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MEDICINE

PUBLIC HEALTH ON THE FRONTLINE: THECOMING PLAGUE, RECONSIDEREDG. EMILY GHODS-ESFAHANI 09

these events. Overuse of DDT, coupled with a revolutionin agricultural economics, turned farmlands that werepreviously alive with diverse plant and insect life intomonocultured breeding grounds for the blight of malaria.As plant diversity declined under the plow of farmerscultivating only cash crops, the biodiversity of insects

was reduced to pestilential imbalance.With dwindling competition due to theseagricultural practices and the use ofDDT, the surviving insects overwhelmedfarm land, feeding on the cash cropsplanted to alleviate rampant privationand malnutrition. Disastrously, farmersresponded by increasing the use of DDT;resistant mosquitoes survived the spraying,while their natural competitors died off. Resistance to antibiotics only ampliedthe malaria crisis. Between 1980 and 1986,the sensitivity of malaria to chloroquinedecreased by ten-fold each year, a totaldecrease of 1,000,000 fold. Approximatelythree-fourths of all malaria victims wouldbecome 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 eliminatea target micro-organism, it creates a selective regime thatreduces the relative tness of non-resistant organisms, andincreases the relative tness of resistant organisms. If,in such conditions, an organism arises (through randommutation) that can resist the antibiotic, it has substantialtness advantages over its competitors and proliferates.The gene for resistance consequently spreads throughthe population. Today, this has occurred to such a degreethat some pathogens now thrive on bleach and other

disinfectants used in hospitals, so that, in many instances,hospital rooms have become Petri dishes for infectiousmicrobes.

In the four species of the protozoan genusPlasmodium which cause malaria in humans, the genefor resistance codes for the synthesis of a membrane-spanning protein that pumps harmful chemicals out of the

In 1994, Pulitzer Prize-winning reporter LaurieGarrett conceived a book whose foresight seemsstunning today. With the growing threat of avian u, theglobal failure to contain pandemic AIDS, and the rapidemergence of multi-drug-resistant (MDR) forms of manyknown pathogens, Garretts The Coming Plague remainsa topical and essential read for thoseinterested in microbial ecology and publichealth.

By the twentieth centurys end,MDR forms of gonorrhea, tuberculosis,Staphylococcus aureus (Staph),Streptococcus, inuenza, herpes and HIVemerged hand in hand with the potentialtriple threat of airborne cancer-causingviruses, airborne AIDS and, most recently,airborne avian u. Biology teaches us thatsuch variations in organisms are due torandom mutations, and that selective forcesact on these mutations to make them moreor less frequent in a population. Garrettclaims that the selective regime whichencourages the proliferation of mutantorganisms like MDR pathogens has

been shaped by social causes; society has selected thesemutant pathogens through poor public health policies anda vast eco-biological imbalance perpetuated by humanitysdesire to dominate the planet.

Beginning her analysis with the percolating can-do optimism that characterized post-WWII America,Garrett chronicles the unpredictability of emerginginfectious diseases, and public healths failure in the faceof most major outbreaks. With the discovery of penicillin,the eradication of smallpox, and a nascent campaign toeliminate malaria, scientists declared that humanity couldclose the book on infectious diseases. Not even a decade

later, public health ofcials would have to grapple withone of their greatest failureswhich Garrett chronicleswith grim precision.

In 1958, an international crusade began with theaim of eradicating a pathogen that beleaguered SoutheastAsia, India, and Africa - malaria. The chosen solution wasDDT, an insecticide to kill the mosquitoes that carriedthe parasite. Almost instantaneously, however, mosquitopopulations 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

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protozoan cells. As a mosquito inserts its proboscis intoan MDR malaria-stricken human being, it introduces thatstrain of malaria into its abdomen. Once in the mosquitoabdomen, lateral gene transfer allows resistant parasitesto donate plasmids (segments of DNA) that containresistant gene factors to parasites that lack these factors.

Four decades after being optimistically set onwiping malaria off the face of the Earth, the World HealthOrganization (WHO) declared that no effective strategyfor malarial control existed. But Garrett chillingly conveysthat malaria would not be WHOs only public healthcatastrophe. In 1990, WHO declared that all infectionsof the upper respiratory tract should be assumed to bebacterial, and therefore treated with antibiotics. Theineffectiveness of this policy lies in the signicant detailthat most infections of the upper respiratory tractwiththe notable exception of Streptococcus pneumoniaeare viral. Antibiotics have no effect on viruses; they areexclusively meant to treat bacterial infections.

To Garrett, WHOs scorched-earth policy ofantibiotic misuse has had consequences that far exceedthose of the patient not being relieved of their originalailment, because when antibiotics are improperlyprescribed, they result in resistant forms of bacteria.Perhaps as a consequence of antibiotic use and misuse,some Staphylococcus bacteria are so advanced in plasmidexchange that they have evolved membrane spanningproteins that scan passing DNA, looking for useful genesthat encode resistance factors. When found, the proteinpulls those factors into the bacterium to incorporate theplasmid into the bacterias own DNA. As the microbes outwitted their hosts, it becameincreasingly clear that public health ofcials neededa strategy, or at least an organization, to localize aneffective response in the face of endemics, epidemics,and pandemics. Experts in the eld of public healthand microbiology, so called disease cowboys like D. A.Henderson and Joe McCormick, conducted microbesearch and destroy missions while they worked to round-

up the necessary strategies. When asked if WHO was equipped to handleany emergency in public health, Henderson retorted, bythe time WHO realized there was an AIDS epidemic,it already existed on four continents. Thats WHOpreparedness and emergency response for you. Thesorry state of WHOs 34 multi-national labs, establishedto detect outbreaks of viral diseases and immediately

report them to WHO headquarters in Geneva, also speakto WHOs readiness for public health disasters. Only onehalf of these labs can diagnose yellow fever, and nonehave the equipment necessary to detect hemorrhagicfevers such as Ebola, Lassa, Marburg, or Machupoallof which have reemerged in Africa and South America,at intervals unpredictable even for experts in tropicalmedicine.

The obvious next choice for emergency responsewould be the U.S. Center for Disease Control (CDC).Yet, as it turns out, there is no protocol by which federalor state agencies report outbreaks to the CDC, delaying

or eliminating the possibility of suppression at the onsetof an epidemic. As a result, the incidence of AIDS inthe U.S. is underreported by a conservative estimate of20%. To Garrett, the solution to these crises in publichealth does not lie in trusting that microbes will promptlyroll over and die in response to eradication efforts, unaidedby that process that affords their exibility: evolution.Public healths response to epidemics only amplies theepidemic by iatrogenic meansin other words, inducedby the very activities conceived to combat them: thehealthcare 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 HIVand other viruseswe have provided hundreds uponthousands of microbes with walking test tubes in whichto test their mutations. And so humanity must brace itselffor the coming plague.

Gonorrhea viewed by uorescent microscopy. The bacteria arelabeled with uorescent antibodies.Image courtesy of CDC.

Tuberculosis bacteria viewed under 1000X magnicationand stained with acid-fast Ziehl-Neelsen stain.Image courtesy of CDC and Dr. George P. Kubica

SPRING 2006