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20 Viral Infections
Jennifer W.
Janelle, M.D.
Clinical Professor of Medicine, Division of Infectious Diseases,
Department of Medicine
University of Florida College of Medicine
Richard J.
Howard, M.D., Ph.D., F.A.C.S.
Robert H. and Kathleen M. Axline Professor of Surgery, Division
of General Surgery and Transplantation, Department of Surgery
University of Florida College of Medicine
Approach to
Viral Exposure
Compared with primary care physicians, such as internists,
family physicians, and pediatricians, surgeons are seldom called
on to treat viral infections. Viral infections nonetheless
deserve the attention of surgeons because these infections can
cause illness in patients after operation, albeit infrequently,
and can spread to the hospital staff. Some viral infections
(e.g., infections with the hepatitis viruses, HIV, and
cytomegalovirus [CMV]) can result from administration of blood
or blood products or can be transmitted to hospital personnel
through needle-stick injury. Viral infections can also result
from organ transplantation or trauma (e.g., rabies, which is
transmitted by the bite of an infected animal). Some viruses,
especially the herpesviruses, frequently infect immunosuppressed
patients, in whom the viruses can cause severe illness and even
death. In many surgical practices, there are increasing numbers
of immunosuppressed patients, including organ transplant
recipients; patients with cancer; patients receiving cancer
chemotherapy, steroids, and other immunosuppressive drugs; the
elderly; and the malnourished. Some viral infections can cause
neoplastic disease for which operation may become necessary.
Examples are hepatitis B virus (HBV) and hepatitis C virus (HCV),
which are implicated in the etiology of hepatocellular
carcinoma; Epstein-Barr virus (EBV), which can cause a lethal
lymphoproliferative disorder in immunosuppressed patients; and
human T cell lymphotropic virus type I (HTLV-I), which can
induce a T cell leukemia. Viral infections very likely can cause
other neoplasms as well.
Prevention of
Transmission of HIV, Hepatitis B Virus, and Hepatitis C Virus
Transmission from Patients to Health Care Workers
The Centers for Disease Control and Prevention (CDC) has
published extensive recommendations for preventing transmission
of HIV, the etiologic agent of AIDS.15 Applicable to
clinical and laboratory staffs,3,4 to workers in
health care settings [see Table 1]1
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Table
1 - Precautions to Prevent Transmission of HIV1
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Universal Precautions
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1.
All health care workers should use
appropriate barrier precautions routinely to
prevent skin and mucous membrane exposure when
contact with blood or other body fluids of any
patient is anticipated. Gloves should be worn
for touching blood and body fluids, mucous
membranes, or nonintact skin of all patients;
for handling items or surfaces soiled with blood
or body fluids; and for performing venipuncture
and other vascular-access procedures. Gloves
should be changed after contact with each
patient. During procedures that are likely to
generate aerosolized droplets of blood or other
body fluids, masks and protective eyewear or
face shields should be worn to prevent exposure
of mucous membranes of the mouth, nose, and
eyes. Gowns or aprons should be worn during
procedures that are likely to generate splashes
of blood or other body fluids.
2.
Hands and other skin surfaces should be
washed immediately and thoroughly if
contaminated with blood or other body fluids.
Hands should be washed immediately after gloves
are removed.
3.
All health care workers should take
precautions to prevent injuries caused by
needles, scalpels, and other sharp instruments
or devices during procedures; when cleaning used
instruments; during disposal of used needles;
and when handling sharp instruments after
procedures. To prevent needle-stick injuries,
needles should not be recapped, purposely bent
or broken by hand, removed from disposable
syringes, or otherwise manipulated by hand.
After they are used, disposable syringes and
needles, scalpel blades, and other sharp items
should be placed in puncture-resistant
containers for disposal; the puncture-resistant
containers should be located as close as
practical to the area of use. Large-bore
reusable needles should be placed in a
puncture-resistant container for transport to
the reprocessing area.
4.
Although saliva has not been implicated
in HIV transmission, to minimize the need for
emergency mouth-to-mouth resuscitation,
mouthpieces, resuscitation bags, or other
ventilation devices should be available for use
in areas in which the need for resuscitation is
predictable.
5.
Health care workers who have exudative
lesions or weeping dermatitis should refrain
from all direct patient care and from handling
patient care equipment until the condition
resolves.
6.
Pregnant health care workers are not
known to be at greater risk for contracting HIV
infection than health care workers who are not
pregnant; however, if a health care worker
acquires HIV infection during pregnancy, the
infant is at risk for infection resulting from
perinatal transmission. Because of this risk,
pregnant health care workers should be
especially familiar with and strictly adhere to
precautions to minimize the risk of HIV
transmission.
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Additional Precautions
for Invasive Procedures
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1.
All health care workers who participate
in invasive procedures must use appropriate
barrier precautions routinely to prevent skin
and mucous membrane contact with blood and other
body fluids of all patients. Gloves and surgical
masks must be worn for all invasive procedures.
Protective eye-wear or face shields should be
worn for procedures that commonly result in the
generation of aerosolized droplets, splashing of
blood or other body fluids, or the generation of
bone chips. Gowns or aprons made of materials
that provide an effective barrier should be worn
during invasive procedures that are likely to
result in the splashing of blood or other body
fluids. All health care workers who perform or
assist in vaginal or cesarean deliveries should
wear gloves and gowns when handling the placenta
or the infant until blood and amniotic fluid
have been removed from the infant's skin and
should wear gloves during postdelivery care of
the umbilical cord.
2.
If a glove is torn or a needle-stick or
other injury occurs, the glove should be removed
and a new glove used as promptly as patient
safety permits; the needle or instrument
involved in the incident should also be removed
from the sterile field. In the event of an
injury, postexposure evaluation should be sought
as soon as possible.
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and in other occupational settings,1 and to
health care workers performing invasive procedures,15
these precautions are appropriate for preventing transmission
not only of HIV but also of other blood-borne viruses, including
HBV and HCV. The recommendations share the objective of
minimizing exposure of personnel to blood and body secretions
from infected patients, whether through needle-stick injury or
through contamination of mucous membranes or open cuts.
Despite the apparently low risk of such exposure, the CDC
recommends enforcement of these as well as other standard
infection control precautions, regardless of whether health care
workers or patients are known to be infected with HIV or HBV.
The CDC has taken the position that blood and body fluid
precautions should be used consistently for all patients because
medical history and physical examination cannot reliably
identify all patients infected with HIV or other blood-borne
pathogens and because in emergencies there may be no time for
serologic testing. If these universal precautions are
implemented, as the CDC recommends,15 no additional
precautions should be necessary for patients known to be
infected with HIV.
The CDC does not recommend routine HIV serologic testing for
all patients.15 HIV serologic testing of patients is
recommended for management of health care workers who sustain
parenteral or mucous membrane exposure to blood or other body
fluids, for patient diagnosis and treatment, and for counseling
associated with efforts to prevent and control HIV transmission
in the community.15
Nevertheless, some hospitals and physicians are likely to
perform serologic testing of patients if it is possible that
health care workers will be exposed to the patients' blood or
other body fluids, as would be the case with patients undergoing
major operative procedures or receiving treatment in intensive
care units. Those who favor routine preoperative testing of
patients undergoing invasive procedures maintain that
precautions are more likely to be followed and additional steps
taken to lower the likelihood of virus transmission from
patients to health care workers when it is known which patients
are HIV positive.6,7 If such policies are adopted,
the CDC advocates certain principles: (1) obtain consent for
testing, (2) inform patients of results and provide counseling
to seropositive patients, (3) ensure confidentiality, (4) ensure
that seropositive patients will not receive compromised care,
and (5) prospectively evaluate the efficacy of the program in
reducing the incidence of exposure of health care workers to
blood or body fluids of patients who are infected with HIV.
Although possible acquisition of HIV infection is the major
concern for any health care worker who is exposed to blood
products in the workplace, acquisition of viral hepatitis is
actually much more likely. From a single needle-stick exposure,
the estimated average risk of HIV transmission is 0.3%, whereas
that of HCV transmission ranges from 0% to 10%.8 The
risk that HBV will be transmitted from a single needle-stick
exposure varies according to the hepatitis B e antigen (HBeAg)
status of the source patient, ranging from 1% to 6% for HBeAg-negative
patients to 22% to 40% for HBeAg-positive patients.911
That health care workers are at increased risk for hepatitis B
is indicated by the seroprevalence of HBV in this population,
which is two to four times that in the general United States
population (6% to 15% versus < 5%).9,12 This
seroprevalence is expected to decrease with the availability of
the hepatitis B vaccine and the mandate from the Occupational
Safety & Health Administration (OSHA) directing that all health
care workers potentially exposed to blood or other potentially
infectious material either be offered hepatitis B vaccine free
of charge, demonstrate immunity to hepatitis B, or formally
decline vaccination.13 That vaccination has been
effective in decreasing the incidence of hepatitis B in health
care workers is shown by the decrease in infection rates from
174/100,000 in 1982 to 17/100,000 in 1995.14 Most
series have not found the seroprevalence of HCV to be higher in
health care worker groups at risk than in the general
population.14 That hepatitis B and hepatitis C are
much more common than HIV in health care workers is a strong
argument for using universal precautions in all patients.
One reason why hepatitis B is so much more transmissible than
HIV is the greater number of virus particles in the blood of
hepatitis B carriers. These persons have blood concentrations of
108 to 109 virus particles/ml, compared
with 102 to 104/ml for persons with HIV
infection and 106/ml for persons with HCV infection.
The extensive guidelines that have been established by the
CDC for the care of patients with HBV infection4,1517
also apply to patients with HIV infection. Patients known to
have hepatitis B, hepatitis C, or AIDS need not be put in a
private room unless they are fecally incontinent or are shedding
virus in body fluids. Health care workers should wear gloves and
gowns when they have contact with or may have contact with a
patient's blood, feces, or other body fluids. Needles used for
drawing blood should be disposed of with special care: they must
not be reused, recapped, or removed from the syringe. Hands must
be washed before and after direct contact with the patient or
with items that have been in contact with the patient's blood,
feces, or body fluids.
Published recommendations also provide guidelines for health
care workers who are not directly involved in patient care
(e.g., housekeeping personnel, kitchen staff, and laundry
workers).17 No additional precautions are necessary
for these individuals because their risk of acquiring HIV, HCV,
or HBV is so low; in fact, transmission to them has not been
documented. However, staff should be educated about appropriate
procedures. Workers should wear gloves when handling blood and
body fluids of all patients and should wear masks in areas where
blood may spatter (e.g., the dialysis unit or the obstetrics
unit).
Transmission from Health Care Workers to Patients
To date, there have been only two reports of HIV transmission
from infected health care workers to patients. In one report,
DNA sequence analysis linked a Florida dentist with AIDS to HIV
infection in six of his patients.18 In the other, an
orthopedic surgeon in France may have transmitted HIV to one of
his patients in the course of an operation.19 Despite
extensive investigation, no break in infection control
precautions was documented in either case, nor was any clear-cut
means of transmission identified.
HBV transmission from health care workers to patients is
known to occur. Nineteen case reports have documented
physician-to-patient transmission.2032 Eighteen of
the 19 physicians were surgeons; seven of the surgeons were
gynecologists, three were cardiac surgeons, and one was an
orthopedic surgeon. All of the physicians were positive for
HBeAg. Three of the gynecologists made a practice of handling
needle tips. Of the 135 patients studied, 121 had clinical
hepatitis B, and 14 had only serologic evidence of infection.
Forty-one of the 135 patients were accounted for by the only
nonsurgeon, a family practitioner from rural Switzerland. There
are many additional cases of HBV having been transmitted by
dentists and oral surgeons. In addition, three patients'
relatives, two members of a surgeon's family, and one laboratory
technician became infected.
In five studies, patients of 16 health care workers
(including two surgeons) who were positive for hepatitis B
surface antigen (HBsAg) were prospectively followed for evidence
of hepatitis.3337 A total of 784 patients were
followed and were compared with 656 patients cared for by health
care workers who were HBsAg negative. None of the patients
acquired overt hepatitis or became seropositive for HBsAg. Eight
(1.02%) of the 784 patients cared for by HBsAg-positive health
care workers developed antibody to HBsAg (anti-HBs), but so did
six (0.91%) of the 656 patients cared for by health care workers
who were negative for HBsAg. These reports suggest that the
likelihood of infected surgeons' or other health care workers'
transmitting HIV or HBV to their patients is extremely low.
Chronic carriers of HBsAg who are seronegative for HBeAg are
much less likely to transmit HBV than persons who are HBeAg
positive.
Before the cases of transmission of HIV from the dentist to
six of his patients were reported, the CDC had not taken a
position on whether HBV- or HIV-infected surgeons should be
allowed to continue practicing medicine. After these cases were
reported, the CDC held meetings of health care professionals and
other interested parties and published its recommendations on
July 12, 1991.38 These recommendations called for
physicians not to perform 'exposure-prone invasive procedures'
unless they sought counsel from an expert review panel and were
advised under what circumstances, if any, they might be allowed
to continue to perform these procedures. Physicians would have
to notify prospective patients of their seropositivity. These
recommendations were strongly resisted by the medical community
because at that time, only one health care worker, the dentist,
had been implicated in transmitting HIV to his patients, no
mechanism of transmission had been elucidated, no other patients
had HIV transmitted by a health care worker, and invasive
procedures that were 'exposure prone' (exposing the patient to
blood of the health care worker) were impossible to define.
After subsequent meetings, the CDC abandoned its attempts to
define exposure-prone procedures but did not alter its
recommendations. Rather, it left it up to the states to define
exposure-prone procedures. Subsequently, the President's
Commission on AIDS recommended that HIV-infected health care
workers should not have to curtail their practices or inform
their patients of their infection.
Transmission of HCV from health care workers to patients has
been reported. In one such case, a cardiac surgeon transmitted
HCV to at least five patients during valve replacement surgery.39
In another, an anesthesiologist in Spain may have infected more
than 217 patients by first injecting himself with narcotics,
then giving the remainder of the drugs to his patients.40
At present, no recommendations exist for restricting the
professional activities of health care workers with HCV
infection.
Management of
Viral Exposure
HIV
The CDC has issued recommendations for the management of
potential exposure of health care workers to HIV.1,4,41
If a health care worker is exposed by a needle stick or by a
splash in the eye or mouth to any patient's blood or other body
fluids, and the HIV serostatus of the patient is unknown, the
patient should be informed of the incident and, if consent is
obtained, tested for serologic evidence of HIV infection. If
consent cannot be obtained, procedures for testing the patient
should be followed in accordance with state and local laws.
Testing of needles or other sharp instruments associated with
exposure to HIV is not recommended, because it is unclear
whether the test results would be reliable and how they should
be interpreted.41
Health care workers exposed to HIV should be evaluated for
susceptibility to blood-borne infection with baseline testing,
including testing for HIV antibody. If the patient who is the
source of exposure is seronegative and exhibits no clinical
evidence of AIDS or symptoms of HIV infection, further follow-up
of the health care worker is usually unnecessary.41
If the source patient is seropositive or is seronegative but has
engaged in high-risk behaviors, baseline and follow-up
HIV-antibody testing of the health care worker at 6 weeks, 3
months, and 6 months after exposure should be considered.41
Seroconversion usually occurs within 6 to 12 weeks of exposure;
infrequently, it occurs considerably later. Three cases of
delayed HIV seroconversion among health care workers have been
reported.4244 In all three patients, an HIV antibody
test yielded negative results at 6 months but positive results
at some point during the following 1 to 7 months. In two cases,
coinfection with HCV had occurred and took an unusually severe
course. At present, it is unclear whether coinfection with these
two viruses directly influences the timing or severity of either
infection, but most experts recommend close monitoring for up to
1 year for health care workers exposed to both viruses in whom
serologic evidence of HCV infection develops.
Treatment of the exposed health care worker should begin with
careful washing of the exposure site with soap and water. Mucous
membranes should be flushed with water. There is no evidence
that either expressing fluid by squeezing the wound or applying
antiseptics is beneficial, though antiseptics are not
contraindicated. The use of caustic agents (e.g., bleach) is not
recommended.
Any health care worker concerned about exposure to HIV should
receive follow-up counseling regarding the risk of HIV
transmission, postexposure testing, and medical evaluation,
regardless of whether postexposure prophylaxis is given. HIV
antibody testing should be performed at specified intervals for
at least 6 months after the exposure (e.g., at 6 weeks, 3
months, and 6 months). The risk of HIV transmission is believed
to depend on several factors: how much blood is involved in the
exposure, whether the blood came from a source patient with
terminal AIDS (thought to be attributable to the presence of
large quantities of HIV), whether any host factors are present
that might affect transmissibility (e.g., abnormal CD4 receptors
for HIV), and whether the source patient carries any aggressive
HIV viral mutants (e.g., syncytia-inducing strains). Factors
indicating exposure to a large quantity of the source patient's
blood (and thus a high risk of HIV transmission) include a
device visibly contaminated with the patient's blood, a
procedure that involved a needle placed directly in a vein or
artery, and a deep injury.45
During the follow-up period, especially the first 6 to 12
weeks, exposed health care workers should follow the U.S. Public
Health Service recommendations for preventing further
transmission of HIV.14 These recommendations include
refraining from blood, semen, or organ donation and either
abstaining from sexual intercourse or using measures to prevent
HIV transmission during intercourse.46
The circumstances of the exposure should be recorded in the
worker's confidential medical record and should include the
following:
1.
The date and time of the exposure.
2.
Details of the exposure, including (a) where and how the
exposure occurred, (b) the type and amount of fluid or other
material involved, and (c) the severity of the exposure (for a
percutaneous exposure, this would include the depth of injury
and whether fluid was injected; for a skin or mucous membrane
exposure, it would include the extent and duration of contact
and the condition of the skin-chapped, abraded, or intact).
3.
A description of the source of the exposure, including
(if known) whether the source material contained HIV or other
blood-borne pathogens, whether the source was HIV positive, the
stages of any diseases present, whether the patient had
previously received antiretroviral therapy, and the viral load.
4.
Details about counseling, postexposure management, and
follow-up.41
The data currently available on primary HIV infection
indicate that systemic infection does not occur immediately.
There may be a brief window of opportunity during which
postexposure antiretroviral therapy may modify viral
replication. Findings from animal and human studies provide
indirect evidence of the efficacy of antiretroviral drugs in
postexposure prophylaxis. The majority of these studies included
zidovudine (AZT); consequently, all postexposure prophylaxis
regimens now in use include AZT. Combination treatment regimens
using nucleoside reverse transcriptase inhibitors and protease
inhibitors have proved effective. Accordingly, most experts now
recommend dual therapy with two nucleosides (zidovudine and
lamivudine) for low- to moderate-risk exposures. For high-risk
exposures, most experts would add a protease inhibitor (usually
either indinavir or nelfinavir) to the two nucleoside reverse
transcriptase inhibitors. These medications should be started as
soon as possible after the exposure (within hours rather than
days) and should be continued for 4 weeks.
An important component of postexposure care is encouraging
and facilitating compliance with the lengthy course of
medication. Therefore, careful consideration must be given to
the toxicity profiles of the antiretroviral agents chosen. All
of these agents have been associated with side effects, include
GI (e.g., nausea or diarrhea), hematologic, endocrine (e.g.,
diabetes), and urologic effects (e.g., nephrolithiasis with
indinavir). According to some early data, 50% to 90% of health
care workers receiving combination regimens for postexposure
prophylaxis (e.g., zidovudine plus 3TC, with or without a
protease inhibitor) reported one or more subjective side effects
that were substantial enough to cause 24% to 36% of the workers
to discontinue postexposure prophylaxis.4749
Whether antiretroviral agents should be chosen for
postexposure prophylaxis on the basis of the resistance patterns
of the source patient's HIV remains unclear. Transmission of
resistant strains has been reported5052; however, in
the perinatal clinical trial that studied vertical transmission
of HIV, zidovudine prevented perinatal transmission despite
genotypic resistance of HIV to zidovudine in the mother.53
Further study of the significance of genotypic resistance is
necessary before definitive recommendations can be made.
Hepatitis
B
Both passive immunization with hepatitis B immune globulin (HBIG)
and active immunization with hepatitis B vaccine (HB vaccine)
are currently available for prophylaxis against hepatitis B [see
Table 2].
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Table
2 - Recommendations for Hepatitis B Prophylaxis after
Percutaneous or Permucosal Exposure15
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Hepatitis B Vaccination Status of Exposed
Person
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HBsAg Status of Source of Exposure
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HBsAg-Positive
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HBsAg-Negative
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Untested or Unknown
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Unvaccinated
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Give single dose of HBIG
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Initiate HB vaccine series
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Initiate HB vaccine series
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Initiate HB vaccine series
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Previously vaccinated
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Test exposed person for
anti-HBs
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Known responder
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If anti-HBs levels are
adequate,* no treatment is needed; if they are
inadequate, give an HB vaccine booster dose
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No treatment is needed
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No treatment is needed
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Known nonresponder
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No response to
three-dose vaccine series: give two doses of
HIBG or one dose of HBIG plus revaccination
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If source is at high risk
for hepatitis B infection, consider proceeding
as if source had been demonstrated to be
HBsAg-positive
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No response to
three-dose vaccine series plus revaccination:
give one dose of HBIG as soon as possible and a
second dose 1 mo later
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No treatment is needed
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Test exposed person for
anti-HBs
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Test exposed person for
anti-HBs
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Response unknown
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If anti-HBs levels are
adequate,* no treatment is needed; if they are
inadequate, give one dose of HBIG plus an HB
vaccine booster dose
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No treatment is needed
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If anti-HBs levels are
adequate,* no treatment is needed; if they are
inadequate, initiate revaccination
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* An adequate anti-HBs level is
³ 10 mlU/ml,
which is approximately equivalent to 10 sample ratio
units (SRU) on radioimmunoassay or a positive result on
enzyme immunoassay.
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Passive Immunoprophylaxis
HBIG is prepared by Cohn ethanol fractionation from plasma
selected to contain a high titer of anti-HBs; this process
inactivates and eliminates HIV from the final product. In the
United States, HBIG has an anti-HBs titer of at least 1:100,000
by radioimmunoassay.54 HBIG provides temporary,
passive protection. It is indicated after low-volume
percutaneous or mucous membrane exposure to HBV; it is not
effective for high-volume exposure (e.g., blood transfusion).
The recommended dose of HBIG for adults is 0.06 ml/kg I.M.
Passive prophylaxis with HBIG should begin as soon as possible
after exposure-ideally, within 24 hours.54
Active Immunoprophylaxis
Two types of HB vaccine are currently licensed in the United
States, plasma-derived vaccine (Heptavax-B) and recombinant
vaccine (Recombivax HB and Engerix-B). Heptavax-B contains
alum-adsorbed 22 nm HBsAg particles purified from human plasma
and processed to inactivate the infectivity of HBV and other
viruses. Plasma-derived vaccine is no longer being produced in
the United States, but similar vaccines are produced and used in
China and other countries. In the United States, use of
Heptavax-B is limited to persons allergic to yeast. Recombivax
HB and Engerix-B are prepared by recombinant DNA technology in
common baker's (or brewer's) yeast, Saccharomyces cerevisiae.
For primary vaccination, three I.M. injections (into the
deltoid muscle in adults and children and into the anterolateral
thigh muscle in infants and neonates) are given, with the second
and third doses 1 and 6 months after the first dose.54
The dose for Heptavax-B and Engerix-B is 20 ΅g (volume, 1.0 ml)
for persons older than 11 years, and that for Recombivax HB is
10 ΅g (1.0 ml) for persons older than 19 years and 5 ΅g (0.5 ml)
for persons 11 to 18 years of age. For immunologically impaired
patients, including hemodialysis patients, the dose is 40 ΅g for
all three vaccines. For postexposure prophylaxis with Engerix-B,
a regimen of four doses given soon after exposure and 1, 2, and
12 months afterward has been approved.
HB vaccine is more than 90% effective at preventing infection
or clinical hepatitis in susceptible persons. Protection is
virtually complete in persons who develop adequate antibody.
Routine testing for immunity after vaccination is not
recommended, but testing should be considered for persons at
occupational risk who require postexposure prophylaxis for
needle-stick exposure.
Between 30% and 50% of persons who have been vaccinated will
cease to have detectable antibody levels within 7 years, but
protection against infection and clinical disease appears to
persist.54,55 The need for booster doses has not been
established. Revaccination of individuals who do not respond to
the primary series will produce adequate antibody in 15% to 25%
of cases after one additional dose and in 30% to 50% after three
additional doses.56
Although effective HB vaccines have been available since
1982, the incidence of hepatitis B in the United States
continued to increase in the first decade of HB vaccine use. In
1991, the Advisory Committee for Immunization Practices (ACIP),
citing the safety of the vaccine and the evidence of continuing
spread of HBV, recommended universal vaccination of all infants
born in the United States.57
Recommendations for Exposure to
Blood That Contains (or May Contain) HBsAg
Acute exposure The U.S. Public Health Service has
provided recommendations for hepatitis B prophylaxis after
accidental percutaneous, mucous membrane, or ocular exposure to
blood that contains (or may contain) HBsAg [see Table 2].43
These recommendations are based on consideration of several
factors: (1) whether the source of the blood is available, (2)
the HBsAg status of the source, and (3) the hepatitis B
vaccination and vaccination-response status of the exposed
person. After exposure, a blood sample should be obtained from
the person who was the source of the exposure and should be
tested for HBsAg. The hepatitis B vaccination status and the
anti-HBs response status (if known) of the exposed person should
be reviewed. Because passive administration of antibody with
HBIG does not inhibit the active antibody response to HB
vaccine, the two can be given simultaneously
Chronic exposure The U.S. Public Health Service
recommends that persons who are at risk for exposure to HBV
receive the HB vaccine series [see Table 3].54
Health care workers who are at increased risk for acquiring
hepatitis B include all physicians (especially surgeons),
dentists, and laboratory and support personnel, such as nurses
and technicians who work in the operating room or who have
contact with infected patients, blood or blood products, or
excreta. Because of their frequent exposure to blood and their
high risk of hepatitis B, all surgeons should receive HB
vaccine. As of 1994, however, only 50% of surgeons had been
vaccinated, despite the proven efficacy and safety of the
vaccine and surgeons' increased risk of exposure.58
Hospital personnel who do not have frequent contact with blood
or blood products (e.g., the janitorial, laundry, and kitchen
staffs) need not be vaccinated.
Screening of personnel and patients for anti-HBs before
vaccination is indicated only for individuals in high-risk
groups; it has not been found to be cost-effective outside these
groups.
Hepatitis
C
The only tests currently approved by the U.S. Food and Drug
Administration for diagnosis of hepatitis C are those that
measure antibody to HCV. These tests detect anti-HCV in at least
97% of infected patients, but they cannot distinguish between
acute, chronic, and resolved infection.59 The
positive predictive value of enzyme immunoassay (EIA) for
anti-HCV varies depending on the prevalence of the infection in
the population. Therefore, supplemental testing of a specimen
with a positive EIA result with a more specific assay (e.g., the
recombinant immunoblot assay [RIBA]) may detect false positives,
especially when asymptomatic persons are being tested.
Qualitative polymerase chain reaction (PCR) testing for HCV RNA
can also be used to identify HCV. This test can detect HCV at
concentrations as low as 100 to 1,000 viral genome copies/ml,
and it can detect HCV RNA in serum or plasma within 1 to 2 weeks
after viral exposure and weeks before alanine aminotransferase
(ALT) levels rise or anti-HCV appears.59 Under
optimal conditions, the reverse transcriptase PCR assay for HCV
can identify 75% to 85% of persons who are anti-HCV-positive and
more than 95% of persons with acute or chronic hepatitis C.59
Quantitative assays for measuring HCV RNA are also available but
are less sensitive and should not be used as primary tests for
confirming or excluding the diagnosis of HCV infection or
monitoring the end point of treatment. 59 The data
currently available on prevention of HCV infection with immune
globulin (IG) indicate that this approach is not effective as
postexposure prophylaxis for HCV infection.59
Interferon may have a role in the treatment of acute hepatitis
C: several studies have shown that interferon may delay or
prevent the onset of chronic hepatitis C in patients treated
early in the course of acute HCV infection.6062
Rabies
The CDC has made recommendations for the prevention of rabies
in people bitten by animals [see Table 4].63
Bite wounds should always be thoroughly scrubbed with soap and
water. Postexposure antirabies treatment includes both rabies
immune globulin (RIG) and human diploid cell (rabies) vaccine
(HDCV). The decision to administer such treatment should be
based on the following considerations.
Species and Availability of
Biting Animal
In the United States, rabies is most commonly transmitted by
skunks, raccoons, foxes, and bats. Livestock occasionally
transmit the virus, but rodents and lagomorphs (i.e., rabbits
and hares) are rarely infected.64 In different parts
of the country, different animals predominate in the
transmission of the virus. The likelihood that domestic cats or
dogs in the United States will be infected varies from region to
region. The chances of rabies transmission by a domestic animal
that has been properly immunized are minimal.
Whether an animal is available for observation after biting
someone also influences the need for antirabies prophylaxis. In
certain cases, an animal that bites a person must be killed and
tissue from its brain checked for the presence of rabies by
fluorescent antibody tests as soon as possible [see Table 4].
Table 4
|
Table
4 - Rabies Postexposure Prophylaxis63
|
Animal Species
|
Condition of Animal at Time of Attack
|
Treatment of Exposed Person*
|
|
|
|
Healthy and available for
10 days of observation
|
None, unless animal
develops rabies
|
|
Domestic
|
Dog, cat
|
Rabid or suspected rabid
|
RIG (20 IU/kg)
and HDCV§ (five 1.0 ml doses
intramuscularly, on days 0, 3, 7, 14, and 28)
|
|
|
|
Unknown (escaped)
|
Consult public health
officials. If treatment is indicated, give RIG
and HDCV
|
|
Wild
|
Skunk, bat, fox, coyote,
bobcat, raccoon, other carnivores
|
Regard as rabid unless
proved negative by laboratory tests||
|
RIG (20 IU/kg)
and HDCV (five 1.0 ml doses intramuscularly, on
days 0, 3, 7, 14, and 28)
|
|
Other
|
Livestock, rodents,
lagomorphs (rabbits and hares)
|
Consider individually.
Local and state public health officials should
be consulted on questions about the need for
rabies prophylaxis. Bites of squirrels,
hamsters, guinea pigs, chipmunks, gerbils, rats,
mice, other rodents, and lagomorphs almost never
call for antirabies prophylaxis.
|
*All bites and wounds should immediately be
thoroughly cleansed with soap and water. If antirabies
treatment is indicated, both rabies immune globulin
(RIG) and human diploid cell rabies vaccine (HDCV)
should be given as soon as possible, regardless of the
interval from exposure. (The administration of RIG is
the more urgent procedure. If HDCV is not immediately
available, start RIG and give HDCV as soon as it is
obtained.) Local reactions to vaccines are common and do
not contraindicate continuing treatment. Discontinue
vaccine if fluorescent antibody tests of the animal are
negative.
During the usual holding period of 10
days, begin treatment with RIG and HDCV at first sign of
rabies in a dog or cat that has bitten someone. The
symptomatic animal should be killed immediately and
tested.
The full dose should be infiltrated
around the wounds; any remaining RIG should be given
I.M. at a site distant from that of vaccine
administration. If RIG is not available, use antirabies
serum, equine (ARS). Do not use more than the
recommended dosage of RIG or ARS.
§HDCV should be administered into the
deltoid (not the gluteus) muscle in adults and
adolescents. In children, it may be administered into
the upper thigh.
||The animal should be killed and tested
as soon as possible. Holding for observation is not
recommended.
|
Type of Exposure
Infected animals transmit rabies primarily by biting,
although licking may introduce the virus into open cuts in skin
or mucous membranes. Transmission occasionally occurs as a
result of aerosol exposure: the virus may be excreted in the
urine and feces of infected bats, aerosolized during urination
and defecation, and then inhaled, for example, by spelunkers
exploring caves.
Circumstances of the Bite
An unprovoked attack is more indicative of a rabid animal
than is a provoked attack.
If the animal shows signs of rabies or the patient has been
bitten by a wild animal that is not captured, the patient should
be treated as soon as possible with both RIG and HDCV. The
recommended dose of RIG for postexposure prophylaxis is 20
IU/kg.63 If anatomically feasible, the entire dose of
RIG should be infiltrated into the area around the wound.65,66
Postexposure HDCV should be given I.M. in five 1.0 ml doses on
days 0, 3, 7, 14, and 28.63 Those with adequate
preexposure immunization should receive two 1.0 ml doses of HDCV
I.M. on days 0 and 3 but should receive no RIG. For adults, the
vaccine should be administered in the deltoid area. For
children, the anterolateral aspect of the thigh is also
acceptable. The gluteal area should never be used for HDCV
injections, because administration in this area results in lower
neutralizing antibody titers.63 HDCV must not be
given in the same region as RIG.
The CDC recommends that preexposure immunization be
considered for high-risk groups, such as animal handlers,
certain laboratory workers and field personnel, and persons
planning to stay for more than 1 month in areas where canine
rabies is highly prevalent and access to appropriate medical
care is limited. The recommended preexposure regimen is 0.1 ml
of HDCV on days 0, 7, and 21 or 28.67 Testing for
adequate antibody response is not necessary for persons at low
risk for exposure, but administration of booster doses every 2
to 3 years is recommended for those at high risk for exposure.
Postexposure treatment for persons who have received preexposure
immunization consists of 1 ml HDCV on days 0 and 3 only, without
RIG.68
Although only a few cases of clinical rabies occur each year
in the United States, approximately 30,000 persons a year are
given postexposure prophylaxis. In 1992, 49 states, the District
of Columbia, and Puerto Rico collectively reported 8,644 cases
of animal rabies and one case of human rabies to the CDC.69
The total expense associated with one rabid dog in California
was $105,790, even though no human contracted rabies.70
This amount represents the costs of human antirabies treatment,
vaccination of other animals, and animal-containment programs.
Discussion
Size and
Structure of Viruses
Viruses are among the smallest and simplest of
microorganisms. Human viruses can be as small as 18 to 26 nm in
diameter (parvoviruses) or as long as 300 nm (vaccinia virus),
slightly longer than Chlamydia (a bacterium). Viruses do
not have the complex enzyme systems required for synthesis of
nucleic acid precursors, they lack ribosomes for protein
synthesis, and they have no energy-generating mechanism.
Consequently, they cannot replicate outside cells.
Figure 1a - Cytomegalovirus
Figure 1b - Typical Herpesvirus
A typical herpesvirus consists of a central
core containing DNA; an icosahedral capsid, a surrounding layer
of protein made up of 162 individual capsomers; and an envelope,
a membrane coat acquired when the virus buds from the nuclear
membrane of the host cell.
The core of a virus is made of either RNA or DNA, but never
both. The nucleic acid can be either single stranded or double
stranded. This nucleic acid core is surrounded by the capsid,
which is a protein coat made up of capsomers, repetitive
subunits consisting of one protein or at most a few. Because the
viral nucleic acid must code for coat proteins, a limitation in
the number of capsid proteins conserves viral nucleic acid. The
capsid protects the nucleic acid from nucleases in the
environment, serves as its vehicle of transmission from one host
to another, and plays a role in the attachment of the virus to
the receptor sites on susceptible cells. The complete nucleic
acid-protein coat complex is termed the nucleocapsid. For many
viruses, the nucleocapsid is the complete virus particle, the
virion. Other viruses, such as herpesviruses, may acquire an
envelope, an additional lipid-containing membrane coat around
the nucleocapsid, by budding through a membrane of the host cell
[see Figures 1a and 1b]. Some viruses may also have an
enzyme associated with their core that replicates the nucleic
acid. Examples are the DNA polymerase of the HBV and the reverse
transcriptase of retroviruses.
Classification of Viruses
Viruses, like other organisms, are classified into families,
genera, and species, but most viral species do not have formal
names and in practice are referred to by common names (e.g.,
cytomegalovirus, coxsackievirus, Norwalk virus, and
varicella-zoster virus). Viruses can also be classified by
chemical characteristics and by structural characteristics
determined from electron microscopy (e.g., dimensions and site
of assembly). Viruses are categorized into two broad groups
depending on whether their nucleic acid is RNA or DNA. These two
groups can be subdivided first according to whether the nucleic
acid is single stranded or double stranded and then according to
the presence or absence of an envelope. Single-stranded RNA
viruses that replicate by means of a DNA step (i.e.,
retroviruses) are grouped separately from those that do not.
Identification of Viruses
Viruses can be identified by means of (1) serologic tests,
(2) isolation of virus, (3) histologic examination, (4)
detection of viral antigens, (5) detection of viral nucleic
acid, and (6) electron microscopy. One or more of these
techniques may be applicable to a given viral infection.
Specimens must be handled properly to maximize the likelihood
of identifying the virus. If isolation of the virus is desired,
blood and tissue samples should be taken promptly to the
virology laboratory and inoculated onto the appropriate cell
line. Samples obtained at night or on weekends can be placed in
a balanced salt solution or tissue culture medium and kept in a
refrigerator until taken to the laboratory. If microscopic
identification of the virus is planned, specimens must be
preserved appropriately. Routine preservation in formalin, for
example, permits visualization of viral inclusions by routine
staining and light microscopy. For identification of viral
antigens by immunofluorescence techniques, the tissue specimen
should be immediately frozen, preferably in liquid nitrogen.
Specimens to be examined by electron microscopy must be placed
in glutaraldehyde or another appropriate fixative.
Serologic
Tests
The antibody response to viral antigens can be detected in
the serum of patients with viral infections. An IgM response
usually indicates recent exposure to the virus, whereas the
presence of IgG reflects past exposure.
For most acute primary infections, serum obtained during late
recovery or after recovery (convalescent serum) has an increased
antibody titer, compared with serum obtained early in the course
of the disease (acute serum). Most tests are performed on an
initial serum dilution of 1:2 or 1:10 and on serial twofold
dilutions thereafter. A fourfold increase in titer (indicated by
reactivity of a two-tube dilution) usually represents a
significant increase in antibody response and is considered to
constitute seroconversion. An immunocompromised host may
occasionally fail to mount an antibody response.
Some viruses are so common that patients may already have
antibody titers when the disease is first suspected.
Herpesviruses are ubiquitous and are present in many healthy
people in latent form. At the onset of herpesvirus infections,
patients may already have the corresponding antibody.
Nevertheless, their antibody titer will almost always increase
significantly after recovery.
A variety of serologic tests are available in the clinical
laboratory: complement fixation, radioimmunoassay, enzyme-linked
immunosorbent assay (ELISA), immunofluorescence, immune
precipitation, immune blotting, latex agglutination, virus
neutralization, indirect hemagglutination, immune adherence
hemagglutination, and hemagglutination inhibition. None of these
serologic tests is appropriate for identification of all
viruses.
Isolation
of Virus
The isolation of virus requires appropriate specimen
collection and inoculation into animals or onto appropriate cell
lines. Blood sent for virus isolation should be unclotted
because some viruses, such as herpesviruses, are found primarily
in lymphocytes. If cell-associated viruses are suspected,
lymphocytes should be inoculated directly onto target cells.
Several types of cells are available for growing viruses, and no
single cell line is appropriate for all of them. Therefore, it
is helpful to the laboratory to know which virus the clinician
suspects.
Figure 2 - Cells Infected with
Cytomegalovirus
Cells infected with cytomegalovirus become
large and round (arrows). Note the uniform appearance of
adjacent uninfected cells.
Viruses that grow in cell monolayers in tissue culture have
cytopathic effects that can be recognized under the microscope
(e.g., rounding, transformation, or death) [see Figure 2].
Some viruses, such as rubella, produce no direct cytopathic
effects but can be detected because they inhibit the cytopathic
effects of a second test virus. This phenomenon is called viral
interference. Other viruses (e.g., myxoviruses) cause changes in
the cell membrane so that red blood cells adhere to the cell
surface (hemadsorption). The identity of isolated viruses can be
confirmed by use of specific antisera that are known to inhibit
viral growth.
Tissue suspected of containing an encephalitis or other
neurotropic virus can be minced and the extract injected
intracerebrally into an infant mouse. If the mouse dies and
bacteria cannot be cultured from the brain, the injected
material presumably contained such a virus. If antiserum of
known specificity neutralizes the virus, the specificity of the
antiserum indicates the specific identity of the virus. The
criterion for neutralization is that inoculation of neutralized
virus will not kill the mouse.
Histologic
Examination
Figure 3 - Kidney Biopsy inCytomegalovirus
Infection
Kidney biopsy shows
cytomegalovirus-infected tubular epithelial cells (arrows). In
such cells, a dark intranuclear inclusion is surrounded by a
clear halo. Inclusions usually indicate sites of previous or
current viral replication.
Histologic examination of biopsy and autopsy tissues may
demonstrate changes that are typical of certain viruses. Members
of the herpesvirus group can be characterized by intranuclear
inclusions surrounded by a clear halo [see Figure 3]. RNA
viruses usually produce inclusions in the cytoplasm; for
instance, dark-staining intracytoplasmic inclusions in the brain
tissue of animals or patients are diagnostic of rabies infection
and are called Negri bodies. Inclusion bodies are either masses
of closely packed virus particles or remnants of prior virus
replication.
Detection
of Viral Antigens
Viral antigens can be detected in tissues by techniques
employing their corresponding antibodies. If virus is present,
these antigens may be visible microscopically under ultraviolet
light either by direct immunofluorescence (i.e., in tissue
sections stained with fluorescein-labeled antiviral antibody) or
by indirect immunofluorescence (i.e., in tissue sections exposed
first to antiviral antibody and then to fluorescein-labeled
anti-g-globulin
antibody). Fluorescence microscopy requires specimens that are
fresh frozen (preferably in liquid nitrogen). Immunofluorescence
staining of cells in tissue culture can detect viral antigens
before cytopathic effects are evident. Viral antigens in
formalin-fixed tissue can be identified by immunohistochemical
microscopy (e.g., using peroxidase-labeled antibodies).
Detection
of Viral Nucleic Acid
Viral nucleic acids can be detected in body fluids and
tissues at virus concentrations too low to be detected by other
means. The PCR permits amplification of even a small number of
copies of viral nucleic acid. In theory, even a single copy of a
specific DNA can be detected by PCR. Before PCR is performed,
DNA can be synthesized from viral RNA by means of reverse
transcriptase. The PCR product can be detected by gel
electrophoresis and compared with known viral DNA. This test is
currently being used to diagnose CMV infection and is more
sensitive than current serologic testing for HCV. Nucleic acid
hybridization can detect viral nucleic acid in tissue specimens.
Epstein-Barr virus genomes can be detected in this way in
EBV-related cancers and lymphoproliferative disorders.
Electron
Microscopy
Although seldom used routinely, electron microscopy allows
rapid identification (in a matter of hours) of viruses in body
fluids, tissues, and tissue extracts. Identification of viruses
in body fluids and tissue extracts by this method is easier if
the samples are first concentrated by ultracentrifugation,
evaporation, or ultrafiltration. HBV has been observed in
specimens from hepatitis patients only after
ultracentrifugation.
Epidemiology
of Viral Infections of Interest to Surgeons
Viral infections are spread to humans via several patterns of
transmission: (1) direct transmission from humans with
symptomatic infection (e.g., HBV, HCV herpesviruses, and HIV),
(2) transmission from asymptomatic human carriers (e.g., HBV,
HCV, HIV, and varicella-zoster virus), (3) transmission from
arthropods (e.g., encephalitis and dengue viruses), and (4)
transmission from other animals (e.g., rabies virus).
Viral infections are common in immunosuppressed patients in
general and especially in recipients of organ transplants, who
must take immunosuppressive drugs to prevent rejection. The
overwhelming majority of these infections are caused by members
of the herpesvirus family (e.g., CMV, herpes simplex viruses,
varicella-zoster virus, and EBV); infections with HBV and with
papovaviruses (e.g., human papillomavirus, which causes warts,
and BK virus) are also frequent.
Because surgical patients are frequently given transfusions
of blood or blood products and because hospital staff often
incur accidental needle-stick injury, viruses that can be
transmitted by these routes are of prime interest to surgeons
and their patients. Examples of such viruses are HBV, hepatitis
D, HCV, HIV, HTLV-I, and the herpesviruses, including EBV and
CMV. These viruses can also be transmitted by organ
transplantation either from the cells of the organ itself (e.g.,
HBV in liver cells or CMV in kidney cells) or from blood that
has not been completely removed from the organ. Changes in donor
acceptance and screening policies over time have increased the
safety of the blood supply and should continue to do so in the
future [see Table 5].71
HIV
Two serotypes of HIV, HIV-1 and HIV-2, have been identified.
Both can cause AIDS. HIV-1 accounts for virtually all cases of
AIDS in the United States and equatorial Africa. HIV-2 is found
almost exclusively in West Africa; only a few cases of HIV-2
infection have occurred in the United States.
Because AIDS patients are immunodepressed, they are
sus-ceptible to opportunistic infections and neoplasms,
especially non-Hodgkin lymphoma, Pneumocystis carinii
pneumonia, and Kaposi sarcoma. AIDS is most prevalent in the
United States among male homosexuals, abusers of I.V. drugs, and
hemophiliacs. Since the implementation of testing for
blood-borne HIV and the near-elimination of HIV from blood
products, the incidence of HIV infection in the hemophiliac
population has diminished markedly; however, in recent years,
the incidence in the heterosexual population has been increasing
rapidly.
HIV can be transmitted by transfusion of whole blood, packed
red cells, plasma, factor VIII concentrates, factor IX
concentrates, and platelets. The likelihood that a person will
become infected with HIV after receiving a single-donor blood
product that tests positive for HIV approaches 100%.7273
Before the advent of serologic testing for HIV in 1985, 0.04% of
1,200,000 blood donations in the United States were estimated to
be HIV positive.74 AIDS has developed in more than
8,500 recipients of blood transfusions, blood components, or
transplanted organs or tissue.
Federal regulations now require that all prospective blood
and plasma donors be screened for antibody to HIV by ELISA.
Because this test yields a low rate of false positive results,
assay by the more sensitive Western blot electrophoresis is
always used to confirm positive ELISA results. Routine testing
of blood donors has greatly reduced HIV transmission via blood
transfusions, but infection can still occur if the donor has
been infected with HIV but has not yet developed antibody.75
The risk of HIV transmission via transfusion of screened blood
that is negative for HIV is estimated to be one in 200,000 to
one in 2,000,000 per unit transfused in the United States.76
Antibody to HIV usually develops within 4 weeks to 6 months of
HIV infection.77 From the time of infection until the
appearance of antibody, infected individuals will test negative
by ELISA or Western blot, and their blood might still be used
for transfusion.
HIV and AIDS can also be transmitted by organ
transplantation.78 So far, only a small number of
patients have been found to be infected in this way, but more
will undoubtedly be reported. These patients received
transplants before HIV testing of potential donors became
possible. All prospective organ and tissue donors now should be
tested for HIV infection and other blood-borne viral infections.
HIV infection is also a potential problem in health care
workers, who are exposed to a large and growing population of
AIDS patients. In the United States, an estimated 1.0 to 1.5
million people are infected with HIV but as yet have no
symptoms. HIV transmission from blood, tissue, or other body
fluids can occur in the health care setting as a result of
percutaneous injury (e.g., from needles or other sharp objects),
contamination of mucous membranes or nonintact skin (e.g., skin
that is chapped, abraded, or affected by dermatitis), prolonged
contact with intact skin, or contamination involving an
extensive area.79 HIV infection may be contracted
through a variety of sources including blood, semen, vaginal
secretions, visibly bloody fluids, and a number of other fluids
for which the precise risk of transmission is undetermined
(e.g., cerebrospinal, synovial, pleural, peritoneal,
pericardial, and amniotic fluid). Infection may also be
contracted from concentrated HIV used in research settings.79
The results of multiple prospective studies quantifying
transmission risk associated with a discrete occupational HIV
exposure indicate that the average risk of HIV transmission
associated with needle punctures or similar percutaneous
injuries is approximately 0.3%. The estimated risk of
transmission from mucocutaneous exposure to HIV-contaminated
material is 0.03%. As of December 1999, the CDC had received
reports of 56 U.S. health care workers in whom documented HIV
seroconversion was temporally related to occupational HIV
exposure. Of these 56, 48 had percutaneous exposures, five
mucocutaneous exposures, two both percutaneous and mucous
membrane exposures, and one an unknown route of exposure.80
Another 138 possible cases of occupational HIV transmission-six
involving surgeons-have been reported in persons with no risk
factors for HIV transmission other than workplace exposure;
however, seroconversion after a specific exposure was not
documented. There may be other health care workers who also have
acquired HIV infection from needle-stick or mucous membrane
exposure but have not been reported, either because they and
their patients have not been tested or because they have other
risk factors for HIV infection
The concentration of virus in the blood or serum of
antigen-positive individuals is several orders of magnitude less
for HIV than for HBV. The number of needle-stick exposures to
HIV that have actually led to a positive test result for HIV has
been extremely small, whereas hepatitis B occurs in as many as
40% of health care workers exposed to the virus by needle-stick
injury. Despite this relatively low infectiousness, AIDS is much
more feared than hepatitis B because AIDS is often fatal.
Although hepatitis B is usually not fatal and is often of short
duration, several health care workers die of hospital-acquired
hepatitis B and hepatitis C each year.
Hepatitis
Several viruses can cause hepatitis. Hepatitis A virus (HAV)
and HBV cause what were formerly known as infectious hepatitis
and serum hepatitis, respectively. HCV is the major cause of
parenterally transmitted non-A, non-B hepatitis. Hepatitis E
virus is a common cause of epidemic non-A, non-B hepatitis,
which is chiefly found in developing countries in Africa and
Asia. Hepatitis D virus (HDV, formerly called the delta agent)
is defective or incomplete and is pathogenic only in the
presence of HBV. The hepatitis viruses are the most common
infectious agents to which hospital personnel may be exposed.
Herpesviruses can also cause serious and sometimes fatal
hepatitis, especially in severely immunocompromised patients,
such as recipients of organ or bone marrow transplants and
patients receiving intensive chemoth |
