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OCR for page 8
.
Descriptive Epidemiology of
Occupational Infections of
Laboratory Workers
A. INTRODUCTION
The precise incidence of occupational infections
among laboratory workers is not known. During the
past century, however, an extensive literature has
documented that such infections have occurred with
regularity and have occasionally resulted in death.
The overall mortality rate of reported cases is 4 per-
cent [1001. Published reports have dealt largely with
single cases or outbreaks, retrospective studies, and
passively collected anecdotal information. For the
most part, historical accounts of laboratory-associ-
ated infections have listed only individual cases with
no attempt at the difficult task of determining the
size of the populations at risk. Furthermore, there is
no central focus of responsibility or authority in the
United States that maintains a comprehensive data
base or conducts surveillance of occupational infec-
tions in laboratory workers who regularly or occa-
sionally handle microorganisms or viruses.
B. THE EPIDEMIOLOGIC TRIAD
The components of the epidemiologic triad asso-
ciated with laboratory-acquired infections are the host,
the infectious agent, and the environment. Although
most of the data relevant to these three factors have
been collected retrospectively and are incomplete, an
evaluation of the information that is available pro-
vides some insight into the complexity of the prob-
lem.
1. The Host
Comprehensive and current data are not available
on the demography of laboratory workers (the host)
who risk occupational infection with the agents they
handle in their daily activities. Published surveys
[28], however, indicate that the number of workers
employed by public health and clinical laboratories
is substantial, having been estimated at 250,000 in
1977. A more recent survey conducted in 1983 by
the Occupational Safety and Health Administration
(OSHA) [138] estimated that there are 370,000 em-
ployees in clinical laboratories, 45,000 employees in
federal government laboratories, and 127,000 em-
ployees in academic laboratories. Additionally, the
number of physicians' office laboratories in which
one or more persons are employed may exceed
100,000 facilities. Of the combined total of more
than 640,000 workers, as many as 500,000 may regu-
larly or occasionally work with infectious agents or
with blood, serum, urine, or other body fluids or
tissues that may contain an infectious agent.
The surveys cited above do not include all seg-
ments of the general population of laboratory work-
ers at potential risk of occupational exposure to in-
fectious agents or their toxic or sensitizing metabolic
products. Among the segments inadvertently ex-
cluded are a substantial but unknown number of per-
sons whose duties may involve either regular or oc-
casional handling of infectious materials: e.g., those
persons working in animal and avian disease diag-
nostic or research laboratories, environmental labo
ratories, industrial and biologics production labora-
tories, forensic laboratories, and in laboratory animal
production and care facilities. Consequently, the
estimate of 500,000 workers who may be at risk of
occupational infections probably represents a signifi-
cant underestimation of the true number.
2. The Infectious Agent
Data are also not uniformly available about the
8
OCR for page 9
DESCRIPTIVE EPIDEMIOLOGY OF OCCUPATIONAL INFECTIONS
second epidemiologic component, the infectious
agent. Details about the kinds of infectious agents
encountered in the various categories of laboratories
and the frequency with which such agents are handled
are unknown. National morbidity data [311 indicate
that hepatitis B virus (HBV) infections are wide-
spread in the general population and that a pool of
new cases and chronic carriers numbering several
million may exist. For example, 1.0 to 1.5 percent of
all admissions to large urban hospitals are positive
for hepatitis B surface antigen (HBsAg) [451. A1-
though blood samples from these patients are poten-
tially infectious, their identity is usually unknown
throughout the hospitalization. These data suggest
that HBV represents the specific infectious agent
most likely to be transmitted in the clinical labora-
tory occupational setting.
3. The Environment
The third component of the epidemiologic triad,
the laboratory environment, is also poorly defined.
The physical features, including safety equipment
and adequacy of the facility, vary widely. Although
a number of federal, state, and private sector organi-
zations (e.g., Health Care Financing Administration,
OSHA, College of American Pathologists, Joint
Commission on the Accreditation of Healthcare Or-
ganizations, American Association of Blood Banks,
and various state agencies) do regulate, license, ac-
credit, or inspect clinical laboratories, there is no
consensus among these various organizations about
the standards for laboratories operating under their
respective jurisdictions. There is a current voluntary
national code of laboratory practice [105] that de-
scribes features of a laboratory facility recommended
for work with infectious agents, but there is no na-
tional authority that regulates laboratory operations
conducted solely on an intrastate basis.
C. LABORATORY-ASSOCIATED
INFECTIONS
1. Infectious Agents Presenting the Highest
Risk
The series of survey summaries of laboratory-
associated infections described by Pike in 1976 [100]
indicates that, as a group, bacterial infections were
the most frequently reported occupationally associ-
ated infections of laboratory workers during the first
9
seven and one-half decades of the twentieth century.
Viral and rickettsial infections were more frequently
reported during the latter half of this time period. Of
the 3921 cases reported, the five most frequently
recorded infections in rank order were: brucellosis,
Q fever, typhoid fever, viral hepatitis (all ~es), and
tuberculosis. Most of these diseases were prevalent
and important public health problems in our recent
past, and their etiologic agents were handled com-
monly in clinical and diagnostic laboratories at that
time.
While the compilations of laboratory-associated
infections cited above provide a historical perspec-
tive of the hazards of occupational infection, these
data are not necessarily indicative of present-day risk
of infection. For example, brucellosis, the most fre-
quently reported occupational infection, was formerly
a major and widespread disease in human and animal
populations. More than 6000 human cases were
reported in the United States in 1947 [301. As the
incidence of brucellosis declined in domestic animal
reservoirs, there was a corresponding decline in cases
in the human population. By 1963, the annual num-
ber of cases reported had declined to 407 [431. Of
this number, only one case, a Brucella suds infection,
was specifically identified as being laboratory asso-
ciated.
Sharp decreases have been observed also in the
annual number of reported cases of typhoid fever. In
1942, there were almost 6000 cases; in 1952, 2341
cases; and in 1984, 390 cases, of which approxi-
mately 70 percent were acquired during foreign travel
[301. Similarly, reported cases of tuberculosis de-
creased from 121,000 in 1950 to 22,500 in 1984 [301.
As the incidence of the "top five" diseases has de-
creased in the general population, there has been
generally a corresponding decrease in the number of
laboratory specimens received and examined that
contain these agents. This decrease in numbers of
specimens containing the infectious agents has cer-
tainly reduced the probability of occupational expo-
sure. On the other hand, newly emerging diseases or
newly recognized organisms may increase the risks
of infection for laboratory personnel.
Tuberculosis is an interesting example of the lat-
ter situation. The recognition of the existence of
species of mycobacteria other than Mycobacterium
tuberculosis, M. bovis, and M. avium has required
that specimens suspected of containing mycobacteria
be subjected to increased laboratory manipulations,
in order to recover as well as to identify the organ
~e . .
OCR for page 10
10
isms. Such increased manipulations are not without
inherent risks to laboratory personnel. The recent
report of Miller et al. [84] summarizes the collective
experience of several investigators and shows that
tuberculosis has ranked among the top six causes of
laboratory-associated infections for more than 25
years. These published reports probably represent
only the "tip-of-the-iceberg" of laboratory-associated
cases of tuberculosis. For example, the laboratory
tuberculosis consultant at the Centers for Disease
Control (CDC) has, at the time of this writing, been
asked to assist in 13 investigations of laboratory-
associated tuberculous infection, none of which has
been published [741. In these 13 investigations, 72
of 275 (26 percent) exposed individuals were found
to have been infected with tubercle bacilli (i.e., re-
cent tuberculin conversion); if untreated, 10 percent
of these individuals would be expected to develop
active tuberculosis. The fraction of exposed person-
nel infected in the different outbreaks ranged from
19 to 55 percent. Airborne dissemination was sus-
pected in all instances.
It has recently been recognized that both acquired
immunodef~ciency syndrome (AIDS) [32,33,119,122]
and intravenous drug abuse [36] may be contributing
factors to the recent increase in morbidity from tu-
berculosis. Other factors that are suspected of play-
ing a role are the influx of immigrants from Central
America and the increasing numbers of homeless
people. These factors can only cause an increase in
the risk of mycobacterial infection for laboratory
personnel. Despite excellent published surveys of
the frequency of such infections, it appears obvious
that many cases occur that are not reported in the
medical literature.
Q fever differs from the other "top five" occupa-
tional infections in that this rickettsial disease has
remained a relatively obscure public health problem
of unknown incidence and sporadic distribution.
However, Q fever is a proven and continuing hazard
in those few facilities in which work with infected
animals or human tissues is conducted, or in which
the agent is propagated. This rickettsial agent is
remarkably resistant to dessication and inactivation,
and 10 or fewer organisms may produce infection via
the respiratory route [142].
Hepatitis of varied etiology continues to be a
community as well as an occupational health hazard
among certain high-risk groups, including laboratory
workers. Over the past 15 years, the incidence of
BIOSAFEI Y IN THE LABORATORY
HBV infections has shown a progressive annual in-
crease, while in the same period, the number of re-
ported cases of hepatitis A virus (HAY) infection has
decreased [311. In 1983, for the first time, the num-
ber of HBV cases exceeded those caused by HAV.
While laboratory hazards of HAV infection are re-
stricted primarily to persons working with experi-
mentally or naturally infected chimpanzees, HBV
poses a persistent and continuing hazard to all cate-
gories of laboratory workers handling clinical speci-
mens of human origin. HBV has been demonstrated
in a wide range of body fluids and tissues typical of
those received and handled in clinical laboratories.
The number of infectious virus particles may reach
concentrations in excess of 100,000,000 per millili-
ter of blood. Since the early 1970s, when procedures
for the serologic differentiation of HAV and HBV
came into general use, HBV has become the leading
cause of occupationally acquired infection among
laboratory and health care workers [811. Studies by
Jacobsen and co-workers in Utah demonstrated a
prevalence of clinical HBV infection in clinical labo-
ratory personnel that was 14 times greater than that
in the general population, i.e., 0.84 cases/100,000
versus 0.06 cases/100,000, respectively [701. Ele-
vated HBV infection rates or incidences of serologic
markers were demonstrated in public health labora-
tory workers in the United Kingdom [64], in clinical
chemistry workers in Denmark [114], and in small
rural hospitals [45], as well as in large urban hospi-
tals in the United States [661. Osterholm and An-
drews [97] have demonstrated annual infection rates
for HBV and non-A/non-B hepatitis that exceeded
10,500 cases/100,000 in the staffs of hospital dialy-
sis units, while employees in nondialysis units of
these hospitals exhibited a rate of approximately 500
cases/100,000. The ratio of HBV to non-A/non-B
hepatitis infections was greater than 5 to 1.
Lauer found HBV antigen on one-third of the
surfaces of work areas, equipment, and laboratory
implements sampled in a large, modern medical cen-
ter laboratory [76]. Collins found visible blood on
the labels of 17 percent of tubes of blood specimens,
and feces on the external surfaces of 6 percent of the
containers of He stool samples received at a public
health laboratory in England. Four to five percent of
laboratory services request forms received by an-
other public health laboratory in England were visi-
bly blood stained [421. Bond et al. demonstrated that
HBV remains viable and infectious after being dried
. ~,
OCR for page 11
DESCRIPTIVE EPIDEMIOLOGY OF OCCUPATIONAL INFECTIONS
in serum and held for seven days at ambient labora-
tory environmental conditions of 25°C and 42 per-
cent relative humidity t201.
The primary routes of occupational infection with
HBV, in rank order, are as follows: accidental paren-
teral self-inoculation with infectious fluids (needle
sticks) [45,811; exposure of the mucous membranes
of the eyes, nose, or mouth to infectious materials;
and, possibly, contamination of the skin with infec-
tious materials.
In a joint advisory notice, the U.S. Departments
of Labor, and Health and Human Services, have in-
formed employers about the serious occupational
infection problems of HBV, human immunodefi-
ciency virus (HIV), and other blood-borne diseases
[1391. In this advisory, federal health officials esti-
mated that as many as 18,000 health-care workers
may be infected in a single year with HBV. Of these
cases, as many as 12,000 may be occupationally
associated. It was further estimated that nearly 10
percent of the cases will become long-term carriers
of the virus, and that more than 200 health care
workers may die as the result of the HBV infection or
associated complications.
The evidence is overwhelming that, of all indige-
nous pathogens, HBV has the greatest potential for
transmission within the occupational setting of the
clinical laboratory. This conclusion is based upon
the comparatively high frequency of asymptomatic
carriers, the high titers of virus in blood and other
body fluids, the stability of the virus on work sur-
faces and other items in the laboratory, the low infec-
tious dose, the multiple routes of infection, and the
demonstrated occupational incidence of infection.
An essential consideration in the occupational
risk assessment of HBV and other infectious agents
for which only Biosafety Level 2 (see Appendix A)
practices are recommended is the lack of evidence
suggesting that occupational transmission occurs by
means of true infectious aerosols, i.e., inhalation of
respirable particulates typically less than 5 microns
. .
In ~ .lameter.
While not among the most prevalent occupational
infections recorded by Pike (i.e., the "top five") [100],
shigellosis is historically and currently a continuing
occupational risk. The low oral infectious dose (on
the order of 100 viable organisms) facilitates trans-
mission in the occupational setting, as well as in the
general population [1421. In a retrospective study of
more than 20,000 British medical laboratory work
11
ers, shigellosis was the third most frequently recorded
occupational infection, following viral hepatitis and
tuberculosis [641.
2. Infectious Agents Presenting the Lowest
Risk
In contrast to the proven occupational infection
hazard of HBV and the other "top five" agents, a
number of infectious agents handled in laboratories
have exhibited a consistent history of remarkably
low incidence or absence of reported occupational
infections. Examples of such agents include rabies
virus, Creutzfeldt-Jakob agent (CJA), Vibrio chol-
erae, Clostridium tetani, and HIV. While the conse-
quences of infection with any of these five agents are
serious, the cumulative history of laboratory experi-
ence attests to the low risk of transmission in the
laboratory setting.
In the almost 100-year history of work with ra-
bies virus in diagnostic and research laboratories,
often in the most primitive of facilities and without
preexposure immunization of personnel, only two
documented cases of laboratory-associated infections
have been recorded. Both cases occurred under con-
ditions involving the manipulation of relatively large
quantities of high-titer virus suspensions: one in a
production facility [27] and the other in a research
laboratory [291. Exposure of personnel to aerosols
of high-titer virus suspensions was the most plau-
sible explanation for each of these two unusual cases.
Neither the quantity nor the concentration of the
virus in the materials handled, nor the procedures
performed, was typical of the conditions in a diag-
nostic or clinical laboratory.
Creutzfeldt-Jakob agent, a slow virus causing
transmissible viral dementia, is an infectious agent
that can be passed serially from human to human,
and from human to susceptible nonhuman primates
or rodents. Extensive experience with CJA and the
clinical disease (CJD) up until the present time has
indicated that "none of the people in closest contact
with patients with CJD (wives, friends, employee
contacts, members of the medical or nursing profes-
sions, or paramedical personnel) appears to have a
higher risk of contracting CJD than does the general
population. Not a single case of CJD has yet been
reported to have occurred in workers most exposed
to infectious tissues from patients with CJD (neu
OCR for page 12
12
ropathologists, research scientists, and laboratory
personnel). Thus, despite proven person-to-person
transmissibility of the disease by invasive procedures,
the risk of acquiring CJD by any means other than
tissue penetration by contaminated materials must be
very small indeed" [231. It should be noted that two
accounts of the occurrence of CJD in laboratory work-
ers were recently published, although the causal rela-
tionship between the disease and occupational expo-
sure was not established in either case [85,1131.
While cholera is periodically epidemic in tropical
and subtropical countries, only 12 laboratory-associ-
ated infections have been reported during this cen-
tury [1001. The very high oral dose required for
infection, of the order of 100,000,000 viable organ-
isms [142], is undoubtedly a major reason for the
small number of laboratory-associated cases.
Although Pike recorded five laboratory exposures
to toxin of Clostridium tetani produced in vitro [100],
there have been no recorded cases in laboratory work-
ers of occupational infections or intoxications with
C. tetani, C. botulinum, or their respective toxins.
Few infectious agents have generated more con-
cern and anxiety over potential occupational expo-
sure and hazards of infection than has HIV. Active
prospective surveillance, however, has shown that
fewer than 1 percent of overt exposures (including
needle sticks) of people attending patients with AIDS
or with other manifestations of HIV infection, have
resulted in seroconversion of the exposed individuals
[351. The majority of those health care workers with
reported occupationally acquired HIV infection have
a history of needle stick exposure to blood of in-
fected patients in the clinical setting. As of February
1988, there have been three reported seroconversions
in laboratory workers. One of these three cases
occurred in a medical technologist who spilled blood
from an infected patient on her ungloved hands and
forearms while manipulating an apheresis machine
[351. The other two recorded cases occurred in em-
ployees of large-scale virus production facilities
propagating HIV for research or reagent use [36,1431.
One of these two workers had an overt parenteral
exposure to a concentrated virus preparation. The
other worker had no recognized accidental occupa
BIOSAFETY IN THE LABORATORY
tional exposure or any risk behavior linked to HIV
infection.
Despite the low incidence of transmission in the
laboratory, the potentially life-threatening conse-
quences of HIV infection mandates that all labora-
tory workers who handle blood, body fluids, tissues,
or cultures utilize those laboratory practices and per-
sonal protective measures identified as 'universal
Precautions" by the CDC, which are recommended
for the prevention of transmission of HIV and other
blood-borne diseases [341.
Common to each of these infectious agents with a
demonstrated low risk of occupational infection is
the fact that primary occupational infection is associ-
ated with one of the following exposures: accidental
parenteral inoculation (e.g., needle stick); contami-
nation of the mucous membranes of the eyes, nose,
or mouth with infectious droplets (par~culates typi-
cally greater than 5 microns in diameter); ingestion;
or penetration of the intact or broken skin by the
agent. There is no documented risk of transmission
by means of an infectious aerosol (particulates typi-
cally less than 5 microns in diameter) generated dur-
ing the manipulation of clinical materials or of diag-
nostic quantities of the agent.
3. Other Infectious Agents
Except for some exotic microbial agents, the oc-
cupational risk of infection with virtually any bio-
logical agent falls between the extremes observed
with the"top five" and the"low-risk" groups of
infectious agents described above. The recommended
facilities, equipment, and microbiological practices
necessary for the handling of infectious agents are
detailed in Chapter 3 and in Appendix A, which is a
reprinting of the Centers for Disease Control (CDC)/
National Institutes of Health (NIH) publication, Bio-
safety in Microbiological and Biomedical Laborato-
ries [1051. These guidelines should be followed
when contemplating work with any potentially infec-
tious agent. Recommendations for handling HIV, an
infectious agent that was identified after the CDC/
NIH publication, are reproduced in Appendixes B
and C [34,36,381.
Representative terms from entire chapter:
laboratory workers
