Download Resurgent and emergent disease in a changing world

Resurgent and emergent disease in a
changing world
Mitchell L Cohen
Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for
Disease Control and Prevention, Atlanta, Georgia, USA
Emerging infectious diseases pose important public health problems for both the
developed and developing world. Many new or previously unrecognized
bacterial, fungal, viral, and parasitic diseases have emerged within the past two
decades. At the same time, many once-controlled infections have re-emerged or
become resistant to antimicrobial therapy. This emergence is the result of changes
in society, technology, the environment, and the microbes themselves, and these
changes have had often unpredictable consequences. Important factors
influencing emergence include changes in human demographics and behaviour,
changes in technology and industry, changes in economic development and land
use, increasing and rapid international travel and commerce, microbial adaptation
and change, and the breakdown of public health measures. Addressing emerging
infectious diseases will require international and interdisciplinary partnerships to
build an appropriate infrastructure to detect and respond to these often
unanticipated threats to health.
Correspondence to
Mitchell L Cohen,
Division of Bacterial and
Mycotic Diseases (C09),
National Center for
Infectious Diseases,
Centers for Disease
Control and Prevention
(CDC), 1600 Clifton Road,
Atlanta, GA 30333, USA
For most of the last millennium, life was short and often unexpectedly
ended by an infectious disease. Median life expectancies ranged from
20—40 years, and although the impact of infectious diseases was greatest
among the poor, all classes of society were affected. Endemic infections
led to high infant mortality, and populations remained relatively stable
only by high birth rates offsetting the high death rates. Epidemic
diseases, such as plague and cholera, would devastate entire
communities. In many military campaigns, deaths from infections in
camp would exceed the mortality in battle. Infectious diseases were a
major influence in all aspects of life.
Beginning in the 17th century, a series of changes rapidly influenced
the frequency of infectious diseases. Improved agriculture led to better
nutrition, enabling persons to resist infection or survive illness better. In
the 19th century, improved hygiene and sanitation and safer food and
water reduced the transmission of many infectious diseases. Knowledge
of the specific etiology of infectious diseases for the first time provided
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a scientific basis for prevention strategies and treatment. In the 20th
century, continued environmental improvement and scientific advances,
specifically the advent of immunization and antibiotics, provided
additional ways to prevent transmission as well as treat the individual
patient. So extensive was the impact of these factors that in less than 100
years, the three leading causes of death in the US changed from
tuberculosis, pneumonia, and diarrhoea to heart disease, cancer, and
stroke. Between 1900 and 1985, the rate of natural causes of death for
children aged 1—4 years old in the US fell from 18.4 per thousand to 0.2
per thousand1. The median life span increased from 47 years to almost 76
years. Much of this change resulted from the prevention and treatment of
infectious diseases.
Despite these improvements, there were indications for concern.
Worldwide, infectious and parasitic diseases remained the leading cause
of death, accounting for almost 20 million deaths in 19922. Even in the
developed world, there were troubling trends. In the last two decades,
death rates from respiratory infections and septicemia have increased,
and organisms such as human immunodeficiency virus (HTV) have
emerged to become leading causes of morbidity and mortality. Between
1980 and 1992, the mortality rate from infectious diseases in the US rose
58%, from 41 to 65 per 100 000 population3.
These trends did not go unnoticed. In October 1992, the Institute of
Medicine (IOM) published a report titled, Emerging infections: microbial
threats to health in the United States4. In this report, the IOM defined an
emerging infection as 'a new, emerging, or drug-resistant infection
whose incidence in humans has increased within the past two decades,
or whose incidence threatens to increase in the near future'. Thus,
emerging infectious diseases represent not only the previously
unrecognized bacteria or viruses - Legionella or Ebola - but also the wellrecognized diseases - cholera, coccidioidomycosis, malaria, or dengue that have re-emerged as important public health problems. In this article,
I examine some of the recent trends in emerging infectious diseases,
particularly focusing on bacterial and fungal diseases, and the factors
influencing their emergence.
Trends in emerging infectious diseases
The last two decades have seen a series of newly recognized diseases.
These include bacterial diseases, such as Legionnaires' disease, toxic
shock syndrome, Lyme disease, campylobactenosis, food- and waterborne infections caused by Escherichta coli O157:H7, Vibrio vulnificus
and Vibrio cholerae O139, Helicobacter infections, ehrlichiosis, and
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Bartonella infections; viral diseases, caused by Marburg virus, Ebola
virus, hantavirus, and HIV; parasitic diseases, such as cryptosporidiosis
and cyclospora infections; fungal diseases, including a variety of molds
and yeasts; and spongiform encephalopathies, such as bovine spongiform encephalopathy, which are not easily categorized.
At the same time, a number of known diseases have re-emerged as
important public health problems. An examination of the bacterial
diseases alone defines the magnitude of this problem. In 1991, cholera
became epidemic in the Western hemisphere for the first time in over
100 years, rapidly spreading to involve almost every nation and causing
over one million cases and 11 000 deaths5. In the early 1990s, diphtheria
became epidemic in many of the nations of the former Soviet Union. The
group A Streptococcus caused clusters of invasive disease in Europe and
the US, capturing the media's attention as the 'flesh-eating' bacterium.
Listerta was first recognized as a foodborne pathogen in the early 1980s
and was subsequently implicated in epidemics especially affecting
pregnant women and compromised hosts. Serogroup A Neisseria
meningitidis remains epidemic in many parts of the world; in 1996, it
caused over 150 000 thousand cases and 16 000 deaths in sub-Saharan
Africa alone6. Strains of serogroups B and C N. meningitidis are causing
clusters of illness in cities and on college campuses in countries of the
developed world. Salmonella ententidis, which is primarily associated
with contaminated shell eggs, has become the most common Salmonella
serotype. In parts of Africa and Asia, multidrug-resistant Shigella
dysenteriae infections are causing epidemics with greater than 10%
mortality rates and hundreds of thousands of fatalities7. Tuberculosis, a
persistent problem of the developing world, accounting for almost 3
million deaths each year, has resurged in many parts of the developed
world, often in a drug-resistant form.
Two areas in the IOM's report on emerging infections received particular
emphasis - foodborne disease and antimicrobial resistance. The report
highlighted the potential of foods to be involved in the emergence of
infectious diseases 'because there were many points at which food safety
could be compromised'. Well-recognized diseases such as salmonellosis,
cholera, and listeriosis have become increasingly important public health
problems. At the same time, new diseases such as campylobacteriosis, and
new organisms such as E. coli O157:H7, and V. cholerae 0139 have
emerged. In the US, the frequency of salmonellosis has doubled since 1970.
Campylobacter was not recognized until the late 1970s but is now known
to be the most common bacterial cause of diarrhoeal disease in the US. E.
coli O157:H7, first recognized m 1982, now accounts for an estimated
20 000 cases and 250 deaths each year in the US. alone8.
The IOM also identified antimicrobial resistance as an important
contributor to the emergence of infectious diseases. In the hospital,
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certain strains of enterococci and Mycobacterium tuberculosis are
essentially untreatable with antimicrobial drugs. Infections with multiple
drug-resistant Gram-negative rods are endemic in many hospitals, the
specific predominant species varying from hospital to hospital. The
greatest public health risk, however, is the increasing frequency of
methicillin-resistant Staphylococcus aureus (MRSA). Of S. aureus
infections in US hospitals, 20—40% are caused by MRSA9. Many of
these strains are multidrug resistant or susceptible only to vancomycin.
Since recent reports from Japan and the US describe S. aureus with
decreased susceptibility to vancomycin, it is only a matter of time before
untreatable staphylococcal infections will be occurring10.
Antimicrobial resistance was once perceived as primarily a problem in
hospital-acquired infections. In recent years, however, communityacquired bacteria have become increasingly drug resistant, posing
important diagnostic and public health dilemmas. Increasing resistance
is being seen in the gonococcus, Haemophilus influenzae, Shigella,
Salmonella, and the pneumococcus. In the developing world, strains of
Shigella dysenteriae and Salmonella typhi are susceptible only to the
newer fluoroquinolones and extended-spectrum cephalosporins. In the
developed world, multiresistant strains of non-typhoid Salmonella are
increasing, and in some areas, such as the UK, strains are becoming
resistant to the newer fluoroquinolones11. Perhaps of greatest concern in
community-acquired infections is the increasing resistance among
pneumococci. In some areas of the US, over 20% of pneumococcal
isolates express high-level resistance to penicillin and 10% are resistant
to extended spectrum cephalosporins12. Some physicians are already
adding vancomycin to the empirical treatment for meningitis. Since
pneumococcal disease accounts for over 2 million cases of pneumonia,
7.5 million cases of otitis media, and 3000 cases of meningitis each year
in the US alone, the emergence of resistance is a grave public health
concern.
Factors influencing emergence
The emergence of infectious diseases is primarily related to change. As
the 19th century orator, Robert G. Ingersoll, pointed out, in nature there
are neither rewards nor punishments, only consequences. Thus, when
there are changes in society or technology, there are consequences. Some
of these consequences may be small; others may be monumental. Many
of the consequences are unexpected. The various changes influencing
emergence affect six factors that were identified by the IOM4. These are
human demographics and behaviour, technology and industry, economic
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development and land use, international travel and commerce, microbial
adaptation and change, and the breakdown of public health measures.
It is helpful to examine the nature of the changes in these areas and the
impact they have on infectious diseases.
Human demographics and behaviour
Important factors in changing human demographics include increases in
the number of susceptible persons, the use of day care, and immigration.
A series of factors are causing a rise in the number of susceptible persons
and the greater the percentage of the population that is susceptible to
infectious diseases, the greater the potential for disease transmission. In
many countries in the developed world, the number of older individuals
is growing. Since aging is associated with an increased susceptibility to
infectious diseases, the potential for disease transmission is also
increasing in these countries. In the US, the percentage of the population
over 65 years was about 4% in 1900 and will reach almost 25% in
204013. Certain underlying diseases are also placing more patients at risk
for various infectious diseases, and these have also increased. For
example, the reported incidence of diabetes mellitus in the US increased
from 0.5% of the nation's population in 1935 to over 3% in 199514. It
is estimated that there are actually 16 million persons with diabetes in
the US, so the true incidence of this disease may be greater than 5% of
the population. The rates for many malignancies are also increasing, and
these patients have increased susceptibility to infectious diseases from
the disease process, during chemotherapy and, in some cases, lifelong
even after cure15. Some of the most highly susceptible patients are those
receiving immunosuppressive therapy following organ transplantation.
Almost 20 000 organ transplants were performed in the US in 199516.
Worldwide, the greatest factor increasing susceptibility may be the
spread of HTV, which has led to millions of persons at increased risk for
a variety of infectious diseases
Societal changes, like the increased use of day care, are also affecting
the emergence of infectious diseases. The increasing frequency of both
parents working outside the home, or of single parent families, has led
to greater use of day care. The combination of susceptible children,
inadequate hygiene, frequent infections, and frequent antimicrobial use
is the perfect setting for the emergence of antimicrobial resistance. Thus,
it is no surprise that day care attendance has been an important factor
associated with the emergence of penicillin-resistant Streptococcus
pneumoniae. A recent Kentucky study demonstrated a 4-fold greater
relative risk for colonization with a high-level penicillin-resistant
Streptococcus pneumoniae among children attending day care17.
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The increase in immigration and changing patterns of immigration are
also contributing to the emergence of infectious diseases. Between 1984
and 1992, 0.5-1.5 million immigrants and refugees were admitted to the
US each year18. In contrast to the previous waves of immigration, many
of these individuals came from parts of the world where certain
infections, such as tuberculosis, are common. This is an important factor
in the resurgence of tuberculosis in the US, as the percentage of patients
who were foreign-born increased from 22% in 1986 to 37% in 199619.
A variety of human behaviours are also influencing the emergence of
infectious diseases. The impact of the sexual revolution on the frequency
of gonorrhoea, syphilis, and HIV is evident. Perhaps less evident is the
impact of other changes, such as changes in eating habits. There are
changes in the types of food that people are eating, how those foods are
prepared, and where the foods are prepared. This can lead to new
exposures to unfamiliar foods or the dependency upon others to handle
and prepare food safely. All these factors have contributed to the
emergence of some of the newer foodborne diseases8. Another important
behaviour influencing the emergence of resistance has been the
unnecessary use of antimicrobial agents. In 1992, over 110 million
courses of antimicrobial drugs were prescribed to outpatients in the
US20. Since three-quarters of these drugs are prescribed for upper
respiratory infections that are often caused by viruses, over half of these
110 million courses may be unnecessary.
Technology and industry
The impact of technology and industry falls into three general areas.
These include new technologies and products, changes in food
production processing and preservation, and changes in industrial
demographics. New technologies and products may have unexpected
disease implications, such as the association of air conditioning and
whirlpool spas with Legionnaires' disease, or new tampons with toxic
shock syndrome, or the fast-food hamburger with E. colt O157:H7.
The second area, changes in how food is produced, processed, and
preserved, has also been important. For example, in the last 50 years
many of the new agricultural production strategies involve intensive
rearing of young animals under environmental conditions that are
conducive to the transmission of infectious diseases. These production
strategies often depend upon increased antimicrobial use. Thus, only
substituting young animals for children, the situation is similar to the
day care setting and has resulted in an increase in antimicrobial
resistance for organisms that are transmitted through the food chain
from animals to humans. Between 1979 and 1989, the frequency of drug
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resistance in human Salmonella isolates almost doubled from 17% to
31% 21 . Today the resistance in humans is the result of antimicrobial use
in animals. The many changes in food processmg and preservation are
also influencing disease emergence. The recent emphasis on 'natural'
foods has led to use of fewer preservatives or secondary barriers to
prevent spoilage. Thus, some foods are protected only by refrigeration.
This has resulted in increasing problems with organisms that grow in the
cold, such as Listeria or Yersinia. The lack of secondary barriers also
increases the risk of food handling errors leading to diseases such as
botulism. In the last 10 years, several outbreaks of botulism have
occurred when 'keep refrigerated' foods were not kept refrigerated.
The third change, that of industrial demographics, is characterized by
consolidations of industry, larger market size, and wider geographic
distribution for a variety of food products. Although these changes have
the potential for greater quality control and better safety, when
something goes wrong, it can really go wrong. Thus, in 1994, an ice
cream product produced by a single company in Minnesota led to
thousands of cases of salmonellosis in over 41 states22.
Economic development and land use
Changes in economic development and land use are often cited in
discussions of emerging viral diseases. Encroachment on rain forests, for
instance, may lead to exposure to new agents such as Ebola or Marburg
viruses. However, such changes are also influencing the emergence of
other infectious diseases. For example, population growth and spread
lead to environmental change and pollution. The inadequacies of
hygiene and sanitation that exist in many of the 'mega cities' in the
developing world are potential ticking time bombs for the emergence of
infectious diseases23. Other types of development and land use practices
are contributing to specific problems. Conservation activities, such as
those directed toward deer populations, have contributed to the
emergence of Lyme disease. Coastal agriculture expansion is leading to
blooms of toxic microorganisms, while coastal population growth is
leading to human faecal contamination of shellfish beds and
transmission of a variety of viral and bacterial pathogens. The variation
in environmental conditions, whether natural or man-made, can lead to
the emergence of infectious diseases. In 1992-1993, the rainfall in the
southwestern US was well above normal; this led to increased
vegetation, and consequentially, to larger rodent populations. The
increase in rodent populations resulted in greater contact with humans
and the eventual outbreak of the first recognized epidemic of hantavirus
infections in the US24.
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International travel and commerce
Advances in technology have had a rapid impact on international travel
and commerce. A person or a food can be almost anywhere in the world
in 24—48 hours. This facility in travel and commerce has increased the
potential for the introduction of emerging pathogens to new geographic
areas by infected travellers, by contaminated food, or even by
transporting vehicles. The latter case is demonstrated by the introduction
of the epidemic strain of V. cholerae from Central and South America into
the oyster beds of Mobile Bay in the US. This introduction was
attributed to the discharge of contaminated bilge water by ships entering
Mobile Bay25.
Microbial adaptation and change
As human-kind is instituting a number of changes, the microbes
themselves are changing. This is leading to the evolution of new
pathogens, the development of new virulence factors, the development
of antimicrobial resistance, and tolerance to adverse environmental
conditions. A good example of this microbial change has been the
emergence of E. coli O157:H7, which probably evolved from an enteropathogenic E. colt that acquired Shigella genes26. As a foodborne
pathogen, it combines the worst of Shigella and Salmonella. Like
Shigella, this organism has a low infectious dose, requiring only a few
organisms to cause disease. This leads to subsequent person-to-person
transmission once the organism is introduced into a community and also
poses a high risk for cross-contamination in the kitchen. This organism
is more similar to Salmonella in its tolerance to adverse environmental
conditions. Thus, it has been associated with outbreaks that were caused
by foods with pH 4.0, conditions that are usually inhibitory to most
bacterial pathogens.
The breakdown of public health measures
The breakdown of public health measures has been the result of a series
of often unrelated factors. Earlier successes in the war against infectious
diseases led to complacency. This, coupled with limited resources and
competing priorities in public health, often led to the transfer of
resources from infectious diseases to other areas or to newly emerging
infections. Thus, the emphasis on noninfectious diseases and the
emergence of HTV has led, in some health departments, to resources
being shifted away from diseases such as tuberculosis. When
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tuberculosis re-emerged, it was frequently caused by drug-resistant
organisms, since much of the curtailed public health activities had been
directed toward assuring infected individuals received complete courses
of appropriate antituberculosis drugs27. In many parts of the world,
sanitation and hygiene are inadequate, and even in parts of the
developed world, the systems are aging or inadequately designed,
increasing vulnerability to outbreaks such as that which occurred in
Milwaukee with over 400 000 cases of cryptosporidiosis28. The impact
of the breakdown of public health measures can easily be seen during
wars, population movements, and natural disasters. One such example
has been the emergence of epidemic dysentery in Africa. Since 1979,
massive epidemics of dysentery caused by Shigella dysentenae type 1
have occurred in cities, rural areas, and refugee camps in Central and
Southern Africa. The epidemics have affected all age groups, often with
case-fatality ratios greater than 10%. In 1991 alone, the disease caused
60 000 deaths in Burundi and at least 200 000 deaths in the rest of
Africa7. In contrast to Shigella species, which are more common in parts
of the developed world, this organism is essentially resistant to all
available oral antimicrobial drugs. Some of the newer fluoroquinolones
are the last remaining effective oral agents.
Conclusion
Infectious diseases have played an important role in the history of humanland and will likely be important in its future. Although great progress has
been made against infectious diseases, humans are vulnerable to the
emergence of new diseases or re-emergence of well-recognized infectious
diseases. The changes in society and technology, often occurring at an
escalating rate, are contributing both to the likelihood of and vulnerability
to this emergence. The impact of these changes and the resultant
emergence are often unpredictable. Thus, addressing emerging infectious
diseases requires a strong public health infrastructure to detect and rapidly
respond to these emerging threats to health.
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