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MEDICINE

PUBLIC HEALTH ON THE FRONTLINE: THE


COMING PLAGUE, RECONSIDERED
G. EMILY GHODS-ESFAHANI 09
these events. Overuse of DDT, coupled with a revolution
in agricultural economics, turned farmlands that were
previously alive with diverse plant and insect life into
monocultured breeding grounds for the blight of malaria.
As plant diversity declined under the plow of farmers
cultivating only cash crops, the biodiversity of insects
was reduced to pestilential imbalance.
With dwindling competition due to these
agricultural practices and the use of
DDT, the surviving insects overwhelmed
farm land, feeding on the cash crops
planted to alleviate rampant privation
and malnutrition. Disastrously, farmers
responded by increasing the use of DDT;
resistant mosquitoes survived the spraying,
while their natural competitors died off.
Resistance to antibiotics only amplied
the malaria crisis. Between 1980 and 1986,
the sensitivity of malaria to chloroquine
decreased by ten-fold each year, a total
decrease of 1,000,000 fold. Approximately
three-fourths of all malaria victims would
become resistant to most malarial drugs,
and a growing black market for anti-
malaria drugs fostered improper use of the antibiotics,
compounding the problem of resistance.
Each time an antibiotic drug is used to eliminate
a target micro-organism, it creates a selective regime that
reduces the relative tness of non-resistant organisms, and
increases the relative tness of resistant organisms. If,
in such conditions, an organism arises (through random
mutation) that can resist the antibiotic, it has substantial
tness advantages over its competitors and proliferates.
The gene for resistance consequently spreads through
the population. Today, this has occurred to such a degree
that some pathogens now thrive on bleach and other
disinfectants used in hospitals, so that, in many instances,
hospital rooms have become Petri dishes for infectious
microbes.
In the four species of the protozoan genus
Plasmodium which cause malaria in humans, the gene
for resistance codes for the synthesis of a membrane-
spanning protein that pumps harmful chemicals out of the
In 1994, Pulitzer Prize-winning reporter Laurie
Garrett conceived a book whose foresight seems
stunning today. With the growing threat of avian u, the
global failure to contain pandemic AIDS, and the rapid
emergence of multi-drug-resistant (MDR) forms of many
known pathogens, Garretts The Coming Plague remains
a topical and essential read for those
interested in microbial ecology and public
health.
By the twentieth centurys end,
MDR forms of gonorrhea, tuberculosis,
Staphylococcus aureus (Staph),
Streptococcus, inuenza, herpes and HIV
emerged hand in hand with the potential
triple threat of airborne cancer-causing
viruses, airborne AIDS and, most recently,
airborne avian u. Biology teaches us that
such variations in organisms are due to
random mutations, and that selective forces
act on these mutations to make them more
or less frequent in a population. Garrett
claims that the selective regime which
encourages the proliferation of mutant
organisms like MDR pathogens has
been shaped by social causes; society has selected these
mutant pathogens through poor public health policies and
a vast eco-biological imbalance perpetuated by humanitys
desire to dominate the planet.
Beginning her analysis with the percolating can-
do optimism that characterized post-WWII America,
Garrett chronicles the unpredictability of emerging
infectious diseases, and public healths failure in the face
of most major outbreaks. With the discovery of penicillin,
the eradication of smallpox, and a nascent campaign to
eliminate malaria, scientists declared that humanity could
close the book on infectious diseases. Not even a decade
later, public health ofcials would have to grapple with
one of their greatest failureswhich Garrett chronicles
with grim precision.
In 1958, an international crusade began with the
aim of eradicating a pathogen that beleaguered Southeast
Asia, India, and Africa - malaria. The chosen solution was
DDT, an insecticide to kill the mosquitoes that carried
the parasite. Almost instantaneously, however, mosquito
populations resistant to DDT emerged. At the same time,
chloroquine-resistant strains of malaria surfaced.
Sobering consequences followed hard upon
The Coming Plague:
Newly Emerging Diseases in a World Out of Balance
Laurie Garrett
768 pages. Penguin (Non-Classics)
Image courtesy of Tim Shen
DARTMOUTH UNDERGRADUATE JOURNAL OF SCIENCE 42
protozoan cells. As a mosquito inserts its proboscis into
an MDR malaria-stricken human being, it introduces that
strain of malaria into its abdomen. Once in the mosquito
abdomen, lateral gene transfer allows resistant parasites
to donate plasmids (segments of DNA) that contain
resistant gene factors to parasites that lack these factors.
Four decades after being optimistically set on
wiping malaria off the face of the Earth, the World Health
Organization (WHO) declared that no effective strategy
for malarial control existed. But Garrett chillingly conveys
that malaria would not be WHOs only public health
catastrophe. In 1990, WHO declared that all infections
of the upper respiratory tract should be assumed to be
bacterial, and therefore treated with antibiotics. The
ineffectiveness of this policy lies in the signicant detail
that most infections of the upper respiratory tractwith
the notable exception of Streptococcus pneumoniae
are viral. Antibiotics have no effect on viruses; they are
exclusively meant to treat bacterial infections.
To Garrett, WHOs scorched-earth policy of
antibiotic misuse has had consequences that far exceed
those of the patient not being relieved of their original
ailment, because when antibiotics are improperly
prescribed, they result in resistant forms of bacteria.
Perhaps as a consequence of antibiotic use and misuse,
some Staphylococcus bacteria are so advanced in plasmid
exchange that they have evolved membrane spanning
proteins that scan passing DNA, looking for useful genes
that encode resistance factors. When found, the protein
pulls those factors into the bacterium to incorporate the
plasmid into the bacterias own DNA.
As the microbes outwitted their hosts, it became
increasingly clear that public health ofcials needed
a strategy, or at least an organization, to localize an
effective response in the face of endemics, epidemics,
and pandemics. Experts in the eld of public health
and microbiology, so called disease cowboys like D. A.
Henderson and Joe McCormick, conducted microbe
search and destroy missions while they worked to round-
up the necessary strategies.
When asked if WHO was equipped to handle
any emergency in public health, Henderson retorted, by
the time WHO realized there was an AIDS epidemic,
it already existed on four continents. Thats WHO
preparedness and emergency response for you. The
sorry state of WHOs 34 multi-national labs, established
to detect outbreaks of viral diseases and immediately
report them to WHO headquarters in Geneva, also speak
to WHOs readiness for public health disasters. Only one
half of these labs can diagnose yellow fever, and none
have the equipment necessary to detect hemorrhagic
fevers such as Ebola, Lassa, Marburg, or Machupoall
of which have reemerged in Africa and South America,
at intervals unpredictable even for experts in tropical
medicine.
The obvious next choice for emergency response
would be the U.S. Center for Disease Control (CDC).
Yet, as it turns out, there is no protocol by which federal
or state agencies report outbreaks to the CDC, delaying
or eliminating the possibility of suppression at the onset
of an epidemic. As a result, the incidence of AIDS in
the U.S. is underreported by a conservative estimate of
20%.
To Garrett, the solution to these crises in public
health does not lie in trusting that microbes will promptly
roll over and die in response to eradication efforts, unaided
by that process that affords their exibility: evolution.
Public healths response to epidemics only amplies the
epidemic by iatrogenic meansin other words, induced
by the very activities conceived to combat them: the
healthcare system. And so, with Harvard economist Dick
Levins, Garrett sadly concludes that humans are utterly
incapable of embracing complexity.
With this indictment and our neglect of the
microbescoupled with the growing pandemic of HIV
and other viruseswe have provided hundreds upon
thousands of microbes with walking test tubes in which
to test their mutations. And so humanity must brace itself
for the coming plague.
Gonorrhea viewed by uorescent microscopy. The bacteria are
labeled with uorescent antibodies.
Image courtesy of CDC.
Tuberculosis bacteria viewed under 1000X magnication
and stained with acid-fast Ziehl-Neelsen stain.
Image courtesy of CDC and Dr. George P. Kubica
SPRING 2006 43