**Health Seminar Series - Emerging Diseases**

**January 28, 2000**

Session 2 -- Concept of Diseases Emergence & the Surveillance Systems
for Infectious and Occupational/Environmental Diseases

Ms. Catherine Angotti introduced the second session in the Health
Seminar Series on Emerging Diseases, the sixth of a series of continuing
education programs sponsored by NASA's Occupational Health Program,
Office of Health Affairs (OHA), in cooperation with the Uniformed
Services University of the Health Sciences (USUHS). She introduced the
speakers for this session: Dr. David Morens, Medical Epidemiologist at
the National Institute of Allergy and Infectious Diseases, National
Institutes of Health gave the first presentation.

Dr. Morens introduced the audience to some of the concepts and issues of
emerging infectious diseases, discussed some of the principles of
emerging infectious diseases, touched on some examples that would be
presented by speakers in upcoming weeks, and ended with an historical
example. Dr. Morens discussed infectious diseases in evolutionary terms.
He referred to Newly Emerging and Re-Emerging Infectious Diseases as
"NEREIDs." Emerging infections have been in the news media, the subject
of motion pictures, books, and television documentaries. Emerging
infectious diseases are major causes of mortality worldwide; in fact,
pneumonia and influenza (categorized together) is usually reported as
the sixth leading cause of death in the U.S. Every year, these diseases
take the lives of many Americans. Dr. Morens pointed out that emerging
infectious diseases are not a modern issue. Going back about 30-40
years, there arose the notion in the Western nations that we had
essentially conquered infectious diseases. In 1969, the Surgeon General
stated that "the war against infectious diseases has been won." Dr.
Morens posed the question: What happened? He then presented the
historical perspective.

In 1347, the plague epidemic (a newly emerging infectious diseased
reached Europe and wiped out between 25 and 50% of the known population
of the world (20-40 million people). There is a lot of literature on the
plagues of mankind. There was an epidemic of bubonic plague in London in
1665. Physicians and wealthy people to protect them from diseases,
although they didn't know the cause of the disease wore protective
masks. Moving forward to 1832, this was the year when the concept of
emerging diseases was crystallized. For two years, cholera inched slowly
toward Europe from India and appeared in Paris in 1832. There was a lot
of literature about this epidemic, and it saw the birth of modern
epidemiology, modern public health methods, and modern concepts of
emerging infectious diseases. In 1902, H.G. Wells wrote that "it is
conceivable, too, that some pestilence may presently appear, some new
disease, that will destroy, not 10 or 15 or 20 % of the Earth's
inhabitants as pestilences have in the past, but 100%, and so end our
race." The threat of emerging diseases was well known and established in
the popular literature. Moving forward to more recent times, there was
the famous pan-epidemic of the "Spanish Flu" in 1918-1919. Attempts have
been made to identify the cause of that epidemic using PCR expansion of
RNA fragments from tissues of people who died and were autopsied.
Evidence to date suggests that there is nothing different about that
virus that would suggest why it was so fatal. An epidemic of this
magnitude in the U.S. in today's terms would kill over a million people
in the period of a few months. Today, there are over 13,000 types of
infectious organisms/diseases. Diseases are emerging at a very rapid
rate. The modern concept crystallized in 1992 with the Institute of
Medicine report on Emerging Infectious Diseases. It has been very
influential in educating a generation of scientists and physicians on
these threats and the principles of emerging infectious diseases.

Dr. Morens discussed some definitions. The definition of emerging
infectious diseases that is related to the IOM review is: "Infections
that have newly appeared in the population, or have existed but are
rapidly increasing in incidence or geographic range." Dr. Morens called
these "NEREID's." In Greek mythology it is "an often malevolent nymph of
Greek folklore dwelling in springs or trees as well as in the sea." This
is a good description of infectious diseases---they are malevolent; they
are small; and they dwell in the environment. Dr. Morens discussed
concepts of disease emergence. Until the modern biological era, we
didn't know emerging diseases were infectious and were caused by
microorganisms. Some of the primitive concepts haven't died even today.
For example, there was the concept that infectious diseases arose from
miasmas, or poisoned airs that are released into the environment. A
group of three investigators have even published a book "Viruses from
Outer Space." How should we think about emerging infectious diseases?
Rather than think about this in a medical or biomedical way (e.g.,
things "out there" are bad and will make us sick), Dr. Morens introduced
the concept articulated by Richard Dawkins in 1976, called "The Selfish
Gene." He said, "In the beginning was simplicity...At some point a
particularly remarkable molecule was formed by accident. We will call it
the Replicator...\[with\] the extraordinary property of being able to
create copies of itself...Now they go by the names of genes, and we are
their survival machines." The key terms are "genes" and "survival."
Dawkins argues that survival of the fittest does not happen at the level
of large animal; it happens at the level of the gene, and the organism
is merely the packaging for the gene. The organism is merely a strategy
for the genes that they surround. An influenza virus is not so much an
infection as a battle between two nucleic molecules. Dr. Dawkins says
that viruses may well have originated as collections of breakaway genes.
What do some other thinkers say about these concepts? Dr. Jared Diamond,
a biologist who has written a Pulitzer prize-winning book, *Guns, Germs,
and Steel*, has looked at this issue of infectious diseases, and has
said that humans and their pathogens are locked in an escalating
evolutionary contest, with natural selection playing the role of umpire.
Dr. Joshua Lederberg, a Nobel laureate, seems to echo Dr. Diamond---he
sees a Darwinian struggle mobilizing the genetic diversity of human
immune cells to respond to unpredictable invaders.

Dr. Morens discussed some of the principles of actual disease emergence.
What causes new diseases to emerge? All epidemiologists think of
diseases as being the products of combinations of three factors: the
agent, the host, and the environment. Think about newly emerging
diseases as the result of the interaction of viral, bacterial, parasitic
(agent) factors combined with host factors, e.g., population crowding,
natural and acquired immunity, immuno-deficiencies through poor
nutrition, etc., and environmental factors. These three factors combine
to produce diseases and epidemic diseases. There a lot of different ways
to think of this. There are different factors that interact together to
produce different emerging infectious diseases. Dr. Morens discussed
some emerging infectious diseases that can be attributed to some of
these factors. We start with agent factors---under that category there
is the category of microbial change and adaptation. An example is
Brazilian purpuric fever (about 10 years ago). It was attributed to a
genetic mutation in an old bacterium. Here, a generic mutation occurred
which caused it to suddenly become deadly. Other examples are resistant
stapholococci, resistant malaria, HIV (which evolved to adapt to man),
and acute hemorrhagic conjunctivitis. Also in the same category of
agent, we see microbial partnership and synergism. For example, people
with HIV develop secondary complicating infections, sometimes with
organisms that are not normally pathogens. Everybody knows about the
relationship between influenza and bacterial pneumonia and the mortality
rate can be high, particularly in elderly people. Moving to the host
category, we see human demographic and behavioral factors. One example
is dengue fever. The epidemics begins to occur as population centers
(e.g., Bangkok, Saigon) begin to become more crowded an urbanized (after
World War II). Travel and commerce explain the emergence of many
diseases, certainly acute hemorrhagic conjunctivitis. It has been spread
almost entirely between major air routes. Other examples are
tuberculosis and recent epidemics of West Nile virus (imported to new
locales by travel and commerce). Under aspects of environment, we see
ecological change. An example of that are the outbreak of hanta virus
pulmonary syndrome, the outbreaks of Bolivian hemorrhagic fever, and the
increasing epidemic of rabies. We also have technology and
industry---for example the recent food-borne epidemics. The fact that we
can mass produce, process, and ship foods over great geographic
distances provides for the possibility for something contaminated to be
widely spread and dispersed and cause epidemics of diseases in locales
where they have not been seen before.

Finally, there is the breakdown of public health. The best example is
what happened 10 years ago with respect to tuberculosis in the U.S.
After the great successes in the control of tuberculosis in the 1950's,
we became complacent that this disease was almost wiped out. Many state
health department programs, which had been major, were reduced to the
point that many state health departments had no effective public health
or laboratory control programs for tuberculosis at all. The tuberculosis
re-emerged, partly due to the HIV epidemic. Part of the breakdown in
public health is the breakdown in public health laboratory systems. The
revolution in genetic technology has left many poor health departments
cashed strapped and unable to introduce new technology, further
weakening the system. In addition, there has been a very recent increase
in anti-vaccinationism, the popular distrust of "good" vaccines, and the
unwillingness of parents to have their children vaccinated has led to
the re-emergence of diseases that were once controlled.

Dr. Morens shared an example of Dr. Diamond regarding the stages in
microbial host switches. Many of the microorganisms that have emerged
and are problems for humans have emerged from animals and made a host
switch to human beings. He relates this to the time when man stopped
being a hunter/gatherer and began to farm and have permanent residence,
leading to cities and social systems. That time period was about
8,000-10,000 years ago. That socialization of mankind (and close contact
with domesticated animals) provided a major opportunity for precursor
organisms of other animals to make the host switch to man. This argument
helps as think about these things, but it shouldn't be carried too far.
For example, most historians and microbial archeologists believe that
various skin organisms were adapted to human beings long before they
gathered in cities. Although human beings did have infectious diseases
prior to the socialization period, they tended to be mostly bacteria
that lived in the respiratory tract, GI tract, or on the skin.

Dr. Morens gave same examples of current emerging diseases. A number of
microbial threats appeared in the 1990's---both new and old diseases:
hantavirus, dengue fever, cholera, anthrax, lassa fever, Bolivian
hemorrhagic fever, diphtheria, Rift Valley fever, yellow fever, and
plague.

We can make lists of these emerging and re-emerging diseases and the
lists are huge. Most people who work in the field of microbiology and
infectious diseases are genuinely concerned. There is increasing
antibiotic resistance due, in part, to the overuse and inappropriate use
of antibiotics. Physicians should play a more active role in controlling
this problem. We now know there is an increasing problem with
vancomycin-resistant enterococci, particularly in hospitals. There has
been increasing resistance in staphylococcus aureus. What would happen
if staphylococci became resistant to all known antibiotics? We would see
a return to the way things were done during the Civil war days, e.g., a
high amputation rate and high mortality. Hantavirus has been recognized
as having an epidemic local focus over much of the U.S. The South
American variant of this disease is 50% fatal and is not only
transmitted by rodents, but can be acquired person to person. Dengue
fever epidemics have exploded in recent years. The mosquitoes that carry
dengue cover as many as 20-21 states. In fact, there was a small
outbreak in Texas this year. For the first time in many decades, an
American died of dengue fever. Plague has made a return in many parts of
the world and is also found in the U.S.

Dr. Morens shared an example of an historical epidemic. In 1875, Fiji
was isolated from world commerce by distance; the shortest distance was
from Australia, which took about 19 days. In addition, there were
quarantine laws. Britain administered Fiji's laws. For infectious
diseases that took less than 19 days, there was a system in place to
keep them out. In 1875, Fiji decided to seek cession to the British
crown, and Fiji was to become part of the British Commonwealth. During
the nine months of transition, there was ineffective government health
control. The old king was honored by being sent to Australia for a state
visit; he took his son and about 100 people. At that time, Sydney was
experiencing a measles epidemic and the Fijians had never been exposed.
Six days from arriving back in port in Fiji, the King's son had acquired
measles. The quarantine laws were broken down, no quarantine flag was
flown, and all the Fijians went to shore. The result was an epidemic of
measles (an emerging infectious disease for Fiji) that killed about 30%
of all people on Fiji. Why did measles kill so many people? We didn't
know at that time what we know now. Death from measles in developed
countries is generally due not to the measles itself, but to
complicating bacterial pneumonia. This was first learned in World War I.
Complicating the situation in Fiji was a Vitamin A deficiency among the
population, which is associated with mortality in measles. It is very
likely that some of the same factors associated with disease emergence
today were seen in Fiji in 1875---microbial partnership and synergism,
human demography and behavior, travel and commerce, and the breakdown of
public health.

Infectious diseases and emerging infectious diseases are important and
will affect the lives of many health professionals.

Questions:

KSC: Re the resistance to vancomycin, the prevalence seemed to be higher
in larger hospitals. We are told that one of the primary causes of
resistance is the overuse of antibiotics by primary practitioners. Does
the epidemiological evidence support this? It is not clear how an
antibiotic-resistant organism can emerge in a five to seven day course
of treatment in an otherwise healthy individual.

Dr. Morens: The general principle is that antibiotics encourage the
emergence of resistant organisms. In the case of vancomycin-resistant
enterococci, the story is not really clear. We don't really know the
epidemiology of this organism. It is studied most often in hospitals.
What is happening in the community? This is still a question. With
respect to the latter part of the question, the current thought is that
there is a hospital flora that is created and changes over time. Over a
period of months or years, the continued use of antibiotics selects for
this hospital flora, which may in some cases become established in human
carriers.

Moscow: We understand examples of microbial synergism; what about some
examples of possible microbial antagonism (infection with one microbial
organism might limit or prevent infection of another)?

Dr. Morens: This is a very good point. A general answer would be that
infectious disease people presume that in some cases, infections with an
organism can limit or inhibit infections with another. We know, for
example, that when a viral infection occurs, certain cytokines may be
released, like interferon, which may limit or prevent infections from
other virus, simply by regulating the immune system. Whether this has an
effect on the emergence of diseases, I don't know, but it would be
interesting to study. The emergence of organisms, usually new viruses,
for example, emerge from old viruses; what you get is a family of
viruses, some old, some new. The new ones will often be cross-reactive;
in some cases, antibodies to the old ones can prevent or limit the
spread of the newly emerging one.

HQ: Please comment on emerging non-infectious diseases; please clarify
the concept for these as compared to emerging infectious diseases.

Dr. Morens: The terminology of emerging infectious diseases came about
as applied to infection; only in very recent times have some people
began to talk about emerging non-infectious diseases. The history and
the background to discuss these is not quite as well developed. However,
the idea is analogous; not only are there new emerging infectious
diseases, but also newly emerging non-infectious diseases. They fall
into two categories: (1) chronic diseases, and (2) diseases associated
with lifestyle and human behavior. In Western nations, the last century
saw a huge epidemic of myocardial infarction, which peaked around 1950,
then it began to decline, even before there was good prevention and
treatment. The idea that chronic diseases can emerge and disappear is an
established one. A leading theory now is that much cardiovascular
disease is actually an infectious disease; however, the evidence is
quite not there yet. A large number of the chronic and lifestyle
associated diseases, e.g., cancers, heart disease, may be proven to be
infectious in origin.

Dr. Wesley Farr, Associate Professor of Medicine and Director of
International Health Program at the Robert C. Byrd Health Sciences
Center, West Virginia University, discussed surveillance systems for
emerging infectious and occupational/environmental diseases. He reviewed
the traditional systems for surveillance of infectious diseases, systems
for surveillance of non-infectious occupational/environmental diseases,
and newer systems for surveillance of emerging infectious disease.
Surveillance is defined as the systematic, ongoing observation of the
occurrence and distribution of disease within a population and of the
events or conditions that increase or decrease the risk of such disease
occurrence. Surveillance can be active or passive, prospective or
retrospective, ongoing or intermittent, incident or prevalent,
comprehensive or limited, and rotating or sentinel. A physician or local
health worker initiates passive surveillance when they report an
observed case in compliance with regulations. Active surveillance
involves a public health worker regularly consulting physicians,
clinics, hospitals, and laboratories requesting information.
Surveillance site can be random or there can be sentinel sites. An
example of a network that uses sentinel sites is the WHO Global
Influenza Surveillance Network. Disease reporting is the most
fundamental form of surveillance. Disease reporting is used to detect
trends or distribution of diseases and public health agencies can
initiate investigative or control measures. The elements of disease
surveillance are: collection of data, analysis of data, interpretation
of data, and dissemination of data. Data is collected at the local level
and assembled at district, provincial, or state levels. It is aggregated
at the national level, with international reporting to WHO. The
activities of the local health care provider are to report each case by
telephone, FAX, or mail to the local and state health departments. In
the future, we hope to see internet-based reporting. The local health
department can be city, county, or regional. It uses the reports in
allocating health services. They follow up on infectious diseases, plan
programs, and measure the effectiveness of services and program. The
State Health Department has an Office of Vital Statistics; it maintains
files for permanent reference and prepares reports for transmission to
the National Center for Vital Statistics. The U.S. Public Health Service
prepares and publishes the national reports on notifiable diseases,
publishes analysis of data on health and social issues, and fosters
complete and uniform disease registration.

There can be several pitfalls in surveillance, both underestimation and
overestimation. Underestimation can result from inadequate surveillance,
insufficient culturing, inadequate microbiologic techniques, failure to
recognize multi-pathogen problems, failure to recognize low frequency
clusters, or failure to recognize diseases caused by uncommon pathogens.
Overestimation can occur when there are changes in definitions,
increased surveillance, improvements in culturing techniques, and
comparison of numerator data instead of rates. The local health care
provider needs to recognize and report rare or unusual events as well as
reportable diseases. For example, one local health care provider, Dr.
Bruce Tempest, reported on the local Four Corners outbreak in May 1993.
In late May, a CDC staff was sent to Albuquerque. By June 4, Hantavirus
was identified as the possible etiology. This was a major surprise,
because Hantavirus had never been associated with respiratory disease.
By the end of July, the CDC had published interim recommendations for
risk reduction. This is an excellent example of a surveillance system
that worked well and shows the significant of the role of the local
health care provider.

Dr. Farr discussed prevention of emerging infectious diseases and
referred to the CDC publication "Preventing Emerging Infectious
Diseases---A Strategy for the 21^st^ Century." The four main goals are:
surveillance and response; applied research; infrastructure and
training; and prevention and control. The objectives of the first goal
are to strengthen infectious disease surveillance and response; improve
methods for gathering and evaluating surveillance data; assure the use
of surveillance data to improve public health practice and medical
treatment; and strengthen the global capacity to monitor and respond to
emerging infectious diseases. The CDC has set up the Epidemiology and
Laboratory Capacity (ELC) Program and the Emerging Infections Programs
(EIPs) and is assisting providers in developing provider-based sentinel
programs. In 1995 to 1998, the CDC has established ELCs in 30 states and
localities; by 2002, they want to have ELCs in all 50 states. They also
hope to strengthen the EIP network by increasing demographic and
geographic representation and enhancing the laboratory and
epidemiological capacity. Another activity is the use of sentinel
networks. The CSC hopes to integrate public health information and
surveillance, use integrated health care delivery systems, and use new
tools to improve surveillance. For example, molecular epidemiology is
being used to determine the country of origin of measles. Most of the
cases of measles in the U.S. are imported. The CDC has proposed a
nationwide computer system for electronic surveillance, and about \$65
million has been proposed in the 2001 budget. It will replace the system
that relies on phone calls and post cards. This will move the doctor's
report from clinic to local and state health department to CDC
instantaneously. In summary, surveillance is used to detect the changes
in the rates of infectious diseases, develop control programs, and to
monitor the effectiveness of control programs.

Dr. John E. Parker, Professor of Medicine and Community Medicine,
Institute of Occupational and Environmental Health, West Virginia
University, focused on non-infectious diseases. He discussed the
purposes of surveillance, provided some examples of activities in the
U.S. and internationally, discussed the concept of sentinel health event
recognition, and provided some examples of newly recognized disorders.
Surveillance is important to identify new hazards, define the magnitude
of the problem, track trends, target interventions, and evaluate the
success or failure of intervention efforts. For non-infectious diseases,
it is often challenging to recognize these diseases because they mimic
many common medical problems. For example, asthma is a common problem
that may or may not have a workplace or environmental etiology. For
occupational and environmental diseases, it is really the etiology and
not the pathology that is often the distinguishing feature. It takes a
very astute clinician to recognize this. Identification of the
environment is important for the proper management of the individual and
for the protection of other exposed populations. This allows us to
target many of the public health activities. Fortunately, astute
clinician recognition is common. The clinician has to makes a connection
between the specific diseases and the exposures. The clinician may be
aided by the recognition of a rare disease or by the recognition of a
cluster of disease in a specific environment. The clinician must have a
mechanism to report it in order to bring the multi-team approach that is
needed to establish the workplace etiology of the disease. Dr. Parker
provided same examples of occupational activities that occur at the
state and national levels. State occupational surveillance activities
include hearing loss, burns, silicosis, and asthma. National
occupational surveillance activities include lead intoxication, coal
workers lung disease, and workplace injuries and fatalities.
International surveillance activities include silicosis (looking for
national and global trends). Dr. Parker talked about some sentinel
health events due to environmental or occupational causes. If we know
that a hazardous substance has toxicity, we may choose to look for the
impact of that toxin in the workplace. If a workplace etiology has not
been identified for some disease, it is much more difficult to track
that disorder. If sentinel health event is filed as a preventable or
unnecessary work-related disease, it can stimulate workplace or
environmental evaluation from a medical or industrial hygiene
standpoint. Often it is the industrial hygiene colleagues who provide
the best information on how to prevent disease, either by product
substitution, engineering control, or the use of personal protective
equipment. Dr. Parker provided three examples that resulted in the
identification of a new agent causing a disease: some outbreaks of acute
respiratory illness in the last decade that resulted from leather spray
exposure; severe lung disease (in Spain) associated with BOOP in textile
spraying; and interstitial lung disease (later called "flock worker's
lung') in workers at a nylon flock plant in Rhode Island, associated
with airborne dust and respirable contaminants during the cutting
process.

Occupational and environmental diseases present many challenges. There
is a need for ongoing surveillance, sentinel health reporting, outbreak
investigation, and a role for the astute clinician. There is an
important interface between clinical medicine and public health. Many
agencies are interested in Environmental Health, e.g., WHO, EPA, NASA,
DOE, DOD, CDC, NIH, and several regulatory agencies (OHSA, MSHA). There
are many challenges in proving exposure environmental health links. It
requires multidisciplinary sciences. There are flaws in reporting
mechanisms and they need to be improved, including the opportunity for
physicians to more easily report disorders that they suspect are of
occupational or environmental cause. In addition, our ability to
anticipate disease would be better served by improved hazard
surveillance as well as better toxicology work in predicting hazards,
especially when products are reformulated or reintroduced.

Questions:

KSC: I admire the individual practitioner who can report these cases. If
we want to get accurate information on the prevalence of disease, we
have to be careful about the obligations put on hospitals. Physicians
are sometimes discouraged from testing patient, e.g., for HIV, due to
the legal requirements for obtaining consent and then for following them
if they tested positive. This made it quite expensive. A lot of doctors
in practice will see cluster of cases and hopefully, with the
internet-based system, it will be easier to report them. Obviously,
reporting in a journal is quite challenging. Some examples are: carpal
tunnel syndrome in women who worked manufacturing parachutes; metal fume
fever in welders; and cases of women gluing their eyelids together
because of the tactile similarity of eye drop bottles and the bottles
used to hold glue that is used to adhere artificial nails.

Dr. Parker: Those were some excellent additional examples as well as a
reminder of the impediments for doing a good search for occupational and
environmental etiologies. There are a number of disincentives, which are
described in the Kern article in the Annals of Internal Medicine (1998).
There are a number of financial and political disincentives to establish
the workplace etiology of disease and they are well described in this
article.

HQ: We understand that as much as 70-80% of total death is attributed to
lung disease. Do you have any statistics that have shown what percentage
is due to environmental and occupational diseases?

Dr. Parker: I don't have any recent estimates; I do recall a number of
60% from a Journal of Occupational Medicine article in 1993. The Center
for Environmental Health and/or NIOSH may have some other estimates of
occupational and environmental etiologies of disease. They are common,
and we are challenged; many of the common disorders, e.g., low back
pain, which may or may not be occupational, are difficult to identify in
etiology.

With respect to historical examples, Dr. Parker noted that there were
astute clinicians that recognized chronic beryllium disease in the
1940's; they were to be commended for that recognition. There is an
important public health role for the astute clinician.

Dr. Morens extended the interesting history of emerging occupational
diseases even further back than the chimney sweep story. One of the
first examples of an occupational disease that was emerging and
recognized by astute clinicians occurred in Germany in the 1600's; it
was called colica pictonum, an occupational disease associated with lead
contamination of wine. Epidemic investigations were conducted separately
by Gockel and Stockhausen. Both of those epidemic investigations show
the power of an astute observer to recognize an occupational disease.
Epidemics of colica pictonum continued through the 1800's, up through
the middle of the 19^th^ century and were written about by other
observers. Another example was the mercury poisoning associated with the
hat-making industry that gave rise to the phrase, "mad as a hatter.". As
late as the 1920's, there were huge epidemics of mercury poisoning in
workers in the hat industry, concentrated in the New England states. The
U.S. Public Health Service conducted extensive investigations to resolve
this problem. The history of emerging occupational diseases is very long
and very fascinating.