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U.S. Department of Labor |
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Regulations (Preambles to Final Rules) |
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• Record Type: |
Occupational Exposure to Bloodborne Pathogens |
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• Section: |
4 |
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• Title: |
IV. Health Effects |
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A. Introduction. Certain
pathogenic microorganisms can be found in the blood of infected individuals. For
the purposes of this standard, OSHA is referring to these microorganisms as
"bloodborne pathogens" and to the diseases that they cause as
"bloodborne diseases." These bloodborne pathogens may be
transmitted from the infected individual to other individuals by blood or
certain other body fluids, for example, when blood-contaminated needles are
shared by intravenous drug users. Because it is the exposure to blood or
other body fluids that carries the risk of infection, individuals whose occupational
duties place them at risk of exposure to blood or other potentially
infectious materials are also at risk of becoming infected with these
bloodborne pathogens, developing disease and, in some cases, dying. Infected
individuals are also capable of transmitting the pathogens to others. A
discussion of two of the most significant bloodborne pathogens, hepatitis B
virus, and human immunodeficiency virus, follows. This includes a discussion
of each of the viruses, the disease each causes, modes of transmission, and
documented risk of infection resulting from occupational exposure. In
addition, a discussion of other bloodborne diseases, hepatitis C, delta
hepatitis, syphilis, and malaria, is included. B. Hepatitis Viruses Hepatitis
means "inflammation of the liver," and can be caused by a number of
agents or conditions including drugs, toxins, autoimmune disease, and
infectious agents including viruses. The most common causes of hepatitis are
viruses. There are four types of viral hepatitis which are important in the
U.S. (Exs. 6-449; 6-430; 6-199). Hepatitis A, formerly called
"infectious" hepatitis, is spread by fecal contamination and is not
generally considered to be a significant risk to healthcare workers, although
episodes of transmission to healthcare workers in hospitals have been
reported (Exs. 6-449; 6-456; 6-449; 6-456). Hepatitis B, formerly called
"serum" hepatitis, is a major risk to healthcare workers and is
extensively discussed in this document. Delta hepatitis may coinfect with
hepatitis B or may infect persons already infected with HBV and can increase
the severity of acute and chronic liver disease in these individuals (Ex.
6-470). Nosocomial infection with this virus has been reported (Ex. 234
Lettau, et. al., 1986). Non-A, non-B hepatitis is caused by viral agents
other than hepatitis A and hepatitis B. Two that have been identified are
hepatitis E, previously known as enterically transmitted (ET) non-A, non-B
hepatitis and hepatitis C, previously known as parenterally transmitted (PT)
non-A, non-B hepatitis. Hepatitis E transmitted by the fecal-oral route and
has occurred both in epidemic and sporadic forms in parts of Asia, North and
West Africa and Mexico. It is not known whether the virus is present in the
United States or Western Europe. Parenterally transmitted non-A, non-B
hepatitis is caused by at least one bloodborne virus, designated hepatitis C
virus (HCV). This virus is efficiently transmitted by blood transfusion and
by needle sharing among IV drug users (Exs. 6-430; 6-449; 6-286G) As there
are reports of occasional transmission of HCV to healthcare workers, this
virus is discussed further in this document (Exs. 6-39; 6-455; 286G). (1) Hepatitis B Hepatitis
B virus (HBV) infection is the major infectious bloodborne occupational
hazard to healthcare workers. The Hepatitis Branch of the Centers for Disease
Control (CDC) estimates that there are approximately 8,700 infections in
healthcare workers with occupational exposure to blood and other potentially
infectious materials in the United States each year (Ex. 298). These
infections cause over 2,100 cases of clinical acute hepatitis, 400-440
hospitalizations and approximately 200 deaths each year in healthcare
workers. Death may result from both acute and chronic hepatitis. Infected
healthcare workers can spread the infection to family members or rarely, to
their patients. [For detailed discussion, see Section V, Quantitative Risk
Assessment.] The use of hepatitis B vaccine, engineering and work practice
controls, and personal protective equipment will prevent almost all of these
occupational hepatitis B infections. Efforts to reduce blood exposure and
minimize puncture injuries in the workplace setting will reduce the risk of
transmission of all bloodborne hepatitis viruses. HBV: Biology Hepatitis
B is caused by the hepatitis B virus (HBV) that attacks and replicates in
liver cells (Exs. 6-430; 6-449). The virus has an inner core and an outer
shell structure. The inner core contains DNA, enzymes, and various proteins,
including the hepatitis B core antigen (HBcAg) and hepatitis B e antigen
(HBeAg). The outer shell is composed of a lipoprotein called hepatitis B
surface antigen (HbsAg), formerly called the Australia Antigen. The HbsAg is
produced in great excess by liver cells replicating the virus, and is found
in the form of small spheres and larger tubular particles in the blood of
infected persons. The plasma derived hepatitis B vaccines are composed of a
highly purified preparation of these excess HBsAg particles which are immunogenic
but not infectious. There is a readily available laboratory test for HBsAg,
and its presence in blood indicates than an individual is currently infected
with the HBV, and is potentially infectious to others. Highly infectious HBV
carriers and persons with acute Hepatitis B are also HBeAg-positive. TABLE IV-1. Hepatitis nomenclature (Ex. 286G p.6,7) ___________________________________________________________________ Abbreviation Term Definition/Comments___________________________________________________________________ HBV Hepatitis B Etiologic agent of "serum" virus hepatitis also known as Dane particle. HBsAg Hepatitis B Surface antigen(s) of HBV surface detectable in a large quantity antigen in serum; several subtypes identified. HBeAg Hepatitis Be Soluble antigen of HBV; correlates antigen with HBV replication, high titer HBV in serum, and infectivity of serum. HBcAg Hepatitis B No commercial test available. Core antigen Anti-HBs Antibody to Indicates past infection with HBsAg and immunity to HBV, passive antibody from HBIG, or immune response from HB vaccine. Anti-HBe Antibody to Presence in serum of HBsAg HBeAg carrier indicates lower titer of HBV. Anti-HBc Antibody to Indicates prior infection with HBcAg HBV at some undefined time. IgM anti-HBc IgM class Indicates recent infection antibody to with HBV; detectable for 4-6 HBcAg months after infection. IG Immune Contains antibodies to HBV globulin lower-titer antibodies to (previously HBV. ISG, immune serum globulin, or gamma globulin)HBIG Hepatitis B Contains high-titer anti- immune bodies to HBV. globulin________________________________________________________________________
HBV: Disease Outcomes Infection
with the hepatitis B virus in a susceptible person can produce two types of
outcomes: self-limited acute hepatitis B and chronic HBV infection (Exs.
6-430; 6-449). Similarly, the human body can mount two types of response to
HBV infection. The most frequent response seen in healthy adults is
development of self-limited acute hepatitis and the production of an antibody
against HBsAg, called anti-HBs. The production of this antibody coincides
with the destruction of liver cells containing the virus, elimination of the
virus from the body, and signifies lifetime immunity against reinfection. Persons
having this response also develop an antibody against the core protein,
called anti-HBc, and usually maintain both anti-HBc and anti-HBs in their
blood for life. Unfortunately,
the destruction of liver cells in an attempt to rid the body of this
infection often leads to clinically apparent acute hepatitis B. About one
third of infected individuals have no symptoms when infected with the virus,
one third have a relatively mild clinical course of a flu-like illness which
is usually not diagnosed as hepatitis, and one third have a much more severe
clinical course with jaundice (yellowing of the eyes and skin), dark urine,
extreme fatigue, anorexia, nausea, abdominal pain, and sometimes joint pain,
rash, and fever. These symptoms require hospitalization in about 20% of
jaundiced cases, and often cause several weeks to months of work loss even in
those cases that do not require hospitalization. Fulminant hepatitis, which
is about 85% fatal with even the most advanced medical care, develops in
about 1-2% of reported acute hepatitis B cases, and an estimated 1 per 1000
HBV infections (Ex. 6-217). The
second type of response - development of chronic HBV infection - has more
severe long term consequences (Exs. 6-430; 6-449). About 6% to 10% of
newly-infected adults cannot clear the virus from their liver cells and
become chronic HBV carriers. These individuals continue to produce HBsAg for
many years, usually for life. They do not develop anti-HBs, but do produce
anti-HBc antibody. HBV carriers are at high risk of developing chronic
persistent hepatitis, chronic active hepatitis, cirrhosis of the liver, and
primary liver cancer. About 25% of carriers develop chronic persistent
hepatitis, a relatively mild, non-progressive form of chronic liver disease,
and 25% develop chronic active hepatitis. The latter is a progressive,
debilitating disease that often leads to cirrhosis of the liver after 5-10
years (Exs. 5-5; 6-448). Patients with end-stage cirrhosis may develop
ascites (fluid accumulation in the abdomen), esophageal bleeding from
distended veins (causing patients to vomit large volumes of blood), coma, and
death. Chronic HBV infection has been estimated to cause 10% of the
25,000-30,000 deaths that occur due to cirrhosis in the U.S. each year (Ex.
6-199). The
DNA of HBV in chronic carriers can integrate into the DNA of the host liver
cell. This integration may lead to malignant transformation of the liver
cell, and development of primary hepatocellular carcinoma (PHC) (Exs. 6-419;
6-443). PHC is almost uniformly fatal if diagnosed after symptoms appear. Patients
with PHC usually die within four to six months after diagnosis. PHC usually
develops in HBV carriers after a latency period of 20 to 60 years. In parts
of the world where HBV infection is a common childhood infection, PHC is one
of the leading causes of cancer death. In Taiwan, for example, Beasley and
colleagues have found that 5 per 1000 adult male HBV carriers develop PHC
each year, and estimate that approximately 25% of all HBV carriers, and 40%
of male HBV carriers, will die from either PHC or cirrhosis (Ex. 6-419). The
relative risk of developing PHC in an HBV carrier compared to a non-carrier
in his studies is 100. Studies in the United States and in Great Britain,
where HBV infection usually occurs in adulthood, have shown 13 to 40 fold
increased risk of developing PHC among HBV carriers (Exs. 6-640; 6-444). This
may be compared to the relative risk of lung cancer in smokers vs.
non-smokers of 10-20. Studies in many other populations worldwide have
confirmed this extremely high relative risk. The
causal link between HBV carriage and PHC is not only based on epidemiologic
studies, but is confirmed by both animal and molecular biological studies
(Exs. 6-449; 6-443). Other animal species can become infected with HBV-like
viruses (which belong to the same virus family - Hepadna viruses), and
woodchucks, Pekin ducks, ground squirrels, and other species that become
infected may develop a carrier state. These carrier animals develop primary
liver cancers at very high rates. Molecular biological studies have shown
that PHC tumor cells contain integrated HBV DNA in virtually all humans and
animals cases of PHC (Ex. 6-443). There
is likely a higher risk of developing PHC if infection occurs from perinatal
(mother to child) transmission, or from infection during childhood than from
infection in adulthood. Although persons who develop HBV carriage during
adulthood are at increased risk of developing PHC, the exact risk of
developing PHC following adult infection has not been established. The risk
observed in blood donors in the United States is probably an underestimate,
as PHC is most likely in persons with chronic liver disease or cirrhosis and
who are excluded from such studies because they cannot be blood donors. In
addition, many carriers will die of other causes before they develop PHC
because of the long latency of this cancer. Nevertheless, it has been
estimated that, in the U.S., about 25%-33% of all PHC cases, or 750-1000 PHC
cases annually, result from HBV infection. HBV: Modes of Transmission Workplace:
HBV is spread via several routes: parenteral (by direct inoculation through
the skin), mucous membranes (blood contamination of the eye or mouth),
sexual, and perinatal (from infected mother to newborn infant) (Exs. 6-430;
6-449). The most efficient mode of transmission is direct inoculation of
infectious blood, such as might occur during blood transfusion, needle
sharing by IV drug users, or needlestick or other sharp instrument injury in health care workers>>. One milliliter of HBsAg positive
blood may contain 100 million infectious doses of virus; thus, exposure to
extremely small inocula of HBV-positive blood may transmit infection. In
different studies, 7% to 30% of susceptible healthcare workers sustaining
needlestick puncture injuries from HBsAg positive patients became infected if
they did not receive post-exposure prophylaxis (Exs. 4-27; 4-28). Since 1972,
all units of blood collected for transfusion in the U.S. have been screened
for HBsAg, greatly decreasing the incidence of transfusion related HBV
infection. Blood
and blood-derived body fluids (serous exudates and fluids from internal body
cavities) contain the highest quantities of virus and are the most likely
vehicles for HBV transmission (Exs. 6-430; 6-449). Certain other body fluids
such as saliva and semen contain infectious virus but at 1000-fold lower
concentration (Ex. 6-445). Other body fluids such as urine or feces contain
only small quantities of virus unless they are visibly contaminated with
blood. Direct
inoculation of infectious blood may occur in less apparent ways. Preexisting
lesions on hands from injuries incurred at the workplace or at home or from
dermatitis may provide a route of entry for the virus (Ex. 6-427). In
addition, transfer of contaminated blood via inanimate objects or
environmental surfaces has been shown to cause infection in the healthcare
workplace (Exs. 6-464; 6-433; 4-461.) In general, fewer than 20% of infected
healthcare workers report discrete needlestick injuries from a known infected
patient. The importance of this finding should not be underestimated. Although
gloving will not stop direct puncture injuries, it can provide a barrier
between blood and an open lesion. Infectious
sera placed in both the eye and mouth of experimental animals has induced HBV
infection (Exs. 6-430; 6-449). Splashes of blood or serum into the
individual's eye or mouth in clinical settings or in the laboratory must be
regarded as potentially serious exposures. While there has been concern about
the potential infectivity of aerosols generated by dental, medical, and
laboratory equipment, and although HBsAg may be found in large particles of
"spatter" that travel short distances, OSHA is not aware of any
data that link HBV transmission with aerosols through inhalation. Transmission
in Other Settings: Sexual transmission of HBV infection is an efficient mode
of viral spread as HBsAg has been found in both semen and vaginal secretions
(Exs. 6-430; 6-445). Deposition of virus onto mucous membranes and trauma to
tissue causing small lesions may both play roles in transmission. Approximately
30% of spouses or regular sexual partners of acutely infected HB patients
become infected. Spouses of chronic carriers, who have a much longer duration
of infectivity, escape infection less frequently. Preventing transmission of
HBV infection to the spouse/sexual partners of infected healthcare workers is
an additional benefit derived from and reason for controlling this disease
(Ex. 6-425). Non-sexual
family contacts of HBV carriers are also at risk of infection. Although the
relative importance of various transmission modes has not been determined in
families, in various studies about 40-60% of household contacts of carriers
identified by blood donation had markers of HBV infection (Exs. 6-420;
6-430). Daily exposure to the carrier for many years presents occasions for
sharing razors or toothbrushes, exposure to blood and other events that could
result in infection. Family contacts of adopted carrier children have been
shown to have a higher prevalence of infection than families who do not live
with a carrier. Perinatal
infection with the HBV is an efficient mode of transmission with particularly
severe consequences. Mothers positive for both HBeAg and HBsAg will infect
70% to 90% of their newborns, most of whom will become chronic HBV carriers
(Exs. 6-419; 6-199). These carriers have a 25% chance of dying from cirrhosis
or PHC. They also remain infectious to others and can perpetuate the cycle of
perinatal transmission. Fortunately, treatment of newborns at birth with
hepatitis B immune globulin (HBIG) and hepatitis B vaccine is 85% to 95%
effective in preventing these infants from becoming carriers (Exs. 6-419;
6-199). To be able to treat these infants at birth, their mothers must be
recognized as carriers before delivery. The Immunization Practices Advisory
Committee (ACIP) of the U.S. Public Health Service has recommended that all
pregnant women in the U.S. be screened for HBsAg during an early prenatal
visit (Ex. 6-424). Because pregnant healthcare workers may, if infected,
transmit HBV to their newborn infants, prevention of HBV infection is
critical in women of child bearing years who work in occupations where they
are at risk for exposure. HBV: Epidemiology HBV
infection does not occur uniformly in the U.S. population. There is a
substantial difference in the reported numbers of hepatitis B cases by
geographical region. The presence of certain populations with a high
percentage of individuals who are carriers may result in higher prevalence
rates for certain defined areas, such as parts of Alaska and the U.S. Trust
Territories. HBV infection is more prevalent in certain ethnic and racial
groups, and is especially prevalent in certain "high risk" groups
defined by occupation and lifestyle (Exs. 6-430; 6-449; 6-199). The
prevalence of HBV antibodies in the general population, reflecting the
percentage of the population ever infected, is 3% to 4% for whites and 13% to
14% for blacks (Ex. 6-390). Foreign born Asians have a prevalence of antibody
of greater than 50%. The HBsAg prevalence, reflecting the percentage of the
population who are HBV carriers, is 0.2% for whites, 0.7% for blacks, and up
to 13% for foreign born Asians. The high prevalence in the last group is a
reflection of the fact that most HBV infections in Asia occur in childhood. The
ACIP has listed a number of groups who are at substantial risk for HBV
infection and should receive the hepatitis B vaccine (Ex. 286G). Healthcare
workers and public safety workers, who have contact with blood or certain
body fluids, and staff of institutions for the developmentally disabled are
included on this list. Transmission
to Healthcare Workers: Although outbreaks of clinical hepatitis have been
reported for many years (Exs. 6-438; 6-459), it was not until the 1970's that
the risk to healthcare workers from HBV infection was well defined. The first
studies noted that dentists were more likely than attorneys to have had
clinical hepatitis (Ex. 6-441). When HBsAg and antibody testing became
available, it was possible to show that the type of hepatitis that occurred
more commonly in healthcare workers was hepatitis B. Dentists and physicians
were 4 to 10 times more likely to have serologic markers indicating previous
HBV infection than first time blood donors, and the prevalence of markers
increased significantly with years in practice (Exs. 6-440; 6-65; 4-13; 4-16;
4-12; 4-15; 6-68). During
the next decade, dozens of studies were published measuring the prevalence of
HBV markers in various healthcare occupational groups, and in various
healthcare settings (Exs. 6-427; 6-88; 6-72; 6-54; 6-53; 6-44; 640; 4-14). The
prevalence of markers was studied in hospitals of all sizes and types, in
various sized communities, serving all types of populations. Studies were
also done on a wide variety of individual occupational groups at meetings and
through special studies. Most of the studies relied upon the voluntary
cooperation of the study population, so there is some chance for bias to be
introduced into any estimate of HBV prevalence. Healthcare workers who know
they are infected with HBV at the time of study or who know they are HBV
carriers may decline to participate in a study which they may feel could
jeopardize their careers. This would lead to an underestimate of the
prevalence of HBV infection among <<health care workers>>.
The most useful studies showed that risk of HBV infection in hospital
personnel was increased several-fold over that in blood donors, that risk was
closely related to frequency of contact with blood and not related to contact
with patients per se, and that risk was directly related to duration in the
occupation (Exs. 6-440; 6-65; 4-12; 4-13; 4-15; 4-16). Certain studies
attempted to quantify the frequency of blood and needle exposure in various
categories of healthcare workers, and relate this to risk of infection (Ex.
4-16). The following general observations can be made from these studies: (1)
These studies revealed that workers exposed to blood on the job had a
prevalence of HBV markers several times that of non-exposed workers and the
general population. The prevalence of markers increased with years on the
job. (2)
The prevalence of HBV markers was related to the degree of blood exposure or
frequency of needle exposure, and not to patient contact per se. Persons
working in operating rooms, emergency rooms, labs, and dialysis units had a
higher marker prevalence than persons working on medical or pediatric wards,
who in turn had a higher prevalence than clerical workers, social workers,
and administrators. (3)
Groups at high risk include (but are not limited to): medical technologists,
operating room staff, phlebotomists and intravenous therapy nurses, surgeons and
pathologists, oncology and dialysis unit staff, emergency room staff, nursing
personnel, staff physicians, dental professionals, laboratory and blood bank
technicians, emergency medical technicians, and morticians (Ex. 6-199). Most
infected healthcare workers are unaware that they have been exposed to or
infected with HBV. Approximately 1% (or more) of hospitalized patients are
HBV carriers; most HBV carrier patients seen in the healthcare setting are
not symptomatic, are unaware that they are carriers, and their medical charts
do not contain this information (Ex. 6-427). <<Health care
workers>> may take extraordinary precautions when dealing with a
known carrier, but are often unaware that they may treat five carriers for
each one they recognize. This is a key point in understanding the rationale
for the concept of "universal precautions", and for use of the
hepatitis B vaccine in workers with exposure to blood. Although the risk of
encountering HBV carriers may vary in the hospital setting, being highest in
inner city referral hospitals dealing with high risk groups such as drug
abusers and homosexual men, risk will be present in any work setting where
human blood is encountered. The risk of HBV carriage in the general
population is uniform (i.e. does not markedly vary within each region of this
country), and high risk groups such as Southeast Asian refugees, the
developmentally disabled individuals, and occult drug abusers may be found in
rural as well as urban settings (Ex. 6-390). Percutaneous
exposure to blood through needlesticks and cuts with other sharp instruments
are visible and efficient modes of transmission, but reported injuries do not
account for the majority of infections in healthcare workers (Exs. 6-65;
6-427). This fact often goes unrecognized by worker's compensation boards,
which sometimes deny coverage to infected workers unless they had reported a
discrete needlestick or similar injury from a HBsAg positive patient. Some
workers doing traumatic procedures get cuts, needlesticks or large blood
exposures so frequently that they do not bother to report them; other workers
become infected when the blood of an unsuspected HBV carrier gets into a
small preexisting skin lesion or is rubbed into the eye. Prevention of these
occupational infections is the goal of this standard. Transmission
from HCWs to Patients: Transmission of HBV from healthcare workers to
patients is an uncommon but extremely serious consequence of healthcare
worker infection. More than twenty clusters of patients infected in this way
have been reported, although instances involving only one or a few patients
may go unrecognized or unreported (Exs. 6-103; 6-446; 6-476; 4-471; 6-144). Most
clusters of these cases have involved oral surgeons, dentists, gynecologists,
or surgeons, occupations where significant blood exposure, trauma, and use of
sharp instruments occur routinely. Some episodes have involved transmission
to between 20 and 55 patients, with deaths and secondary transmission to
family members of patients occurring (Exs. 6-103; 6-144). Most
healthcare workers who have transmitted to patients have several factors in
common (Exs. 6-476; 6-471): (1)
The dentists and surgeons were chronic HBV carriers, had high titers of virus
in their blood (HBeAg positive), and were unaware that they were infected. (2)
Transmission occurred most frequently during the most traumatic procedures. (3)
The dental personnel who transmitted did not routinely wear gloves. However,
some infected HCWs continued to transmit HBV to patients in spite of the use
of gloves and additional precautions. (4)
The dentists and surgeons often had a personal medical problem (such as
exudative dermatitis on the hands), or used techniques that made transmission
more likely. Several of the gynecologists used their index fingers to feel
for the tip of the suture needle when they were performing deep abdominal
surgery. The
most recent guidelines for HIV and HBV infected healthcare workers were
published after the record for this rulemaking closed and are not contained
in the record. These guidelines, "Recommendations for Preventing
Transmission of Human Immunodeficiency Virus and Hepatitis B Virus to
Patients During Exposure-Prone Invasive Procedures," were published in
Morbidity and Mortality Weekly Report, Vol. 40, on July 12, 1991. Transmission
Via the Environment: Transmission of HBV infection from exposure to
contaminated environmental surfaces has been documented to be a mode of HBV
spread in certain settings, particularly hemodialysis units (Exs. 6-56;
6-446; 6-480; 6-461). The virus can survive for at least one week dried at
room temperature on environmental surfaces, and medical procedures as well as
disinfection and sterilization techniques must be adequate to prevent the
spread of this virus (Exs. 6-422; 6-458). HBV contaminated blood from the
surface of dialysis machines and carried on the hands of medical personnel to
patients has been postulated as one mechanism of transmission in dialysis
units. Unsterilized or improperly sterilized acupuncture needles have been
implicated as the cause of two outbreaks of HBV infection in patients (Ex.
6-439). Potential problems of environmental contamination in the dental
operatory have been discussed in the CDC guidelines for dentistry (Ex.
6-490). HBV
is thought to be far less resistant to sterilization and disinfection
procedures than microbial endospores or mycobacteria used as reference
criteria (Ex. 6-421). Any sterilization or disinfection procedure or sterilizing
agent or high level disinfectant will kill the virus if used as directed. Diluted
solutions (1:10-1:100) of sodium hypochlorite (household bleach) are
particularly effective, if used properly, and inexpensive, although they may
be corrosive or damaging to certain materials. Certain low-level
"germicides" such as quaternary ammonium compounds are not
considered to be effective against the virus (Ex. 6-422). Unfortunately,
soaking medical and dental instruments in these solutions is a common and potentially
dangerous procedure, since health workers may handle the sharp instruments
soaked in these solutions with a false sense of security. Hepatitis B Vaccine In
1982 a safe, immunogenic and effective hepatitis B vaccine derived from human
plasma was licensed in the U.S. and was recommended for use in healthcare
workers with blood or needle exposure in the workplace (Ex. 6-199). A second
vaccine, produced in yeast by recombinant technology was first licensed in
1987 (CDC, Ex. 6-200). Since the introduction of these vaccines, OSHA
estimates a minimum of 2,568,974 persons in the United States have been
vaccinated, 2,029,189 of whom are healthcare workers. HB vaccination is the
most important part of any HBV control program, because gloving and other
protective devices cannot completely prevent puncture injuries from needles
and other sharp instruments. Early
efforts to immunize healthcare workers were hindered by fear that the plasma
derived vaccine might be unsafe. The AIDS epidemic was just being recognized,
and there was concern that the plasma derived hepatitis B vaccine might
contain the infectious agent causing AIDS. Concerns about the safety of the
plasma derived vaccine have been adequately studied and addressed (CDC, Ex.
6-199). The procedures used to manufacture the vaccine were shown to
inactivate HIV virus and representatives of all known viral groups. The
vaccine was shown not to contain HIV DNA, and those receiving vaccine do not
develop anti-HIV antibodies. This vaccine is no longer available in the U.S.
The yeast-derived vaccines contain no human plasma and there is no
possibility that they could be infectious for HIV (6-200). The
currently licensed hepatitis B vaccines are given intramuscularly in the deltoid,
in three doses over a six month period. These vaccines, when given according
to manufacturers directions, induce protective antibody levels in 85% to 97%
of healthy adults. Protection against both the illness and the development of
the carrier state lasts at least nine years (the duration of follow-up
studies) and perhaps considerably longer. Although antibody in many
individuals will decay below detectable levels within seven years after
immunization, if these individuals are exposed to HBV, they develop a rapid
(anamnestic) antibody response and do not become ill or develop the HBV
carrier state (Exs. 6-200; 6-435). For persons with normal immune status, the
ACIP has not recommended that a booster dose of hepatitis B vaccine be given
after the initial series but may do so in the future if it appears that
immunity conferred by the vaccine wanes after some period of time. However,
vaccine-induced protection is less complete for hemodialysis patients and may
last only as long as antibody levels remain above 10 mIU/ml. For these
individuals, the need for booster doses should be assessed by annual antibody
testing. Booster doses should be given when antibody levels fall below 10
mIU/ml (Ex. 286G). Persons
planning hepatitis B vaccine programs may consider the need for
pre-vaccination and post-vaccination testing for antibody (Exs. 6-200;
6-199). Prescreening may be cost-effective, depending on the likelihood of
prior HBV infection. An algorithm to help assist with this determination has
been published by the ACIP (Ex. 6-199). Discussions on the issues surrounding
the option of post-vaccination testing have also been published. At this time
post-vaccination testing is not considered necessary unless poor response to
vaccine is anticipated (such as for those who have received vaccine in the
buttock, persons > 50 years of age and persons known to have HIV
infection), subsequent patient management depends on knowing the immune
status (such as with dialysis patients and staff) or there may be a need to
know whether the person ever responded to vaccine for management of
post-exposure prophylaxis (Ex. 286G). Post-exposure prophylaxis Percutaneous
and mucous membrane exposures to blood occur and will continue to occur in
the healthcare setting (Exs. 6-431; 6-468). HBV infection is the major
infectious risk that occurs from these exposures, and needlesticks from HBsAg
positive individuals will infect 7% to 30% of susceptible healthcare workers
(Exs. 6-27; 4-28). Pre-exposure vaccination is the most effective method for
preventing such infection. However, it can be expected that some individuals,
who initially decline vaccination, will experience an exposure incident. Fortunately,
effective post-exposure prophylaxis exists for HBV exposures if appropriate
protocols are followed. The February 9, 1990 recommendations of the
Immunization Practices Advisory Committee specify that if the source
individual is known to be HBsAg-positive then the exposed individual should
be given hepatitis B immunoglobulin (HBIG) and the hepatitis B vaccine series
be initiated (286G). Hepatitis B vaccine is recommended for any previously
unvaccinated healthcare worker who has a needlestick or other percutaneous
accident with a sharp instrument or permucosal (ocular or mucous membrane)
exposure to blood (Ex. 286G, p. 19). (2) Non-A, non-B hepatitis Non-A,
non-B hepatitis in the United States is caused by more than one viral agent. (Exs.
6-437; 6-429; 6-449). Studies have shown that parenterally transmitted (PT)
non-A, non-B hepatitis accounts for 20-40% of acute viral hepatitis in the
U.S. and has epidemiologic characteristics similar to those of hepatitis B
(Ex. 6-39). Recently, a virus designated as Hepatitis C virus (HCV) was
cloned and has been shown to account for a large proportion of parenterally
transmitted non-A, non-B hepatitis in this country (CDC/NIOSH, Ex. 298). An
immunoassay that detects antibody to HCV has been developed and was licensed
in May 1990 for use in screening blood donors. Because the test is so new,
there is not enough data to define how important this pathogen is in the
occupational setting. Further research will help in clearly defining the
importance of bloodborne transmission of this virus in the workplace. The principal mode of transmission in the
United States is bloodborne; therefore,
persons at greatest risk for infection include IV drug users, dialysis
patients and transfusion recipients. Over 90% of all post-transfusion
hepatitis is due to the non-A, non-B virus(es). These hepatitis viruses cause
not only acute hepatitis, but may also lead to chronic hepatitis; an average
of 50% of patients who have acute PT non-A, non-B hepatitis infection later
develop chronic hepatitis with potential for progression to cirrhosis and for
infectivity to others for the duration of life (Exs. 6-429; 6-449, 286G). The
amount of virus present in the blood of acutely or chronically infected
persons is modest, usually less than 1000 infectious doses per milliliter,
although occasionally up to 1000 times higher (Ex. 6-423). Thus, relative
infectivity of blood is 100 to 100,000 fold lower than with hepatitis B
virus. Relative infectivity of other body fluids is not known. Some
evidence indicates that non-A, non-B hepatitis also presents an occupational
risk to healthcare workers. At least one episode of transmission of non-A,
non-B hepatitis from an acutely infected patient to a nurse by needlestick
has been reported (Ex. 6-455). One case-control study has shown an increased
risk of non-A, non-B hepatitis for patient care and lab workers (Ex. 6-39). Furthermore,
non-A, non-B hepatitis transmission from infected patients to other patients
and to staff has been reported in hemodialysis units; several outbreaks have
been observed in this setting, and an incidence of 1.8% of non-A, non-B hepatitis
among hemodialysis patients nationwide was observed in 1983 (Exs. 6-462;
6-386). While pathways of transmission in this setting have not been
rigorously documented, nor has survival of HCV defined, bloodborne
transmission by environmental contamination, similar to that of HBV, may
occur. In
their May 1990 post-hearing comment, CDC/NIOSH supplied some additional
information about non-A, non-B hepatitis and hepatitis C virus (HCV). Non-A,
non-B hepatitis is poorly reported at a national level and the best estimates
of U. S. disease burden and risk groups come from the CDC Sentinel Counties
Study of Viral Hepatitis. Extrapolating from this surveillance study, it is
estimated that there were 170,000 non-A, non-B hepatitis infections in the
U.S. 1988. Of these 3,400 (2%) were among <<health care
workers>>. The estimates of non-A, non-B hepatitis attributable to
occupational exposure come from the Sentinel Counties Study. In 1988, 2% of
cases of non-A, non-B hepatitis were related to occupational exposure. Recently,
a virus has been cloned that appears to account for a large proportion of
cases of non-A, non-B hepatitis in the U. S. and has been designated
hepatitis C virus (HCV). In May 1990, an immunoassay that detects antibody to
HCV (anti-HCV) was licensed for use in screening blood donors. Preliminary
studies indicate that approximately 70% of patients with non-A, non-B
hepatitis in the U. S. are anti-HCV positive when tested at the appropriate
time in the course of their illness. At this time no data are available on
the rate of HCV infection among <<health care workers
or the risk of infection from various exposures. However, it is known that
the risk of chronic liver disease following acute non-A, non-B hepatitis is
approximately 50% (CDC/NIOSH Ex. 298). Because
the primary mode of transmission is blood to blood contact, and a large
asymptomatic carrier reservoir exists, precautions to prevent non-A, non-B
hepatitis transmission in the workplace are identical for those of other
bloodborne viruses such as HBV (Exs. 6-461; 6-74; 6-426). Several studies
have evaluated the efficacy of immunoglobulin (IG) prophylaxis following
parenteral exposure, but results have been equivocal (Exs. 6-447; 6-436). Nevertheless,
the CDC considers it reasonable to give IG as treatment to a healthcare
worker after percutaneous exposure to blood from a known non-A, non-B
infected patient (Ex. 6-199). C. Human Immunodeficiency Virus In
June of 1981, the first cases were reported in the United States of what was
to become known as Acquired Immunodeficiency Syndrome (AIDS) (Ex. 6-382). Investigators
described an unusual illness characterized by Pneumocystis carinii pneumonia
(PCP) and Kaposi's sarcoma (KS) that developed in young, homosexual men
without a known underlying disease or cause for immunosuppression (Exs.
6-359; 6-380). By
early 1982, 159 AIDS cases had been identified in 15 states, the District of
Columbia and 2 foreign countries. All but one of them were men and over 92%
of them were homosexual or bisexual (Ex. 6-359). By the end of 1982, cases of
AIDS were reported among children, intravenous (IV) drug users, blood
transfusion recipients, hemophilia patients treated with clotting factor
concentrates, and Haitians (Exs.6-380; 6-349). In 1983 the disease was also
documented among female sexual partners of male IV drug users in the U.S. and
among Africans (Ex. 6-349). By the end of 1985, all 50 states, the District
of Columbia and three U.S. territories had reported AIDS cases (Ex. 6-359). During
1983 and 1984, French and American scientists independently isolated a human
virus associated with AIDS. Dr. Luc Montagnier and co-workers, of the
Institute Pasteur in Paris, called it lymphadenopathy associated virus (LAV).
Dr. Robert Gallo and co-workers at the National Cancer Institute identified
this virus as human T-cell lymphotropic virus type III (HTLV-1) (Ex. 6-380). Eventually
human immunodeficiency virus type 1 (HIV-1) became the universally accepted
term for the virus (Ex. 6-383). (In this document, unless specifically noted,
HIV refers to HIV-1.) The Centers for Disease Control estimates that in the
United States, between 1 million and 1.5 million persons are infected with
HIV-1 (Ex. 6-356). In addition, CDC reports in the August 1991 issue of
HIV/AIDS Surveillance that as of July 1991, 186,895 cases of AIDS had been
reported to the CDC, 3,199 of whom are children less than 13 years old. At
least 116,734 (63.5%) of the adult/adolescent cases had died as well as 1,677
(52.4%) of the pediatric cases. Although the rate of spread of HIV-1 in the
future is unknown, scientists with the U.S. Public Health Service have
estimated that in the United States alone, a cumulative total of more than
365,000 cases of AIDS will have been reported by the end of 1992 with 80,000
new cases diagnosed during that year (Ex. 6-356). It is projected that there
will be 66,000 deaths that year and 263,000 cumulative deaths. It is expected
that a total of 172,000 AIDS patients will require medical care in 1992. Of
perhaps greater importance for healthcare workers is the 1.0 to 1.5 million
persons who are infected with HIV, often unknowingly so, and who require
medical treatment for related or unrelated conditions. For example, in 1987,
Baker and colleagues examined 203 anonymous serum samples from a group of
critically ill or severely injured patients with no history of HIV infection
treated at the Johns Hopkins University Hospital Department of Emergency
Medicine (Ex. 6-111). They found that six patients (3% of the sample) were
seropositive for HIV antibody. In particular, all seropositives were trauma
victims between the ages of 25 and 34 who were bleeding and their treatment
involved multiple invasive procedures. In a more recent study in 1988 at an
inner city emergency department, Kelen and co-workers tested blood samples
from 2,302 consecutive adult patients for the presence of HIV antibodies. One
hundred nineteen patients (5.2%) were seropositive for HIV. Of this group 92
(77%) had "unrecognized HIV infection" (Ex. 6-370). There
are reports of at least 30 healthcare workers who apparently were infected
with HIV through occupational exposure to blood or other potentially
infectious materials (Ex. 286U). Of the cases of HIV infection associated
with occupational exposure discussed in this section, five occurred outside
the United States. The number of known work related HIV seroconversions among
healthcare workers is approximately 24 at present. However, many infections
are likely to go unrecognized for several years until the HIV-infected
individual develops AIDS. If effective preventive procedures are not
instituted, the number of occupational HIV infections is likely to increase
as the number of infected individuals requiring healthcare increases. The
increasing number of individuals with AIDS, the large number of unidentified
HIV infections, and the reports of occupational infection all indicate that
healthcare workers are at risk for occupationally acquired HIV infection. HIV: Biology HIV
is a member of a group of viruses known as human retroviruses. Its genetic
material is ribonucleic acid (RNA) rather than deoxyribonucleic acid (DNA),
the genetic material found in most living organisms. The virus particle is
comprised of a core containing the RNA and viral enzymes surrounded by an
envelope consisting of lipids and proteins (Ex. 6-380, p.131-154). Because
they lack the cellular machinery necessary to reproduce, all viruses must
reproduce intracellularly, that is, within the host cell. HIV replicates in
human macrophages and T4 lymphocytes, two types of human cells that are vital
components of the immune system. T4 lymphocytes and a few other cell types
have protein molecules on their surfaces called CD4 antigens or receptors. HIV
particles bind with the CD4 receptor sites of the hosts' cells and then
release their viral RNA. The RNA is then transcribed by viral enzymes into
double-stranded DNA that is incorporated into the DNA of the host cell. The
viral DNA then serves as a template to produce more virus particles. The
transcription of RNA to DNA is the reverse of what occurs in most organisms
and thus HIV is called a retrovirus. The process occurs with the aid of the
viral enzyme reverse transcriptase, which is considered to be a marker for
retrovirus production (Exs. 6-384; 6-175; 6-380, pp. 186-249). HIV gradually
depletes the number of cells which are essential for host immune function,
rendering the infected individual increasingly susceptible to opportunistic
infections (Exs. 6-360; 6-380, pp. 131-154). Circulating
macrophages are also considered a reservoir as well as another target for HIV
infection. Since some macrophages can circulate freely throughout the body,
they may actually transport HIV to the brain which may lead to neurologic
complications (Ex. 6-384). HIV: Serological Testing Infection
with HIV may be identified through testing the blood for the presence of HIV
antibodies. Tests were first licensed for use in the United States in 1985 and
have been used routinely to screen donated blood, blood components and blood
products, and by physicians and clinics to diagnose HIV infection in patients
(Ex. 6-380, pp. 1-17). The military also uses the antibody tests to screen
recruit applicants and active duty personnel for HIV infection (Ex. 6-380,
pp. 1-17). Although the antibodies do not appear to defend or protect the
host against HIV, they serve as markers of viral infection. Most people
infected with HIV have detectable antibodies within 6 months of infection,
with the majority generating detectable antibodies between 6 and 12 weeks
after exposure (Ex. 6-204). The
enzyme-linked immunosorbent assay (ELISA or EIA) technique used to detect HIV
antibodies is sensitive, economical and easy to perform. However, as with all
laboratory determinations, this test can produce a false positive result,
that is, the test gives a positive result when HIV antibody is not present. Therefore,
current recommendations include repeating the ELISA test if the first test is
positive. If the second test is also positive, another test, usually
employing the Western blot technique, is used to validate the ELISA results. A
positive ELISA test and a positive Western blot result indicate the presence
of HIV antibodies and HIV infection (Ex. 6-345). Although
many new tests are still in the experimental stages, one that is being
developed uses the polymerase chain reaction (PCR) technique. This test
detects integrated viral DNA rather than antibody and it may have the
potential to detect HIV infection earlier than currently available antibody
tests (Ex. 6-329). HIV: Transmission HIV
has been isolated from human blood, semen, breast milk, vaginal secretions,
saliva, tears, urine, cerebrospinal fluid, and amniotic fluid; however,
epidemiologic evidence implicates only blood, semen, vaginal secretions and
breast milk in the transmission of the virus (Ex. 6-317). Documented modes of
HIV transmission include: engaging in sexual intercourse with an HIV-infected
person; using needles contaminated with the virus; having parenteral, mucous
membrane or non-intact skin contact with HIV-infected blood, blood components
or blood products; receiving transplants of HIV-infected organs and tissues
including bone, or transfusions of HIV-infected blood; through semen used for
artificial insemination and perinatal transmission (from mother to child
around the time of birth) (Exs. 6-349; 6-327; 6-310; 286U). HIV
is not transmitted by casual contact. Studies evaluating nearly 500 household
contacts of individuals diagnosed with AIDS reveal no cases of HIV infection
of household members who had no other risk factors for the virus (including
no sexual contact with or exposure to blood from the infected person) (Ex.
6-349). Friedland and Klein examined household members who lived with a
person with AIDS for at least 3 months and within an 18-month period prior to
the onset of symptoms in the infected person (during which time infection was
presumably present.) Other household members had been unaware of the infected
individual's HIV status, and had not taken precautions during this time
period (Ex. 6-349). This study produced no evidence that HIV was transmitted
by shaking hands or talking, by sharing food, eating utensils, plates,
drinking glasses or towels, by sharing the same house or household facilities
or by "personal interactions expected of family members" including
hugging and kissing on the cheek or lips. Other studies have shown that HIV
is not transmitted by mosquitoes or other animals (Ex. 6-328). The
vast majority of people with AIDS in the United States can be placed in known
transmission categories and the proportion of infected persons associated
with each group has remained relatively stable since reporting began in this
country in 1981. For adults and adolescents, the transmission categories are
shown in Table IV-2. Table IV-3 displays the transmission categories for
children less than 13 years old. TABLE IV-2(1) AIDS TRANSMISSION CATEGORIES ___________________________________________________________________ Percent of cumulative total of AIDS casesTransmission Group for Adults/Adolescents____________________________________________________________________Homosexual/bisexual men 59% Intravenous drug users 22% (female and heterosexual male) Homosexual/bisexual 7% contact and IV drug users Hemophilia/coagulation 1% disorder Heterosexual contact: 5% Sex with IV drug user; Sex with person with hemophilia; Sex with bisexual male; Sex with transfusion recipient with HIV infection; Sex with HIV-infected person risk not specified; Born in Pattern II country.(2) Sex with person born in Pattern II country. Receipt of blood transfusion, 2% blood components or tissue(3) Other/Undetermined(4) 4%__________________________________________________________________ Footnote(1) HIV/AIDS Surveillance, August, 1991, p. 8. Footnote(2) Pattern II transmission is observed in areas of central,eastern and southern Africa and in some Caribbean countries. In thesecountries, most of the reported cases occur in heterosexuals and themale-to-female ratio is approximately 1:1. Intravenous drug use andhomosexual transmission either do not occur or occur at a low level. Footnote(3) Includes 14 transfusion recipients who received bloodscreened for HIV antibody and 1 tissue recipient. Footnote(4) "Other" refers to 3 healthcare workers who seroconverted toHIV and developed AIDS after occupational exposure to HIV-infected blood."Undetermined" refers to patients whose mode of exposure to HIV isunknown. This includes patients under investigation; patients who died,were lost to follow-up, or refused interview; and patients whose mode ofexposure to HIV remained undetermined after investigation. TABLE IV-3(1) AIDS TRAMSMISSION CATEGORIES____________________________________________________________________Pediatric (< 13 years old) Percent of cumulative Exposure Category. total of pediatric AIDS cases.Transmission Group Cases____________________________________________________________________ Hemophilia/coagulation disorder 5% Mother with/at risk for HIV infection: 84% IV drug use Sex with IV drug user Sex with bisexual male Sex with person with hemophilia Born in Pattern - II country Sex with person born in Pattern - II country Sex with transfusion recipient with HIV infection Sex with HIV-infected person, risk not specified Receipt of blood transfusion, blood components, or tissue Has HIV infection, risk not specified Receipt of blood transfusion, blood 9% components, or tissue Undetermined 2%_______________________________________________________________ Footnote(1) HIV/AIDS Surveillance, August, 1991, p. 9.
Some
types of exposures are clearly more efficient at transmission than others. The
risk of infection following receipt of transfused blood from an HIV-infected
donor is approximately 90 percent (Ex. 6-371). The risk of perinatal
transmission from an HIV infected mother is estimated to be 30-50 percent or
higher (Exs. 6-384; 6-349). Besides the particular type of exposure, other
variables contributing to the likelihood of transmission may include susceptibility
of the host, the virulence of the particular strain, the stage of infection
of the source, and the size of inoculum the individual is exposed to (Exs.
6-348; 6-349). This last factor, the actual amount of virus, may be very
important in the likelihood of transmission since, it appears, there is a
greater probability of infection from HIV contaminated blood transfusions
(890 infections per 1,000 persons transfused with contaminated blood) than
from accidental needlesticks with needles that have been contaminated with
HIV (3-5 infections per 1,000 persons injured with contaminated needles)
(Exs. 6-384; 6-349; 6-371). HIV: Clinical Manifestations of Disease HIV
adversely affects the immune system, rendering the infected individual
vulnerable to a wide range of clinical disorders. These conditions, some of
which tend to recur, can be aggressive, rapidly progressive, difficult to
treat, and less responsive to traditional modes of treatment. They usually
lead to the death of the HIV infected patient (Ex. 6-361). The CDC has
divided disease progression into several stages according to types of
infections or symptoms reported. Group
I: Within a month after exposure, an individual may experience acute
retroviral syndrome, the first clinical evidence of HIV infection. This is a
mononucleosis-like syndrome with signs and symptoms that can include fever,
lymphadenopathy, myalgia, arthralgia, diarrhea, fatigue, and rash. Acute
retroviral syndrome is usually self-limiting and followed or accompanied by
the development of antibodies (Ex. 6-270). Group
II: Although most persons infected with HIV develop antibodies to the virus
within 6-12 weeks after exposure, most of these individuals are asymptomatic
for months to years following infection. However, they can transmit the virus
to others throughout this time (Ex. 6-270). Group
III: Although no other signs or symptoms are experienced, some HIV-infected
patients will develop a persistent, generalized lymphadenopathy (PGL) that
lasts more than 3 months (Ex. 6-270). Group IV: Epidemiologic
data indicates that most persons who are infected with HIV will eventually
develop AIDS (Ex. 6-384). AIDS can result in severe opportunistic infections
that an individual with a normal immune system would only rarely experience,
as well as a wide range of neurologic and oncogenic or neoplastic processes
(Ex. 6-270). The clinical manifestations of patients in this group may vary
extensively. Some of these patients may experience "constitutional
disease," also known as HIV "wasting syndrome," which may be
characterized by severe, involuntary weight loss, chronic diarrhea, constant
or intermittent weakness, and fever for 30 days or longer (Ex. 6-270). This
syndrome in and of itself may result in death. Individuals with AIDS may also
develop HIV encephalopathy, dementia, myelopathy or peripheral neuropathy. This
may occur when HIV infects mononuclear cells present in the cerebrospinal
fluid surrounding the brain and spinal cord or infects these cells within the
brain or spinal cord. Persons with dementia experience varying degrees of
cognitive disability or impairment of intellectual function and motor
disability or dysfunction. Effects ranging from apathy and depression to
memory loss and severe dementia may interfere with a person's occupation as
well as activities of daily living and can ultimately be fatal (Exs. 6-270;
6-380, pp. 548-578). In addition, the virus is capable of affecting the
peripheral nervous system causing severe pain and weakness or numbness in the
limbs (peripheral neuropathy) (Ex. 6-270). According
to CDC's case definition, there are specific diseases that are considered
indicators of AIDS if laboratory tests for HIV were not performed or gave
inconclusive results and no other known causes of immunodeficiency are present
(Ex. 6-157). Among these are parasitic diseases such as Pneumocystis carinii
pneumonia, the most common opportunistic infection and cause of death in AIDS
patients; fungal diseases such as candidiasis of the esophagus, trachea,
bronchi or lungs; viral diseases such as cytomegalovirus disease of an organ
other than the liver, spleen or lymph nodes; cancer/neoplastic diseases such
as Kaposi's sarcoma affecting persons under 60 years of age; and bacterial
infections such as Mycobacterium avium complex (Exs. 6-157; 6-361). In
addition to the diseases listed above there are diseases caused by organisms
such as disseminated or extra-pulmonary Mycobacterium tuberculosis (TB) which
may be considered indicative of AIDS if substantiated by reactive
HIV-antibody tests (Ex. 6-157). Unlike adults, children under 13 years of age
can be classified as having AIDS if they experience lymphoid interstitial
pneumonia or pulmonary lymphoid hyperplasia (LIP-PLH complex). Children who
are seropositive for HIV can be classified as having AIDS if they experience
recurring serious bacterial infections such as septicemia, pneumonia,
meningitis, Hemophilus, Streptococcus or other pyogenic bacteria (Ex. 6-157).
AIDS
is primarily managed by treating clinical disease symptoms, but conventional
therapy cannot reverse the immunodeficiency (Ex. 6-361). Currently,
researchers are testing experimental drugs and conducting a number of
treatment protocols on patients at various stages of infection or disease. At
this time, only one antiviral drug, Zidovudine or Retrovir TM, (formerly
known as azidothymidine or AZT) has been approved by the FDA for some
patients, specifically those who have experienced Pneumocystis carinii
pneumonia (PCP), or are symptomatic for AIDS related illness and have less
than 200 T4 cells/ml (Ex. 6-479). Although some patients have had to
discontinue the drug due to severe side effects, clinical trials have shown
the drug to prolong the life of AIDS patients (Ex. 6-383, pp. 153-165). There
is no vaccine to prevent HIV infection (Ex. 6-384). HIV: Workplace Transmission Occupational
transmission of HIV has been documented in healthcare workers. The
information submitted to the public record indicates that as of May 1990,
there are at least 65 case reports of healthcare workers whose HIV infections
are associated with occupational exposure. Among these are 30 case reports
that have been individually published in the scientific literature or are in
press (CDC/NIOSH, Ex. 298). Eighteen of these cases seroconverted following a
documented exposure incident. Thirteen of the seroconversions were caused by
parenteral exposure to blood or blood-containing body fluids (11 by
needlesticks and 2 by cuts with a sharp object). Five seroconversions
involved blood contamination of mucous membranes or non-intact skin and one
was due to parenteral exposure to concentrated HIV-I (Ex. 286U). The dates of
seroconversion could not be documented for the remaining 12 individually
published cases because no baseline serologic data had been obtained. Documented
cases of seroconversions in healthcare workers as of May 1990 are presented
in Table IV-4. Additional cases of possible occupational transmission in
healthcare workers as of May 1990 are presented in Table IV-5. TABLE IV-4(1) Documented seroconversions in health workers_________________________________________________________________Author and Country Type of ARS(2)reference exposure_________________________________________________________________1. Editorial United Needlestick yes Kingdom2. Stricof USA Needlestick yes3. Oksenhandler France Needlestick yes4. Neisson-Venant Martinque Needlestick yes 5. CDC(3) USA Non-intact skin yes6. CDC USA Mucous membrane no7. CDC USA Non-intact skin yes8. Gioannini Italy Mucous membrane yes9. Michelet France Needlestick yes10. Wallace USA Needlestick yes11. Barnes USA Sharp object yes12. Ramsey USA Needlestick no13. CDC USA Needlestick yes/AIDS14. Marcus USA Needlestick yes15. Marcus USA Two needlesticks yes16. Gerberding USA Needlestick yes17. Weiss, CDC USA Sharp object NR(4)18. CDC USA Cutaneous NR(4)______________________________________________________________________ Footnote(1) From Marcus, R. et. al., Transmission of HumanImmunodeficiency Virus (HIV) in Health-care Setting Worldwide. Bulletin ofthe World Health Organization, 67 (5); 577-582 (Ex. 6-286U). Footnote(2) ARS: acute retroviral syndrome. Footnote(3) CDC: Centers for Disease Control, USA. Footnote(4) NR: not reported. TABLE IV-5 Possible cases of occupational transmission of HIV(*)_______________________________________________________________________Author and reference Country Type of exposure_______________________________________________________________________1. Bygbjerg Denmark Surgical practicein Zaire 2. Belani USA Palm prick fromhospital waste 3. Anonymous France Worked in intensive care unit4. Grint United Kingdom Home-health provider,non-intact skin 5. Weiss, McCray USA Colonic Biopsy Needlestick6. Weiss, CDC USA Two needlesticks7. Weiss, CDC USA Two exposure/ unknown source8. Weiss, CDC USA Concentrated virus on skin9. Klein USA Multiple needlesticks10. Ponce de Leon Mexico Needlestick puncture wound11. Schmidt Federal Needlestick Republic of Germany12. Lima Italy Needlestick _________________________________________________________________ Footnote(*) From Marcus, R. et. al., Transmission of HumanImmunodeficiency Virus (HIV) in healthcare settings worldwide. Bulletin ofthe World Health Organization, 67 (5); 577-582 (1989).
Twenty-five
published cases of HIV infection associated with occupational exposure are
summarized below. These cases represent a spectrum of healthcare personnel
including, among others, nurses, laboratory workers and a dentist. For the 25
cases, HIV status was determined by HIV-antibody testing. Baseline blood
samples analyzed for HIV-antibody revealed that at least 18 of these
individuals were not infected with HIV at the time of the exposure incident. However,
subsequent blood tests determined that eventually all of the 18 seroconverted
to an HIV-positive-antibody status, indicating the presence of HIV infection.
All 25 denied other known risk factors for HIV infection, but in cases where
the baseline serologic data were unknown, other modes of transmission cannot
be ruled out. Nevertheless, all cases were investigated for risk factors and
none were identified. Case Reports CASE
1: A hospital healthcare worker sustained an accidental self-inflicted
injection of "several milliliters of blood while obtaining blood in a
vacuum collection tube from an AIDS patient" (Ex. 6-365). The healthcare
worker subsequently seroconverted to an HIV-antibody-positive status and has
since developed AIDS. Having determined there were no other HIV risk factors
for this individual, investigators concluded the worker acquired the
infection occupationally. CASE
2: In November 1985, a previously healthy, 33 year old United States Navy
hospital corpsman punctured his fingertip while disposing of a phlebotomy
needle used to draw blood from a patient who was later diagnosed with
Pneumocystis Carinii pneumonia and serologically tested HIV-positive (Ex.
6-337). Upon learning of this diagnosis two weeks after the incident, the
corpsman submitted to HIV serology testing on a monthly basis and was
HIV-negative for 3 months. Five months after the incident, he experienced a
characteristic acute retroviral syndrome, which was self-limiting. Six months
after the incident he tested HIV-positive. He reported a negative history of
other risk factors for HIV, and his wife was seronegative. CASE
3: Weiss and co-workers reported that a laboratory worker, who worked with
concentrated HIV-1, tested seropositive for the virus (Ex. 6-187). Clinical
evaluation revealed no signs or symptoms of HIV-related illness. As part of
routine laboratory duties, this individual was involved in several possible
exposure circumstances such as decontaminating equipment, cleaning up spills
or touching potentially contaminated surfaces with gloved hands. Virus-positive
culture fluid had occasionally leaked from equipment and contaminated
centrifuge rotors. Although reportedly using Biosafety level 3 precautions,
the subject was not fully knowledgeable with and did not strictly follow
these practices all of the time. The
subject did not recall any direct skin exposure but did report having had a
nonspecific dermatitis on the arm, although the "affected area was
always covered by a cloth laboratory gown." The individual also reported
incidents where he had pinholes or tears in his gloves and had to change them
immediately. Strains
of HIV-1 isolated from different individuals generally differ significantly,
but the HIV-1 isolated from this subject was indistinguishable from 1 of the
2 predominant HIV genotypes this individual worked with in the laboratory. Although
no specific exposure incident had been identified, the investigators
concluded that the subject acquired the HIV infection in the laboratory, most
likely through undetected skin contact with the concentrated virus. CASE
4: A female phlebotomist reported that blood splattered on her face and in
her mouth when the top of a 10-ml vacuum blood collection tube flew off while
she was collecting a patient's blood (which subsequently tested HIV-positive)
(Ex. 6-109). The HCW was wearing gloves and glasses and reported that no
blood got in her eyes. She reported no open wounds but did have facial acne. She
washed off the blood immediately after exposure. Her blood tested
HIV-negative one day post-exposure and 8 weeks later. However, when donating
blood 9 months after exposure, she was HIV-antibody positive. She denied
having other known risk factors for HIV. CASE
5: A female medical technologist was exposed to a blood spill that covered
most of her hands and forearms while she was manipulating an apheresis
machine; a machine that separates blood components, retains some, and returns
the remainder to the donor (Ex. 6-109). Although she was not wearing gloves,
she did not report any open wounds on her hands or any mucous membrane
exposure. However, she did have dermatitis on her ear and may have touched
that ear. Eight weeks after the incident she experienced symptoms of acute
retroviral syndrome. She was HIV-negative 5 days post exposure; however, 3
months after exposure she was HIV-antibody positive. She denied having other
known risk factors for AIDS. Her husband also denied any risk factors for
AIDS and tested HIV seronegative. CASE
6: Neisson-Vernant and co-workers reported that a "24-year-old female
student nurse pricked the fleshy part of her index finger with a needle used
to draw blood from an AIDS patient." She did not recall injecting blood.
Two months later signs and symptoms of acute retroviral illness appeared,
including fever and a macular eruption lasting 3 days. Although she tested
HIV-negative 1 month after the incident, she tested positive 6 months after
exposure. She denied all other risk factors for HIV and her husband tested
HIV negative 6 and 9 months after her exposure (Ex. 6-93). CASE
7: Michelet and co-workers reported a case of occupationally acquired HIV
infection in a female nurse in France (Ex. 6-369). Having drawn a blood
sample in a vacuum tube from an individual with AIDS, she stuck her finger
with the large-bore needle of the adapter, but reportedly did not inject any
blood. Immediately after the incident, she placed her finger in 0.5% sodium
hypochlorite solution in accordance with the hospital's guidelines. Twenty-three
days after exposure, she developed signs and symptoms of acute retroviral
syndrome, including abdominal cramps, nausea, vomiting, and diarrhea. She
later experienced anorexia, fatigue and facial palsy. Clinical evaluation
found generalized lymphadenopathy. Although she tested HIV-antibody negative
13 days after the incident she was HIV-antibody positive 71 days
post-exposure. Investigators failed to identify any risk factor for HIV for
the nurse or her husband, who tested HIV-antibody negative 62 days after his
wife's exposure incident. CASE
8: An NIH clinical laboratory worker sustained a cut that penetrated through
a glove and the skin when a vial of HIV-infected blood broke in the worker's
hand (Ex. 6-348). Although initially testing negative, the individual
subsequently tested positive and investigators have linked the infection with
the accident. CASE
9: Oksenhendler and co-workers reported that a female nurse in France stuck
her finger superficially while recapping a needle contaminated by bloody
pleural fluid from a patient positive for both HBsAg and HIV. Immediately
post-exposure she received the hepatitis B vaccine and specific
immunoglobulin. She experienced acute retroviral syndrome including fever, fatigue
and vomiting 25 days after the incident. Fifty three days after exposure, she
developed an acute "anicteric" hepatitis (possibly related to the
primary HIV infection.) Although she tested HIV-negative after the exposure
(days 1 and 13), she tested HIV-positive on day 68. She and her husband
denied other known risk factors for HIV and her husband tested seronegative
for HIV 110 days after the incident (Ex. 6-18). CASE
10: A nurse from England received a needlestick injury to a finger while
resheathing a hypodermic needle on a syringe containing an AIDS patient's
blood from an arterial line (Ex. 4-41). A small amount of blood may have been
injected as well. Signs and symptoms of acute retroviral syndrome presented
13 days after exposure with a rash developing 17 days after the incident. Although
she tested HIV-negative 27 days post injury, she was determined to be
HIV-positive on day 49. She denied other known risk factors for HIV. CASES
11, 12 and 13: Marcus and co-workers reported 3 cases of healthcare workers
who seroconverted to an HIV antibody-positive status (Ex. 6-372). One
healthcare worker sustained a deep needlestick injury inflicted by a
co-worker with a 21-gauge needle while attempting to resuscitate an AIDS
patient. The healthcare worker was HIV-antibody and antigen negative the day
after the exposure. Four weeks after the incident the worker experienced
fever, "shaking chills," night sweats, lymphadenopathy, and malaise
which lasted about 4 days. One hundred twenty-one days after the exposure the
worker tested HIV-seropositive. The healthcare worker denied other known risk
factors for HIV and a recent sex partner tested HIV-seronegative. A
second healthcare worker accidentally stuck herself on two occasions with
needles that had been used on HIV-infected patients. The first exposure
occurred while recapping a needle that had been used on a patient with AIDS. Ten
days later the worker stuck herself with a needle that had been used to draw
blood from a symptomatic HIV-infected individual. "After removing the
tube of blood from the plastic needle holder, the healthcare worker placed
the needle holder upright on its base, such that the needle was pointed
vertically into the air. The healthcare worker then turned away and
subsequently injured herself on the exposed needle." The worker tested
positive for HIV-antibody and antigen 21 days after the first exposure (11
days after the second.) She developed an acute viral illness four weeks after
the first incident, characterized by shaking chills, dehydration, nausea,
malaise, bilateral lymphadenopathy and a weight loss of more than 10 pounds. During
this illness she was HIV-antibody negative; however, lymphocyte cultures were
positive for HIV-antigen and reverse transcriptase, an enzyme which serves as
a marker for HIV. The healthcare worker tested HIV-antibody positive on day
121 after the first exposure (111 days after the second exposure.) Four
months after the exposure incidents, the worker's spouse tested HIV-antibody
negative. A
third case, a healthcare worker, received a deep intramuscular needlestick
injury with a large bore needle and syringe unit visibly contaminated with
blood from an AIDS patient (Exs. 4-39; 6-367). Fourteen days after the
incident, acute retroviral syndrome developed. Although HIV-antibody negative
9 days post-exposure, the healthcare worker was determined HIV-antibody
positive on day 184. The worker and the worker's spouse denied any other risk
factors for AIDS and the spouse tested HIV-antibody negative 239 days after
the incident. CASE
14: Marcus and co-workers and McCray and co-workers reported a case where a
female nurse received a puncture wound from a colonic biopsy needle (visibly
contaminated with blood and feces) used in an AIDS patient (Exs. 6-372;
4-39). She tested HIV-positive approximately 10 months after exposure
although there were no serologic baseline data before or immediately after
the incident. She denied other risk factors for AIDS; however, her sexual
partner also tested HIV-positive and heterosexual transmission therefore
cannot be ruled out. CASE
15: Gerberding and co-workers reported a case of a healthcare worker who
acquired HIV infection after sustaining a deep needlestick injury with an
HIV-contaminated needle (Ex. 6-375). CASE
16: Ramsey and co-workers, conducted a prospective evaluation of 44
healthcare workers exposed to HIV and reported that one healthcare worker
seroconverted to an HIV-antibody positive status after sustaining a
needlestick from an HIV-contaminated needle (Ex. 6-373). The worker had been
followed for at least 90 days after the exposure incident and had not
reported any signs or symptoms of acute-retroviral illness. CASE
17: Gioannini and co-workers reported that a 37-year-old intensive care nurse
in Italy "had her hands, eyes and mouth heavily splashed" with
blood from an HIV-infected hemophiliac. Beginning 11 days post-exposure, the
nurse developed signs and symptoms of acute retroviral illness including
fever, fatigue, chills, arthralgia, cervical and axillary lymphadenopathy and
arthritis. She was hospitalized 18 days after the incident due to the
severity of her symptoms plus progressive increases of aminotransferase
levels. During her 55 day hospital stay the worker developed an acute,
anicteric non-A non-B hepatitis, which may have been associated with HIV
infection. HIV antigen was detected in her blood on day 21 and by day 43 she
had seroconverted to an HIV-antibody-positive status (Ex. 6-334). CASE
18: A 32-year-old mother tested HIV-positive subsequent to providing extensive
healthcare to her male child with a "congenital intestinal
abnormality" (Ex. 4-37). Having received multiple blood transfusions
(one of which was from an HIV-positive source) the child was tested and
determined HIV-positive at 24 months of age. Although the mother did not
report any needlestick or other parenteral exposure to the child's blood, she
recalled having had frequent hand contact with the child's blood and body
fluids. She did not wear gloves and did not wash her hands immediately after
exposure. She did not report having open wounds or exudative dermatitis on
her hands. One month after the child tested HIV-positive, the mother was
determined to be seronegative for HIV. However, 4 months later she was
determined to be HIV-antibody-positive. She reported a negative history for
other risk factors for HIV for herself and the child. The child's father was
seronegative for HIV. Investigators concluded the mother most probably
acquired the infection by providing her infected child healthcare that
involved extensive exposure to blood and body fluids without using infection
control practices. CASE
19: A laboratory worker apparently became infected in a laboratory accident
(Exs. 6-187; 6-368; 6-312). He handled large volumes of HIV in a high containment
laboratory under contract with NIH, performed techniques to concentrate the
virus as part of a commercial process and reportedly followed biosafety
guidelines. He was tested and found to be HIV-seropositive. The lab worker
was not informed of his HIV status until 16 weeks after he tested
HIV-positive. At that time, he recalled having cut his finger with a blunt
stainless steel needle while cleaning a piece of contaminated equipment. He
had tested HIV-negative 4 to 6 months prior to the laboratory incident but
tested HIV-positive 6 to 9 months post exposure. Biosafety officials were of
the opinion that the accident probably caused the infection. The laboratory
worker has not participated in any studies that could determine whether he is
infected with a laboratory strain of HIV. CASE
20: Klein and co-workers reported a male dentist who had tested
HIV-seropositive (Ex. 6-366). He denied having other risk factors for the
virus. Although he did not recall treating a patient with AIDS, he had
treated patients at high risk for HIV infection. He reported having frequent
open lesions or "obvious breaks in the skin" on his hands; however,
he only intermittently used personal protective equipment. His wife, although
refusing to be tested for HIV, denied other HIV-risk factors. There was no
report of baseline or convalescent serology and exposure to HIV-positive
blood cannot be documented. CASE
21: A healthcare worker applied pressure to an HIV-infected patient's
arterial catheter insertion site to stop bleeding (Ex. 6-109). During the
procedure, she may have had a small amount of blood on her index finger for
20 minutes before washing her hand. She did not wear gloves during this
procedure and although she reported no open wounds, her hands were chapped. Twenty
days after exposure, she developed symptoms of acute retroviral syndrome
lasting 3 weeks. Blood she had donated 8 months prior to the exposure was
HIV-negative. However, blood donated 16 weeks after the incident was
HIV-positive. She denied having other known risk factors for HIV. No baseline
data or serologic testing results were obtained immediately following
exposure for this case. CASE
22: A female healthcare worker received accidental needlestick injuries when
drawing blood from AIDS patients in two incidents separated in time by 4
months (Ex. 6-258). She had her first blood test for HIV 8 months after the
second exposure and was found HIV-positive. Although previously healthy, she
developed a persistent mild lymphadenopathy 3 months after the second incident
and intermittent diarrhea which started 5 months after that incident. She
denied other HIV risk factors. Her long-term sex partner also denied any HIV
risk factors, and he repeatedly tested HIV-antibody-negative over an 8-month
period following the healthcare worker's positive test result. HIV was
obtained from the male partner's peripheral lymphocytes within 13 months
after the second incident but could not be obtained several months later. Heterosexual
transmission could not be ruled out for the healthcare worker but seems less
likely than parenteral transmission in this case. CASE
23: A male laboratory worker, was found to be HIV-positive when first tested
(Ex. 6-258). The worker recalled having received 2 parenteral exposures to
blood from persons of unknown HIV status. He sustained an accidental
needlestick and a cut on the hand while processing blood 8 and 16 months
respectively prior to being tested. Although asymptomatic when tested, he has
experienced transient cervical lymphadenopathy. He denied all known risk
factors for HIV, but non-occupational transmission could not be ruled out in
this case as no serologic data were available immediately after the
exposures. CASE
24: Grint and co-workers reported that a 44-year-old woman from England, although
not a healthcare worker, developed AIDS after providing healthcare services
for a Ghanaian man with a postmortem diagnosis of AIDS (Ex. 6-333). She
recalled having small cuts on her hands, an exacerbation of chronic eczema,
and frequent skin contact with his body secretions and excretions. There was
no report of baseline or convalescent serology. CASE
25: Ponce de Leon and co-workers reported that a 39-year-old male laboratory
technician in Mexico acquired AIDS occupationally and died as a consequence
of this disease (Ex. 6-326). From 1971 to 1986 he worked as a laboratory
technician in a company that processed blood and blood products and where
infection control procedures were not "customary." He reported
experiencing many accidental punctures and blood contact with his
"teguments and mucosa". The worker also recalled a laboratory
accident "in late 1985 in which a deep cut in his right hand was grossly
contaminated with plasma." Early in 1986 he experienced an acute illness
characterized by fever and lymphadenopathy lasting several days. In 1987 the
worker experienced a seven-month illness characterized by persistent
diarrhea, weight loss, persistent oral thrush, intermittent fever,
generalized lymphadenopathy, anisocoria and signs of meningitis. He eventually
was hospitalized on December 11, 1987 two weeks after dizziness, mental
confusion and vomiting ensued. Tests revealed the presence of the
opportunistic infection cryptococcoses. The worker tested
HIV-antibody-positive and was diagnosed as having AIDS. The patient died on
December 18,1987. He had denied other risk factors for HIV and his wife was
seronegative for HIV-antibody. HIV: Epidemiology A
number of prospective studies and surveys have been conducted to determine occupational
risks for HIV infection. Marcus and co-workers reported that the Centers for
Disease Control has been conducting a national prospective study which began
in 1983, to assess initially the risk of Acquired Immunodeficiency Syndrome
and later, with the advent of HIV-antibody testing, the risk of HIV among
healthcare workers exposed to the blood or body fluids of persons with HIV
infection (Ex. 6-372). In 1986, data were reported on the first 451
healthcare workers who had entered the study and had been tested for HIV
antibody (Ex. 4-39). Initially, individuals were considered eligible for the
study if they had been exposed to the blood or body fluids of a patient with
AIDS or AIDS-Related illness by a needlestick, a cut with a sharp object or
contamination of an open wound or mucous membrane. Thereafter, subjects were
enrolled only if they had parenteral, mucous membrane or non-intact skin
exposure to the blood of an HIV-infected individual. As
of July 31, 1988, a cohort of 1201 healthcare workers with exposure to
HIV-contaminated blood has been followed. Of these, 751 (63%) were nurses,
164 (14%) were physicians or medical students, 134 (11%) were technicians or
laboratory workers, 90 (7%) were phlebotomists, 36 (3%) were respiratory
therapists and 26 (2%) were housekeeping or maintenance staff. Upon
enrollment the subjects provided investigators with epidemiologic data
including demographic information, medical history, details of the exposure
circumstances, infection control precautions used and post-exposure
treatment. Nine hundred sixty-two (80%) of the subjects had sustained
needlestick injuries, 103 (8%) had been cut with a sharp object, 79 (7%) had
contaminated an open wound and 57 (5%) have had a mucous membrane exposure. Seven
hundred seventy-nine (65%) of the exposed healthcare workers were exposed in
a patient room, on a ward or in an outpatient clinic; 161 (14%) in an
intensive care unit; 87 (7%) in an operating room; 84 (7%) in a laboratory;
62 (5%) in an emergency room; and 28 (2%) in a morgue. The
1,201 subjects had blood samples drawn and tested for the presence of
HIV-antibodies. Acute blood specimens collected within 30 days after exposure
were obtained and tested from 622 subjects. Exposed healthcare workers were
retested at 6 weeks, 3 months, 6 months and 12 months after the exposure
incident to determine if seroconversion had occurred. Seroconversions were
defined as healthcare workers who were seronegative for HIV antibody within
30 days after occupational exposure and seropositive 90 days or more after
the exposure incident. Nine
hundred sixty-three subjects had been followed for at least 6 months, 860
(89%) of whom had sustained either a needlestick injury or a cut with a sharp
instrument. Of these, four were seropositive yielding a seroprevalence rate
of 4/860 = 0.47%. One of the four was first tested for HIV-antibody 10 months
after sustaining a needlestick exposure to blood of an HIV-infected patient
(see CASE 14). As there was no available acute blood specimen collected within
30 days after exposure this case cannot by definition be considered a
seroconversion. The remaining 3 HIV-seropositive subjects (see CASES 11, 12,
and 13) had HIV-seronegative acute blood specimens and were thus considered
seroconversions, yielding a seroconversion rate of 3/860 = 0.35%. Weiss
and co-workers, conducted a prospective study to assess the risk of HIV in
laboratory workers (Ex. 6-187). Invitations to participate in the study were
issued to workers with possible exposure risk in 15 laboratory facilities
from 6 states. Of the 265 subjects studied, 225 had laboratory exposure
(including 99 who worked with concentrated HIV and 126 who worked with blood
containing HIV, non-infectious viral proteins, or cloned viral DNA), 30
worked with AIDS patients in support of the laboratory and 10 were clerical
staff working in the laboratory environment. Of the 225 laboratory workers,
10 reported one or more episodes of parenteral exposure to HIV, including
needlesticks or cuts, and 35 reported one or more episodes of skin contact
with HIV. Participants completed a questionnaire focusing on workplace
exposure to human retroviruses, biosafety precautions used at the facility
and by the subject, accidents occurring in the laboratory or other areas and
the non-occupational factors such as drug use, sexual activity and
transfusion history. Eight (3%) of the 265 reported non-occupational risk
factors for the virus. Of the 225 workers with laboratory exposure, ten
reported parenteral virus exposure, and 35 reported 1 or more skin contacts. Thirteen
workers reported that they did not wear gloves at all times when working with
HIV-infective material. Blood samples from all subjects were analyzed for HIV
antibodies by enzyme-linked immunosorbent assay and confirmed by tests such
as immunoblots and radioimmune assays. One individual who worked with
concentrated HIV-1 was seropositive for the virus upon entering the study
(See CASE 3). The HIV isolated from the subject's blood was shown to be
genetically identical to a strain of HIV used in the laboratory, thus
strongly implicating occupational exposure as the source of infection. The
authors concluded that the most plausible source of exposure was contact of
the worker's gloved hand with culture supernatant fluid containing concentrated
virus, followed by inapparent exposure to skin. No HIV seroconversions were
identified in the other study participants during the period of prospective
follow-up. The authors calculated that the rate of HIV infection was 0.48 per
100 person-years for laboratory personnel in this study. Gerberding
and co-workers are conducting a prospective cohort study to assess the risk
of transmitting HIV to healthcare workers intensively and frequently exposed
to the more than 1600 patients with AIDS and AIDS-related conditions at San
Francisco General Hospital (Exs. 6-375; 6-353). After inviting the hospital
healthcare workers to participate in the study, investigators recruited a
cohort of 623 subjects between 1984 and 1988. At the time of enrollment blood
samples from each subject were tested for HIV antibody. Upon entering the
study, each subject was asked to complete a confidential, self-administered
questionnaire designed to elicit information regarding demographic
characteristics; employment history; medical history; type, frequency,
duration and intensity of exposures to HIV-infected patients or laboratory
specimens from such patients; a description of infection-control procedures;
and non-occupational risk factors for HIV infection. Subjects who described
non-occupational risk factors for AIDS on the questionnaire were excluded
from this study, leaving 468 for prospective follow up. Forty-four percent
were physicians (57 of whom were surgeons), 30% were nurses and 11% were
laboratory technicians. Of these, 11% worked solely on AIDS units or research
laboratories and 26% worked in the operating room, emergency room or
intensive care unit. Two hundred twelve of the subjects reported having had
accidental exposure (with some having had multiple exposures) to HIV-infected
blood by needlestick or by splashes to mucous membranes or nonintact skin. Of
the one hundred eighty subjects who received follow-up HIV-antibody testing
at least 6 months after exposure, Gerberding and co-workers reported that
only one, a healthcare worker who had sustained a deep needlestick injury
with an HIV-contaminated needle seroconverted to HIV antibody positive (CASE
15), yielding a seroconversion rate of 1/212 = 0.47%. Klein
and co-workers, conducted a study to assess the occupational risk of HIV
among individuals working in the dental profession (Ex. 6-366). Dental
professionals in the boroughs of Manhattan and the Bronx in New York City
received a mailing requesting their participation in the study. Others were
also recruited during dental meetings in the New York City metropolitan area
(between October 1985 and May 1987), and during the annual meeting of the
American Dental Association in Miami Beach (October 1986). Written consent
was given and questionnaires were completed by a cohort of 1,360 dental
professionals. The questionnaires addressed the issues of demographics
(including type, duration and location of practice), behavior or other risk
factors related to AIDS, "precautions used when treating patients, type
and estimated numbers of patients treated, estimated number of accidental
parenteral inoculations," and HBV vaccination status. Blood samples were
then obtained and analyzed for HIV antibodies by EIA and, if reactive,
confirmed by Western blot assay. The blood samples of those subjects who had
not received the hepatitis B vaccine were analyzed for HBV antibodies as
well. Twenty-five participants who reported no or "uncertain"
contact with patients and 13 subjects for whom blood samples were not
obtained were excluded from the study. For 13 participants who reported
non-occupational risk factors for HIV, including 10 homosexual or bisexual
men, 2 heterosexual intravenous drug users and 1 homosexual or bisexual IV
drug user, blood samples were analyzed separately. Among those who reported
non-occupational risk factors, 4 were found to be HIV-antibody positive. The
remaining cohort of 1,309 subjects consisted of 1,132 dentists, 131 dental
hygienists and 46 dental assistants. Most of the dentists were male and 5%
were oral surgeons. Nearly all of the dental hygienists and assistants were
female. About half of the participants practiced in cities where large
numbers of AIDS cases have been reported. Although the vast majority of
subjects reportedly worked either with AIDS patients (15%) or with patients
at high risk for AIDS (72%), only 31% of the dentists and 8% of dental
assistants reported always wearing gloves when performing dental treatment;
most of them did report using gloves intermittently. Seventy three percent of
the hygienists reported always wearing gloves while working with patients. Most
of the dentists and dental hygienists used masks, eye protection and
disposable gowns intermittently, although the majority of dental assistants
never used these infection control procedures. Nearly all subjects who used
precautions reported they had increased their use of precautions since 1983
due to concern about AIDS. Approximately 94% of the subjects reported
sustaining accidental "parenteral inoculations with sharp instruments,"
ranging from one to as many as 7,500 within a 5-year period. Serologic test
results revealed that at least 21% of the subjects who had not receive the
hepatitis B vaccine had been infected with HBV; however, only 1 subject, a
male dentist, was seropositive for HIV (see CASE 20). Klein
and co-workers concluded that there is a risk of dental professionals
acquiring HIV occupationally. Because the study represents a point prevalence
survey, the HIV seroconversion rate among dental personnel cannot be estimated
from it. Henderson
and co-workers are conducting a prospective study that began September, 1983,
to assess the risk of nosocomial transmission of HIV to healthcare workers
(Exs. 6-377; 6-352). Investigators invited healthcare workers with varying
degrees of occupational exposure to more than 1000 HIV-infected patients seen
at the Clinical Center at the National Institutes of Health (NIH) to
participate in the study. As of October 1988, the cohort being followed
consisted of healthcare workers, including clinical and research laboratory
personnel as well as healthcare workers providing direct patient care. Blood
was obtained from each subject at the time of enrollment and every 6 months
thereafter. The samples were tested for the presence of HIV antibody by ELISA
and if reactive, were then confirmed by Western blot. Upon enrollment and
every six months thereafter, questionnaires were completed to obtain
demographic information, job description, type and frequency of procedures
performed on HIV-infected patients, type and frequency of patient blood or
body fluid exposure, and type and frequency of exposure to patient specimens.
Questions regarding non-occupational risk factors were not included. Two
categories of exposure were defined: "physical contact with either a
patient or specimen container in routine work"; and "adverse"
exposure, either parenterally (by a needle, scalpel or other sharp object
contaminated with blood or body fluids from HIV-infected patients) or by
splash to the mouth, nasal or conjunctival membranes (by blood, urine,
saliva, sputum or feces from an HIV-infected patient). Three hundred
fifty-nine of the subjects in the cohort reported collectively 482
percutaneous or mucous membrane exposures to blood or body fluids from
HIV-infected patients (Ex. 286U). These individuals were evaluated
separately, given more comprehensive initial and follow-up questionnaires,
and were requested to provide serologic baseline samples as close as possible
to the time of exposure as well as yearly samples thereafter. All adverse
exposures were followed for at least 6 months (ranging from 6 to 63 months.) One
subject who had been cut with a sharp object subsequently experienced an
acute retroviral syndrome and developed antibodies to HIV (Ex. 6-348). For 6 subjects,
blood samples were positive for HIV antibody at the time of entry into the
study. None of the 6 had reported an adverse exposure to blood or body
fluids. However, upon reevaluation, all 6 described having at least one
non-occupational risk factor for HIV infection. Healthcare Workers with AIDS Further
evidence of occupational transmission is provided by reports of healthcare
workers who have AIDS, but have no identifiable risk for infection (Ex.
6-378). As of September 30, 1990, there were at least 69 healthcare workers
with AIDS for whom no risk factors have been identified after thorough
investigation. This group was comprised of 13 physicians, 1 of whom was a
surgeon; 2 dental workers; 8 nurses; 14 aides/ attendants; 12 housekeeping or
maintenance workers; 7 technicians; 2 therapists; 3 embalmers; 1 paramedic
and 7 others. Of these, 35 reported needlestick and/or mucous membrane
exposures to the blood or body fluids of patients during the 10 years
proceeding their diagnosis of AIDS. However, none of the source patients was
known to be HIV-infected at the time of exposure, and none of the workers was
evaluated at the time of exposure to determine HIV-infection status or to
document seroconversion (Ex. L6-666). While data on these cases are less complete
compared to the case reports mentioned earlier, it is reasonable to assume
that at least some of them resulted from occupational exposure (CDC/NIOSH,
Ex. 286). Human Immunodeficiency Virus Type 2 A
case of AIDS in a person from Africa, caused by another human retrovirus,
human immunodeficiency virus type 2 (HIV-2), was diagnosed and reported for
the first time in the United States in December, 1987 (Ex. 6-308). Since then
the CDC has received reports of additional cases of HIV-2 occurring in the West
Africans that were diagnosed in the United States. HIV-2 appears to be
similar to HIV-1 in modes of transmission and natural history but has not yet
been studied in as much detail. Although HIV-2 is unquestionably pathogenic,
there is still much to be learned regarding its epidemiology, pathogenesis
and efficiency of transmission. Although only a few cases of HIV-2 has been
reported in the United States, the infection is endemic in West Africa, where
it was first linked with AIDS in 1986. There have also been cases of HIV-2
infection reported among West Africans living in Europe. HIV-2 surveillance
is being conducted in the United States to monitor the frequency of
occurrence using specific tests not yet available commercially (Ex. 6-308). The
National Institute for Occupational Safety and Health reports that it is
likely that additional human retroviruses will be discovered in the future
(Ex. 22-634) . D. Other Bloodborne Pathogens Several
additional infectious diseases are characterized by a phase in which the
causative agent may circulate in blood for a prolonged period of time. With
the exception of syphilis and malaria, these diseases are rare in the United
States. Syphilis:
Syphilis is caused by infection with Treponema pallidum, a spirochete. Syphilis,
a sexually transmitted infectious disease, is increasingly prevalent in the
United States; 35,147 cases were reported in civilians in 1987 (Ex. 6-465). Marked
increases occurred in 1987. The 25% increase over the 1986 rate was the
largest single-year increase since 1960. Moreover the incidence of 14.6 cases
per 100,000 persons in 1987, equal to that of 1982, is the highest rate since
1950. The natural history of syphilis is characterized by an incubation
period of 10 to 90 days during which the patient is seronegative and
asymptomatic (Ex. 6-495). Subsequent to this incubation period, a primary
stage occurs, usually characterized by the appearance of a single lesion, or
chancre, and normally accompanied by reactivity in serologic tests. Untreated,
the primary lesion heals in weeks. Within weeks to months, a variable
systemic illness, the secondary stage, characterized by rash, fever and
widespread hematogenous and lymphatic dissemination of spirochetes occurs. All
infected persons have reactive serologic tests in this stage (Ex. 6-495). Furthermore,
the highest levels of spirochetemia (spirochetes present in blood) are
reached during this period. Over two-thirds of patients then go into a latent
phase when they are asymptomatic. After a variable period of latency, the
rest progress to a tertiary stage with high morbidity and mortality including
involvement of skin, bones, central nervous and cardiovascular system (Ex.
6-495). During latency and tertiary syphilis, spirochetemia is markedly
reduced, as is infectivity. However during the course of untreated syphilis,
spirochetes may be intermittently found in the bloodstream, and syphilis can
probably be transmitted through the course of the illness, though not as
readily as during the primary and secondary stages (Ex. 6-495). Although
syphilis is primarily transmitted sexually and in utero, a few cases of
transmission by needlestick, by tattooing instruments, and by blood
transfusion have been documented (Exs. 6-453; 6-496). A reported transmission
has occurred by needlestick exposure to the blood of a patient with secondary
syphilis, resulting in a chancre on the hand (Ex. 6-453). Preventive
treatment of an exposed healthcare worker with an antibiotic during the
incubation period would be expected to prevent serological test positivity
and the potential for permanent reactivity on treponemal testing, as well as
preventing the manifestations of infection. Malaria:
Malaria is a potentially fatal mosquito-borne parasitic infection of the
blood cells characterized by paroxysms of fever, chills, and anemia; 944
cases were reported in the United States in 1987 (Ex. 6-465). Malaria is an
important health risk to immigrants from numerous malaria-endemic areas of
the world and to Americans who travel to such areas. Moreover, transmission
by mosquito vector has been documented in some areas of the United States. Malaria
is characterized by a prolonged erythrocytic phase during which the causative
agent, one of several species of the Plasmodium genus, is present in the blood.
In many nations, malaria is among the most common transfusion-related
infectious diseases. In temperate countries, it is only occasionally reported
(Ex. 498). Malaria has also been transmitted by needlestick injury; in one
incident, malaria was transmitted to a child who received a unit of blood and
to the recipient's physician, who stuck himself with a needle (Ex. 467). Babesiosis:
Babesiosis is a tick-borne, parasitic disease similar to malaria which is
caused by the intraerythrocytic parasite Babesia microti. It is endemic in
certain islands off the northeastern coast of the United States. Transmission
by transfusion of fresh blood from asymptomatic donors has been reported (Ex.
454). Brucellosis:
Brucellosis is a febrile illness caused by members of the genus Brucella. It
is typically associated with occupational exposure to livestock or with
ingestion of unpasteurized dairy products; 129 cases were reported in 1987
(Ex. 6-465). It is characterized by fever and weakness, sweats and
arthralgia. Transmission by blood transfusion has been reported; in one
incident, brucellosis and syphilis were transmitted in the same unit of blood
to one recipient (Ex. 6-496). Leptospirosis:
Leptospirosis, a prolonged illness characterized by fever, rash, and occasionally
jaundice, is caused by strains of Leptospira interrogans, a spirochete. The
septicemic phase, during which leptospira are present in the bloodstream of
patients, usually resolves within 1-2 weeks. It is typically acquired by
contact with urine of infected animals, including cattle, swine, dogs, and
rats; 43 cases were reported in 1987 (Ex. 6-465). No cases of nosocomial
transmission by blood have been reported. Arboviral
infections: Arboviral infections generally do not lead to high or sustained
levels of viremia in humans, therefore, there is little potential for
person-to-person transmission of these infections through blood products or
needlestick exposure. The exception is Colorado tick fever (CTF) caused by a
tick-borne virus which infects red blood cells. Within 3-14 days following
tick exposures, the patient experiences fever, chills, headache, muscle and
back aches. Several hundred cases are reported annually and transmission by
blood transfusion has been documented (Ex. 6-416). Relapsing
fever: Relapsing fever is a rare disease, caused by pathogenic Borreliae,
transmitted by lice or ticks and characterized by recurring febrile episodes
separated by periods of relative well-being. In the United States, a few
cases of tick-borne relapsing fever are reported in localized geographic
areas (Western United States). Though very rare, occupational transmission as
a result of patient care practices has been reported. Infections have been
attributed to blood from the vein of a patient squirting into the nose of a
technician and, in another incident, splashing into another HCW's eye from a
placental specimen (Ex. 6-488). Creutzfeldt-Jakob
disease: Creutzfeldt-Jakob disease, a rare disease with worldwide
distribution, is a degenerative disease of the brain caused by a virus. It is
believed to be transmitted by ingestion of or inoculation with infectious
material, primarily neural tissue. No cases of nosocomial transmission by
blood have been reported, although rare instances of transmission have
occurred secondary to homologous dura mater implants, receipt of human growth
hormone, and insertion of unsterilized stereotactic electrodes which had been
inserted into the brains of Creutzfeldt-Jakob disease patients and then used
on others (Ex. 6-492). There is a report of a case of Creutzfeldt-Jakob
Disease, confirmed by autopsy, in a neuropathology histopathology technician.
She had been employed in the neuropathology facility for 22 years and her
duties included rinsing formalin-fixed brains and processing, cutting and
staining sections of brain. Log records indicated that during her tenure two
individuals with CJD were autopsied, 16 and 11 years prior to the technicians
illness. It is not known how this individual became infected (Ex. 6-546). The
record contains a number of articles discussing suggested precautions for
handling materials from patients with CJD (Exs. 6-541; 6-542; 6-543; 6-544;
6-545 6-548). Human
T-lymphotropic Virus Type I: Human T-lymphotropic virus type I (HTLV-I), the
first human retrovirus to be identified, is endemic in southern Japan, the
Caribbean, and in some parts of Africa, but it is also found in the United
States, mainly in intravenous drug users (Ex. 6-493). The virus can be
transmitted by transfusion of cellular components of blood (whole blood, red
blood cells, platelets) (Ex. 6-499). HTLV-I has been associated with a
hematologic malignancy known a adult T-cell leukemia/lymphoma and with a
degenerative neurologic disease known as tropical spastic paraparesis or
HTLV-I-associated myelopathy. There is some evidence that the neurologic
disease may be associated in some cases with blood transfusion (Ex. 6-494). No
cases of occupy-tonal acquisition of HTLV-I infection have been reported. Viral
hemorrhagic fever: The term viral hemorrhagic fever refers to a severe, often
fatal illness caused by several viruses not indigenous to the United States,
but very rarely introduced by travelers coming from abroad. These illnesses
are characterized by fever, sore throat, cough, chest pain, vomiting, and in
severe cases, hemorrhage, encephalopathy and death. Although a number of
febrile viral infections may produce hemorrhage, only the agents of Laesa,
Marburg, Ebola, and Crimean-Congo hemorrhagic fevers are known to have caused
significant outbreaks of disease with person-to-person transmission,
including nosocomial transmission (Ex. 6-417). Blood and other body fluids of
patients with these illnesses are considered infectious. Any patient
suspected of illness due to one of these agents should be reported
immediately to the local and state health departments and to the Centers for
Disease Control. The bacterial and parasitic diseases listed above are
treatable with antibacterial or antimalarial drugs. No specific therapy is
available for the viral diseases, with the exception of Laesa fever. Precautions
designed to minimize transmission of the more important bloodborne viral
diseases, namely HIV, hepatitis B, and non-A, non-B hepatitis, would be
effective in minimizing occupational transmission of all the above agents in
the clinical setting. [56 FR 64004, Dec. 6, 1991; 57 FR 29206, July
1, 1992] |
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