anti malaria resistance

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MOUNT SINAI JOURNAL OF MEDICINE 76:468-473, 2009 468

Historical Perspectives on Malaria:The Rockefeller Antimalaria Strategy inthe 20th CenturyDarwin H. Stapleton, PhD

Emeritus, The Rockefeller University, New York, NY

OUTLINEINSUSCEPTIBILITY O F MALARIA TO CONTR OL

BY INOCULATIONFocus ON THE MOSQUITO VECTORStrategy of the Rockefeller FoundationTyphus and the Advent ofDichlorodiphenyltrichloroethaneApplication ofDichlorodiphenyltrichloroethane tothe Control of MalariaDECLINE IN THE U SE OFDICHLORODIPHENYLTRICHLOROETHANE: ATTENTION TO

NEW APPROACHES

ABSTRACTMalaria, a serious disease for all of human history,was not effectively handled until methods for controlof its insect vector, the Anopheles mosqui to , weredeveloped at the beginning of the 20th century. TheRockefeller Foundation's antimalaria program spreadvector-control strategies throughout the world, and itsadop tion of dichlorodiphen yltr ichloroethane duringWorld War II created an especially powerful andeffective malaria control strategy. However, insectresistance to dichlorodiphenyltr ichloroethane andrestr ictions on dichlorodiphenyltr ichloroethane usedue to its long-term environmental effects arefactors in the persistence of malaria as a serioushealth problem. Mt Sinai J Med 76:468-473,2009. 2009 Mount Sinai School of Medicine

Address Correspondence to:Darwin H. StapletonRockefeller Archive CenterSleepy Hollow, NYEmail: [email protected]

Key Words : dichlorodiphenyltr ichloroethane, mal-aria, Rockefeller, Foundation, typhus.Malaria, a disease transmitted from human to

human by mosquitoes, is currently estimated to beresponsible for 350 to 400 million infections annuallyacross th e glob e, an d at least 1 million of th oseinfections result in death for the infected individuals.^Malaria is a major and continuing challenge formedicine in the 21st century.

Malaria was definitely identified as a specificdisease in the latter 1800s and became the objectof coordinated attempts to control or eliminate it inthe 20th century. However, i t remains endemic intropical regions across the globe and is intertwinedwith socioeconomic conditions, affecting particularlythe poverty-stricken and those with little or no accessto health care. The history of malaria control forthe last 100 years is suggestive of the c om plex setof problems associated with zoonotic diseases.^'^This historical review focuses on the RockefellerFoundation's antimalaria strategy in the first half ofthe 20th century, a strategy that has deeply influencedsubsequent global attempts at malaria control .

Until the mid-1800s, malaria was relativelyinseparable from various other fevers, particularlyepidemic fevers that struck in the summers in bothtropical and temperate zones. For example, thefamous yellow fever epidemic that in 1793 struckPhiladelphia, then the capital of the new UnitedStates, and killed abo ut 10% of the pop ulat ion,probably had both malaria and yellow fevervictims, although the deaths of the latter were farmo re dram atic and more frequent.' '^ Co ntem pora rymisunderstanding of the etiology of the diseasemade effective short-term responses impossible: ittook a quarter-century before the city 's investmentin a municipal water system and improvements insewerage (which drastically reduced breeding placesfor mosquitoes) proved to be the means of ending


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MOUN T SINAI JOUINAL OF MEDICINE 469

the epidemics. '^ Political and technological changes,rather than increased knowledge of disease, endedthe fever years in Philadelphia.The potential foundation for disease controldeveloped in the mid-19th century with the fruitfulintersection of scientific and investigative medicine.As the germ theory of disease origin and transmissiontook hold, new possibilities for understandingand controlling disease emerged. Vector-carrieddiseases, such as malaria, were more complexmatters than human-to-human diseases, but theywere also susceptible to the new scientific-medicaltools of analysis. Alphonse Laveran recognized themalaria parasite in the blood of infected personsin 1880.Giambattista Grassi did research that in1898 recognized particular mosquito species ascarriers of malaria, having established that they werecarrying the malaria parasite. At virtually the sametime, Ronald Ross demonstrated conclusively thatthere was a malaria pathway between humans andmosquitoes.^ The very fact that these milestoneswere accomplished by a Frenchman, an Italian, anda British subject working in India shows both theinternationality of concern about malaria and that thetools of modern science could be brought to bear ondisease research almost anywhere on the globe.

controlling the disease for those already infected.^Early in the 20th centuiy, the systematic distributionof quinine in some areas of the world allowedthe malaria-infected to carry out life tasks withoutsuffering malaria's debilitating symptoms.^F OC US ONTHE MOS QUITO VEC TOR

The other approach to malaria control has been toattack the mosquito vector. Following the successof antimosquito campaigns in Cuba (1900-1901)and the Panama Canal Zone (1905-1914), whichsignificantly reduced yellow fever incidence in thoseareas, primarily through mosqu ito control, antimalariaprograms adopted the same environmental strategies,which ranged from screening windows to coveringall water-collecting devices to draining swamps.^^'^^Later additions to such environmental strategiesincluded managing irrigation practices to interruptmosquito larvae propagation and introducing themosquito larvae-eating fish Gamhusia. Most of thesemeasures, which did nothing for those alreadyinfected but which attempted to limit or stop thetransmission of malaria by reducing the mosquitopopulation, required constant vigilance.

INSUSCEPTIBILITY OF MALARIA TOCONTROL BY INOCULATIONHowever, unlike several other major diseasesof mankind that were attacked and vanquishedwithin a few decades after Pasteur showed theway with a rabies vaccine, malaria did notprove susceptible to control by some inoculation.

The malaria parasite, havingevolved with human beings overseveral thousand years, is awilyadversary that thus far hasdefeated all direct assaults ofscientific medicine.

The malaria parasite, having evolved with humanbeings over several thousand years, is a wilyadversary that thus far has defeated all direct assaultsof scientific medicine.Until the 1930s, only quinine, derived from thebark of the Cinchona tree of South America, whosecurative properties were known in pre-Columbiantimes, provided a consistent dnig-based means of

Strategy of the Rockefeller FoundationIn 1915, the International Health Board, a philan-thropic institution funded by John D. Rockefeller,took on the challenge of malaria control, first byexperimenting with various strategies in mral areas ofthe southeastern United States and then by extendingits experiments to several malarious regions aroundthe world.^'''^^ (i 1928, the International HealthBoard, having worked in tandem with the Rock-efeller Foundation from the beginning, was mergedwith the Rockefeller Fo undation. The foundation con-tinued the board's antimalaria program for anotherquarter-century.)Typical of the Rockefeller-funded projects wasthe work undertaken from 1924 to 1938 in Italy,where malaria had been a problem in agricultural andcoastal regions since time immemorial. The Italiangovernment had instituted a vigorous program ofquinine distribution at the beginning of the centuryand also carried out long-term engineering projects tofill swamps and estuaries. However, the Rockefellerofficer in charge, Lewis Hackett, belittled theseameliorative measures and initiated demonstrationprojects that focused on the mosquito vector. Afteridentifying the malaria-carrying mosquitoes specificto Italy and after studying the favored environmentsDOI:10.1002/MSJ


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470 D . H. STAPLETON: HISTORICAL PERSPECTIVES ON

of those mosquitoes, Hackett centered his work onspraying mosquito habitats with Paris Green, a highlytoxic double salt of copper and arsenic that hadbeen identified recently as a mosquito larva killer.^"^'^^Hackett elaborated on his work in Malaria in Europe,which became virtually a handbook for malariologistsof his era. 18.19This strategy was derided by a 1930 League ofNations report, which argued that general sanitationmeasures and the distribution of quinine improvedthe health of more people than antimosquitocampaigns did. Rockefeller officers countered byarguing that those approaches did little or nothing tobreak the malaria transmission cycle and pointedout that, in ttaly and in their work in areas asdifferent as India and Mexico, they had arguablysuccessful antimosquito projects.^"-^^ The foundationremained wedded to mosquito control as its methodof attacking malaria, in particular concentrating onthe effective use of insecticides.The antimalaria program was carried out inthe framework of a global Rockefeller publichealth program that emphasized the control ofseveral other major diseases, including yellow fever,ancylostomiasis (hookworm), and influenza.^^ Theprogram generally attempted to create model projectswherever the Rockefeller approach was welcomedand then to train a generation of public health leaderswho would continue the scientific-technical strategyit favored. Malaria projects as widespread as thesouthern United States, Columbia, Italy, India, andthe Philippines were expected to infiuence the courseof public health work throughout the world.^^"^^

Typhus and the Advent ofDichlorodiphenyltricMoroethaneNonetheless, by the end of the 1930s, globalmalaria control remained a vision that was far fromrealization. It was the advent of dichlorodiphenyl-trichloroethane (DDT)-a powerful new insecti-cide-during Wodd War II that created unanticipatedpossibilities. The story of DDT begins with the threatof another zoonotic disease: typhus.It was the advent ofdichlorodiphenyltrichloroethane(DDT)-a powerful newinsecticide-during World War IIthat created unanticipatedpossibilities.

At the outbreak of Wodd War II, publichealth officials had every reason to anticipate that

major typhus epidemics would occur, particuladyin European populations weakened by years ofeconomic privation and by the opportunities forinfection in crowded refugee camps, internmentcamps, prisoner-of-war camps, ghettos, slave-laborfacilities, and concentration camps.^*^ The bestmeans of controlling typhus epidemics at that timeremained strict personal sanitation; this was based onknowledge that typhus is transmitted by the humanbody louse, which has evolved w ith hum ans to favorwoven fabric as a habitation. The alternatives tocontrol by sanitation at the time were the use ofinsecticides and vaccines, but the insecticides mosteffective against lice were ingeneral highly toxic tohumans, and the vaccines available were still in trialor untested inpotential epidemic circumstances.The Rockefeller Foundation began a modestantityphus program in 1940 by connecting with theHarvard University laboratory of Hans Zinsser, whohad for many years been investigating the familyof Rickettsia microbes and had already publishedhis classic historical work. Rats, Lice and HistoryPOver the next months, with the increasing likelihoodof the entry of the United States into the war,typhus research grew into a significant element ofthe Rockefeller Foundation's public health program.Because of the foundation's extensive connections,it could survey, study, and otherwise learn abouttyphus virtually throughout the world. Moreover,it could test typhus vaccines in the field withcollaboration from local authorities who alreadyknew and trusted the motives of the foundation.These tests initially included promising but u ltimatelydisappointing trials of existing vaccines in venuesas disparate as vulnerable populations in Spainand young men at the New York State VocationalInstitution in the Hudson River Valley town of WestCoxsackie. By the time of the entry of the UnitedStates into the war in December 1941, the foundationhad decided that an attempt to develop a typhusvaccination was unlikely to succeed in the short run.That decision soon was reinforced by a request fromthe US National Research Council Subcommittee onTropical Diseases to investigate "the advisability ofundertaking a study of various delousing methodsin N[ew] Y[ork]."^^ The next month, the foundationcreated a laboratory for the study of louse-bornetyphus as a unit of the foundation's researchlaboratory located on the campus of the RockefellerInstitute in New York City.^^The foundation's antityphus laboratory, whichsoon became known as the louse lab, quickly estab-lished a collaborative agreement with the Bureauof Fntomology and Quarantine of the US Depart-ment of Agriculture by which the bureau would test

DOI:10.1002/MSJ


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MOU NT SINAI JOURNAL OF MEDICINE 4 7 1

insecticides and the foundation would test them andother louse-control methods on human subjects infield conditions. It quickly became apparent that thefound ation's 30 years of fieldwork in public healthand i ts global network of contacts were advantagesthat a government agricultural laboratory did not pos-sess. After successfully establishing a colony of lice inNew York, the foundation was able carry out tests oflouse-control methods on conscientious objectors ina forestry camp in the United States and in a villagein Mexico.

However, the foundation's anti typhus programsoon was radically altered by the identification ofDDT as a powerful insecticide that could control thehum an bod y lou se. In August 1942, J.R. Geigy Co.of Switzerland shipped to its office in New York asample of this new insecticide, which then was sentto the Bureau of Entomology and Quarantine. Earlyin 1943, the foundation learned from the Bu reauabou t DDT's wonderful properties, and it was able tocarry ou t its ow n te sts in April. By July 1943, a teamof foundation officers in Algeria was testing DDT asa lousicide.

The result of the Rockefeller team's workwas the crea tion of an effective insecticide-deliverymethodology based on DDT that could control thehuman body louse. Their methodology was put to thetest during an incipient typhus epidemic in Naplessoon after the Allied invasion of Italy. A combinationof wartime privation and overcrowding of the civilianpopulation, a depleted local health system, andrefugees from the Balkans, who presumably werethe locus of the infection, created the conditions fora rapid rise in typhus cases in Naples in December194330 -j-j^g Rockefeller team from North Africawas called in and "formed the backbone" of theintensive project that even tually du sted 1.3 millionpeople with insecticides.^^ This event has generallybeen recognized by historians as the first cleardemonstration of the control of human disease byDDT.3233

Application ofDichlorodiphenyltrichloroethane to theControl of MalariaYet it was also essentially the end of the foun-dation's anti typhus experiments because DDT hadconvincingly de mo nstra ted its effectiveness a nd fur-ther experimentation seemed unwarranted. TheRockefeller Foundation instead turned its attentionto experiments with DDT for mosquito larva controlin Italy, essentially renewing the antimalaria projectthat it had carried out there from 1924 to 1938. Thefoundation found DDT so effective that it decided

to attempt the eradication of mosquitoes from theentire island of Sardinia, a demonstration project thatit carried out from 1946 to 1951.In Sardinia, the Rockefeller Foundation, with

financial support from the United Nations Relief andReconstruction Administration and the Italian govern-ment, created a highly organized team that sought tolocate and spray every breeding place of anophelinemosquitoes in Sardinia, with the goal of eradicat-ing them from the island. In an area approximatelythe size of the state of New Hampshire, there weremountains, swamps, forests, villages, and small citiesthat had to be mapped, sampled, and efficientlysprayed. Visitors from throughout the world stud-ied the administration, methodology, and technologyassociated with the Sardinian project, which was suc-cessful in eliminating the scourge of malaria from theisland. After that great effort, the foundation yieldedleadership in the malaria field to the recently createdWorld Health Organization, whose global antimalariaprograms, beg inning in 1955, have continu ed thefoundation's insecticide-based strategies."^'^''^^ Withonly a glimmer of hope for a malaria vaccine, itappears that insecticides will be the mainstay ofantimalaria work for the foreseeable future.'^

DECLINE IN THE USE OED ICH L O RO D IPH E N Y L -TRICHLOROETHANE :A T T E N T IO N T O N E W A PPRO A CH E S

In the last decade, renewed recognition of malaria 'sterrible burden in tropical regions has brought boththe US govern me nt and the G ates Foundation intothe antimalaria fight, pouring billions of dollarsinto a range of approaches to malaria control.^^'^^This has also raised the profile of DDT, whoseuse was declining, particularly after its deleteriousenviro nm ental effects we re recog nized . In 1999, agroup of scientists urged the United Nations toreconsider its plan to push for a global ban onDDT, and they were successful.'*

Malaria can no longer beregarded as a rural disease. . . .Acquired resistance by m osquitoesdefeats each new generation ofinsecticides. . . . Ma ny insecticidesare persistent over years andmigrate through ecological cyclesto cause unanticipated effects.


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Rockefeller Foundation in Italia: 1922-1934. Rome,Italy: Editori Laterza; 2003-18 . Hackett LW. Malaria in Europe: An E cological Study.London, England; Oxford University Press; 1937.19- Stapleton DH. Hackett, Lewis Wendell. In; BynumWF, Bynum H, eds. Dictionary of Medical Biography.Westport, CT; Greenwood Press; 2007.20 . Muraleedharan VR, Veeraraghavan D. Anti-malarialpolicy in the Madras presidency; an overview of theearly decades of the twentieth centuiy. Med Hist 1992;36 ; 2 9 0 - 3 0 5 .

21 . Birn A-E. Eradication, control, or neither? Hookwormvs . malaria strategies and Rockefeller public health inMexico. Parassitologia 1998; 40; 137-147.22 . Earley J. To Cast Out Disease: A History of theInternational Health Division of the RockefellerFoundation (1913-1951). New York, ^P'; OxfordUniversity Press; 2004.23 . Stapleton DH. Malaria eradication and thetechnological model; the Rockefeller Foundation andpublic health in East Asia. In; Yip K-C, ed. Disease,Colonialism, and the State: Malaria in Modem East

Asian History. Hong Kong; Hong Kong UniversityPress ; 2009; 71 -8 4.24 . Rodriguez PM. De ratones , vacunas y hombres;el programa de fiebre amarilla de la FundacinRockefeller en Colombia, 1932-1948. Dynamis 2004;24; 1 1 9 - 1 5 5 .25 . Stapleton DH. Technology and malaria control; thecareer of Rockefeller Foundation engineer FrederickW. Knipe. Parassitologia 2000; 42; 39-68.26 . A step in prep ared ness against typhus. RockefellerFound Trustees Confidential Bull 1940; 16-18.27 . Zinsser H. Rats, Lice and History: A Study in Biography.Boston, MA; Little, Brown, and Co.; 1934.28 . Joh ann es H. Bauer diary, 22 Janua ry 1942, box5, Record Group [hereafter RG] 12.1, RockefellerFoundation Archives [hereafter RFA], RockefellerArchive Center, Sleepy Hollow, New Y ork, USA; extractfrom Tmstees' Minutes, 11-12 September 1942, folder261, box 32, series 100, RG 1.1, RFA.29 . Stapleton DH. A lost chapter in the early history ofDDT; the development of anti-typhus technologiesby the Rockefeller Foundation's louse laboratory,1942 -1944 . Technol Cult 2005; 46; 513 -540.30 . Soper FL, Davis WA, Markham FS, Riehl LA. Typhusfever in Italy, 1943-1945, and its control with lousepow der. In; Kerr JA, ed. Building the Health Bridge:Selections from the Works of Fred L. Soper, M.D.Bloomington, IN; Indiana University Press; 1970;3 8 4 - 4 1 5 .

31. Turner TB. Sicily and Italy. In; Taylor RR, Lada J, HoofEC, eds. Preventive Medicine in World W ar II. Vol 8.Washington, DC; Office of the Surgeon General; 1976;308.32 . Russell EP III. 'Speaking of annihilation'; mobilizing forwar against human and insect enemies , 1914-1945.J Am Hist 1996; 82; 1523-1524.33 . Williams TI. A Short History of Twentieth-Century

Technology, c. 1900-c. 1950. New York, NY; OxfordUniversity Press; 1982; 328.34 . Farley J. Mosquitoes or malaria? Rockefeller campaignsin the American south and Sardinia. Parassitologia1994; 36; 165- 173 .35 . Brown PJ. Failure-as-success; multiple meaningsof eradication in the Rockefeller FoundationSardinia Project, 1946-1951. Parassitologia 1998; 40;1 1 7 - 1 3 0 .36 . PATH Malaria Vaccine Initiative. Available at;h t tp ; / /www .malariavaccine.org . Accessed June 2009.37 . European Malaria Vaccine Initiative. Available at;h t tp ; / /www.em vi.org . Accessed June 2009-38 . Garrett L. The re turn of infectious dise ase. Foreign Aff

1996; 88 ; 66 -79 .39 . Shell ER. Resurgence of a deadly disease. AtlMon 1997;280; 45-60 .40 . Open letter to DDT treaty negotiators. Availableat ; h t tp ; / /www.malaria .org/DDT. .open.html. AccessedSeptember 2008.41 . Kamat V. Resurgence of malaria in Bombay (Mumbai)in the 1990s; a historical perspective. Parassitologia2000; 42; 135-148.42 . Commoner B. Tfce Closing Circle: Nature, M an andTechnology. New York, NY; Bantam Books; 1971;163.43 . Curtis J, Profeta T. After Silent Spring: The UnsolvedProblems of Pesticide Use in the United States.New York, NY; Natural Resources Defense Council;1993; 8 - 1 8 .44 . Fske nazi B, Chevrier J, Rosas LG, et al. The PineRiver Statement; human health consequences of DDTuse. Environ Health Perspect. do i ; / /10 .1289 /ehp . l l748 .Available at ; h t tp ; / /www.ehponline.org .45 . WorldWatch Institute. Vital Signs, 2007-2008: TheTrends That Are Shaping Our Future. New York, NY;W.W. Norton & Co.; 2007; 124-125.Ad. van den Berg H. Global status of DDT and itsalternatives for use in vector control to preven t disea se.Environ Health Perspect. doi; / /10 .1289/ehp.0900785.Available at ; h t tp ; / /www.ehponline.org .47 . Okie S. A new attack on malaria. N Engl J Med 2008;358; 2425-2428 .

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