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Frontiers
Tracking a Killer: Following Cholera With Every Available Means
October 1996
In 1991, the world watched as Peru came face to
face with a killer: cholera. The ancient scourge of the earth had returned.
More than 6,000 people died in Peru's epidemic and a simultaneous
one that hit several African nations.
Unfortunately, cholera is not the only ancient disease to resurface
recently, says microbiologist Rita Colwell, past President and current
Chairman of the Board of the American Association for the Advancement
of Science (AAAS). Communicable diseases as a whole are resurging.
"Why this is happening isn't clear, but some factors are obvious," she
says. "Poverty continues to be a huge problem. Increasing populations,
especially those millions lacking food, housing, and safe drinking
water, create the environment for these diseases to occur."
For more than 20 years, Colwell has received grants from NSF, the
National Institutes of Health (NIH), the National Oceanic and Atmospheric
Administration (NOAA), and the National Aeronautics and Space Administration
(NASA) to track cholera and help stop the massive epidemics it causes.
Within NSF, Colwell's most current work is connected with the threat
of global climate change, says Paul Filmer, program manager for the
Inter-American Institute for Global Change (IAI).
"We have 17 countries working together to investigate important issues
as the world faces global change," explains Filmer. "Disease is one
of those issues. What Rita is doing is examining how climate change
might be affecting the increased cases of cholera."
It's a new project, and one that will build on all of the detective
work that Colwell and hundreds of other researchers have performed
so far.
At the 1996 AAAS meeting in Baltimore, Colwell talked about some of
that work in her President's Lecture, "Global Change: Emerging Disease
and New Epidemics." Some parts of the mystery surrounding cholera have
been solved. But others are still unfolding, thousands of years after
the disease was first discovered.
To ferret out what triggers cholera epidemics, epidemiologists must
become renaissance researchers. Their methods include straight-forward
tasks such as questioning the victims, but also involve oceanography,
ecology, microbiology, marine biology, medicine, and even remote sensing.
"This interdisciplinary approach provides us with an understanding
of an historic scourge of humankind and hopefully its prevention in
the future," says Colwell.
DISEASE DETECTIVES
Over a hundred years ago, when physician John Snow lived in
England, these sophisticated techniques did not exist. But when London
was gripped with the cholera epidemic of 1854, Snow wondered how the
disease operated.
He did not know, of course, the real killers were bacteria.
Germ theory was not yet widely accepted. But it was obvious that
the disease moved.
Snow recorded what was actually happening. He used a map of
London and carefully marked every infected household. Then, asking
what each of these houses had in common, he made the connection--all
of the infected households took their water from the Broad Street
well. The disease, Snow realized, moved through the water.
In one of the more dramatic myths of epidemiological history,
Snow is reputed to have removed the pump handle from the Broad
Street well, thereby forcing London residents to use another
water source, while he garnered credit for ending the epidemic.
"In reality," Colwell comments, "Snow never claimed removal
of the pump handle had anything to do with ending the epidemic.
Snow did understand, however, that the disease was spread more
easily by contaminated water than by person-to-person contact."
CHAMELEON BACTERIUM
Since then, scientists have proved that cholera stems
from bacteria which moves through unclean water. In fact, the deadly
disease was caused by only one type of bacterium -- Vibrio cholerae
01. Hundreds of other similar Vibrio strains exist,
but none of these are toxic. This is what researchers thought,
anyway.
And then, in 1992, more people started getting sick.
Bewilderingly, the new Asian epidemic attacked people who had already contracted
and recovered from cholera. Like survivors of the measles or chicken pox, cholera
survivors develop antibodies thought to make them immune to future infections.
Furthermore, even though the symptoms were the same as cholera, tests of the
water showed no signs of the known bacterium culprit.
With more sophisticated tests, however, researchers soon found that V.
cholerae 01 had been replaced by a new epidemic genotype, V. cholerae
0139. The change involved only one protein, but that protein was the
one used by the human immune system and by scientists to identify the presence
of cholera.
"It was only the coat of the bacterium that was different," Elisabeth Bik,
a molecular biologist at the National Institute of Public Health and Environmental
Protection in the Netherlands, told Discover magazine. "Ninety-nine
percent of the bacterium is still 01, but a small region of the chromosome
has been changed."
Unfortunately, such changes put a damper on the idea of globally effective
vaccines.
Many vaccines use nonlethal forms of a disease to trick our immune systems
into producing antibodies. When the real disease comes along, our bodies think
they have already met this invader and are ready to fight. But there won¹t
be a universal vaccine if our bodies can't see past the disguise of an old
bacterium.
"The immune system looks at the coat, so that is what is recognized," Bik
continues. "In that way the new bacterium is so totally different from the
old one that you cannot expect to make a vaccine against one strain that will
protect against both types."
All of which makes prevention even more important.
THE PLACE CHOLERA CALLS HOME
Understanding how cholera lives and moves through water has been a
goal since Snow started his research in the 1850s. Undoubtedly, cholera thrives
in water polluted by sewage. But where do those bacteria come from before they
enter the rivers and wells?
Studies by Colwell and her students beginning in the late 1960s showed a connection
between cholera and the marine environment. With this in mind, Colwell and
her colleague, Anwarul Huq, focused on Bangladesh where the outbreaks are seasonal.
From 1987 to 1990, Colwell, Huq and other team members collected biweekly samples
of river and pond water and its plankton.
It was the plankton that proved most interesting.
Classifying these microbes, the researchers found the expected groups of zooplankton
(small animals, such as copepods) and phytoplankton (small plants, such as
green algae).
They also tested for the presence of cholera. When they found it, they used
statistical analyses to determine which of the various combinations of plants,
animals, temperatures, salinity, etc. were most likely to be supporting the
bacteria.
"The results clearly showed a correlation of V. cholerae 01 with copepods," says
Colwell.
If cholera use copepods as hosts, they can survive in seawater long enough
to be carried around the globe.
Which is exactly what they do.
Attached to the copepods, the bacteria move with the tides and floods. They
drift into the estuaries and drinking water, growing in numbers where there
are more nutrients, and shrinking when the seasons dry out.
VISUAL CUES
But there's one more important clue in the mystery of cholera. Cholera-bearing
copepods travel with phytoplankton, their main food source. "The two forms of
plankton are tightly linked in time and space," Colwell writes.
This is important because when weather conditions are right, phytoplankton
burst into active growth, an occurance also known as algal blooms or plumes.
There is evidence to suggest that the blooms provide the copepods (and therefore
the bacteria) with a feast that triggers rapid copepod and bacterial expansion
and cholera epidemics.
Significantly, in terms of prevention, these blooms can be detected by satellites.
With this understanding of cholera's ecology, scientists have found a new
tool in the battle against the disease: they can use satellite imaging.
"Although V. cholerae cannot be detected in any state by remote sensing
techniques, remote sensing has been used successfully to quantify phytoplankton
concentrations in the open oceans," Colwell writes. "The tight linking of zooplankton
and V. cholerae indicates remote sensing will be useful in tracking V.
cholerae associated with plankton plumes in coastal areas and major rivers
where cholera is known to be endemic, i.e., the plume of the Ganges."
The plan, says Colwell, is to use joint NSF, NIH and NASA funding to track
the plumes and continue to test them for cholera. The work is especially crucial
in warm areas where global change may increase the number and size of these
algal blooms.
The use of satellite data is just getting started, but eventually,
Colwell expects it will help provide a warning system. Residents who know a
plume is moving toward their water supply will have a chance to take precautions
such as finding another water source, using filtration, or adding chlorine.
The warning system won't kill cholera. It won't even stop every epidemic,
since some bacteria probably by-pass the copepod transport and use other, less
studied methods. But by developing a warning system, scientists may have time
to catch up with an ancient scourge of the earth before it wreaks full effect
of its killer capacity.
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