in urban, inner-city
populations: 5.2 to 6.0% among emergency department patients in
inner-city Baltimore, Md. (157, 191), and 5.5% among non-obstetric
hospitalized patients in Denver, Colo. (K. Krasinski, W. Borkowski, D. Bebenroth,
and T. Moore, Letter, N. Engl. J. Med. 318:185, 1988).
In a CDC study conducted in six emergency departments in three urban and
three suburban areas of New York, N.Y., Chicago, Ill., and Baltimore,
Md., the overall rate of HIV infection ranged from about 4 to 9 per
100 patient visits (178). The study found that many patients' HIV
infections were unrecognized at the time of initial presentation to the
hospital. The percentage of patients whose HIV infection was unknown to
hospital emergency department workers was about 70% in the three inner
city hospitals and ranged from 40 to 90% in the three suburban
Incidence of Occupationally Acquired HIV Infection
As of 30 June 1999, a total of 191 U.S. workers had been reported to the
CDC's national surveillance system for occupationally acquired HIV
infection (Table 5) (65). Fifty-five HCWs had known occupational HIV
exposures, with a baseline negative HIV test and subsequent documented
seroconversion. Fifty of these exposures were to HIV-infected blood, one
was to visibly bloody fluid, one was to an unspecified fluid, and three
were to concentrated virus in a laboratory. Of the 55 HCWs, 47 sustained
percutaneous exposures, 5 had mucocutaneous exposures, 2 had both a
percutaneous and a mucocutaneous exposure, and 1 had an unknown route of
exposure. Twenty-five of these HCWs have developed AIDS.
Of the 191 U.S. workers reported to the CDC's surveillance system,
136 have been reported as possible cases of occupationally acquired HIV
infection. None of these HCWs reported behavioral or blood transfusion
risk factors, and all reported occupational exposures to blood, body
fluids, or laboratory specimens containing HIV. However, the time or
source of infection was undocumented, usually because no baseline serum
sample was available to establish seronegativity at the time of
The CDC's surveillance system likely does not reflect the full extent of
occupationally acquired HIV infection because of underreporting of known
infections or underrecognition of HIV infection. Studies of HCWs in
hospital settings suggest that many percutaneous injuries are not
reported (129, 177). Also, HCWs may not complete postexposure follow-up
serologic testing (D. Cardo and the Health Care Worker Surveillance
Study Group, Abstr. 6th Annu. Meet. Soc. Healthcare Epidemiol. Am.,
abstr. 67, 1996).
HIV Seroprevalence Surveys among HCWs
HIV seroprevalence surveys provide a way of indirectly assessing the
risk of occupationally acquired HIV infection. The CDC has conducted two
voluntary anonymous seroprevalence surveys of surgeons in different
specialties. In 1992, a seroprevalence survey was done among general
surgeons, obstetricians, gynecologists, and orthopedic surgeons
practicing in moderate to high AIDS incidence areas. Of the
770 participating surgeons, one general surgeon, who reported
nonoccupational risk factors for HIV infection on an anonymous
questionnaire, was HIV positive (209). In 1991, a seroprevalence survey
was done among surgeons attending the annual meeting of the American
Academy of Orthopaedic Surgeons. Of the 3,420 participants, two
surgeons, both of whom reported nonoccupational risk factors, were HIV
positive (258). Other seroprevalence studies similarly have shown low
rates of HIV seropositivity among HCWs without nonoccupational risk
factors for HIV infection (Table 6) (20, 66, 71, 80, 82, 107, 117, 118,
123, 163, 215, 264; P. Ebbensen, M. Melbye, F. Scheutz, A. J. Bodner,
and R. J. Bigger, Letter, JAMA 256:2199, 1986; C. Siew, S. E. Gruninger,
and S. A. Hojvat, Letter, N. Engl. J. Med. 318:1400-1401, 1988).
One limitation of seroprevalence studies is that the extent of
occupational and nonoccupational exposure to HIV among tested workers is
usually unknown. Also, the rates may be underestimates if individuals
deferred testing because they knew they were or suspected they might be
HIV positive. Nonetheless, these seroprevalence surveys indicate that
there was not a high rate of undetected HIV infection among the HCWs
studied, many of whom had substantial opportunity for occupational
RISK OF OCCUPATIONAL TRANSMISSION OF HBV FROM PATIENTS TO WORKERS
Risk of HBV Infection Postexposure
The probability of HBV transmission after an occupational exposure is
dependent upon the concentration of infectious virions in the implicated
body fluid, the volume of infective material transferred, and the route
of inoculation (e.g., percutaneous or mucosal).
HBV is present in high titers in blood and serous fluids, ranging from a
few virions to 109 virions per ml (142). The virus is present in
moderate titers in saliva, semen, and vaginal secretions (154). The
titer in semen and saliva is generally 1,000 to 10,000 times lower than
the corresponding titer in serum (44, 269). Other body fluids such as
urine and feces contain very low levels of HBV unless contaminated with
blood (91, 106, 149).
One of the most common modes of HBV transmission in the health care
setting is an unintentional injury of an HCW from a needle contaminated
with HBsAg-positive blood from an infected patient (5). The average
volume of blood inoculated during a needlestick injury with a 22-gauge
needle is approximately 1 µl (V. M. Napoli and J. E. McGowan, Letter,
J. Infect. Dis. 155:828, 1987), a quantity sufficient to contain up to
100 infectious doses of HBV (243). The risk of transmission after a
needlestick exposure to a nonimmune person is at least 30% if the source
patient is HBeAg positive but is less than 6% if the patient is HBeAg
negative (17, 120, 277). Blood from patients with HBsAg titers below the
threshold of detection using routine serologic tests is rarely
infectious (4). While overt percutaneous injuries are efficient modes of
HBV transmission, other less-obvious exposures may also lead to
occupationally acquired HBV infection. In a case series of HBV-infected
HCWs, fewer than 10% recalled a specific percutaneous injury, while
29 to 38% recalled caring for an HBsAg-positive patient within 6 months
prior to their onset of illness (35; A. K. R. Chaudhuri and E. A. C. Follet,
Letter, Br. Med. J. 284:1408, 1982).
HBV Seroprevalence among Patients
The risk of acquiring HBV is related to the prevalence of HBV infection
in the patient population with which the HCW works. Patients who are
HBsAg positive, either from acute or chronic infection, are potential
sources of infection. Patients who are acutely infected may not be
recognized since acute infection is symptomatic in only 10% of children
and 30 to 50% of adults. Chronic HBV infection is often asymptomatic.
HCWs who work in settings with patient populations with a relatively
high prevalence of HBV infection, such as urban and tertiary-care
hospitals (which more commonly serve groups at high risk for HBV
infection, such as injecting drug users), have been shown to be at
greater risk of occupational HBV infection than those who work in rural
or community hospitals (133).
Prior to the implementation of guidelines for hepatitis B prevention,
patients in hemodialysis centers had high rates of HBV infection, which
posed an increased risk for workers in this setting (43, 189). However,
between 1976 and 1993, the annual incidence of HBV infection decreased
from 3.0 to 0.1% among hemodialysis patients and from 2.6 to 0.02% among
staff members (254). Outbreaks of HBV infection in hemodialysis centers
rarely occur today. When these outbreaks do occur, they are most often
traced to failure to implement recommended infection control practices
(11, 56, 198).
Trends in the Incidence of Occupationally Acquired HBV Infection
The number of HCWs infected annually with HBV in the United States is
estimated from data reported to the CDC Viral Hepatitis Surveillance
Program (VHSP). Annual estimates are derived by applying the proportion
of people who acquired HBV occupationally in the health care setting in
a given year as reported to the VHSP to the estimated number of HBV
infections that occurred in that same year. For example, the CDC
estimates that in 1985 about 12,000 HCWs became infected with HBV (48).
This figure is derived from the proportion of people who acquired HBV
occupationally in the health care setting in 1985 (6% of patients in the
Viral Hepatitis Surveillance Program reported employment in a medical or
dental field for 6 months prior to date onset of illness, and two-thirds
of these patients were estimated to work in settings with potential
exposure to blood or body fluids) and the estimated number of HBV
infections that occurred in the United States in 1985 (300,000).
The incidence of HBV infection among HCWs has decreased substantially
since the early 1980s (54). The estimated number of HBV infections among
HCWs declined from 17,000 (386 per 100,000) in 1983 to 400 (9.1 per
100,000) in 1995 (176). The estimated incidence of HBV infections among
HCWs in 1983 was about threefold higher than the incidence of HBV
infections in the general U.S. population (122 per 100,000) and declined
by 1995 to more than fivefold lower than the incidence in the general
U.S. population (50 per 100,000).
The absolute decline in the number of HBV infections among HCWs is
attributed to the implementation of standard precautions in health care
settings, including the increasing use of barrier precautions and
personal protective devices and increasing levels of hepatitis B
vaccination coverage among HCWs (21, 126, 282) (see Hepatitis B
Vaccination Coverage among HCWs [below]).
HBV Prevalence among HCWs
Prior to the availability of the hepatitis B vaccine, numerous
cross-sectional surveys showed that HCWs had a three- to fivefold higher
seroprevalence of HBV infection than the general U.S. population (48,
89, 93, 239, 241, 253). Prevalence rates of HBV infection of 13 to 18%
have been demonstrated among surgeons, and infection rates up to 27%
have been demonstrated among dentists and oral surgeons (246, 278). By
comparison, about 4% of first-time blood donors in the United States
during the 1970s had serological markers of HBV infection (246).
Prevalence of previous infection with HBV has been found to increase
with increasing age and to be directly related to the number of years
employed as an HCW (78, 209, 241, 253). HCWs with frequent blood or
needlestick exposures have a twofold higher prevalence of HBV infection
than other HCWs (125). Physicians and dentists in specialties that
involve frequent blood or needlestick exposure (e.g.,
obstetrician-gynecologists, pathologists, and oral surgeons) have a
significantly elevated risk of HBV infection compared to specialists
with less-frequent blood or needlestick exposure (e.g., pediatricians
and psychiatrists) (278).
RISK OF OCCUPATIONAL TRANSMISSION OF HCV FROM PATIENTS TO WORKERS
Risk of HCV Infection Postexposure
HCV is transmitted efficiently by large exposures to blood such as
through transfusion of blood or blood products from infectious donors.
Overt percutaneous exposures to HCV (e.g., accidental needlestick
injuries) also have been documented as means of HCV transmission.
The risk that an HCV-infected individual will transmit the virus may be
related to the type and size of the inoculum and the route of
transmission as well as the titer of virus, but data on the threshold
concentration of virus needed to transmit infection are insufficient.
Neither the presence of antibody nor the presence of HCV RNA is a direct
measure of infectivity.
Prior to the discovery of HCV, a significant association was noted
between acquiring acute non-A, non-B (NANB) hepatitis and employment in
patient care and laboratory work (12). A case-control study among
British blood donors found that having been an HCW was a risk factor for
having HCV infection (196). A number of case reports have documented
occupational HCV transmission from anti-HCV-positive patients to HCWs in
a variety of settings (234, 263, 268; A. M. Herbert, D. M. Walker,
K. L. Davies, and J. Bagg, Letter, Lancet 339:305, 1992; A. B. Jochen,
Letter, Lancet 339:304, 1992; F. Marranconi, V. Mecenero, G. P. Pellizer,
M. C. Bettini, M. Conforto, A. Vaglia, C. Stecca, E. Cardone, and F. de
Lalla, Letter, Infection 20:111, 1992; E. Perez-Trallero, G. Cilla, and
J. R. Saenz, Letter, Lancet 344:548, 1994). A history of accidental
needlestick exposures among HCWs has also been independently associated
with anti-HCV positivity (219).
Follow-up studies of HCWs who sustained percutaneous exposures to blood
from anti-HCV-positive patients have found variable rates of HCV
transmission (30, 140, 161, 223, 247, 284). However, the average
incidence of anti-HCV seroconversion after needlestick or sharps
exposure from a known anti-HCV-positive source patient is 1.8% (range,
0 to 7%) (10, 64). In one study conducted in Japan, which included PCR
testing for HCV RNA in source patients and HCWs, the risk of
transmission after a needlestick exposure from a source patient with HCV
RNA-positive blood was 10% (186). No infections have been associated
with mucous membrane or nonintact skin exposures in prospective studies
conducted to date; however, there have been two case reports of HCV
transmission as a result of a blood splash to the conjunctiva (232; G. Ippolito,
V. Puro, N. Petrosillo, G. De Carli, G. Micheloni, and E. Magliano,
Letter, JAMA 280:28, 1998).
The importance of mucous membrane and inapparent parenteral exposures in
HCV transmission in the health care setting is not well defined. HCV
typically circulates at low titers in infected serum in comparison to
HBV (32, 88). Saliva may contain HCV but has not been epidemiologically
linked to transmission. HCV RNA has not been detected in urine, feces,
or vaginal secretions from patients who have virus circulating in the
blood (96, 144). The relatively few studies examining risk factors for
infection and conflicting results highlight the need for further studies
to better define the factors influencing infectivity and risk factors
for acquiring HCV infection among HCWs.
HCV Seroprevalence among Patients
The prevalence of anti-HCV among different population subgroups who may
serve as a reservoir for transmission in the health care setting is
highly variable in the United States (6). Anti-HCV seroprevalence rates
among blood donors are <0.5%, while higher rates have been observed
among hemodialysis patients (~20%) and hemophilia patients (~60% to 90%)
(15). The anti-HCV seroprevalence rates among hospitalized patients have
been reported to range from 2 to 18% (159, 175). Data from the Third
National Health and Examination Survey, conducted during the period
1988 to 1994, have indicated that an estimated 1.8% of Americans have
been infected with HCV (13).
The prevalence of anti-HCV among persons on dialysis is consistently
higher than in other hospitalized patient groups. The prevalence of
anti-HCV among dialysis patients ranges from 8 to 36% in the United
States (213) and from 1 to 47% worldwide (188). The increased prevalence
of anti-HCV among patients on dialysis has been associated with several
factors, including previous blood transfusion, increased years the
patient has been on dialysis, mode of dialysis (patients on peritoneal
dialysis are at lower risk than hemodialyzed patients), increased
prevalence of HCV infection among patients in the dialysis unit, history
of previous organ transplantation, and history of illegal injection drug
use (194, 213). Studies have consistently demonstrated an association
between anti-HCV positivity and increasing years on dialysis; this
association is independent of blood transfusion (67, 110, 131, 134, 203,
240; U. Schlipkoter, M. Roggendorf, K. Cholmakov, A. Weise, V. Gladziwa,
and N. Luz, Letter, Lancet 335:1409, 1990; K. Yamaguchi, Y. Nishimura,
N. Fukoka, J. Machida, S. Veda, Y. Kusumoto, G. Futami, T. Ishii, and
K. Takatsuki, Letter, Lancet 335:1409-1410, 1990).
HCV Seroprevalence among HCWs
Despite an increased HCV infection rate among dialysis patients, staff
members of hemodialysis centers in the United States have been found to
have prevalence rates similar to those seen in other HCWs (255). In
general, seroprevalence surveys among hospital-based HCWs in western
countries have found rates of anti-HCV similar to or lower than that
estimated to occur in the general population (9, 195, 276; G. McQuillan,
M. Alter, L. Moyer, S. Lambert, and H. Margolis, Proc. IX Int. Symp.
Viral Hepatitis Liver Dis., p. 8, 1996). Even among HCWs with high rates
of exposure to blood or needlestick injuries, seroprevalence rates
similar to those found among blood donors (<0.5%) have been observed
The CDC determines national risk factor estimates for acute HCV
infection through a program of intensive surveillance conducted in
several sentinel counties. Between 1991 and 1998, approximately 4% of
acute hepatitis C cases reported to this sentinel surveillance system
were occupationally related (I. T. Williams, M. Fleenor, F. Judson, K. Mottram,
H. Homan, P. Ryder, and M. J. Alter, Abstr. 10th Int. Symp. Viral
Hepatitis Liver Dis, p. 63, 2000).
Several studies examining risk factors for HCV infection among HCWs have
produced conflicting results. One study in New York found 2% of dentists
and 9% of oral surgeons to be anti-HCV positive (162). In that study,
the percentage of professional time spent practicing oral surgery was
directly related to anti-HCV positivity. However, anti-HCV-positive
dentists reported 50% fewer needlesticks during the previous 5 years
than did anti-HCV-negative dentists. In contrast, anti-HCV positivity
was associated with a reported history of frequent needlestick injuries
in a survey of hospital-based HCWs in California (219). However, in
studies among surgeons in several urban areas, no association was
observed with recollection of skin, mucous membrane, or percutaneous
exposure to blood during the last month or year (209; J. I. Tokars, M. Chamberland,
C. Shapiro, C. Schable, A. Wright, D. Culver, M. Jones, P. McKibben,
D. Bell, and the Serosurvey Study Committee, Proc. 2nd Annu. Meet. Soc.
Hosp. Epidemiol. Am., p. 33, 1992).
PREVENTION OF OCCUPATIONAL EXPOSURES TO BLOOD
In 1987 the CDC developed universal precautions to help protect both
HCWs and patients from infection with bloodborne pathogens in the health
care setting (46). These recommendations stress that blood is the most
important source of HIV, HBV, and other blood-borne pathogens and that
infection control efforts should focus on the prevention of exposures to
blood as well as the receipt of HBV immunizations. In 1995, the CDC's
Hospital Infection Control Practices Advisory Committee (HICPAC)
introduced the concept of standard precautions, which synthesizes the
major features of universal precautions and body substance isolation
into a single set of precautions to be used for the care of all patients
in hospitals regardless of their presumed infection status (111). Blood,
certain other body fluids (e.g., semen, vaginal secretions, and
amniotic, cerebrospinal, pericardial, peritoneal, and synovial fluids),
and tissues of all patients should be considered potentially infectious
(46, 47). Standard precautions apply to blood; all body fluids,
secretions, and excretions (except sweat); nonintact skin; and mucous
membranes (111). The core elements of standard precautions comprise (i)
hand washing after patient contact, (ii) the use of barrier precautions
(e.g., gloves, gowns, and facial protection) to prevent mucocutaneous
contact, and (iii) minimal manual manipulation of sharp instruments and
devices and disposal of these items in puncture-resistant containers
(46, 47, 111).
The CDC's recommendations along with the blood-borne pathogen standard
issued by the Occupational Safety and Health Administration (OSHA),
which requires that HBV vaccine be made available to HCWs with risk of
occupational exposure, the development of written exposure control
plans, the use of engineering and work practice controls to reduce
exposures, and annual HCW training (266) have caused widespread adoption
of standard precautions in U.S. hospitals. Several investigators have
attempted to assess the efficacy of standard precautions. For example,
Beekman et al. at the Clinical Center of the National Institutes of
Health found a significant and sustained decrease in percutaneous
injuries associated with the implementation of standard precautions
(21). At the same institution, a comparison of the frequencies of HCWs'
blood exposures on self-reported questionnaires before and after
standard precaution training found a decrease in the mean number of
blood exposures per year among clinical HCWs, from 35.8 to 18.1 (102).
Education of HCWs about needlestick prevention, along with effective
communication and convenient placement of sharps containers, has been
shown to decrease needlestick injuries by 60% among HCWs at a teaching
hospital in California (126).
Personal Protective Barriers, Work Techniques, and Safety Devices
Skin and mucous membrane contacts frequently can be prevented with the
use of barrier precautions, such as gloves, masks, gowns, and goggles,
among HCWs in emergency room, operating room, and medical ward settings
(102, 178, 259, 282). However, the greatest risk of blood-borne pathogen
transmission comes from percutaneous injuries, which are not prevented
by barriers but instead require changes in technique and/or use of
safety devices. For instance, Tokars et al. noted that half of the
percutaneous injuries during surgical procedures occurred when fingers,
rather than instruments, were used during suturing, suggesting that the
use of instruments or other changes in technique might reduce injuries
(256). The use of blunt-tip suture needles during surgical procedures
can significantly reduce suture-related percutaneous injuries. In a CDC
study of blunt suture needle use during gynecological surgical
procedures, researchers found no percutaneous injuries with blunt suture
needles compared to 1.9 injuries per 1,000 conventional curved suture
needles used and 14.2 injuries per 1,000 straight suture needles used
Similarly, changes in the design of sharp instruments can prevent
injuries in nonsurgical settings (151, 152). One study found that
resheathable and bluntable needles reduced percutaneous injuries during
phlebotomy by 23 to 76% (59). Many injuries in the health care setting
are associated with intravenous (i.v.) tubing-needle assemblies. Studies
have found that i.v.-related percutaneous injuries decreased
approximately 72 to 100% following the introduction of needleless
systems (112, 252; Skolnick et al., Letter, N. Engl. J. Med.
318:1400-1401); the greatest reductions were seen with those systems
that did not permit needles to access i.v. lines. Although devices may
be safer for HCWs, it is important that they be assessed for potential
patient care complications. An outbreak of bloodstream infections
associated with a needleless i.v. infusion system raised concerns
regarding the potential for adverse patient outcomes associated with
these devices (86). However, Adams et al. prospectively compared the
incidences of various patient-related adverse outcomes for conventional
and needleless i.v. access systems and found that the needleless system
posed no greater risk of positive catheter tip or adapter fluid
cultures, i.v. site complications, or nosocomial bacteremia (1).
Sterilization, Disinfection, and Environmental Concerns
Most laboratory studies have indicated that HIV is readily susceptible
to a variety of disinfectants (233). The titer of HIV is reduced by
90 to 99% within several hours after drying and then further diminishes
with time (46, 267). The length of time that viable HIV can be detected
depends on the conditions of the experiment, including the initial
concentration of HIV, whether organic or other foreign material is
present that may protect HIV from inactivation, and other factors. There
is no evidence for HIV transmission by environmental surfaces.
In contrast, HBV is resistant to drying, ambient temperatures, simple
detergents, and alcohol and has been found to be stable on environmental
surfaces for at least 7 days (104, 211). Thus, indirect inoculation can
occur via inanimate objects (e.g., contaminated medical equipment or
environmental surfaces). However, HBV has been shown to be inactivated
by several intermediate-level disinfectants, including 0.1%
glutaraldehyde and 500-ppm free chlorine from sodium hypochlorite (i.e.,
household bleach) (29, 105). Heating to 98°C for 2 min also inactivates
While specific animal infectivity studies have not been published, rapid
degradation of HCV occurs when serum containing HCV is left at room
temperature (83). Epidemiologic data also suggest that environmental
contamination with HCV is not a significant route of transmission in the
health care setting.
Standard sterilization and disinfection procedures recommended for
patient care equipment are adequate to sterilize or disinfect items
contaminated with blood or other body fluids from people infected with
blood-borne pathogens, including HIV, HBV, and HCV. Because foreign
material may interfere with the sterilization or disinfection procedure,
devices must first be adequately cleaned. Cleaning before disinfection
is particularly important for devices such as endoscopes that may become
heavily soiled and cannot tolerate heat sterilization (180).
All spills of blood and blood-contaminated body fluids should be
promptly cleaned by a person wearing gloves and using an Environmental
Protection Agency-approved disinfectant or a 1:10 to 1:100 solution of
household bleach. Visible material should first be removed with
disposable towels or other means to prevent direct contact with blood.
The area should then be decontaminated with an appropriate disinfectant
VACCINATION AGAINST HBV INFECTION
Prevention of HBV Infection Using Hepatitis B Vaccine
Hepatitis B vaccine provides both preexposure and postexposure
protection against HBV infection. Two types of hepatitis B vaccine,
plasma-derived and recombinant, have been licensed in the United States,
and both are very effective in preventing HBV infection. The
plasma-derived vaccine is no longer available in the United States. The
currently available vaccines are produced by recombinant DNA technology
(51). Three intramuscular doses of hepatitis B vaccine induce a
protective antibody response in >90% of healthy recipients. Adults who
develop a protective antibody response are protected from clinical
disease and chronic infection. Long-term studies of immunized adults and
children indicate that immune memory remains intact for at least
12 years, even though anti-HBs levels may become low or undetectable
(272, 279, 280). Routine booster doses of hepatitis B vaccine are not
considered necessary (61).
Since it became available in 1981, hepatitis B vaccine has been
recommended for HCWs who have anticipated exposure to blood or body
fluids. It is preferable that HCWs be vaccinated during professional
training or early in their careers, so that they are protected prior to
being at risk of occupational HBV infection.
Persons at occupational risk of infection should be tested for anti-HBs
after vaccination, since knowledge of a person's HBV immune status
allows for the most precise selection of a postexposure prophylaxis
regimen, should an exposure occur. It is recommended that
postvaccination testing be done for all HCWs who are at risk for having
blood or blood-contaminated body fluid exposures (e.g., physicians,
nurses, operating room technicians, dentists, dental hygienists,
emergency medical technicians, phlebotomists, laboratory technologists
and technicians, physician assistants, and nurse practitioners). Testing
is not indicated for persons at low risk of mucosal or percutaneous
exposure to blood or body fluids or HBV infection (e.g., public safety
workers and HCWs without direct patient contact). When indicated,
postvaccination testing should be done 1 to 2 months after completion of
the three-dose series.
Persons who do not respond to the primary vaccine series should complete
a second three-dose vaccine series or be evaluated to determine if they
are HBsAg positive. Revaccinated persons should be retested at the
completion of the second vaccine series. Nonresponders to vaccination
who are HBsAg negative should be considered susceptible to HBV infection
and should be counseled regarding precautions to prevent HBV infection
and the need to obtain hepatitis B immunoglobulin (IG) prophylaxis for
any known or probable parenteral exposure to HBsAg-positive blood.
Hepatitis B Vaccination Coverage among HCWs
Since 1982, hepatitis B vaccine has been recommended for HCWs with
frequent blood or needle exposures (45). However, hepatitis B vaccine
was not widely used among HCWs in the 1980s. In a survey of U.S.
hospitals conducted during 1990 by OSHA, 91% of hospitals had hepatitis
B vaccination programs for employees, and of these, 64% paid for the
cost of vaccinating high-risk employees (i.e., those involved in direct
patient care and laboratory work) (181). However, it was estimated that
only 46% of high-risk employees had received the hepatitis B vaccine.
Barriers to vaccine use among HCWs included the high cost of the
vaccine, failure of employers to offer the vaccine at low or no cost,
and a perception among some HCWs that they would not benefit from
In 1991, OSHA issued a standard that required employers to offer
hepatitis B vaccine at no cost to employees with reasonably anticipated
contact with blood or other potentially infectious materials (266). This
standard does not require the employer to conduct postvaccination
testing or to provide booster doses of hepatitis B vaccine. Employees
who administer first aid only as a collateral duty to their routine work
assignment (e.g., teachers) do not need to be offered the hepatitis B
vaccine until they give aid involving exposure to blood or other
potentially infectious materials. If an exposure incident occurs, the
employee should be evaluated for postexposure prophylaxis (PEP) in
accordance with the recommendations of the Advisory Committee on
Immunization Practices (ACIP) (60).
Subsequent to the issuance of the OSHA guidelines, hepatitis B
vaccination coverage substantially increased among HCWs, especially
among younger HCWs. In 1991 and 1992, surveys indicated that
approximately 90% of orthopedic and hospital-based surgeons aged 20 to
29 years from urban areas had received the hepatitis B vaccine. However,
among surgeons who had practiced more than 10 years, 25% had not
received the hepatitis B vaccine and were susceptible to HBV infection
(209; Tokars et al., Proc. 2nd Annu. Meet. Soc. Hosp. Epidemiol. Am., p.
33, 1992). A survey conducted among 150 hospitals in 1992 found that 51%
of the employees who were eligible to receive hepatitis B vaccine had
completed the vaccination series (2). By 1994, a telephone survey of
113 hospitals found that 67% of eligible employees had completed the
hepatitis B vaccination series (176). Vaccination coverage was highest
among personnel with frequent exposure to infectious body fluids and
lowest for employees at low risk for exposure. Coverage levels among
eligible employee groups surveyed in 1994 were 81% among phlebotomists,
72% among nurses, 71% among physicians and residents, 63% among nurse
aides, 59% among custodial and security personnel, 44% among clerical
administrative staff, and 44% among food service workers.
MANAGEMENT OF OCCUPATIONAL EXPOSURES
Although exposure prevention remains the best strategy for protecting
HCWs from occupationally acquired infection, exposures are nevertheless
likely to occur. Employers should have in place a system that includes
written protocols for prompt reporting, evaluation, counseling,
treatment, and follow-up of occupational exposures that may place a
worker at risk of blood-borne pathogen infection. Employers also must
establish exposure control plans and comply with incident reporting
requirements mandated by OSHA (50, 266). Access to clinicians who can
provide postexposure care should be available during all work hours,
including nights and weekends. Persons responsible for providing
postexposure counseling should be familiar with evaluation and treatment
protocols and the facility's procedures for obtaining drugs for PEP
The prompt reporting of exposures is important, not only for management
of the exposure but also for identification of workplace hazards and
evaluation of preventive measures. Reporting systems should include
ready access to expert consultants as well as safeguards to protect the
confidentiality of the exposed worker. Unfortunately, a significant
proportion of percutaneous injuries are not reported to hospital
surveillance systems (range, 5 to 60%) (59, 129, 177, 183, 204). Timely
and complete reporting of exposures can be facilitated by education of
HCWs and a supportive, nonpunitive response by employers. HCW education,
including orientation and in-service programs, should familiarize HCWs
with their personal risk of occupational blood-borne pathogen exposure,
measures to prevent such exposures, and the principles of postexposure
management. HCWs must understand the importance of reporting exposures
immediately after they occur, since certain indicated interventions
(e.g., PEP for HIV and HBV) must be initiated promptly to be effective
(38, 50, 114).
Exposure Assessment and Emergency Management
Upon reporting an exposure, the HCW should be evaluated and counseled
regarding the risk of blood-borne pathogen infection, the potential
usefulness of PEP for HIV and/or HBV, the need for follow-up evaluation,
and precautions to prevent possible HIV transmission to others during
the follow-up period (50). Risk evaluation should include an assessment
of factors that may increase or decrease the probability of infection
First aid, if necessary, should be administered as quickly as possible.
Puncture wounds and other cutaneous injury sites should be washed with
soap and water, and exposed oral and nasal mucous membranes should be
vigorously flushed with water. Eyes should be irrigated with clean
water, saline, or sterile irrigants (50, 115). Although there is no
evidence that antiseptics for wound care reduce the risk of blood-borne
pathogen transmission, their use is not contraindicated. The use of
bleach or other caustic agents that cause local tissue trauma is not
After any exposure, efforts should be made to identify and evaluate
clinically and epidemiologically the source patient for evidence of HIV,
HBV, and/or HCV infection. The source patient should be informed of the
incident and consent should be obtained for HIV, HBV, and HCV testing.
The circumstances of the exposure should be recorded in a confidential
medical record. Data collection should include demographic information
about the exposed worker, details about the exposure itself (including
date, time, job duty being performed, type of exposure, amount and type
of fluid or material involved, type of device used, and severity of
exposure), a description of infection control precautions used,
information about the source patient, and details about postexposure
management, counseling, and follow-up (50, 114).
Postexposure Chemoprophylaxis for HIV
Background. Information from a retrospective case-control study of HCWs
from France, the United Kingdom, and the United States suggesting that
ZDV PEP may reduce the risk for HIV transmission after occupational
exposure to HIV-infected blood (55), along with data on ZDV efficacy in
preventing perinatal transmission (81) and evidence that PEP prevented
or ameliorated retroviral infection in some studies in animals (27),
prompted the Public Health Service (PHS) to publish a statement on
management of occupational exposures to HIV in 1996 (57). The PHS
subsequently published expanded and updated recommendations for
occupational HIV exposure management for HCWs in May 1998 (63). These
guidelines have been supported by groups such as the International AIDS
Society USA (42).
ZDV and other reverse transcriptase inhibitors may be important for PEP
by preventing early viral dissemination. Studies of HIV-infected
patients have shown that other antiretroviral agents, such as the
reverse transcriptase inhibitor lamivudine, and the class of protease
inhibitors that includes saquinavir and indinavir (IDV) significantly
decrease plasma HIV levels, especially when used in combination with ZDV
(100). Protease inhibitors may be useful for prophylaxis based on the
site of activity in the replication cycle (i.e., after viral integration
has occurred) in addition to demonstrated effectiveness in reducing
Animal studies. PEP has prevented or ameliorated retroviral infection in
some studies with animals, particularly when it was administered soon
after exposure (199, 230, 242, 251, 262). However, the application of
animal studies, especially those using nonhuman retroviruses, is
uncertain. In addition to the use of nonhuman retroviruses, many
variables, such as viral inoculum size, antiretroviral dose,
administration route, time to onset of treatment, and dose interval, may
influence the apparent effectiveness of the treatment under study (27).
Human studies. There are few data with which to assess the efficacy of
PEP in humans. The optimal study design for determining the efficacy of
ZDV for PEP would be a prospective, placebo-controlled trial. However,
this has not been possible because of the requirement for a large number
of HCWs and the relatively low rate of HIV seroconversion following
occupational exposure (S. W. LaFon, B. D. Mooney, J. P. McCullen, K. H. Pattishall,
M. L. Smiley, M. D. Rodgers, and S. N. Lehrman, Program Abstr. 30th
Intersci. Conf. Antimicrob. Agents Chemother., abstr. 489, 1990). In the
absence of such a trial, other sources of data have been used to assess
the use of ZDV for PEP.
In a multicenter, double-blind, placebo-controlled clinical trial of ZDV
to prevent perinatal HIV transmission, ZDV therapy was associated with a
67.5% reduction in the risk of mother-to-infant HIV transmission (53).
The protective effect of ZDV was only partly explained by reduction of
the HIV titer in maternal blood, suggesting a possible direct
prophylactic effect of ZDV (248). Additionally, a recent
placebo-controlled study in Thailand showed that a short-term antenatal
regimen of ZDV reduced the risk for perinatal HIV transmission by 51%
(62). Also, the CDC retrospective case-control study found that PEP with
ZDV was associated with a decrease of approximately 81% in the risk for
HIV seroconversion among HCWs who had a percutaneous exposure to
HIV-infected blood (39).
However, any protection afforded is not absolute. Failure of ZDV PEP to
prevent HIV infection in HCWs has been reported (156, 174; G. Weisburd,
J. Biglione, M. M. Arbulu, J. C. Terrazzino, and A. Pesiri, Program
Abstr. XI Int. Conf. AIDS, abstr. pub. C. 1141, 1996). Additional
failures of ZDV PEP have been described among individuals exposed to an
inoculum of HIV-infected blood larger than what would be expected from a
needlestick. These non-HCW cases included one blood transfusion, one
suicidal self-inoculation, one assault with a needle-syringe, and two
instances of accidental intravenous infusion of HIV-infected blood
components during nuclear medicine procedures (156). Possible factors
that may have contributed to the apparent failures in these instances
include exposure to a ZDV-resistant strain of HIV, a high-titer and/or
large-inoculum exposure, delayed initiation and/or short duration of
PEP, and possible factors related to the host (e.g., cellular immune
system responsiveness) and/or to the source patient's virus (e.g.,
presence of syncytium-forming strains) (63).
PHS recommendations for chemoprophylaxis. Chemoprophylaxis should be
recommended to exposed workers after occupational exposures associated
with a known risk for HIV transmission, should be considered for
exposures with a negligible risk, and may not be warranted for exposures
that do not pose a known risk for HIV transmission (Fig. 1). For
exposures for which PEP is considered appropriate, exposed workers
should be informed that (i) knowledge about the efficacy and toxicity of
drugs used for PEP is limited; (ii) only ZDV has been shown to prevent
HIV transmission in humans; (iii) there are no data to address whether
adding other antiretroviral drugs provides any additional benefit for
PEP, but some experts recommend combination drug regimens because of
increased potency and concerns about drug-resistant virus; (iv) data
regarding toxicity of antiretroviral drugs in persons without HIV
infection or who are pregnant are limited; and (v) any or all drugs for
PEP may be declined by the exposed worker. HCWs who have HIV
occupational exposures for which PEP is not recommended should be
informed that the potential side effects and toxicity of taking PEP
outweigh the negligible risk of transmission posed by the type of
FIG. 1. Determining the need for HIV PEP after an occupational
exposure. This algorithm is intended to provide guidance for
occupational exposures to blood, fluid containing visible blood, or
other potentially infectious fluid or tissue through a percutaneous
injury or through contact with a mucous membrane or nonintact skin.
Follow steps 1 through 3 to determine the PEP recommendation. Adapted
from reference 63.
Most HIV exposures will warrant only a two-drug regimen, using two
nucleoside analogue reverse transcriptase inhibitors, usually ZDV and
lamivudine. The addition of a third drug, usually a protease inhibitor
(i.e., IDV or nelfinavir), should be considered for exposures that pose
an increased risk for transmission or when resistance to the other drugs
used for PEP is known or suspected. ZDV-resistant strains of HIV can be
transmitted and have been reported to cause primary infections (99; G. Ippolito,
P. Del Poggio, C. Arici, G. P. Gregis, G. Antonelli, and E. Riva,
Letter, JAMA 272:433-434, 1994). If the exposure source is unknown or
the HIV status of the source patient cannot be tested, information about
the circumstances of the exposure should be assessed to determine the
risk for transmission of HIV. Certain situations, as well as the type of
exposure, may suggest an increased or decreased risk; an important
consideration is the prevalence of HIV in the population group (i.e.,
institution or community) from which the contaminated source material
was derived. Decisions regarding appropriate management should be
individualized based on the risk assessment (63).
PEP should be initiated as soon as possible (i.e., within hours of the
exposure). The interval within which PEP should be started for optimal
efficacy is not known. The optimal duration of PEP also is unknown.
Because 4 weeks of ZDV appears sufficient to be protective in HCWs (39),
PEP probably should be administered for 4 weeks, if tolerated. When PEP
is used, drug toxicity monitoring should include a complete blood count
and renal and hepatic chemical function tests at baseline and 2 weeks
after starting PEP.
Counseling and follow-up. All HCWs with occupational exposure to HIV
should receive follow-up counseling, postexposure testing (Table 7), and
medical evaluation, regardless of whether they receive PEP. HIV antibody
testing should be performed for at least 6 months postexposure (e.g., at
6 weeks, 12 weeks, and 6 months). HIV testing using EIA should be
performed on any HCW who has an illness that is compatible with an acute
retroviral syndrome. HIV antibody testing using EIA should be used to
monitor for seroconversion. The routine use of direct virus assays
(e.g., PCR for HIV RNA) to detect infection in exposed HCWs generally is
not recommended (34, 113, 114).
The psychological impact of an occupational HIV exposure may be
considerable and should be addressed during counseling and follow-up
(236). Experts have found that supportive counseling is an important
part of management (98, 114, 135, 136). To prevent the possibility of
further transmission to others, the HCW should be advised to refrain
from donating blood, semen, or organs during the follow-up period and to
refrain from breast-feeding when safe and effective alternatives are
available. To prevent HIV transmission to sexual contacts, all exposed
HCWs should abstain from, or use latex condoms during, sexual
intercourse throughout the follow-up period, especially during the first
6 to 12 weeks after the exposure, when most HIV-infected persons are
expected to seroconvert (63).
Toxicity. An important goal of PEP is to encourage and facilitate
compliance with the prescribed regimen. Therefore, the toxicity profile
of antiretroviral agents is a relevant consideration. All of the
antiretroviral agents have been associated with side effects (63). Side
effects associated with many of the nucleoside analogue reverse
transcriptase inhibitors are chiefly gastrointestinal (e.g., nausea or
diarrhea). Rare but serious side effects, such as seizures, have been
reported with ZDV PEP (M. D'Silva, D. Leibowitz, and J. P. Flaherty,
Letter, Lancet 346:452, 1995). The use of protease inhibitors has been
associated with new onset of diabetes mellitus, hyperglycemia, diabetic
ketoacidosis, and exacerbation of preexisting diabetes mellitus (266a;
M. D. Dubé, D. L. Johnson, J. S. Cumer, and J. M. Leedon, Letter, Lancet
350:713-714, 1997). Nephrolithiasis has been associated with IDV use
(including in HCWs using the drug for PEP) (S. A. Wang and the HIV PEP
Registry Group, Program Abstr. Infect. Dis. Soc. Am. 35th Annu. Meet.,
abstr. 482, 1997); however, the incidence of this potential complication
may be limited by drinking at least 48 oz (1.5 liters) of fluid per 24-h
period (19). Rare cases of hemolytic anemia also have been associated
with the use of IDV. Nelfinavir, saquinavir, and ritonavir have all been
associated with the development of diarrhea; however, this side effect
usually responds to treatment with antimotility agents that can be
prescribed for use, if necessary, at the time any one of these drugs is
prescribed for PEP. The manufacturer's package insert should always be
consulted for questions about potential drug interactions.
Postexposure Prophylaxis for HBV
PEP with hepatitis B vaccine and hepatitis B IG among persons
susceptible to HBV is highly effective in preventing infection after an
exposure. Management of HCWs after percutaneous (e.g., needlestick,
laceration, or bite) or mucosal (e.g., mucous membrane or ocular)
exposure to potentially infectious body fluids must include
consideration of (i) the HBsAg status of the source of exposure and (ii)
the hepatitis B vaccination and vaccine response status of the exposed
HCW. The ACIP of the PHS and HICPAC have provided detailed advice on
postexposure immunoprophylaxis (60). Table 8 provides a guide to
recommended management for various HBV exposures. Ideally,
immunoprophylaxis should be initiated as soon as possible after a
percutaneous or permucosal exposure; its value beyond 7 days after
exposure is unclear.
Postexposure Management of HCV
HCV prophylaxis. Several studies have attempted to assess the
effectiveness of prophylaxis with IG for the prevention of
posttransfusion NANB hepatitis. However, the results from these studies
are difficult to compare and interpret because of lack of uniformity in
diagnostic criteria, varied study designs (including some lacking
blinding and control groups), and administration of the first dose of IG
prior to rather than after exposure in all but one study (164, 231,
238). Data from these studies have not been reanalyzed since anti-HCV
testing became available. Beginning in 1992, IG has been manufactured
from plasma that has been screened for anti-HCV. Therefore, if
protective antibody does exist, screening and removal of anti-HCV-positive
units may reduce the effectiveness of IG as PEP for HCV. An experimental
study conducted with chimpanzees found that IG with a high titer of
anti-HCV administered 1 h after exposure to HCV did not prevent
infection or disease (168).
In 1994, the ACIP reviewed the available data and concluded that there
was no support for the use of IG as PEP for hepatitis C (7). The ACIP
based its recommendation on the facts that (i) no protective antibody
response has been identified following HCV infection, (ii) prior studies
of IG use to prevent posttransfusion NANB hepatitis may not be relevant
in making recommendations regarding postexposure prophylaxis for
hepatitis C, and (iii) experimental studies with chimpanzees showed IG's
lack of efficacy in preventing infection after exposure.
There have been no controlled studies assessing the effectiveness of
antiviral agents (e.g., alpha interferon) for HCV PEP among HCWs.
Although the specific mechanism of action is poorly understood, an
established infection may need to be present for interferon to be
effective (192, 216). Therefore, PEP with alpha interferon prior to
demonstration of HCV infection is not recommended.
Substantial challenges exist in the development of an effective vaccine
against HCV, including the significant heterogeneity of the HCV genome
and the lack of protective immunity elicited by HCV in the host (222).
The development of an effective vaccine against HCV awaits a better
understanding of the molecular biology of and immune response to this
Follow-up of HCWs after an occupational exposure to HCV. There is
currently no effective PEP for HCV infection. In the absence of
effective prophylaxis, persons who have been exposed to HCV may benefit
from knowing their infection status so they can seek evaluation for
chronic liver disease and treatment. The CDC recently issued
recommendations that individual institutions implement policies and
procedures for follow-up after percutaneous or permucosal exposure to
anti-HCV-positive blood (64a). The purpose of follow-up testing is to
address individual workers' concerns about their risk and outcome and to
identify persons who might benefit from antiviral therapy. At a minimum,
such policies should include (i) baseline testing of the source for
anti-HCV, (ii) baseline and follow-up (e.g., at 4 to 6 months) testing
of the exposed person for anti-HCV and ALT activity (Table 6) (if
earlier diagnosis of HCV infection is desired, testing for HCV RNA may
be performed at 4 to 6 weeks), (iii) confirmation by supplemental anti-HCV
testing of all anti-HCV results reported as positive by EIA, and (iv)
education of HCWs about the risk for and prevention of transmission of
all blood-borne pathogens, including HCV, in occupational settings, with
the information routinely updated to ensure accuracy.
While interferon has a proven efficacy in treating chronic hepatitis C,
there is no specific therapy of proven benefit for acute hepatitis C
(109). Several studies have suggested that early therapy with alpha
interferon may be effective in preventing progression from acute to
chronic disease (36, 200, 270). However, there are no data indicating
that treatment begun early in the course of chronic infection is less
effective than treatment begun in the acute phase of infection.
MANAGEMENT OF INFECTED HCWS
Transmission of HIV from Infected HCWs to Patients
There have been two reported instances of HIV transmission from HCWs to
patients. In July 1990, the CDC reported a case of transmission of HIV
from a Florida dentist to a patient during an invasive dental procedure
(49). Subsequent epidemiologic investigation and molecular genetic
sequencing identified five additional patients who were infected while
receiving care from the dentist. Each of the six patients had no other
identified risk factors for acquiring HIV, and each was infected by a
strain of HIV that closely matched that of the dentist by genetic
sequencing analysis. Although the specific incidents that resulted in
HIV transmission to these patients are uncertain, evidence strongly
supports dentist-to-patient rather than patient-to-patient transmission
(72, 206). A second case, reported in 1997, involved an orthopedic
surgeon in France, who probably became infected with HIV in 1983 and had
performed surgical procedures on 3,004 persons since that time. An
epidemiologic investigation found one person among these patients who
was HIV seronegative before a prolonged surgical procedure performed by
the surgeon in 1992 and who subsequently was HIV seropositive. No other
risk factors were documented for the patient, and nosocomial
transmission of HIV from the surgeon to the patient was confirmed by an
evaluation of viral sequences from both persons (28).
Retrospective investigation data. Even before reports of the Florida
dentist case were published, many health departments, hospitals, and
other agencies were conducting investigations of HIV-infected HCWs and
notifying patients who had received care from these providers.
Retrospective studies of a number of HIV-infected dentists, surgeons,
and physicians revealed no evidence of HCW-to-patient HIV transmission
during patient care (Table 9). A summary of all published and
unpublished investigations of which the CDC was aware through January
1995 showed no documented cases of HIV transmission among
22,171 patients treated by HIV-infected HCWs, including a breast
surgeon, a general surgeon, two obstetrics and gynecology residents, two
orthopedic surgeons, and several dentists (227). Epidemiologic and
laboratory follow-up of 110 of the 113 identified seropositive patients
showed that the majority (90 of 110 [82%]) were either documented as
having been infected before receiving care from the infected HCW or had
established risk factors for acquiring HIV; 15 did not have clearly
established risks but had had opportunities for potential exposure to
HIV; and five had no identified risk (227). Genetic sequence analysis
was done on HIV strains from three HCWs and 30 seropositive patients,
including three of the five patients who had no identified risk and
13 of the 15 patients with potential but undocumented risks for
exposure. In no instances were the viral strains of patients and HCWs
found to be related (227). Although limited by the lack of complete
availability of HIV test results, procedure records, and information
about the stage of the HCW's HIV infection during the time the worker
did procedures, these results are consistent with conclusions by the CDC
and others that the risk of HIV transmission from HCWs to patients is
very low (25, 52).
Transmission of HBV from Infected HCWs to Patients
Since the introduction of serologic testing in the 1970s, there have
been at least 46 reports worldwide of HBV-infected HCWs transmitting HBV
to patients during invasive procedures (24). The number of patients
infected by a single HCW ranged from 1 to more than 50. Most reports of
HCWs transmitting HBV to patients occurred prior to the widespread use
of barrier precautions in some HCW groups (e.g., gloves by dentists),
and many have involved readily apparent deficiencies in infection
control practices. Although clusters in which there were no apparent
deficiencies have occasionally occurred, investigations indicate that
when HCWs adhere to recommended infection control procedures the risk of
HBV transmission from HCW to patient is low.
A combination of factors is believed to be responsible for HBV
transmission from HCWs to patients (52). One factor associated with
increased risk of transmission is the HCW being HBeAg positive,
indicating a higher level of infectivity (137, 138, 217, 218, 221, 275).
In the United Kingdom, several episodes of HBeAg-negative surgeons
transmitting HBV have been reported (127, 128, 145, 250). These surgeons
were found to be carriers of a precore mutant strain of HBV that
prevents expression of HBeAg but allows the expression of infectious
virus. No such transmission has been reported from other parts of Europe
or Japan, where the frequency of this strain appears more common (31,
201), or from the United States, where the frequency of this strain is
unknown. Other factors believed to be responsible for HBV transmission
from infected HCWs to patients include contamination of surgical wounds
or traumatized tissue either from unintentional injury to the HCW during
invasive procedures and/or a major break in standard infection control
practices (e.g., not wearing gloves during an invasive procedure).
Clusters of HBV transmission from HCW to patient have been reported even
when deficiencies of surgical technique or infection control practice
could not be identified. In 1991, an HBeAg-positive cardiothoracic
surgeon was determined to have transmitted HBV to 19 (13%) of
142 patients (132). In a simulation in which the surgeon tied surgical
knots continuously for 1 h, visible skin separations were observed on
his index fingers and HBsAg was detected in the saline used to rinse out
his gloves. Whether these phenomena contributed to transmission is not
Transmission of HCV from Infected HCWs to Patients
There are no reported cases of HCV transmission from infected surgeons
or dentists to patients in the United States. Worldwide, there are three
reports of HCV transmission from infected health care providers (95,
101; P. Brown, News, Br. Med. J. 319:1219, 1999). Between 1988 and
1993 in Spain, five patients developed acute HCV infection after
undergoing heart valve replacement. On investigation, the cardiovascular
surgeon was determined to have chronic hepatitis C and was implicated in
the transmission of HCV to these patients (101). However, the factors
responsible for transmission could not be identified.
In the United Kingdom, an HCW was found to be the probable source of
infection during the investigation of a patient who developed acute HCV
after cardiothoracic surgery (95). A retrospective investigation of
277 (91%) of the 304 other patients who had undergone invasive
procedures performed by this surgeon found no additional cases of
transmission. A third case, also in the United Kingdom, involving HCV
transmission to one patient from a gynecologist, is currently under
investigation (P. Brown, News, Br. Med. J. 319:1219, 1999).
The CDC also is aware of a retrospective investigation of an HCV-infected
plastic surgeon whose infection was diagnosed during a routine physical
examination. HCV testing of 85% of the surgeon's patients was performed
more than 6 months after their surgeries. Although three patients had
evidence of HCV infection as indicated by the presence of anti-HCV
antibodies, no provider-to-patient transmission was detected. One of
these patients was known to have anti-HCV antibody before surgery, and
the other two (one of whom had a history of injection drug use) were
infected with strains that had a viral genotype and/or serotype
different from that of the surgeon's strain (CDC, unpublished data).
In summary, specific factors related to an increased likelihood of
transmission from HCV-infected HCWs to patients have yet to be
identified. Available data indicate that the risk of HCV transmission
from an infected HCW to a patient is extremely low.
Prevention of Infection Transmission from Infected HCWs to Patients
The CDC has looked for episodes of blood-borne virus transmission to
patients in health care settings, and the accumulated data have shown
that the overall risk of blood-borne virus transmission from infected
health care providers to patients is very low and that those for HIV and
HCV specifically are extremely low.
To minimize the risk of blood-borne pathogen transmission from HCWs to
patients, all HCWs should adhere to standard precautions, including the
appropriate use of hand washing, protective barriers, and care in the
use and disposal of needles and other sharp instruments (52). Technique
changes and safer needle devices that potentially reduce percutaneous
injury and recontact rates during surgery may also help reduce risks
(256). Currently available data provide no basis for recommendations to
restrict the practice of HCWs infected with HIV, HBV, or HCV who perform
duties or procedures not identified as exposure-prone, provided the
infected HCWs practice recommended surgical or dental technique and
comply with standard precautions and current recommendations for
sterilization and disinfection (52).
Prevention of HIV and HBV transmission during invasive procedures. The
CDC has characterized exposure-prone procedures as those that include
digital palpation of a needle tip in a body cavity or the simultaneous
presence of the HCW's fingers and a needle or other sharp instrument or
object in a poorly visualized or highly confined anatomic site. During
these procedures the routine use of gloves may not prevent injuries
caused by sharp instruments and does not eliminate the potential for
exposure of a patient to the HCW's blood.
To minimize the risk of HIV and HBV transmission from infected HCWs to
patients during invasive procedures, the CDC issued recommendations in
1991 (52). HCWs who perform exposure-prone invasive procedures and who
do not have serologic evidence of immunity to HBV from vaccination or
previous infection should know their HBsAg status (and, if positive,
their HBeAg status). HCWs who are infected with HBV and are HBeAg
positive and HCWs who are infected with HIV should not perform
exposure-prone procedures unless they have sought counsel from an expert
review panel and been advised under what circumstances, if any, they may
continue to perform these procedures. Such circumstances would include
notifying prospective patients of the HCW's seropositivity before they
undergo exposure-prone invasive procedures.
Since these recommendations have been issued, there has been no report
of HIV transmission and only one report of HBV transmission from an
infected HCW to patients in the United States (132).
HCWs with blood-borne viruses. The Society for Healthcare
Epidemiologists of America has recently issued guidelines that include
recommendations for management of HCWs infected with HIV, HBV, and HCV
(3). Specifically, the society recommended that all HCWs use double
gloving for procedures and that infected providers not be excluded from
any aspect of patient care unless epidemiologically incriminated in the
transmission of infections despite adequate precautions. The American
College of Surgeons has stated that surgeons infected with HBV and HCV
have no reason to alter their practice but should seek expert advice and
appropriate treatment to prevent chronic liver disease (16).
No episode of HCV transmission from an infected HCW to a patient during
surgical or dental care procedures has been observed in the United
States. The CDC does not recommend restriction of HCWs with hepatitis C
from performing invasive procedures.
Future directions in the area of management of blood-borne pathogen
infections in HCWs include more systematic surveillance of
occupationally acquired HIV, HBV, and HCV infection; better definition
of the epidemiology of blood contact and the efficacy of preventive
measures; development and evaluation of new safety devices and
protective barriers; evaluation of PEP; and development and evaluation
of vaccines for HIV and HCV.
A sustained commitment to the occupational health of HCWs will ensure
maximum protection for HCWs and patients and the availability of optimal
medical care for all who need it.
* Corresponding author. Mailing address: Hospital Infections Program,
Mailstop E-68, Centers for Disease Control and Prevention, 1600 Clifton
Rd., Atlanta, GA 30333. Phone: (404) 639-6425. Fax: (404)
639-6459. E-mail: email@example.com .
1. Adams, K. S., C. L. Zehrer, and W. Thomas. 1993. Comparison of a
needleless system with conventional heparin locks. Am. J. Infect.
2. Agerton, T. B., F. J. Mahoney, L. B. Polish, and C. N. Shapiro. 1995.
Impact of the bloodborne pathogens standard on vaccination of healthcare
workers with hepatitis B vaccine. Infect. Control Hosp. Epidemiol.
3. AIDS/TB Committee of the Society for Healthcare Epidemiology of
America. 1997. Management of healthcare workers infected with hepatitis
B virus, hepatitis C virus, human immunodeficiency virus, or other
bloodborne pathogens. Infect. Control Hosp. Epidemiol. 18:349-363
4. Alter, H. J., P. V. Holland, R. H. Purcell, J. J. Lander, S. M.
Feinstone, A. G. Morrow, and P. J. Schmidt. 1972. Posttransfusion
hepatitis after exclusion of commercial and hepatitis B antigen-positive
donors. Ann. Intern. Med. 77:691-699
5. Alter, H. J., L. B. Seeff, P. M. Kaplan, V. J. McAuliffe, E. C.
Wright, J. L. Gerin, R. H. Purcell, P. V. Holland, and H. J. Zimmerman.
1976. Type B hepatitis: the infectivity of blood positive for e antigen
and DNA polymerase after accidental needlestick exposure. N. Engl.
J. Med. 295:909-913
6. Alter, M. J. 1993. The detection, transmission, and outcome of
hepatitis C virus infection. Infect. Agents Dis. 2:155-166
7. Alter, M. J. 1994. Occupational exposure to hepatitis C virus: a
dilemma. Infect. Control Hosp. Epidemiol. 15:742-744
8. Alter, M. J. 1994. Review of serologic testing for hepatitis C virus
infection and risk of posttransfusion hepatitis C. Arch. Pathol. Lab.
9. Alter, M. J. 1995. Epidemiology of hepatitis C in the West. Semin.
Liver Dis. 15:5-14
10. Alter, M. J. 1997. The epidemiology of acute and chronic hepatitis
C. Clin. Liver Dis. 1:559-568.
11. Alter, M. J., J. Ahtone, and J. E. Maynard. 1983. Hepatitis B virus
transmission associated with a multiple-dose vial in a hemodialysis
unit. Ann. Intern. Med. 99:330-333
12. Alter, M. J., R. J. Gerety, L. Smallwood, R. E. Sampliner, E. Tabor,
F. Deinhardt, G. Frosner, and G. M. Matanoski. 1982. Sporadic non-A,
non-B hepatitis: frequency and epidemiology in an urban United States
population. J. Infect. Dis. 145:886-893
13. Alter, M. J., D. Kruszon-Moran, D. V. Nainan, G. M. McQuillan, F.
Gao, L. A. Moyer, R. A. Kaslow, and H. S. Margolis. 1999. The prevalence
of hepatitis C virus infection in the United States, 1988 through 1994.
N. Engl. J. Med. 341:556-562
14. Alter, M. J., H. S. Margolis, K. Krawczynski, F. N. Judson, A.
Mares, W. J. Alexander, P. Y. Hu, J. K. Miller, M. A. Gerber, R. E.
Sampliner, E. L. Meeks, and M. J. Beach for the Sentinel Counties
Chronic Non-A Non-B Hepatitis Study Team. 1992. Natural history of
community-acquired hepatitis C in the United States. N. Engl. J. Med.
15. Alter, M. J., and E. E. Mast. 1994. The epidemiology of viral
hepatitis in the United States. Gastroenterol. Clin. N. Am. 23:437-455
16. American College of Surgeons. 1999. Statement on the surgeon and
hepatitis. Bull. Am. Coll. Surg. 84:21-24.
17. Anonymous. 1976. Relation of e antigen to infectivity of HBsAg-positive
inoculations among medical personnel. Lancet ii:492-494.
18. Reference deleted.
19. Anonymous. 1996. New drugs for HIV infection. Med. Lett. Drugs Ther.
20. Assogba, U., R. A. Ancelle Park, M. A. Rey, A. Barthelemy, J.
Rottembourg, and J. C. Gluckman. 1988. Prospective study of HIV1
seropositive patients in hemodialysis centers. Clin. Nephrol. 29:312-314
21. Beekman, S. E., D. Vlahow, D. E. Koziol, E. D. McShalley, and J. M.
Schmitt. 1994. Temporal association between implementation of universal
precautions and a sustained, progressive decrease in percutaneous
exposures to blood. Clin. Infect. Dis. 18:562-569
22. Bell, D. M. 1991. Human immunodeficiency virus transmission in
health care settings: risk and risk reduction. Am. J. Med. 91(Suppl.
23. Bell, D. M. 1997. Occupational risk of human immunodeficiency virus
infection in healthcare workers: an overview. Am. J. Med. 102(Suppl.
24. Bell, D. M., C. N. Shapiro, C. Ciesielski, and M. E. Chamberland.
1995. Preventing bloodborne pathogen transmission from health-care
workers to patients. Surg. Clin. N. Am. 75:1189-1203
25. Bell, D. M., C. N. Shapiro, D. H. Culver, W. J. Martone, J. W.
Curran, and J. M. Hughes. 1992. Risk of hepatitis B and human
immunodeficiency virus transmission to a patient from an infected
surgeon due to percutaneous injury during an invasive procedure:
estimates based on a model. Infect. Agents Dis. 1:263-269
26. Bennett, N. T., and R. J. Howard. 1994. Quantity of blood inoculated
in a needlestick injury from suture needles. J. Am. Coll. Surg.
27. Black, R. J. 1997. Animal studies of prophylaxis. Am. J. Med.
28. Blanchard, A., S. Ferris, S. Chamaret, D. Guétard, and L. Montagnier.
1998. Molecular evidence for nosocomial transmission of human
immunodeficiency virus from a surgeon to one of his patients. J. Virol.
29. Bond, W. W., M. S. Favero, N. J. Petersen, and J. W. Ebert. 1983.
Inactivation of hepatitis B virus by intermediate-to-high-level
disinfectant chemicals. J. Clin. Microbiol. 18:535-538
30. Bowden, F. J., B. Pollett, F. Birrell, and E. M. Dar. 1993.
Occupational exposure to the human immunodeficiency virus and other
bloodborne pathogens: a six year prospective study. Med. J. Aust.
31. Boxall, E. H., and A. Ballard. 1997. Fifth of e antigen negative
carriers of hepatitis B virus should not perform exposure prone
procedures. Br. Med. J. 314:144
32. Bradley, D. W., K. Krawczynski, M. J. Beach, and M. A. Purdy. 1991.
Non-A, non-B hepatitis: toward the discovery of hepatitis C and E
viruses. Semin. Liver Dis. 11:128-146
33. Bukh, J., R. H. Miller, and R. H. Purcell. 1995. Genetic
heterogeneity of hepatitis C virus: quasispecies and genotypes. Semin.
Liver Dis. 15:41-63
34. Busch, M. P., and G. A. Satten. 1997. Time course of viremia and
antibody seroconversion following human immunodeficiency virus exposure.
Am. J. Med. 102(Suppl. 5B):117-124
35. Callender, M. E., Y. S. White, and R. Williams. 1982. Hepatitis B
virus infection in medical and health care personnel. Br. Med. J.
36. Camma, C., P. Almasio, and A. Craxi. 1996. Interferon as treatment
for acute hepatitis C: a meta-analysis. Dig. Dis. Sci. 41:1248-1255
37. Reference deleted.
38. Cardo, D. M., K. G. Castro, J. A. Polder, and D. M. Bell. 1994.
Management of occupational exposure to HIV, p. 361-375. In G.
Schochetman, and J. R. George (ed.), AIDS testing: a comprehensive guide
to technical, medical, social, legal, and management issues, 2nd ed.
Springer-Verlag, New York, N.Y.
39. Cardo, D. M., D. H. Culver, C. A. Ciesielski, P. U. Srivastava, R.
Marcus, D. Abiteboul, J. Heptonstall, G. Ippolito, F. Lot, P. McKibben,
D. M. Bell, and the Centers for Disease Control and Prevention
Needlestick Surveillance Group. 1997. A case-control study of HIV
seroconversion in health care workers after percutaneous exposure. N.
Engl. J. Med. 337:1485-1490
40. Carman, W. F. 1997. The clinical significance of surface antigen
variants of hepatitis B virus. J. Viral Hepatitis 4(Suppl. 1):11-20
41. Carman, W. F., F. J. Van Deursen, L. T. Mimms, D. Hardie, R.
Coppola, R. Decker, and R. Sanders. 1997. The prevalence of surface
antigen variants of hepatitis B virus in Papua New Guinea, South Africa,
and Sardinia. Hepatology 26:1658-1666
42. Carpenter, C. C. J., M. A. Fischl, S. M. Hammer, M. S. Hirsch, D. M.
Jacobsen, D. A. Katzenstein, J. S. G. Montaner, D. D. Richman, M. S.
Saag, R. T. Schooley, M. A. Thompson, S. Vella, P. G. Yeni, and P. A.
Bolberding. 1998. Antiretroviral therapy for HIV infection in 1998:
updated recommendations of the International AIDS Society USA panel.
43. Center for Disease Control. 1977. Hepatitis control measures for
hepatitis B in dialysis centers. HEW publication no. [CDC]
78-8358 (Viral Hepatitis Investigations and Control Series). Center for
Disease Control, Atlanta, Ga.
44. Center for Disease Control. 1978. Lack of transmission of hepatitis
B to humans after oral exposure to hepatitis B surface antigen-positive
saliva. Morbid. Mortal. Weekly Rep. 27:247-248.
45. Centers for Disease Control. 1982. Recommendation of the
Immunization Practices Advisory Committee (ACIP) inactivated hepatitis B
virus vaccine. Morbid. Mortal. Weekly Rep. 31:317-322 328.
46. Centers for Disease Control. 1987. Recommendations for prevention of
HIV transmission in health-care settings. Morbid. Mortal. Weekly Rep.
47. Centers for Disease Control. 1988. Update: universal precautions for
prevention of transmission of human immunodeficiency virus, hepatitis B
virus, and other bloodborne pathogens in health-care settings. Morbid.
Mortal. Weekly Rep. 37:377-382387-388.
48. Centers for Disease Control. 1989. Guidelines for prevention of
transmission of human immunodeficiency virus and hepatitis B virus to
health-care and public safety workers. Morbid. Mortal. Weekly Rep.
49. Centers for Disease Control. 1990. Possible transmission of human
immunodeficiency virus to a patient during an invasive dental procedure.
Morbid. Mortal. Weekly Rep. 39:489-493
50. Centers for Disease Control. 1990. Public Health Service statement
on management of occupational exposure to human immunodeficiency virus,
including considerations regarding zidovudine postexposure use. Morbid.
Mortal. Weekly Rep. 39(RR-1):1-14
51. Centers for Disease Control. 1991. 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). Morbid. Mortal. Weekly
52. Centers for Disease Control. 1991. Recommendations for preventing
transmission of human immunodeficiency virus and hepatitis B virus to
patients during exposure-prone invasive procedures. Morbid. Mortal.
Weekly Rep. 40(RR-8):1-9
53. Centers for Disease Control and Prevention. 1994. Zidovudine for the
prevention of HIV transmission from mother to infant. Morbid. Mortal.
Weekly Rep. 43:285-287
54. Centers for Disease Control and Prevention. 1995. Hepatitis
surveillance report, Atlanta, p. 3-6. Centers for Disease Control and
Prevention, Atlanta, Ga.
55. Centers for Disease Control and Prevention. 1995. Case-control study
of HIV seroconversion in health-care workers after percutaneous exposure
to HIV-infected blood France, United Kingdom, and United States, January
1988-August 1994. Morbid. Mortal. Weekly Rep. 44:929-933
56. Centers for Disease Control and Prevention. 1996. Outbreaks of
hepatitis B virus infection among hemodialysis patients California.
Morbid. Mortal. Weekly Rep. 45:285-289
57. Centers for Disease Control and Prevention. 1996. Update:
provisional Public Health Service recommendations for chemoprophylaxis
after occupational exposure to HIV. Morbid. Mortal. Weekly Rep.
58. Centers for Disease Control and Prevention. 1997. Evaluation of
blunt suture needles in preventing percutaneous injuries among
health-care workers during gynecologic surgical procedures New York
City, March 1993-June 1994. Morbid. Mortal. Weekly Rep. 46:25-29
59. Centers for Disease Control and Prevention. 1997. Evaluation of
safety devices for preventing percutaneous injuries among health-care
workers during phlebotomy procedures Minneapolis-St. Paul, New York
City, and San Francisco, 1993-1995. Morbid. Mortal. Weekly Rep.
60. Centers for Disease Control and Prevention. 1997. Immunization of
health-care workers: recommendations of the Advisory Committee on
Immunization Practices (ACIP) and the Hospital Infections Control
Practices Advisory Committee (HICPAC). Morbid. Mortal. Weekly Rep.
61. Centers for Disease Control and Prevention. 1997. Recommendations
for follow-up of health-care workers after occupational exposure to
hepatitis C virus. Morbid. Mortal. Weekly Rep. 46:603-606
62. Centers for Disease Control and Prevention. 1998. Administration of
zidovudine during late pregnancy and delivery to prevent perinatal HIV
transmission Thailand, 1996-1998. Morbid. Mortal. Weekly Rep. 47:151-154
63. Centers for Disease Control and Prevention. 1998. Public Health
Service guidelines for the management of health-care worker exposures to
HIV and recommendations for postexposure prophylaxis. Morbid. Mortal.
Weekly Rep. 47(RR-7):1-34
64. Centers for Disease Control and Prevention. 1998. Recommendations
for follow-up of health-care workers after occupational exposure to
hepatitis C virus. Morbid. Mortal. Weekly Rep. 47:603-606.
64a. Centers for Disease Control and Prevention. 1998. Recommendations
for the prevention and control of hepatitis C virus (HCV) infection and
HCV-related chronic disease. Morbid. Mortal. Weekly Rep. 47(RR-19):1-39
65. Centers for Disease Control and Prevention. 1999. HIV/AIDS
surveillance report, vol. 11, no. 1. Centers for Disease Control and
Prevention, Atlanta, Ga.
66. Chamberland, M. E., L. R. Petersen, V. P. Munn, C. R. White, E. S.
Johnson, M. P. Busch, A. J. Grindon, H. Kamel, P. M. Ness, A. W. Shafer,
and G. Zeger. 1994. Human immunodeficiency virus infection among health
care workers who donate blood. Ann. Intern. Med. 121:269-273
67. Chan, T. M., A. S. Lok, I. K. Cheng, and R. T. Chan. 1993.
Prevalence of hepatitis C virus infection in hemodialysis patients: a
longitudinal study comparing the results of RNA and antibody assays.
68. Charache, P., J. L. Cameron, A. W. Maters, and E. I. Frantz. 1991.
Prevalence of infection with human immunodeficiency virus in elective
surgery patients. Ann. Surg. 214:562-568
69. Reference deleted.
70. Cheynier, R., P. Langlade-Demoyen, M.-R. Marescot, S. Blanhe, G.
Boudin, S. Wain-Hobson, C. Griscelli, E. Vilmer, and F. Plata. 1992.
Cytotoxic T lymphocyte responses in the peripheral blood of children
born to human immunodeficiency virus-1-infected mothers. Eur. J. Immunol.
71. Chirgwin, K., T. K. S. Rao, and S. H. Landesman. 1989. HIV infection
in a high prevalence hemodialysis unit. AIDS 3:731-735[Medline].
72. Ciesielski, C., D. Marianos, C.-Y. Ou, R. Dombaugh, J. Witte, R.
Berkelman, B. Gooch, G. Myers, C.-C. Luo, G. Schochetman, J. Howell, A.
Lasch, K. Bell, N. Economou, B. Scott, L. Furman, J. Curran, and H.
Jaffe. 1992. Transmission of human immunodeficiency virus in a dental
practice. Ann. Intern. Med. 116:798-805
73. Ciesielski, C., and R. P. Metler. 1997. Duration of time between
exposure and seroconversion in healthcare workers with occupationally
acquired infection with human immunodeficiency virus. Am. J. Med.
74. Clerici, M., J. V. Giorgi, C.-C. Chou, V. K. Gudeman, J. A. Zack, P.
Gupta, N. N. Ho, P. G. Nishanian, J. A. Berzofsky, and G. M. Shearer.
1992. Cell-mediated immune response to human immunodeficiency virus
(HIV) type 1 in seronegative homosexual men with recent sexual exposure
to HIV-1. J. Infect. Dis. 165:1012-1019
75. Clerici, M., J. M. Levin, H. A. Kessler, A. Harris, J. A. Berzofsky,
A. L. Linday, and G. M. Shearer. 1994. HIV-specific T-helper activity in
seronegative health care workers exposed to contaminated blood. JAMA
76. Cleveland, J. L., B. Gooch, and S. A. Lockwood. 1997. Occupational
blood exposures in dentistry: a decade in review. Infect. Control Hosp.
77. Cleveland, J. L., S. A. Lockwood, B. F. Gooch, M. H. Mendelson, M.
E. Chamberland, D. V. Valoui, S. L. Roistacher, J. M. Soloman, and D. W.
Marianos. 1995. Percutaneous injuries in dentistry: an observational
study. J. Am. Dent. Assoc. 126:745-751
78. Cleveland, J. L., C. Siew, S. A. Lockwood, S. E. Gruninger, B. F.
Gooch, and C. N. Shapiro. 1996. Hepatitis B vaccination and infection
among U.S. dentists, 1983-1992. J. Am. Dent. Assoc. 127:1385-1390
79. Collins, C. H., and D. A. Kennedy. 1987. Microbiological hazards of
occupational needlestick and `sharps' injuries. J. Appl. Bacteriol.
80. Comodo, N., F. Martinelli, E. De Majo, M. G. Colao, M. A. DiPietro,
F. Manescalchi, M. Salvadori, and E. Lanciotti. 1988. Risk of HIV
infection on patients and staff of two dialysis centers:
seroepidemiological findings and prevention trends. Eur. J. Epidemiol.
81. Connor, E. M., R. S. Sperling, R. Gelber, P. Kiselev, G. Scott, M.
J. O'Sullivan, R. VanDyke, M. Bey, W. Shearer, R. L. Jacobson, E.
Jimenez, E. O'Neill, B. Bazin, J.-F. Delfraissy, M. Culnane, R. Coombs,
M. Elkins, J. Moye, P. Stratton, J. Balsley, and the Pediatric AIDS
Clinical Trials Group Protocol 076 Study Group. 1994. Reduction of
maternal-infant transmission of human immunodeficiency virus type 1 with
zidovudine treatment. N. Engl. J. Med. 331:1173-1180
82. Cowan, D. N., J. F. Brundage, R. S. Pomerantz, R. N. Miller, and D.
S. Burke. 1991. HIV infection among members of the US Army Reserve
Components with medical and health occupations. JAMA 265:2826-2830
83. Cuypers, H. T. M., D. Bresters, I. N. Winkel, H. W. Reesink, A. J.
Weiner, M. Houghton, C. L. van der Poel, and P. N. Lelie. 1992. Storage
conditions of blood samples and primer selection affect yield of cDNA
polymerase chain reaction products of hepatitis C virus. J. Clin.
84. Reference deleted.
85. Danila, R. N., K. L. MacDonald, F. S. Rhame, M. Moen, D. O. Reier,
J. C. LeTourneau, M. K. Sheehan, J. Armstrong, M. E. Bender, M. T.
Osterholm, and the Investigation Team. 1991. A look-back investigation
of patients of an HIV-infected physician: public health implications. N.
Engl. J. Med. 325:1406-1411
86. Danzig, L. E., L. J. Short, K. Collins, M. Mahoney, S. Sepe, L.
Bland, and W. R. Jarvis. 1995. Bloodstream infections associated with a
needleless intravenous infusion system in patients receiving home
infusion therapy. JAMA 273:1862-1864
87. Davis, G. L., J. Y. Lau, M. S. Urdea, P. D. Neuwald, J. C. Wilbur,
and L. Corey. 1994. Quantitative detection of hepatitis C virus RNA with
a solid-phase signal amplification method: definition of optimal
conditions for specimen collection and clinical application in
interferon-treated patients. Hepatology 19:1337-1341
88. Davis, G. L., and J. Y. N. Lau. 1995. Hepatitis C, p. 2082-2114. In
W. S. Haubrich, F. Schaffner, and J. E. Berk (ed.), Gastroenterology,
5th ed. W. B. Saunders and Co., Philadelphia, Pa.
89. Denes, A. E., J. L. Smith, J. E. Maynard, I. L. Doto, K. R. Berquist,
and A. J. Finkel. 1978. Hepatitis B infection in physicians: results of
a nationwide seroepidemiologic survey. JAMA 239:210-212
90. Reference deleted.
91. Di Bisceglie, A. M., G. M. Dusheiko, and M. C. Kew. 1985. Detection
of markers of hepatitis B virus infection in urine of chronic carriers.
J. Med. Virol. 16:337-341
92. Dickinson, G. M., R. E. Morhart, N. G. Klimas, C. I. Bandea, J. M.
Laracuvente, and A. L. Bisno. 1993. Absence of HIV transmission from an
infected dentist to his patients: an epidemiologic and DNA sequence
analysis. JAMA 269:1802-1806
93. Dienstag, J. L., and D. M. Ryan. 1982. Occupational exposure to
hepatitis B virus in hospital personnel: infection or immunization? Am.
J. Epidemiol. 115:26-39
94. Donegan, S. P., K. A. Steger, L. Recla, R. S. Huff, B. G. Werner, P.
A. Rice, and D. E. Craven. 1992. Seroprevalence of human
immunodeficiency virus in parturients at Boston City Hospital:
implications for public health and obstetric practice. Am. J. Obstet.
95. Duckworth, G. J., J. Heptonstall, and C. Aitken. 1999. Transmission
of hepatitis C virus from a surgeon to a patient. The Incident Control
Team. Commun. Dis. Public Health 2:188-192.
96. Dusheiko, G. M., M. Smith, and P. J. Scheuer. 1990. Hepatitis C
virus transmitted by human bite. Lancet 336:503-504
97. Reference deleted.
98. Elmslie, K., M. Ricketts, and L. Mulligan. 1990. Guidelines for
counseling persons who have had an occupational exposure to human
immunodeficiency virus. Can. Dis. Weekly Rep. 19(Suppl. 2):1-3.
99. Erice, A., D. L. Mayers, D. G. Strike, K. J. Sannerud, F. E.
McCutchan, K. Henry, and H. H. Balfour, Jr. 1993. Brief report: primary
infection with zidovudine-resistant human immunodeficiency virus type 1.
N. Engl. J. Med. 328:1163-1165
100. Eron, J. J., S. L. Benoit, J. Jemsek, R. D. MacArthur, J. Santana,
J. B. Quinn, D. R. Kuritzkes, M. A. Fallon, and M. Rubin. 1995.
Treatment with lamivudine, zidovudine, or both in HIV-positive patients
with 200 to 500 CD4+ cells per cubic millimeter. N. Engl. J. Med.
101. Esteban, J. I., J. Gomez, M. Martell, B. Cabot, J. Quer, J. Camps,
A. Gonzales, T. Otero, A. Moya, R. Estaban, and J. Guardia. 1996.
Transmission of hepatitis C virus by a cardiac surgeon. N. Engl. J. Med.
102. Fahey, B. J., D. E. Koziol, S. M. Banks, and D. K. Henderson. 1991.
Frequency of nonparenteral occupational exposures to blood and body
fluids before and after universal precautions training. Am. J. Med.
103. Farci, P., H. J. Alter, D. Wong, R. H. Miller, J. W. Shih, B. Jett,
and R. H. Purcell. 1991. A long-term study of hepatitis C virus
replication in non-A, non-B hepatitis. N. Engl. J. Med. 325:98-104
104. Favero, M. S. 1985. Sterilization, disinfection, and antisepsis in
the hospital, p. 129-137. In E. H. Lennette, A. Balows, W. J. Hausler,
Jr., and H. J. Shadomy (ed.), Manual of clinical microbiology, 4th ed.
American Society for Microbiology, Washington, D.C.
105. Favero, M. S., and W. W. Bond. 1993. Disinfection and
sterilization, p. 565-575. In A. J. Zuckerman, and H. C. Thomas (ed.),
Viral hepatitis: scientific basis and clinical management. Churchill
Livingston, New York, N.Y.
106. Feinman, S. V., B. Berris, A. Rebane, J. C. Sinclair, S. Wilson,
and D. Wrobel. 1979. Failure to detect hepatitis B surface antigen (HBsAg)
in feces of HBsAg-positive persons. J. Infect. Dis. 140:407-410
107. Flynn, N. M., S. M. Pollet, J. R. Van Horne, R. Elvebakk, S. D.
Harper, and J. R. Carlson. 1987. Absence of HIV antibody among dental
professionals exposed to infected patients. West. J. Med. 146:439-442
108. Reference deleted.
109. Fried, M. W., and J. H. Hoofnagle. 1995. Therapy of hepatitis C.
Semin. Liver Dis. 15:82-91
110. Fujiyama, S., S. Kawano, S. Sato, M. Tanaka, M. Goto, Y. Taura, T.
Sato, T. Kawahara, and K. Mizuno. 1992. Prevalence of hepatitis C virus
antibodies in hemodialysis patients and dialysis staff.
111. Garner, J. S., and the Hospital Infection Control Practices
Advisory Committee. 1996. Guideline for isolation precautions in
hospitals. Infect. Control Hosp. Epidemiol. 17:53-80
112. Gartner, K. 1992. Impact of a needleless intravenous system in a
university hospital. Am. J. Infect. Control 20:75-79
113. Gerberding, J. L. 1994. Incidence and prevalence of human
immunodeficiency virus, hepatitis B virus, hepatitis C virus, and
cytomegalovirus among health care personnel at risk for blood exposure:
final report from a longitudinal study. J. Infect. Dis. 170:1410-1417
114. Gerberding, J. L. 1995. Management of occupational exposures to
blood-borne viruses. N. Engl. J. Med. 332:444-451
115. Gerberding, J. L., and D. K. Henderson. 1992. Management of
occupational exposures to bloodborne pathogens: hepatitis B virus,
hepatitis C virus, and human immunodeficiency virus. Clin. Infect. Dis.
116. Gerberding, J. L., C. Littell, A. Tarkington, A. Brown, and W. P.
Schecter. 1990. Risk of exposure of surgical personnel to patients'
blood during surgery at San Francisco General Hospital. N. Engl. J. Med.
117. Gershon, R. R. M., D. Vlahov, H. Farzedegan, and M. J. Alter. 1995.
Occupational risk of human immunodeficiency virus, hepatitis B virus,
and hepatitis C virus infections among funeral service practitioners in
Maryland. Infect. Control Hosp. Epidemiol. 16:194-197
118. Goldman, M., C. Leisnard, J.-L. Vanherweghem, N. Dolle, C.
Toussaint, S. Sprecher, J. Cogniaux, and L. Thiry. 1986. Markers of HTLV-III
in patients with end stage renal failure treated by haemodialysis. Br.
Med. J. 293:161-162
119. Gordin, F. M., C. Gilbert, H. P. Hawley, and A. Willoughby. 1990.
Prevalence of human immunodeficiency virus and hepatitis B virus in
unselected hospital admissions: implications for mandatory testing and
universal precautions. J. Infect. Dis. 161:14-17
120. Grady, G. F., V. A. Lee, A. M. Prince, G. L. Gitnick, K. A. Fawaz,
G. N. Vyas, M. D. Levitt, J. R. Senior, J. T. Galambos, T. E. Bynum, J.
W. Singleton, B. F. Clowdus, K. Akdamar, R. D. Aach, E. I. Winkelman, G.
M. Schiff, and T. Hersh. 1978. Hepatitis B immune globulin for
accidental exposures among medical personnel: final report of a
multicenter controlled trial. J. Infect. Dis. 138:625-638
121. Gretch, D. R. 1997. Diagnostic tests for hepatitis C. Hepatology
122. Gretch, D. R., C. dela Rosa, R. L. Carithers, R. A. Wilson, K.
Lindsay, R. P. Perrillo, and J. Albrecht. 1995. Assessment of hepatitis
C viremia using molecular amplification technologies: correlations and
clinical implications. Ann. Intern. Med. 123:321-329
123. Gruninger, S. E., C. Siew, S.-B. Chang, R. Clayton, J. K. Leete, S.
A. Hojvat, A. C. Verrusio, and E. A. Neidle. 1992. Human
immunodeficiency virus type 1 infection among dentists. J. Am. Dent.
124. Guptan, R. C., V. Thakur, S. K. Sarin, K. Banerjee, and P.
Khandekar. 1996. Frequency and clinical profile of precore and surface
hepatitis B mutants in Asian-Indian patients with chronic liver disease.
Am. J. Gastroenterol. 91:1312-1317
125. Hadler, S. C., I. L. Doto, J. E. Maynard, J. Smith, B. Clark, J.
Masley, T. Eikhoff, C. K. Himmelsbach, and W. R. Cole. 1985.
Occupational risk of hepatitis B infection in hospital workers. Infect.
126. Haiduven, D. J., T. M. Demaio, and D. A. Stevens. 1992. A five-year
study of needlestick injuries: significant reduction associated with
communication, education, and convenient placement of sharps containers.
Infect. Control Hosp. Epidemiol. 13:265-271
127. Halle, M. 1996. Patients want ban on operations by doctors with
hepatitis B. Br. Med. J. 313:576
128. Halle, M. 1996. Surgeon had mutant form of hepatitis B. Br. Med. J.
129. Hamory, B. H. 1983. Underreporting of needlestick injuries in a
university hospital. Am. J. Infect. Control 11:174-177
130. Hansen, M. E., G. L. Miller III, H. Redman, and D. D. McIntire.
1993. Needle-stick injuries and blood contacts during invasive
radiologic procedures: frequency and risk factors. Am. J. Roentgenol.
131. Hardy, N. M., S. Sandroni, S. Danielson, and W. J. Wilson. 1992.
Antibody to hepatitis C virus increases with time on hemodialysis. Clin.
132. Harpaz, R., L. Von Seidlein, F. M. Averhoff, M. P. Tormey, S. D.
Sinha, K. Kotsopoulou, S. B. Lambert, B. H. Robertson, J. D. Cherry, and
C. N. Shapiro. 1996. Transmission of hepatitis B virus to multiple
patients from a surgeon without evidence of inadequate infection
control. N. Engl. J. Med. 334:549-554
133. Harris, J. R., R. F. Finger, J. M. Kobayashi, S. C. Hadler, B. L.
Murphy, R. L. Berkelman, and K. E. Russell. 1984. The low risk of
hepatitis B in rural hospitals: results of an epidemiologic survey. JAMA
134. Hayashi, J., K. Nakashima, W. Kajiyama, A. Noguchi, M. Morofuji, Y.
Maeda, and S. Kashiwaji. 1991. Prevalence of antibody to hepatitis C
virus in hemodialysis patients. Am. J. Epidemiol. 134:651-657
135. Henderson, D. K. 1991. Postexposure chemoprophylaxis for
occupational exposure to human immunodeficiency virus type 1: current
status and prospects for the future. Am. J. Med. 91(Suppl. 3B):312S-319S
136. Henderson, D. K., and J. L. Gerberding. 1989. Prophylactic
zidovudine after occupational exposure to human immunodeficiency virus:
an interim analysis. J. Infect. Dis. 160:321-327
137. Heptonstall, J. 1991. Outbreaks of hepatitis B virus infection
associated with infected surgical staff. Dis. Rep. CDR Rev. 1:R81-R85.
138. Heptonstall, J. 1996. Lessons from two linked clusters of acute
hepatitis B in cardiothoracic surgery patients. Dis. Rep. CDR Rev.
139. Reference deleted.
140. Hernandez, M. E., M. Bruguera, T. Puyuelo, J. M. Barrera, J. M.
Sanchez-Tapias, and J. Rodes. 1992. Risk of needlestick injuries in the
transmission of hepatitis C virus in hospital personnel. J. Hepatol.
141. Ho, D. D., T. Moudgil, and M. Alam. 1989. Quantitation of human
immunodeficiency virus type 1 in the blood of infected persons. N. Engl.
J. Med. 321:1621-1625
142. Hoofnagle, J. H. 1995. Hepatitis B, p. 2062-2063. In W. S. Haubrich,
F. Schaffner, and J. E. Berk (ed.), Gastroenterology, 5th ed. W.
B. Saunders and Co., Philadelphia, Pa.
143. Hoofnagle, J. H., and A. M. Di Bisceglie. 1991. Serologic diagnosis
of acute and chronic viral hepatitis. Semin. Liver Dis. 11:73-83
144. Hsu, H. H., T. L. Wright, D. Luba, M. Martin, S. M. Feinstone, G.
Garcia, and H. B. Greenberg. 1991. Failure to detect hepatitis C virus
genome in human secretions with the polymerase chain reaction.
145. Incident Investigation Team, et al. 1997. Transmission of hepatitis
B to patients from four infected surgeons without hepatitis B e antigen.
N. Engl. J. Med. 336:178-184
146. Reference deleted.
147. Ippolito, G., V. Puro, G. De Carli, and the Italian Study Group on
Occupational Risk of HIV Infection. 1993. The risk of occupational human
immunodeficiency virus infections in health care workers. Arch. Intern.
148. Reference deleted.
149. Irwin, G. R., A. M. Allen, W. H. Bancroft, J. J. Karwacki, H. L.
Brown, R. H. Pinkerton, M. Wilhight, and F. H. Top, Jr. 1975. Hepatitis
B antigen in saliva, urine, and stool. Infect. Immun. 11:142-145
150. Jaffe, H. W., J. M. McCurdy, M. L. Kalish, T. Liberti, G. Metellus,
B. H. Bowman, S. B. Richards, A. R. Neasman, and J. J. Witte. 1994. Lack
of HIV transmission in the practice of a dentist with AIDS. Ann. Intern.
151. Jagger, J., E. H. Hunt, J. Brand-Elnagger, and R. D. Pearson. 1988.
Rates of needle-stick injury caused by various devices in a university
hospital. N. Engl. J. Med. 319:284-288
152. Jagger, J., E. H. Hunt, and R. D. Pearson. 1990. Sharp object
injuries in the hospital: causes and strategies for prevention. Am.
J. Infect. Control 18:227-231
153. Janssen, R. S., M. E. St. Louis, G. A. Satten, S. E. Critchley, L.
R. Petersen, R. S. Stafford, J. W. Ward, D. L. Hanson, N. Olivio, C. A.
Schable, T. J. Dondero, and the Hospital HIV Surveillance Group. 1992.
HIV infection among patients in U.S. acute care hospitals: strategies
for the counseling and testing of hospital patients. N. Engl. J. Med.
154. Jenison, S. A., S. M. Lemon, L. N. Baker, and J. E. Newbold. 1987.
Quantitative analysis of hepatitis B virus DNA in saliva and semen of
chronically infected homosexual men. J. Infect. Dis. 156:299-307
155. Reference deleted.
156. Jochimsen, E. M. 1997. Failures of zidovudine post-exposure
prophylaxis. Am. J. Med. 102(Suppl. 5B):52-55
157. Kelen, G. D., T. DiGiovanna, L. Bisson, D. Kalainov, K. T.
Sivertson, and T. C. Quinn. 1989. Human immunodeficiency virus infection
in emergency department patients: epidemiology, clinical presentations,
and risk to health care workers, the Johns Hopkins experience. JAMA
158. Kelen, G. D., S. Fritz, B. Qaqish, R. Brookmeyer, J. L. Baker, R.
L. Kline, R. M. Cuddy, T. K. Goessel, D. Floccare, K. A. Williams, K. T.
Sivertson, S. Altman, and T. C. Quinn. 1988. Unrecognized human
immunodeficiency virus infection in emergency department patients. N.
Engl. J. Med. 318:1645-1650
159. Kelen, G. D., G. B. Green, R. H. Purcell, D. W. Chan, B. F. Qaqish,
K. T. Sivertson, and T. C. Quinn. 1992. Hepatitis B and hepatitis C in
emergency department patients. N. Engl. J. Med. 326:1399-1404
160. Kelker, H. C., M. Seidlin, M. Vogler, and F. T. Valentine. 1992.
Lymphocytes from some long-term seronegative heterosexual partners of
HIV-infected individuals proliferate in response to HIV antigens. AIDS
161. Kiyosawa, K., T. Sodeyama, E. Tanaka, Y. Nakano, S. Furuta, K.
Nishioka, R. H. Purcell, and H. J. Alter. 1991. Hepatitis C in hospital
employees with needlestick injuries. Ann. Intern. Med. 115:367-369
162. Klein, R. S., K. Freeman, P. E. Taylor, and C. E. Stevens. 1991.
Occupational risk for hepatitis C virus infection among New York City
dentists. Lancet 339:1539-1542.
163. Klein, R. S., J. A. Phelan, K. Freeman, C. Schable, G. H. Friedland,
N. Trieger, and N. H. Steigbigel. 1988. Low occupational risk of human
immunodeficiency virus infection among dental professionals. N. Engl.
J. Med. 318:86-90
164. Knodell, R. G., M. E. Conrad, A. L. Ginsberg, and C. J. Bell. 1976.
Efficacy of prophylactic gamma-globulin in preventing non-A, non-B
post-transfusion hepatitis. Lancet i:557-561
165. Kobayashi, H., M. Tsuzuki, K. Koshimizu, H. Toyama, N. Yoshihara,
T. Shikata, K. Abe, K. Mizuno, N. Otomo, and T. Oda. 1984.
Susceptibility of hepatitis B virus to disinfectants and heat. J. Clin.
166. Koretz, R. L., M. Brezina, A. J. Polito, S. Quan, J. Wilbur, R.
Dinello, and G. Gitnick. 1993. Non-A, non-B posttransfusion hepatitis:
comparing C and non-C hepatitis. Hepatology 17:361-365
167. Reference deleted.
168. Krawczynski, K., M. J. Alter, and D. L. Tankersley. 1996. Effect of
immune globulin on the prevention of experimental hepatitis C virus
infection. J. Infect. Dis. 173:822-828
169. Reference deleted.
170. Langlade-Demoyen, P., N. Ngo-Giang-Huong, F. Ferchal, and E.
Oksenhendler. 1994. Human immunodeficiency virus (HIV) nef-specific
cytotoxic T lymphocytes in noninfected heterosexual contacts of
HIV-infected patients. J. Clin. Investig. 93:1293-1297
171. Laras, A., J. Koskinas, K. Avgidis, and S. J. Hadziyannis. 1998.
Incidence and clinical significance of hepatitis B virus precore gene
translation initiation mutations in e antigen-negative patients. J.
Viral Hepatitis 5:241-248
172. Lau, J. Y., M. Mizokami, J. A. Kolberg, G. L. Davis, L. E.
Prescott, T. Ohno, R. P. Perrillo, K. L. Lindsay, R. G. Gish, K.-P. Qian,
M. Kohara, P. Simmonds, and M. S. Urdea. 1995. Application of six
hepatitis C virus genotyping systems to sera from chronic hepatitis C
patients in the United States. J. Infect. Dis. 171:281-289
173. Liang, T. J., K. Hasegawa, S. J. Munoz, C. N. Shapiro, B. Yoffe, B.
J. McMahon, C. Feng, H. Bei, M. J. Alter, and J. L. Dienstag. 1994.
Hepatitis B virus precore mutation and fulminant hepatitis in the United
States: a polymerase chain reaction-based assay for the detection of
specific mutation. J. Clin. Investig. 93:550-555
174. Lot, F., and D. Abiteboul. 1995. Health-care workers infected with
HIV in France as of June 30, 1995. Bull. Epidemiol. Hebd. 44:193-194.
175. Louie, M., D. E. Low, and S. V. Feinman. 1992. Prevalence of
bloodborne infective agents among people admitted to a Canadian
hospital. Can. Med. Assoc. J. 146:1331-1334
176. Mahoney, F. J., K. Stewart, H. Hu, P. Coleman, and M. Alter. 1997.
Progress toward elimination of hepatitis B virus transmission among
health care workers in the United States. Arch. Intern. Med.
177. Mangione, C. M., J. L. Gerberding, and S. R. Cumings. 1991.
Occupational exposure to HIV: frequency and rates of underreporting of
percutaneous and mucocutaneous exposures by medical housestaff. Am.
J. Med. 90:85-90
178. Marcus, R., D. H. Culver, D. M. Bell, P. U. Srivastava, M. H.
Mendelson, R. J. Zalenski, B. Farber, D. Fligner, J. Hassett, T. C.
Quinn, C. A. Schable, E. P. Sloan, P. Tsui, and G. D. Kelen. 1993. Risk
of human immunodeficiency virus infection among emergency department
workers. Am. J. Med. 94:363-369
179. Reference deleted.
180. Martin, M. A., M. Reichelderfer, and the Association for
Professionals in Infection Control and Epidemiology, Inc. 1994. APIC
guideline for infection prevention and control in flexible endoscopy.
Am. J. Infect. Control 22:19-38
181. Mast, E. E., and M. J. Alter. 1993. Prevention of hepatitis B virus
infection among health-care workers, p. 295-307. In R. W. Ellis (ed.),
Hepatitis B vaccines in clinical practice. Marcel Dekker, Inc., New
182. Mast, S. T., J. D. Woolwine, and J. L. Gerberding. 1992. Efficacy
of gloves in reducing blood volumes transferred during simulated
needlestick injury. J. Infect. Dis. 168:1589-1592.
183. McGeer, A., A. E. Simor, and D. E. Low. 1990. Epidemiology of
needlestick injuries in house officers. J. Infect. Dis. 162:961-964
184. Reference deleted.
185. Mishu, B., W. Schaffner, J. M. Horan, L. H. Wood, R. H. Hutcheson,
and P. C. McNabb. 1990. A surgeon with AIDS: lack of evidence of
transmission to patients. JAMA 264:467-470
186. Mitsui, T., K. Iwano, K. Masuko, C. Yamazaki, H. Yakamoto, F. Tsuda,
T. Tanaka, and S. Mishiro. 1992. Hepatitis C virus infection in medical
personnel after needlestick accident. Hepatology 16:1109-1114
187. Montecalvo, M. A., M. S. Lee, H. DePalma, P. S. Wynn, A. B.
Lowenfels, U. Jorde, D. Wuest, A. Klingamen, T. A. O'Brien, M. Calmann,
and G. P. Wormser. 1995. Seroprevalence of human immunodeficiency
virus-1, hepatitis B virus, and hepatitis C virus in patients having
major surgery. Infect. Control Hosp. Epidemiol. 16:627-632
188. Moyer, L. A., and M. J. Alter. 1994. Hepatitis C virus in the
hemodialysis setting: a review with recommendations for control. Semin.
189. Moyer, L. A., M. J. Alter, and M. S. Favero. 1990. Hemodialysis-associated
hepatitis B: revised recommendations for serologic screening. Semin.
190. Mullins, J. R., and P. B. Harrison. 1993. The questionable utility
of mandatory screening for the human immunodeficiency virus. Am.
J. Surg. 166:676-679
191. Nagachinta, T., C. R. Gold, F. Cheng, P. N. R. Heseltine, and P. R.
Kerndt. 1996. Unrecognized HIV-1 infection in inner-city emergency
department patients. Infect. Control Hosp. Epidemiol. 17:174-177
192. Nakano, Y., K. Kiyosawa, T. Sodeyama, E. Tanaka, A. Matsumoto, T.
Ichijo, M. Mizokami, and S. Furuta. 1995. Acute hepatitis C transmitted
by needlestick accident despite short duration interferon treatment. J.
Gastroenterol. Hepatol. 10:609-611
193. Reference deleted.
194. Natov, S. N., and B. J. Pereira. 1996. Hepatitis C in dialysis
patients. Adv. Renal Replace. Ther. 3:275-283
195. Neal, K. R., J. Dornan, and W. L. Irving. 1997. Prevalence of
hepatitis C antibodies among healthcare workers of two teaching
hospitals: who is at risk? Br. Med. J. 314:179-180
196. Neal, K. R., D. A. Jones, D. Killey, and V. James. 1994. Risk
factors for hepatitis C virus infection: a case-control study of blood
donors in the Trent Region (UK). Epidemiol. Infect. 112:595-601
197. Niitsuma, H., M. Ishii, Y. Saito, M. Miura, K. Kobayashi, H. Ohori,
and T. Toyota. 1995. Prevalence of precore-defective mutant of hepatitis
B virus in HBV carriers. J. Med. Virol. 46:397-402
198. Niu, M. T., L. T. Penberthy, M. J. Alter, C. W. Armstrong, G. B.
Miller, and S. C. Hadler. 1989. Hemodialysis-associated hepatitis B:
report of an outbreak. Dialysis Transplant. 18:542-545.
199. Niu, M. T., D. S. Stein, and S. M. Schnittmann. 1993. Primary human
immunodeficiency virus type 1 infection: review of pathogenesis and
early treatment interventions in humans and animal retrovirus
infections. J. Infect. Dis. 168:1490-1501
200. Noguchi, S., M. Sata, H. Suzuki, K. Ohba, M. Mizokami, and K.
Tanikawa. 1997. Early therapy with interferon for acute hepatitis C
acquired through a needlestick. Clin. Infect. Dis. 24:992-994
201. Noone, P. A., I. S. Symington, and W. F. Carman. 1997. Hepatitis B
and health care workers. Lancet 350:219
201a. Noskin, G. A. 1995. Prevention, diagnosis, and management of viral
hepatitis: a guide for primary care physicians. American Medical
Association, Division of Health Science, Chicago, Ill.
202. O'Briain, D. S. 1991. Patterns of occupational hand injury in
pathology: the interaction of blades, needles, and the dissector's
digits. Arch. Pathol. Lab. Med. 115:610-613
203. Oguchi, H., M. Miyasaka, S. Tokunaga, K. Hora, S. Ichikawa, T.
Ochi, K. Yamada, M. Nagasawa, Y. Kanno, T. Azizawa, et al. 1992.
Hepatitis virus infection (HBV and HCV) in eleven Japanese hemodialysis
units. Clin. Nephrol. 38:36-43
204. O'Neill, T. M., A. V. Abbott, and S. E. Radecki. 1992. Risk of
needlesticks and occupational exposures among residents and medical
students. Arch. Intern. Med. 152:1451-1456
205. Osborn, E. H. S., M. A. Papadakis, and J. L. Gerberding. 1999.
Occupational exposures to body fluids among medical students: a
seven-year longitudinal study. Ann. Intern. Med. 130:45-51
206. Ou, C.-Y., C. A. Ciesielski, G. Myers, C. I. Bandea, C.-C. Luo, B.
T. M. Korber, J. I. Mullins, G. Schochetman, R. L. Berkelman, A. N.
Economou, J. J. Witte, L. J. Furman, G. A. Satten, K. A. MacInnes, J. W.
Curran, H. W. Jaffe, Laboratory Investigation Group, and Epidemiologic
Investigation Group. 1992. Molecular epidemiology of HIV transmission in
a dental practice. Science 256:1165-1171
207. Owens, D. K., M. Holodniy, A. M. Garber, J. Scott, S. Sonnad, L.
Moses, B. Kinosian, and J. S. Schwartz. 1996. Polymerase chain reaction
for the diagnosis of HIV infection in adults: a meta-analysis with
recommendations for clinical practice and study design. Ann. Intern.
208. Panlilio, A. L., D. R. Foy, J. R. Edwards, D. M. Bell, B. A. Welch,
C. M. Parrish, D. H. Culver, P. W. Lowry, W. R. Jarvis, and C. A.
Perlino. 1991. Blood contacts during surgical procedures. JAMA
209. Panlilio, A. L., C. N. Shapiro, C. A. Schable, M. H. Mendelson, M.
A. Montecalvo, L. M. Kunches, S. W. Perry III, J. R. Edwards, P. U.
Srivastava, D. H. Culver, I. B. Weisfuse, V. Jorde, J. M. Davis, J.
Solomon, G. P. Wormser, J. Ryan, D. M. Bell, M. E. Chamberland, and the
Serosurvey Study Group. 1995. Serosurvey of human immunodeficiency
virus, hepatitis B virus, and hepatitis C virus infection among
hospital-based surgeons. J. Am. Coll. Surg. 180:16-24
210. Panlilio, A. L., B. A. Welch, D. M. Bell, D. R. Foy, C. M. Parrish,
C. A. Perlino, and L. Klein. 1992. Blood and amniotic fluid contact
sustained by obstetric personnel during deliveries. Am. J. Obstet.
211. Pattison, C. P., K. M. Boyer, J. E. Maynard, and P. C. Kelly. 1974.
Epidemic hepatitis in a clinical laboratory: possible association with
computer card handling. JAMA 230:854-857
212. Pawlotsky, J.-M. 1997. Measuring hepatitis C viremia in clinical
samples: can we trust the assays? Hepatology 26:1-4
213. Pereira, B. J., and A. S. Levey. 1997. Hepatitis C virus infection
in dialysis and renal transplantation. Kidney Int. 51:981-999
214. Reference deleted.
215. Peterman, T. A., G. R. Lang, N. J. Mikos, S. L. Solomon, C. A.
Schable, P. M. Feorino, J. A. Britz, and J. R. Allen. 1986. HTLV-III/LAV
infection in hemodialysis patients. JAMA 255:2324-2326
216. Peters, M., G. L. Davis, J. S. Dooley, and J. H. Hoofnagle. 1986.
The interferon system in acute and chronic viral hepatitis. Prog. Liver
217. Polakoff, S. 1986. Acute hepatitis B in patients in Britain related
to previous operations and dental treatment. Br. Med. J. Clin. Res.
218. Polakoff, S. 1986. Acute viral hepatitis B: laboratory reports
1980-4. Br. Med. J. Clin. Res. 293:37-38.
219. Polish, L. B., M. J. Tong, R. L. Co, P. J. Coleman, and M. J.
Alter. 1993. Risk factors for hepatitis C virus infection among
healthcare personnel in a community hospital. Am. J. Infect. Control
220. Popejoy, S. L., and D. E. Fry. 1991. Blood contact and exposure in
the operating room. Surg. Gynecol. Obstet. 172:480-483
221. Prentice, M. B. 1992. Infection with hepatitis B virus after open
heart surgery. Br. Med. J. 304:761-764
222. Prince, A. M. 1994. Challenges for development of hepatitis C virus
vaccines. FEMS Microbiol. Rev. 14:273-277
223. Puro, V., N. Petrosillo, and G. Ippolito. 1995. Risk of hepatitis C
seroconversion after occupational exposures in health care workers. Am.
J. Infect. Control 23:273-277
224. Quebbeman, E. J., G. L. Telford, S. Hubbard, K. Wadsworth, B.
Hardman, H. Goodman, and M. S. Gottlieb. 1991. Risk of blood
contamination and injury to operating room personnel. Ann. Surg.
225. Ranki, A., S. Mattinen, R. Yarchoan, S. Broder, J. Ghrayeb, J.
Lehdevirta, and K. Krohn. 1989. T-cell response towards HIV in infected
individuals with and without zidovudine therapy, and in HIV-exposed
sexual partners. AIDS 3:63-69
226. Ridzon, R., K. Gallagher, C. Ciesielski, M. B. Ginsberg, B. J.
Robertson, C.-C. Luo, and A. DeMana, Jr. 1997. Simultaneous transmission
of human immunodeficiency virus and hepatitis C virus from a
needle-stick injury. N. Engl. J. Med. 336:919-922
227. Robert, L. M., M. E. Chamberland, J. L. Cleveland, R. Marcus, B. F.
Gooch, P. U. Srivastava, D. H. Culver, H. W. Jaffe, D. W. Marianos, A.
L. Panlilio, and D. M. Bell. 1995. Investigations of patients of health
care workers infected with HIV: the Centers for Disease Control and
Prevention database. Ann. Intern. Med. 122:653-657
228. Rogers, A. S., J. W. Froggatt III, T. Townsend, T. Gordon, A. J. L.
Brown, E. C. Holmes, L. A. Zhang, and H. Moses, III. 1993. Investigation
of potential HIV transmission to the patients of an HIV-infected
surgeon. JAMA 269:1795-1801
229. Roth, W. K., J.-H. Lee, B. Ruster, and S. Zeuzem. 1996. Comparison
of two quantitative hepatitis C virus reverse transcriptase PCR assays.
J. Clin. Microbiol. 34:261-264[Abstract].
230. Ruprecht, R. M., L. G. O'Brien, L. D. Rossoni, and S.
Nusinoff-Lehrman. 1986. Suppression of mouse viraemia and retroviral
disease by 3'-azido-3'-deoxythymidine. Nature 323:467-469
231. Sanchez-Quijano, A., J. A. Pineda, E. Lissen, M. Leal, M. A.
Diaz-Torres, F. Garcia de Pesquera, F. Rivera, R. Castro, and J. Munoz.
1988. Prevention of post-transfusion non-A, non-B hepatitis by
non-specific immunoglobulin in heart surgery patients. Lancet
232. Satori, M., G. La Terra, M. Aglietta, A. Manzin, C. Navino, and G.
Verzetti. 1993. Transmission of hepatitis C via blood splash into
conjunctiva. Scand. J. Infect. Dis. 25:270-271
233. Sattar, S. A., and V. S. Springthorpe. 1991. Survival and
disinfectant inactivation of the human immunodeficiency virus. Rev.
Infect. Dis. 13:430-447
234. Schlipkoter, U., M. Roggendorf, K. Cholmakow, A. Weise, and F.
Deinhardt. 1990. Transmission of hepatitis C virus (HCV) from a
haemodialysis patient to a medical staff member. Scand. J. Infect. Dis.
235. Reference deleted.
236. Schneiderman, L. J., and R. M. Kaplan. 1992. Fear of dying and HIV
infection vs hepatitis B infection. Am. J. Infect. Control 82:584-586.
237. Reference deleted.
238. Seeff, L. B., H. J. Zimmerman, E. C. Wright, J. D. Finkelstein, P.
Garcia-Pont, H. B. Greenlee, A. A. Dietz, C. M. Leevy, C. H. Tamburro,
E. R. Schiff, R. Zemel, D. S. Zimmon, and R. W. McCollom. 1977. A
randomized, double blind controlled trial of the efficacy of immune
serum globulin for the prevention of post-transfusion hepatitis: a
Veterans Administration cooperative study. Gastroenterology 72:111-121
239. Segal, H. E., C. H. Llewellyn, G. Irwin, W. H. Bancroft, G. P. Boe,
and D. J. Balaban. 1976. Hepatitis B antigen and antibody in the US
Army: prevalence in health care personnel. Am. J. Public Health
240. Selgas, R., R. Martinez-Zapico, M. A. Bajo, J. R. Romero, J. Munoz,
C. Rinon, B. Miranda, and J. L. Miguel. 1992. Prevalence of hepatitis C
antibodies (HCV) in a dialysis population at one center. Perit. Dial.
241. Shapiro, C. N., J. I. Tokars, and M. E. Chamberland. 1996. Use of
the hepatitis B vaccine and infection with hepatitis B and C among
orthopaedic surgeons. J. Bone Joint Surg. 78:1791-1800
242. Shih, C.-C., H. Kaneshima, L. Rabin, R. Namikawa, P. Sager, J.
McGowan, and J. M. McCune. 1991. Postexposure prophylaxis with
zidovudine suppressed human immunodeficiency virus type 1 infection in
SCID-hu mice in a time-dependent manner. J. Infect. Dis. 163:625-627
243. Shikata, T., T. Karasawa, K. Abe, T. Uzawa, H. Suzuki, T. Oda, M.
Imai, M. Mayumi, and Y. Moritsugu. 1977. Hepatitis B antigen and
infectivity of hepatitis B virus. J. Infect. Dis. 136:571-576
244. Reference deleted.
245. Reference deleted.
246. Smith, J. L., J. E. Maynard, K. R. Berquist, I. L. Doto, H. M.
Webster, and M. J. Sheller. 1976. Comparative risk of hepatitis B among
physicians and dentists. J. Infect. Dis. 133:705-706
247. Sodeyama, T., K. Kiyosawa, and A. Urushihara. 1993. Detection of
hepatitis C virus markers and hepatitis C virus genomic-RNA after
needlestick accidents. Arch. Intern. Med. 153:1565-1572
248. Sperling, R. S., D. E. Shapiro, R. W. Coombs, J. A. Todd, S. A.
Herman, G. D. McSherry, M. J. O'Sullivan, R. B. VanDyke, E. Jiminez, C.
Rouzioux, P. M. Flynn, and J. L. Sullivan. 1996. Maternal viral load,
zidovudine treatment, and the risk of transmission of human
immunodeficiency virus type 1 from mother to infant. N. Engl. J. Med.
249. Struve, J., B. Aronsson, B. Frenning, M. Forsgren, and O. Weiland.
1994. Prevalence of antibodies against hepatitis C virus infection among
healthcare workers in Stockholm. Scand. J. Gastroenterol. 29:360-362
250. Sundkvist, T., G. R. Hamilton, D. Rimmer, B. G. Evans, and C. G.
Teo. 1998. Fatal outcome of transmission of hepatitis B from an e
antigen negative surgeon. Commun. Dis. Public Health 1:48-50.
251. Tavares, L., C. Roneker, K. Johnston, S. N. Lehrman, and F. de
Noronha. 1987. 3'-Azido-3'-deoxythymidine in feline leukemia
virus-infected cats: a model for therapy and prophylaxis of AIDS. Cancer
252. Terrell, F., and B. Williams. 1993. Implementation of a customized
needleless intravenous delivery system. J. Intraven. Nurs. 16:339-344
253. Thomas, D. L., S. E. Gruninger, C. Siew, E. D. Joy, and T. C.
Quinn. 1996. Occupational risk of hepatitis C infections among general
dentists and oral surgeons in North America. Am. J. Med. 100:41-45
254. Tokars, J. I., M. J. Alter, and M. S. Favero. 1995. National
surveillance of dialysis-associated diseases in the United States, 1993.
Centers for Disease Control and Prevention, Atlanta, Ga.
255. Tokars, J. I., M. J. Alter, M. S. Favero, L. A. Moyer, E. Miller,
and L. A. Bland. 1994. National surveillance of dialysis associated
diseases in the United States, 1992. ASAIO J. 40:1020-1031
256. Tokars, J. I., D. M. Bell, D. H. Culver, R. Marcus, M. H. Mendelson,
E. P. Sloan, B. F. Farber, D. Fligner, M. E. Chamberland, P. S. McKibben,
and W. J. Martone. 1992. Percutaneous injuries during surgical
procedures. JAMA 267:2899-2904
257. Reference deleted.
258. Tokars, J. I., M. E. Chamberland, C. A. Schable, D. H. Culver, M.
Jones, P. S. McKibben, D. M. Bell, and the American Academy of
Orthopaedic Surgeons Serosurvey Study Committee. 1992. A survey of
occupational blood contact and HIV infection among orthopedic surgeons.
259. Tokars, J. I., D. H. Culver, M. H. Mendelson, E. P. Sloan, B. F.
Farber, D. J. Fligner, M. E. Chamberland, R. Marcus, P. S. McKibben, and
D. M. Bell. 1995. Skin and mucous membrane contacts with blood during
surgical procedures: risk and prevention. Infect. Control Hosp.
260. Tong, S., and C. Trepo. 1997. The HBe-minus mutants of hepatitis B
virus, p. 89-104. In T. J. Harrison, and A. J. Zuckerman (ed.), The
molecular medicine of viral hepatitis. John Wiley and Sons, Ltd.,
Chichester, United Kingdom.
261. Trepka, M. J., A. J. Davidson, and J. M. Douglas, Jr. 1996. Extent
of undiagnosed HIV infection in hospitalized patients: assessment by
linkage of seroprevalence and surveillance methods. Am. J. Prev. Med.
262. Tsai, C.-C., K. E. Follis, A. Sabo, T. W. Beck, R. F. Grant, N.
Bischofberger, R. E. Benveniste, and R. Black. 1995. Prevention of SIV
infection in macaques by (R)-9-(2-phosphonylmethoxyprophyl) adenosine.
263. Tsude, K., S. Fujiyama, S. Sato, S. Kawano, Y. Taura, K. Yoshida,
and T. Sato. 1992. Two cases of accidental transmission of hepatitis C
to medical staff. Hepatogastroenterology 39:73-75
264. Turner, S. B., L. M. Kunches, K. F. Gordon, P. H. Travers, and N.
E. Mueller. 1989. Occupational exposure to human immunodeficiency virus
(HIV) and hepatitis B virus (HBV) among embalmers: a pilot
seroprevalence study. Am. J. Public Health 79:1425-1426
265. Reference deleted.
266. U.S. Department of Labor Occupation Safety and Health
Administration. 1991. 29 CFR Part 1910.1030, Occupational exposure to
bloodborne pathogens: final rule. Fed. Regist. 56:64004-64182
266a. U.S. Food and Drug Administration. 1997. Protease inhibitors may
increase blood glucose in HIV patients. FDA Medical Bulletin 27 .
267. Van Bueren, J., R. A. Simpson, P. Jacobs, and B. D. Cookson. 1994.
Survival of human immunodeficiency virus in suspension and dried onto
surfaces. J. Clin. Microbiol. 32:571-574
268. Vaqlia, A., R. Nicolin, V. Puro, G. Ippolito, C. Bettini, and F. de
Lalla. 1990. Needlestick hepatitis C virus seroconversion in a surgeon.
269. Villarejos, V. M., K. A. Visona, and A. Guitierrez. 1974. Role of
saliva, urine and feces in the transmission of type B hepatitis. N.
Engl. J. Med. 291:1374-1378.
270. Vogel, W., I. Graziadei, F. Umlauft, C. Datz, F. Hackl, S. Allinger,
K. Grunewald, and J. Patsch. 1996. High-dose interferon-alpha2b
treatment prevents chronicity in acute hepatitis C: a pilot study. Dig.
Dis. Sci. 41(Suppl. 12):81S-85S
271. von Reyn, C. F., T. T. Gilbert, F. E. Shaw, K. C. Parsonnet, J. E.
Abramson, and M. G. Smith. 1993. Absence of HIV transmission from an
infected orthopedic surgeon: a 13-year look-back study. JAMA
272. Wainwright, R. B., B. J. McMahon, L. R. Bulkow, D. B. Hall, M. A.
Fitzgerald, A. P. Harpster, S. C. Hadler, A. P. Lanier, and W. L.
Heyward. 1989. Duration of immunogenicity and efficacy of hepatitis B
vaccine in a Yupik Eskimo population. JAMA 261:2362-2366
273. Reference deleted.
274. Reference deleted.
275. Welch, J., M. Webster, A. J. Tilzey, N. D. Noah, and J. E.
Banatvala. 1989. Hepatitis B infections after gynaecological surgery.
276. Werman, H. A., and R. Gwinn. 1997. Seroprevalence of hepatitis B
and hepatitis C among rural emergency medical care personnel. Am. J. Emerg.
277. Werner, B. G., and G. F. Grady. 1982. Accidental hepatitis B
surface antigen positive inoculations: use of e antigen to estimate
infectivity. Ann. Intern. Med. 97:367-369
278. West, D. J. 1984. The risk of hepatitis B infection among health
professionals in the United States: a review. Am. J. Med. Sci. 287:26-33
279. West, D. J., B. Watson, J. Lichtman, T. M. Hesley, and K. Hedberg.
1994. Persistence of immunologic memory for twelve years in children
given hepatitis B vaccine in infancy. Pediatr. Infect. Dis. J.
280. Whittle, H. C., N. Maine, J. Pilkington, M. Mendy, M. Fortuin, J.
Bunn, L. Allison, C. Howard, and A. Hall. 1995. Long-term efficacy of
continuing hepatitis B vaccination in infancy in two Gambian villages.
281. Willy, M. E., G. L. Dhillon, N. L. Loewen, R. A. Wesley, and D. K.
Henderson. 1990. Adverse exposures and universal precautions practices
among a group of highly exposed health professionals. Infect. Control
Hosp. Epidemiol. 11:351-356
282. Wong, E. S., J. L. Stotka, V. M. Chinchilli, D. S. Williams, C. G.
Stuart, and S. M. Markowitz. 1991. Are universal precautions effective
in reducing the number of occupational exposures among health care
workers? A prospective study of physicians on a medical service. JAMA
283. Younossi, Z., and J. McHutchison. 1996. Serologic tests for HCV
infection. Viral Hepatitis Rev. 2:161-173.
284. Zuckerman, J., G. Clewley, P. Griffiths, and A. Cockcroft. 1994.
Prevalence of hepatitis C antibodies in clinical health-care workers.