| Infectious
Diseases: An Ecological Perspective
Mary E. Wilson, M.D. *
Microbes have played a decisive role in human history. Between 1348 and
1352 in many European countries plague was estimated to have killed a
third to a half of the population [1,2]. It was not swords and
guns but imported microbes, carried by explorers over oceans, that defeated
native populations in the Americas [3] and in Australia and southern
Africa the arrival of Europeans killed off local populations by introducing
infectious diseases. Local flora and fauna were also irreversibly altered.
Many of these fertile, temperate, and now less populated lands were subsequently
settled by Europeans [3].
By the middle of the 20th century, infectious diseases were no longer
the major causes of mortality in developed countries. The eradication
of smallpox reinforced the perception that infectious diseases could be
eliminated. Improved sanitation, clean water, and better living conditions,
along with vaccines and antimicrobial agents, brought many infectious
diseases under control in industrialized countries, but infections continued
to kill millions each year in the developing world. Infectious diseases
remain the most common single cause of death in the world today. Of the
51 million deaths worldwide in 1993, an estimated 16.4 million resulted
from infectious and parasitic diseases [4]. In sub-Saharan Africa,
communicable diseases account for more than 70% of the burden of ill health
(as measured by disability adjusted life years), in contrast to about
10% in industrialized countries [5].
Increasingly humans have changed the earth in ways that make it easier
for microbes to move and to reach vulnerable populations. Widespread use
of antimicrobial agents and chemicals produces selective pressure for
the survival and persistence of more resistant populations of microbes,
and also of more resilient insect vectors [6]. Patterns of infectious
diseases are changing globally and on a massive scale [7,8]. Although
poor and disadvantaged people are hardest hit, emerging infectious diseases
have been reported in all regions of the world. A massive outbreak of
cryptosporidiosis in Milwaukee, USA, in 1993 affected more than 400,000
people [9]. Hantavirus pulmonary syndrome was recognized for the
first time in 1993 after an outbreak of fatal pulmonary disease in the
southwestern United States [10]. AIDS, recognized as a distinct
clinical syndrome in 1981, has reached every country of the world, and
the cumulative worldwide total of infected people could reach 30-40 million
by the year 2000.
Diseases such as Lassa fever, AIDS, and Ebola disease have focused attention
on viral infections, but pathogens involved in these changed infectious
diseases also include bacteria, fungi, protozoa, and helminths. Drug resistance
is increasingly reported not only in bacteria but also in viruses, fungi,
protozoa, and helminths. Arthropods, such as mosquitoes, lice, and ticks,
are becoming more resistant to pesticides. Outbreaks of infectious diseases
have caused die offs in species as diverse as beans, rice, seals, dolphins,
lions, chickens, and horses. In 1845 the potato blight fungus, Phytophthora
infestans, already known in North America, was first detected on the other
side of the Atlantic. It spread from the Isle of Wight and destroyed potato
crops across Europe. But the impact was greatest in Ireland, where an
estimated 1 million people died from starvation [11]. In 1970
a fungus attacked hybrid corn and spread throughout the United States,
destroying 15% of the corn crop [12]. Apart from their direct
impact on human health, such events hold important lessons about the ecology
of disease.
More Than Mere Microbes
More than a century ago Koch presented his famous postulates for ascertaining
the cause of infection. Subsequent decades saw the discovery of many infectious
microbes, including viruses. One by one, diseases and microbes were matched
-- and it became clear that determining the cause of disease was not simple.
Today we understand that the concept of the microbe as the cause of an
infection is inadequate and incomplete because it ignores the influence
of the host, the milieu, and the social and physical environment. Yet
medical science still tends to focus on the microbe as the foe, and our
response has often been to seek and destroy the invader.
A more enlightened understanding would embrace an ecological perspective.
Humans have reached such numbers and have developed such technologies
that human activities have a global impact and have changed the earth
for all other biological life [13]. Humans are part of a vast
evolutionary process and all life is interdependent, Students of human
health must look at the health and resilience of the ecosystem and approach
analysis at a systems level.
Three general forces can affect the burden of infectious diseases in
humans: change in abundance, virulence, or transmissibility of microbes;
an increase in probability of exposure of humans to microorganisms; and
an increase in the vulnerability of humans to infection and to the consequences
of infection. A wide range of biological, physicochemical, behavioral,
and social factors influence one or more of these forces. Many are interrelated,
and multiple synergies exist.
Migration
Migration of people has always played a large part in introducing infections
into new populations. [1,14]. John Snow wrote in 1849: "Epidemics
of cholera follow major routes of commerce. The disease always appears
first at seaports when extending into islands or continents [15].
The magnitude and speed of migration today is unparalleled in history.
In 1994 there were an estimated 22 million refugees and 25 million displaced
people worldwide [16]. In the early 1990s, according to the World
Tourism Organization in Madrid, more than 500 million people annually
crossed international borders on commercial aeroplane flights. An estimated
70 million people, primarily from developing countries, work either legally
or illegally in other countries [17]. Much migration is unplanned
and unwanted and leads to settlement in areas or under conditions that
place people at increased risk of infectious diseases.
Because of political conflict or instability, economic pressures, and
environmental changes, masses of people are being displaced [16].
Many refugees seek asylum in developing countries. Refugee camps, resettlement
areas, and temporary shelters are often characterized by crowded living
conditions, poor sanitation, limited access to clean water, little medical
care, poor nutrition, and lack of separation from insects and animals
in the environment. These features increase the probability of exposure
to infections in such vulnerable populations. Many examples document the
ravages of infectious diseases such as cholera, measles, malaria, and
shigella dysentery in these settings. After the movement of 500,000-800,000
Rwandan refugees into Zaire in 1994, almost 50,000 refugees died during
the first month as epidemics of cholera and Shigella dysenteriae type
1 swept through the refugee camps [17].
The massive movement occurring in the world today includes animals, plants,
seeds, insects, and all manner of biological life in addition to humans.
Through their conveyances by air, water, and land, humans have given wings
to plants, animals, and microbes, extending and speeding up their spread
[18]. Air travel accelerated the spread of HIV around the globe.
Introductions of new species of plants and animals can change the ecology
in an area, sometimes extinguishing local species because of predation,
disease, competition, and changes in the habitat [19]. Introducing
insect vectors can affect human health if the vector is capable of transmitting
pathogens to humans.
Many areas of the world are now receptive to the occurrence of viral
infections, such as dengue fever, because of the introduction of Aedes
albopictus [20,21], and the expansion of the range of Aedes aegypti
[22]. The ballast water of ships travelling between Japan and
Coos Bay, Oregon, was found to harbor 356 different species of marine
organisms [23].
Islands are especially vulnerable to invasions. An estimated 1900 species
of endemic plants and more than 5000 species of insects preceded human
colonists in Hawaii. Over centuries, arrivals of humans brought to the
Hawaiian islands rats, mongooses, mosquitoes, cockroaches, English sparrows,
many other animals, and more than 4,500 species of alien plants [24].
When a virulent clone of a pathogen emerges, as has happened with Neisseria
meningitidis, many pathways from one geographical area to another are
available [25]. In 1987 group A meningococcal disease spread throughout
Haj pilgrims in Mecca; they carried the virulent clone home to the United
States, the United Kingdom, Pakistan, other parts of Saudi Arabia and
the Gulf states, and elsewhere [26]. The time frame of past ,
centuries has been telescoped by the magnitude and speed of modern travel.
Borders are porous and microbes readily cross them. When an outbreak of
diphtheria occurs in the new independent states of the former Soviet Union,
populations in other countries also feel the impact: cases linked to the
exposures in the Russian Federation have been reported in Poland, Finland,
Germany, and the United States [27]. On the basis of serological
studies, it is estimated that up to 60% of adults in America and Europe
are susceptible to diphtheria [27].
Climatic Effects
Changes in climate and the environment have many direct and indirect
effects on human health [28,29,30]. Temperature and humidity influence
the abundance and distribution of vectors and intermediate hosts [31,32,33].
Global warming can reshape vegetation zones [34] and can be expected
to change the distribution and abundance of vector borne infections, such
as malaria. Warmer temperatures may allow insects and pests to survive
winters that normally would have limited their populations [35].
An increase in malaria in Rwanda coincided with record high temperatures
and rainfall [36]. In 70 communities in Mexico, median temperature
during the rainy season was the strongest predictor of dengue fever: higher
temperatures increased vector efficiency [37].
Global warming may be contributing to a global epidemic of coastal algal
blooms, though runoffs rich in nitrates, phosphorus, chemical pollutants,
and organic material and overharvesting of fish that graze on plankton
may contribute as well [38]. Consequences to human health are
direct and indirect. Toxic dinoflagellates can sicken humans who eat shellfish.
Toxic algal blooms have also been associated with massive dying off of
marine life.
Extreme climatic events, such as droughts and floods, are expected to
increase with predicted global climate changes [13]. Many disease
outbreaks have occurred after extreme climatic conditions. These include
vector borne infections such as malaria and Venezuelan encephalitis, animal
borne infections such as hantaviruses, and water borne infections such
as cholera and hepatitis E.
Settlement Patterns
Climatic and environmental changes also lead humans to migrate, to develop
new lands, and to live in settings that favor the spread of infectious
diseases. Simultaneously we are seeing increased urbanization and exploration
and clearing of new lands. Both carry risks for infectious diseases. The
huge periurban settlements that have grown, especially in tropical regions,
have risks for infectious diseases similar to those precipitated by resettlement.
Dengue fever is one example of an infection that spreads readily in the
tropical urban environment. Residents come from different geographical
regions and may revisit families in rural areas regularly, providing a
conduit for the carriage of microbes. Clearing and settlement of new lands
disturbs an existing ecosystem and may uncover microbes in soil or animals,
sometimes carried by arthropod vectors, that were previously unrecognized
as human pathogens. Venezuelan haemorrhagic fever, caused by the rodent
borne Guanarito virus, was first recognized in 1989 after a severe outbreak.
Increasing migration into the endemic area and development of new land
may have provided more favorable conditions for the rodents and placed
more people in contact with them [39].
Population growth means people are living in higher densities, heightening
the risk for rapid spread of infections. As of 1990 an estimated 1.3 billion
people in the developing world lacked access to clean water and nearly
2 billion lacked an adequate system for disposing of faeces [5].
More people are being pushed to the margins of habitable land. Much of
the increased urban growth is in areas within 75 miles of the sea, which
are at risk for hurricanes and floodings, and in areas at increased risk
for earthquakes. Increased density of populations and inadequate resources
also make for social and political instability [40]. These multiple
vulnerabilities often converge in a population or geographical region.
New Vulnerabilities
Technological gains are often offset by new vulnerabilities. Interventions
can often have unintended and unexpected consequences. Wide use of antimicrobials
has led to high rates of resistance among many bacteria [6]. Mass
processing and distribution of food has resulted in occasional massive
outbreaks of infections, such as salmonellosis and Escherichia coli 0157:H7,
that could not have occurred without the wide distribution networks. Large
municipal water systems made it possible to infect more than 400,000 people
with Cryptosporidium parvum within a few days [9]. Modern medical
techniques applied with inadequate training and resources have had disastrous
consequences, as shown by dramatic outbreaks of nosocomial Lassa fever
in Nigeria [41] and Ebola disease in Zaire [42]. Transmission
of virus to patients and medical staff resulted from exposure to contaminated
needles and from lack of adequate barriers during surgery.
Changes in climate lead to creation of new habitats that are energy expensive
and provide new avenues for spread of infection. Air and water cooling
systems have been associated with outbreaks of legionnaires' disease.
The natural habitat for Legionella pneumophila, the cause of the disease,
is streams, lakes, and other bodies of water, where it is present in small
numbers. Human inventions such as water cooling towers and water distribution
systems provide favorable conditions for the survival and proliferation
of the bacteria and the means for dissemination. L pneumophila survives
in concentrations of chlorine typically used to treat water.
Influenza in Louisiana, USA, appeared in August and early September 1993,
a time unusual for influenza transmission in the temperate zone [43],
but August had had record breaking high temperatures and low rainfall.
The outbreaks, two in nursing homes and one on a barge, had common features:
shared living areas and shared recirculated (air conditioned) air. Factors
historically associated with influenza outbreaks are crowding and low
humidity. The new habitat of large air conditioned areas may predispose
to influenza transmission outside the expected period.
Many patients with cystic fibrosis can now survive for decades through
attentive medical care. Recent outbreaks of Pseudomonas (Burkholderia)
cepacia in cystic fibrosis centres in Toronto, Canada, and in Edinburgh
were associated with high mortality [44]. Molecular markers allowed
documentation of a lineage adapted for efficient transmission in people
with cystic fibrosis. This highly transmissible clone, which was responsible
for epidemics in these British and North American centres, adheres better
to human epithelial cells than do other isolates of this bacterium. The
appearance of this distinctive clone in different continents was thought
to be related to attendance at international summer camps. Human interventions
at multiple points set the stage for microbial selection and assisted
its amplification and spread.
Fatal Mixtures
The world today is in a state of turbulence and rapid change. The emergence
of infections in many geographical areas is but one manifestation of instability
and stress in the system. Today there are unprecedented opportunities
for mixing of people, animals, and microbes from all geographical areas
in an environment that has been altered by industry, technology, agriculture,
chemicals, and climate change and by the demands of population growth.
Diverse genetic pools are mixing in rates and combinations and in a time
frame too short to allow adaptation through genetic change. Many interventions
have been carried out with too narrow an understanding of their impacts.
The invisible weapons of today's conflicts are micro-organisms. In most
of the wars throughout history, infectious diseases killed more troops
than did the weapons of war. Since the second world war more civilians
than combatants have died from war. In recent conflicts the victims have
often been those whose lives have been upset by the upheaval -- refugees,
displaced populations, children without access to immunization and oral
rehydration fluids, the hungry and vulnerable masses who succumb to infections
that are neither exotic nor new [16]. Earlier in this century
mortality from tuberculosis in many European countries showed a striking
increase in response to war [45].
There is an urgent need to integrate knowledge about infectious diseases
with knowledge of climate and environmental change, migration and population
growth, demography, and the consequences of conflict. All are inextricably
linked and play a part in the changed patterns we are seeing in infectious
diseases.
We have more scientific data about the present and past than ever before.
We have biopsies of the earth, the ice cores, that reveal secrets of past
climatic patterns. Frozen bodies, preserved insects, mice, and mummies
examined by the polymerase chain reaction and other techniques help to
create a fuller knowledge of life in past centuries. Will this translate
into understanding and changed behavior in a way that preserves the health
of humans and the biosphere? Many events suggest that there is a mismatch
between what we know and what we have been able to do. The barriers to
identifying and intervening in infectious diseases are more often social
and political than scientific.
Much recent attention has focused on exotic and previously unrecognized
lethal pathogens. While it is important to study these pathogens and to
identify the events that lead to their appearance and spread, it is essential
not to ignore pathogens that are familiar and thus often less feared.
Influenza, which killed 20 million people in the year after the end of
the first world war, is still a killer and has the capacity to change
rapidly and spread widely throughout the world [46]. Two attributes
of the influenza virus -- its potential for rapid genetic change and its
ease of transmission -- make it a continued threat that is often overlooked
and underestimated.
Progress Without Breakthroughs?
It is difficult to imagine any breakthroughs in social, political,
or scientific arenas that will halt population displacement or the rise
in poverty and disease. What can be done? Others have written persuasively
about the need for enhanced surveillance and global networks. These must
be integrated across disciplines and geographical regions. Several elements
seem essential; we should:
- Recognize the links between population growth, climatic and environmental
change, global migration, and human health and security
- Develop databases that combine information about climate, demography,
population movements, and diseases in humans, animals, and plants
- Identify markers for regions or populations at high risk of epidemic
disease so that we can intervene to reduce the impact of disease
- Continue efforts slow population growth
- Take steps to reduce mass migration and displacement of populations
- Reduce consumption
- Pay more attention to land use and production and disposal of toxins
and chemicals
- Take a broader view and longer time frame when analyzing the potential
impact of interventions
- View human life as part of a constantly evolving biosphere.
Throughout history infectious diseases have waxed and waned. In today's
world, socioeconomic, political, environmental, and climatic changes have
converged to allow many infectious diseases to flourish. But a rise in
infectious diseases is only one of the manifestations of global instability.
Any meaningful response must integrate knowledge from multiple disciplines
and approach the problem at the systems level. To be successful, we must
apprehend infectious diseases in their evolutionary and ecological context.
Examples of changed patterns in infectious diseases
Diseases by previously unrecognized or uncharacterized agents:
Hantavirus pulmonary syndrome (Sin Nombre virus), Lyme disease (Borrelia
burgdorfen),Cat scratch disease (Bartonella henselae), Cryptosporidiosis
(Cryptosporidium parvum), Ehrlichiosis (Ehrlichia chaffeensis)
Geographical expansion of known infectious disease:
Dengue fever (dengue viruses),Yellow fever (yellow fever virus),Malaria
(Plasmodium falciparum), Cholera (Vibrio cholerae)
Increased incidence of previously controlled disease:
Tuberculosis (Mycobacterium tuberculosis), Diphtheria (Corynebacterium
diphtheriae)
Increased resistance to drugs:
* Pneumococcal infections (Streptococcus pneumoniae), Staphylococcal
infections (Staphylococcus aureus), Shigellosis (Shigela dysenteriae),
Malaria (Plasmodium falciparum and P vivax)
Altered expressions of diseases:
* Meningococcal infections (Neisseria meningitidis clone), Bacillary
angiomatosis (Bartonella henselae), Leishmaniasis in HIV infected people,
Mycobacterium avium complex in HIV infected people
New agents (no evidence yet for previous existence):
Escherichia coli 0157:H7, Vibrio cholerae 0139, Equine morbillivirus
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