FORUM Time Limitation and the Role of Research in the Worldwide Attempt To Eradicate Malaria

ANDREW SPIELMAN, URIEL KITRON,1 RICHARD J- POLLACK Department of Tropical Public Health, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115

J. Med. Entomoi. 30(1); (1993) ABSTRACT The U.S. Congress established intense, time-limited, worldwide malaria eradication program in 1958 and assigned operational responsibility the U.S. Agency for International Development (and its predecessors). When the progra.Ti terminated schedule in 1963, =$400 million had been consuir.rid and malaria prevalence had greatly been reduced. Transmission began to; increase thereafter. The open-ended WHO global eradication effort began in 1955 ended'in 196,9 and consumed ^Si5 million during the 1958-1963 period of progress,, mainly proyided.by the United States. Intensified anti-. malaria interventions continued after 'Congress discontinued direct support. Although malariological research discouraged', during the' period ".of time'limitation,' it embraced the conceptual basis for the open-ended period of intervention that followed. This effort saved lives but expended ability intervene against future epidemics and reduced human herd immunity. To avoid the "great gamble" inherent in ambi- tious intervention against this disease, future programs should be designed seek incre- mental, local antimalaria gains.

KEY WORDS malaria, research, health

SOON reduced to its global height of the global malaria eradication effort, nadir in 1963, Clay Huff summarized his presi- and his remarks designed to demonstrate dential address to the American Society of Trop- that "Eradication is the logical goal of every pub- ical Medicine with the words, ". the.promise lic health effort directed against infectious dis- to rid the world of malaria quickly if enough .." (Karefa-Smart 1963). Although the money available somewhat like Rus- physician must render his patients pathogen-free sian roulette. The gamble great; the possi- rapidly possible, the public health practi- bility of failure underestimated ..." (Huff tioner must "Hrst" prevent epidemics. This nat- 1964). The program that he described had largely ural attitudinal dichotomy constitutes proper been created in 1957 by the Congress of the conflict between medicine and public health. United States and endorsed by succession The extraordinary effort required by eradi- of U.S. presidents-Eisenhower, Kennedy, and cation campaign is said to be "intensified" in that Johnson-and assisted by various United the required exceed those of the local Nations agencies, mainly the Pan American economies. Because external inevitably Health Organization (PAHO, then known become exhausted, intensified efforts must be PASB), the World Health Organization (WHO), limited in time. Attempts to suppress malaria and the United Nations Children's Fund particularly time-limited because the anopheline (UNTCEF). vector tends progressively to resist insecticides, '-lealth authorities naturally favor eradication the pathogen loses susceptibility to drugs, finan- Eesser modes of intervention agaipst infec- cial appropriations become exhausted, herd im- tions that threaten their constituencies. John munity declines, the operational staff becomes Karefa-Smart, the Minister of External Affairs of demoralized, and the subject population loses Sieira Leone and the former WHO West African nterest in the effort while learning to expect Area Medical Officer, illustrated this tendency in elatively disease-free state. For these reasons, his well-received keynote address to distin- -my heavily intensified antimalaria program (or guished medical audience that included George intervention against any other vector-borne Macdonald and Thomas H. Weller. One of nfection) must be scheduled to deintensify. (A.S.) also present. Karefa-Smart spoke at the The intervention technologies that support malaria eradication campaign must be fully de- College Medicine, rsity ol' lllim veloped and available for before operations Urbar begin, precisely because the time-horizon is

0022-2585/93/0006-0019S02.00/0 EntomoloRic.tl Society of January 1993 SPIELMAN RESEARCH WORLDWIDE MALARIA ERADICATION

short Professional training, too, must be "The period between the late 1920s and the plete because the program aims also toward the early 1930s probably this century's low point extinction of malariologists; they should in acceptance of the eradication concept in the have little to study (Gramiccia & Beales 1988). prevention of communicable diseases." (Soper Basic research and high-level training had 1965). This in part related to the emergence place in the great gamble that Huff described. ofjungle yellow fever and transient outbreak of Such advocacy would be subversive. this infection that struck Brazil. Time-limitation and rejection of research The concept of eradication began to regain fa- appropriately distinguished the highly intense when the Mediterranean fruit fly elimi- phase of the worldwide malaria eradication pro- nated from Florida (1930-1931) and with F. L. gram from other, less-structured efforts. The dis- Soper's remarkable Anopheles gambiae eradica- cussion that follows analyzes the long-term tion campaign in Brazil (1934-1940). This anti- consequences of this discontinued effort. In par- malaria effort based comprehensive ticular, shall identify the conceptual origins derstanding of the ecology of the target insect, of the promise to eradicate malaria, contrast the considered factors such topography, terrain components of bilateral and multilateral efforts, and drainage systems, included excellent follow the line of reasoning that permitted the veillance system and rested varied intervention tactics to remain in effect long after mentarium of intervention (Soper & realistic hope of eradication abandoned and Wilson 1943). Although the sponsoring agency, describe how research attitudes shifted the the Rockefeller Foundation, appeared to avoid prevalence of malaria began its present ascent the term "eradication" in this first An. gambiae toward another zenith. campaign, its largely responsible for the rehabilitation of the eradication concept. This victory followed by campaign against wartime introduction of An. gambiae Early History of Eradication Efforts (in Upper Egypt), and by the program to eradi- Realistic attempts at disease eradication trace cate Ae. aegypti from Brazil (1942) and the Amer- back to the establishment of the Bureau of Ani- icas whole (1947). A final attempt to apply mal Industry in 1884, for the "suppression and the concept of species eradication to malaria extirpation of contagious disease among domes- directed against An, labranchiae in Sardinia in tic animals" and its attempts to eradicate animal 1946-1950 (Logan 1953, Kitron & Spielman tuberculosis in 1888 and 1892, when the 1989). tary of agriculture proclaimed the United States Initially, vector eradication seemed practical free of bovine contagious pleuropneumonia where infection had recently been introduced, (Hagen 1958). in island other "limited geographical units Eradication efforts directed toward agricul- with definite to be cleaned and with tural pests similarly date to this period. The de- natural protection against reinfestation" (Soper liberate introduction into California, for 1948). Eradication considered feasible if the ple, of Australian lady bird beetle greatly public health burden of the relevant disease reduced the damage caused by the cottony cush- ceeds the cost of eradication, if the vector is vul- ion scale, itself invader from that continent. nerable to attack in of its life stages, In the of human disease, early discus- if the vector be eliminated incrementally sion of eradication analyzes Gorgas' work yel- from limited portions of its range, if natural bar- low fever in Havana in 1901, the Rockefeller riers protect cleared regions from reinfestation, if Foundation sanitary commission for the eradica- necessary funding, labor, and authority avail- tion of hookworm disease in 19.10 and yellow able, and if the presence of the vector effec- fever in 1915: "Preliminary arrangements have tively be monitored. "As long evidence for the been made for survey to determine the feasi- existence of the [vector] species continues to ap- bility of undertaking at this time the eradication pear, the campaign has been failure. There is of yellow fever, and for experiments to test the such thing partial in species erad- practicability of controlling malaria." (Rock- ication; either achieves glorious efeller Foundation 1915). Thus, following the dismal failure" (Soper 1948). The Sardinia exper- disappearance of yellow fever from Cuba and iment would to fit into the latter category. Panama, global eradication considered; but A conceptual prelude to the intensified world- for malaria, less-ambitious goals then spec- wide eradication effort launched in the ified. United States during World War II, after The earliest detailed argument for the eradica- DDT became available for antimalaria interven- tion of malaria to have been expressed by tions. In 1943, L. L. Williams proposed that the insurance actuary who presented eloquent U.S. Public Health Service (USPHS) "sponsor plea for national committee the eradication and coordinate program for malaria eradication of malaria and well-reasoned plan for imple- to be executed through state and local health menting that goal (Hoffman 1917). departments, and that the Congress be requested JOURNAL MEDICAL ENTOMOLOGY Vol. 30, to make appropriation ." Mountin (1944) inevitably to insecticide resistance in vector in- presented this program to the National Malaria sects. The power of DDT stimulated Committee, describing the status of malaria in optimism, coupled with growing anxiety that the United States and the logic of intervention. this power might become lost. Medical entomol- He emphasized that vector Anopheles need not ogists "believed in DDT" and looked toward the be eliminated and described variety of sup- obsolescence of their discipline. Resistance gen- pression that emphasized the role of erally seemed to develop between 5 and 10 yr the USPHS. A congressional appropriation for after the of insecticide intensified malaria "eradication" requested, but against particular target. The usefulness of cured Malaria Control Pro- "Extended DDT, therefore, recognized temporary. gram," because of opposition to the term eradi- This conjunction of events coincided with the cation (Williams 1945). The effort funded in 1947. developing of extraordinary public The Extended Malaria Control Program "rep- health administrator, Fred L. Soper, who resented complete change from previous joyed long history of successful health inter- laria control activities. Larvicides, drainage, and ventions. As officer of the Rockefeller Foun- programs to promote insect-proofing of houses dation, he led the campaigns that eliminated An. abandoned and efforts concentrated gambiae from Brazil and Aedes aegypti from upon the of indoor residual DDT sprays .." much of Latin America, among other accomplish- (Andrews et al. 1950). The concept to target ments. He took leading role in the formation of only the potentially infectious portion of the the Pan American Sanitary Bureau (later to be- tor population and to concentrate selected PAHO) and to structure that agency that regions. In 1947, this principle extended to it independent of WHO. His vision of the entire southeastern quadrant of the United disease-free future readily embraced by States. Hundreds of USPHS jobs and large other physicians and politicians and matched the ervoir of personal pride involved (A. D. mood ofoptimism that dominated the thinking of Langmuir, personal communication). Interest- the time. Soper's immense persuasive and ad- ingly, Alexander Langmuir, who directed this $7 ministrative powers provided the catalyst that million program for the USPHS, terminated the energized the antimalaria program. Interest- effort when he discovered that U.S. of ingly, his published memoirs contain refer- malaria clustered in place and time before to this monumental effort (Soper 1977). this program began. Malaria had already been Soper's long-term associate at the Rockefeller eradicated. Foundation, Paul F. Russell, provided the scien- tific basis for the eradication concept. Russell's Rationale Behind the Intensified Malaria optimism matched that of Soper, and his gentle Eradication Campaign complemented Soper's harsh style- His contemporary treatise "Man's mastery of malar- The of with the availability DDT combined ia" eloquently testiHes to his conviction then emergent understanding of the dynamics of that malaria eradication then "within man's malaria transmission during the 1950s to provide grasp." impetus for the eradication concept. George "Only in recent years, with the development Macdonald, ofthe Ross Institute in London, of the Pan American Health Organization, the structed model of transmission in 1956 based Ronald Ross's original mathematical World Health Organization, the Food and Agri- structs. He formalized the eradication concept by culture Organization of the United Nations, the of the demonstrating that the weak link in the transmis- International Cooperation Administration and sion cycle of malaria lies in the survival of the U.S. UNICEF has there existed adequate adult vector relative to the extrinsic incubation mechanism for coordinating and assisting period of the pathogen. The cycle could most gional and world eradication programs." (Soper readily be broken by increasing mortality among 1958). An administrative basis for the intensified the potentially infectious members of the vector malaria eradication program in place. population; that is, those mosquitoes that had fed In this manner, global malaria eradication de- people. Accordingly, domestic applications of rived from unique combination of circum- residual insecticide, sprayed around human stances that included: growing appreciation of sleeping quarters, emerged the single most the epidemiological importance of vector lon- effective intervention tactic. Intervention gevity, the availability of DDT, of age could be measured in terms of the proportion the dangers of insecticide and drug resistance, of houses treated rather than of their vagile the global domination by the United States, the inhabitants,. DDT the ideal insecticide, emergence of United Nations-based multilateral The element of urgency in the eradication ef- bodies, the personalities of F. L. Soper and P. F. fort derived from the belief that agricultural Russell, and general optimism pointing toward well public health of insecticide leads better world to January 1993 SPIELMAN RESEARCH WORLDWIDE MALARIA ERADICATION

Multilateral Efforts characterized by time limits." "An eradication programme must be looked in its entirety; travel communication International and greatly adequate and continued financial provision for in century, increased the mid-twentieth thereby the whole is necessity Original estimates facilitating importation of malaria while fostering should therefore include statement of the in its "The international cooperation suppression. whole programme, and its costs, from start to countries of the Americas have, for the first time finish. Approval should be sought for the whole." in the PASO, convenient framework through (Anonymous 1963). which the effective teamwork vital to eradica- The duration of eradication effort sub- tion campaigns be carried out, ..." (Soper ject of discussion. "An eradication programme in 1958). "Once the concept of malaria eradication where transmission had not previously accepted, PAHO, WHO, UNICEF, and ICA, [sic] been interrupted might require four all became vitally interested in the careful plan- five years of [indoor residual] spraying. If in this ning, meticulous administration, complete malaria control had already interrupted age, continuing evaluation and coordination of transmission, then the eradication might require malaria prevention in contiguous in- only three four years of spraying and the ternational frontiers required for the of trol programme could certainly be referred to each national eradication program." (Anonymous step towards eradication campaign." (Anon- 1961). ymous 1963). Venezuelan experience had sug- The Eighth World Health Assembly, there- gested that 5-yr span might be reasonable: fore, recommended in 1955 program of time- "Depending upon the nature of the vector, limited eradication of malaria out of for laria be eradicated in 3-5 years. In the "the danger constituted by the potential devel- of certain outdoor-biting vectors, however, erad- opment of anopheline resistance to insecti- ication may not readily occur." (Gabaldon 1956). cides. ." The Assembly expressed "the fear This suggestion of potentially open-ended inter- [that] has arisen that the permanent maintenance vention activity became focus of controversy. of control by of the residual insecticides Somewhat contradictory, however, the might prove impossible owing to the growth of practical operational guidelines specifying that anopheline resistance to them." (Anonymous withdrawal of spraying is "permitted" in India 1963). The Assembly "Requested] governments when the annual parasite index (API) (which de- to intensify plans of nation-wide malaria control scribes incidence of malaria diagnoses based that malaria eradication may be achieved and passive surveillance system) is 0.5 per thou- the regular insecticide-spraying campaigns sand in hyperendemic regions and 0.1 where safely terminated before the potential danger of infection is endemic. In Ceylon, the maximum development of resistance to insecticides in permissible incidence 0.05 and in Indonesia anopheline vectors materializes; [and] De- it 0.1 (Anonymous 1963). These specifica- cide [d] that the World Health Organization tions permitted eradication efforts to be deinten- should take the initiative, provide technical ad- sified before the infection disappeared. In effect, vice, and encourage research and co-ordination the WHO effort open-ended. of in the implementation of pro- its ultimate objective the gramme having U.S. Congressional Action world-wide eradication of malaria...." The de- velopment of insecticide resistance among The tightly reasoned IDAB Report (Interna- tor anophelines created the atmosphere of tional Development Advisory Board) set the ba- gency "that largely responsible for the sic terms for subsequent U.S. action malaria adoption by the Assembly of the policy of eradication (Anonymous 1956a). Wilton L. Hal- malaria eradication" (WHO 1958). A Malaria chaired the committee and Paul F. Rus- Eradication Special Account established in sell served its special consultant. After dis- addition to the regular budget of WHO for the cussing the exceedingly useful antimalaria purpose of receiving "voluntary contributions" properties of indoor residual applications of to be used in funding this operational effort DDT, the report reasoned that "Generally, it well unspecified program of research. takes four years of spraying and four years of Although the Assembly specified firm date surveillance to make of three consecutive for terminating the eradication effort, WHO years of mosquito transmission in recognized that time-limited intensification After that, normal health department activities essential to eradication: "Malaria eradication be depended upon to deal with occasional the ending of transmission of malaria and introduced [Therefore] Eradication the elimination of the reservoir of infective be pushed through in community in pe- in campaign limited in time and carried to such riod of 8-10 years, with not than four to six degree of perfection that, when it to years of actual spraying, without much danger of end, there is resumption of transmission." resistance. But if countries, due to lack of funds, (Anonymous 1957). "Eradication campaigns have to proceed slowly, resistance is almost 10 JOURNAL OF MEDICAL ENTOMOLOGY Vol. 30, tain to appear and eradication will become be victory for side, also prepares poorly for nomically impossible. TIME IS OF THE ES- the long-term consequences of [a persisting dis- SENCE because DDT resistance has appeared ease]. Wars eventually end [and are] followed by in 6 7 years... This is completely unique time of peace." (Kenniston 1989). Paraphrasing moment in the history of man's attack of Russell (but without citation), Elsenhower elab- his oldest and most powerful disease enemies. orated this concept of "unconditional Failure to proceed energetically might postpone der" by stating, "We have it within malaria eradication indefinitely. The Committee power to eradicate from the face of the earth that finds that today the eradication of malaria is tech- age-old scourge of mankind: malaria. We nically practicable in most parts of the world,... barking with other nations in all-out five-year and unless this unique opportunity is exploited campaign to blot out this forever." (quoted without delay, it may be lost due to development in Soper 1958). "No other international health of resistance by mosquitoes to the insecticides program has received such strong and consistent that make eradication technically and economi- support at the very highest levels." (from cally possible now." corded speech by C. L. Williams, 20 September The U.S. World-wide Malaria Eradication Pro- 1966). President John F. Kennedy reiterated this gram commenced in 1958 at the height of the support. in and Cold War, the wake of Sputnik, during His successor, Lyndon B. Johnson, in his State period in which the unprecedented wealth ofthe of the Union message in 1964, said, "Both of my United States permitted it to lead in world af- predecessors committed the United States to fairs. Congress funded the Two program. power- [malaria The Congress has ful senators-Hubert H. Humphrey and F. eradication].... John this objective and has it finan- Kennedy-sponsored the enabling legislation for dorsed supported cially. We will in its malaria eradication under the Mutual Security continue to encourage WHO to eradicate malaria the Act. This act derived from the IIAA, Marshall work throughout world Plan for Europe (1948), and the Point IV Program and will continue to aid friendly nations toward (1949), which later to become embodied in this objective." (quoted by C. L. Williams in the ICA and U.S. Agency for International De- recorded speech. 20 September 1966). Interest- velopment (AID). ingly, these words subordinated the antimalaria It argued that malaria-endemic countries role ofthe United States, for the first time, to that would benefit economically from successful of WHO. President Johnson's next recorded eradication campaign. Improvements in health comment rendered its role still ambiguous for residents offoreign lands would also translate by equating the U.S. antimalaria efforts with that into savings for U.S. of imported against disease for which intervention pro- products. Indeed, the burden of malaria "among gram existed. He stated 9 August 1965, "The laborers who produce the goods pur- American goal is to eradicate malaria and cholera chased by the United States requires the from the world." (quoted by C. L. Williams in erage at least 5 percent of the annual production recorded speech, 20 September 1966). budgets. This constitutes hidden malaria tax of Paradoxically, the infectious enemy to be than one-third billion dollars paid annually engaged in campaign that ignored difficult by the United States its imports." (ibid). Thus, battlegrounds. Representing the ICA before anticipated long-term gain to the U.S. the Senate Appropriations Committee, C. L. omy provided crucial argument in favor of erad- Williams (1957) testified that "Within certain ication. technical limitations [the eradication of Interestingly, malaria eradication autho- laria] is possible through the of tried rized in the legislation that provided appropria- methods, personnel, equipment, and supplies tions for many of the main military alliances of which available could be made avail- the United States. An annual appropriation of able. The only exceptions to this conclusion $23.3 million provided for malaria-related certain of the world known suspected to activities, investment for the time. harbor malaria which relatively inaccessi- The appropriation to be repeated 5-yr ble. The situation in tropical Africa is such period but not to be renewed beyond the that eradication cannot be visualized in the im- stipulated closing date in 1963. This investment mediate future. No doubt malaria and intended to produce endpoint that will be eradicated in these in due time." undeniably irreversible prevalence of Thus, while the eradication campaign proceeded laria. elsewhere in earnest and with pressure to This congressional action offered in the ceed within defined period, tropical Africa context of speech delivered by President well other "inaccessible" to be Dwight D. Elsenhower in which he "declared considered at future date. Consideration of total war, not upon any human enemy, but upon the threat of outbreaks due to human migration the brute forces of poverty and need." A "war and the movements of mosquitoes from such metaphor, with its unstated hope that there will sites postponed. January 1993 SPIELMAN AL.: RESEARCH AND WORLDWIDE MALARIA ERADICATION

The "Mutual Security Act in 1958 contained The statement that remember that made specific authorization for malaria eradication that malaria eradication is technically feasi- line item in the budget. Unfortunately, it ble within 5 years." (quoted from recorded eliminated after 1961, the last year in which it speech by C. F. Williams, 20 September 1966). appeared [phased out entirely by thirds from The Congressional Record indeed includes such 1961 to 1963]. From that time forward, have statement, but the distinction had the problem of competing for malaria eradi- sively fine. cation funds at the country programming level. On 3 March 1966, interagency agreement We hoping that change it back again, signed transferring to the Public Health Ser- but at the moment report little progress." vice the responsibility for the operational phases (from recorded speech by C. L. Williams, 20 of the malaria eradication campaign. CDC per- September 1966). sonnel thenceforth represented the U.S. govern- The scheduled conclusion of U.S. congres- ment in place of AID. The first such interchange sional funding in 1963 transformed the various meeting with WHO representatives in At- existing malaria eradication efforts. The original lanta 22 October 1966. logic behind intensification for both agencies volved around the anticipated loss of effective- Funding of DDT well other residual insecti- cides, and that potential became increasingly The IDAB report estimated that in "1956 manifest crucial operational obstacle. total of about $66 million would be spent for Soper convinced that the cycle of trans- malaria in the world, $44 million by national mission of malaria could be broken everywhere governments, $8 million by international agen- except in Africa within 3-yr period of time. The cies, and $12 million by direct I.C.A. assistance" eradication schedule presented to Congress stip- (Anonymous 1956b). It estimated that "wide- ulated 5-yr effort in order to include 2-yr spread malaria eradication could be carried period in which residual problems could be out for five year (1957-61) total of about $519 eliminated. million. Of this amount, the national govern- The subsequent 1960 ICA Expert Panel ments concerned might appropriate $330 Malaria recognized that the 1957 IDAB projec- million and international agencies S50 mil- tion of 3- 5-yr terminal date for eradication lion, leaving balance of $139 million required overly optimistic. Instead, 8 yr seemed from other I.C.A. could provide this, by reasonable; but that might not be realistic increasing its expenditures to $28 million per in certain situations. The cost ofworldwide erad- year." ICA then assisting 21 countries in ication revised upward >10-fold to total of malaria control in 1956 at cost of ^12, million. $1.3 billion, of which $390 million must be sup- In 1956, before the intensified program began, plied externally. By 1966, the director ofthe AID ICA also provided 57.5% of the UNICEF budget program (C. L. Williams) stated, "We have al- and 50% of the United Nations Technical Assis- ready spent several times the [projected tance (UNTA) budget. Some $689,000 of WHO amount], and the end is still not in sight.... The and UNTA money to be spent eradication U.S. contribution has been very, very substantial in 1956. Interestingly, the WHO Special Account indeed." (from recorded speech by C. L. for Malaria Eradication included in 1956 only Williams, 20 September 1966). $9,900 from Brunei. $4,000 from Taiwan, and In the of transferring responsibility for $48,000 from the Federal Republic of Germany. the conduct of eradication to the Centers for Dis- PASO to spend $193,000 in 1956. UNICEF Control (CDC), Williams addressed the is- to supply ==$7 million in commodities. of time-limitation by saying, "We perhaps The enabling U.S. congressional action esti- gave misleading impression when led many mated that the 5-yr worldwide Malaria Eradica- people to believe that going to be tion Program would cost $515 million, of which cessful in the eradication of malaria within 5 the United States would provide $108 million years. inclined to feel that this and the various multilateral agencies would pay of interpretation. don't believe if you look back $42 million. The annual appropriation would be at all of the careful statements that wrote, the $23.5 million of which $5 million would go to testimony that prepared for Congress and WHO and $2 million to the Pan American Sani- on, don't believe that made such tary Organization. "The program in brief: The commitment. We clearly left that impression, following is proposal that the United States whether intended to do it not. And from Government through the International Cooper- time to time have gotten back from the finan- ation Administration, participate in 5-year cial officers of AID, from congressmen and world-wide program to eradicate malaria in col- from the White House, questions [such as], laboration with the nations of the free world and 'Well, you said that you going to do this in the World Health Organization, the Pan Ameri- 5 years and it has been 9 years; How come? Sanitary Organization, and the United Na- Is the end in sight? How long is it going to be?' tions Children's Fund." The United States 12 JOURNAL MEDICAL ENTOMOLOGY Vol. 30, to "spark all-out effort, utilizing all available permitted element of multilateral support for resources, national and international." intensified spraying to be continued essentially Bilateral U.S. assistance each year to de- without limit of time. vote $16 million of this appropriation toward A definitive General Accounting Office report the objective of intensifying the ongoing antima- (Anonymous 1982) estimated that the total U.S. laria efforts of the "60 nations of the free world" antimalaria expenditure exceeded $989 million and thereby raise total attendant antimalaria for the period between 1950 and 1981, with penditures from $44 million to $61 million. $677.3 million going to bilateral programs, Other nations, where bilateral U.S. programs $131.0 million to multilateral programs (includ- in effect, would be served by the WHO ing $89 million to the general operating budgets appropriation of $5 million. The PASO share of and $42 million to special eradication accounts), this multilateral assistance would be the desig- and $181.2 million in research and development nated $2 million in addition to $4 million ap- ($179 million directly and $2 million through the propriation that would underwrite the various UNDP/World Bank/WHO Special Programme Central and South American nations' share for Research and Training in Tropical Diseases of the antimalaria effort. In contrast, $60 (TDR). Some $114,7 spent before the United million had been devoted to bilateral antimalaria States entered the mode of eradication and $407 programs during the preceding 15 yr. The role of million between 1957 and 1969. WHO, therefore, to assist those nations in which U.S. agencies could not operate. Sequelae Actual AID expenditures between 1958 and 1963 totaled $230 million in hard currency plus Long after malaria eradication formally $200 million in local currencies (provided under abandoned global objective, basic features Public Law 480). The United States contributed of the original eradication strategy remained in 31.2% of the WHO overall budget, 66% of that of effect. The showcase eradication effort of Sri PAHO and 40% of that of UNICEF (including Lanka, for example, converted 6 May $6.5-7 million for malaria eradication). Gramic- 1977 into "an intensive malaria control pro- cia & Beales (1988) estimated that WHO spent gramme" that mainly supported by USAID only, $15,205,969 antimalaria activities during and advised by WHO (A.S., unpublished data). this period, of which $12,500,000 donated Its "attack phase" commenced in 1968 in the by the United States. face of longstanding epidemic and in response "The annual budgets of the Pan American and to ambitious economic development plan. World Health Organizations pitifully small; "The goal of the original AID plan of operations only the United Nations Children's Fund stated in 1977.... The specific technical (UNICEF) became interested and Technical malaria control objectives to be reached during Assistance funds became available through the this period to reduce malaria to less than United Nations could these health organizations per 1,000 population and to eliminate P. undertake active collaboration in malaria falciparum infections.... In 1979, the goal trol." (Anonymous 1961). modified.,.. The specific technical objectives to This availability of U.S. funding transformed be reached during this period to reduce the already-existing WHO eradication program. laria to less than per 1,000 popula- At the height of the campaign, the U.S. congres- tion (sic).... The 1977 document described the sional appropriation amounted to >95% of the project 'a large scale five-year effort,'.... But WHO eradication budget (WHO 1959). The Ma- in 1979, the description specified only that the laria Eradication Special Account from project 'a large scale effort.' Both documents $36,600 in 1957 to $5.1 million in 1958. The specified that.... The primary for large WHO Regular Budget appropriation remained scale and intensive malaria control program in relatively constant at about $0,7 million and the Sri Lanka is to control malaria before this vector Expanded Programme from $0.6 mil- develops resistance to malathion.... Surveil- lion to $0.9 million. This level of funding contin- lance is to provide the basis for terminating the ued until 1963, when the U.S. congressional intensified effort, and the 1977 document in- tribution phased out. In anticipation of the cludes detailed description of detection impending budgetary crisis in the special fund, methodology. No discussion of mechanism of the Thirteenth World Health Assembly decided withdrawal is included in the 1979 document." "that the administrative and operational services The plan of operations of WHO, which contin- of the malaria eradication programme shall be ued unmodified into the 1980's, corresponded to financed from the supplementary budget" of the the 1977 AID document (A. Noguer, personal WHO (WHO 1962). Some $2 million to be communication). "The basic objective of this in- transferred to this account in 1963 and $4 million tensive programme to eradicate P. falci- in 1964. Thereafter, the full $6 million required parum and to reduce the prevalence of P. vivax for the special account to be derived from to acceptable low level. The epidemiological central WHO funding. This of central funds findings during 1978 to 1981 will be considered January 1993 SPIELMAN RESEARCH WORLDWIDE MALARIA ERADICATION 13

Pounds of D.DT (millions)

1961 1962 1963 1964 1965 1966 1967 1968 1969 1970 1971 1972 1973

Fig. I. Quantity of DDT purchased by AID for international antimalaria interventions during the period in which the goal of malaria eradication abandoned.

the basis for reduction withdrawal of spray The confusion that surrounded the goals ofthe operations." Thus, the main sponsoring agency Sri Lankan antimalaria program and the problem- appeared to change the terms of its sponsorship atic criteria for deintensification reflected during the of the program and the main in many other programs. These included the coordinating agency failed to coordinate with "malaria control" efforts proposed for Zanzibar this basic change in direction. in 1981 (Anonymous 1981) and implemented in These rather inconsistent goals for Sri Lanka Indonesia in 1980 (Johnson & Kesavalu 1987), to depend residual applications of Pakistan in 1982 (Scholtens et al. 1990), and Ec- malathion, applied to the exterior well in- uador in 1985 (Breeland et al. 1987). The spon- terior surfaces of all structures in the endemic of these efforts generally resolved the para- region four times during each ofthe first 2 yr, two dox between deintensification and time- times in 1979, and eliminated by 1981 (AID, limitation by invoking the promise of vigorous 1977, unpublished document). The cost of this program of research, while suggesting that effort, which underwritten by the United endless chain of substitute intervention technol- States, the United Kingdom, and The Nether- ogies would become available. lands, exceeded the entire nonmalaria health Indeed, U.S. funding continued to support in- budget of the country. Some 7.5 million pounds tensive antimalaria interventions throughout the of malathion to be applied each year to 1960s. The quantity of DDT that AID provided protect exposed population of ^IZ million to the various country programs to mark people. The various sponsors continued this the degree of "intensification" (Johnson 1973). level of support for nearly another decade (AID, DDT for antimalaria purposes greatest 1986, unpublished report) in the face of in 1963, when 61 million pounds pur- mounting evidence of drug and insecticide resis- chased (Fig. I). But, though the congres- tance, demoralized spray teams and steadily in- sional appropriation for malaria eradication had creasing levels of malaria transmission. The expired, DDT continued almost unabated eradication-oriented methodology that im- throughout the decade. Environmental plemented in 1958 remained intact in Sri Lanka eventually caused the virtual abandonment of from 1976 until external support waned in the this product thereafter. The global eradication late 1980s; only the program strategy changed to effort, in effect, became open-ended. The pro- meet the antimalaria philosophies of the gram continued in clear violation ofthe logic that ment. governed its inception. JOURNAL OF MEDICAL ENTOMOLOGY Vol. 30,

World wide malaria eradication formally The conference appropriated funds abandoned by the WHO at the World Health ($100,000) to stimulate and coordinate Assembly of 1969. The next assembly endorsed national eradication campaigns and this "revised strategy of malaria eradication" and ganized the Office of Malaria Eradica- recommended that "malaria control schemes [be tion. This emergency declaration organized] within the general health services" of in response to the development of countries where transmission continues and sistance, but also justified to offset dorsed "intensifying both fundamental and ap- governments' reluctance to appropriate plied research" (Twenty-third World Health As- funds for the containment eradica- sembly. 1970. WHA23.12). "This will necessitate tion of disease which seemed to be reorientation of the malaria eradication efforts only of minor public health importance. from that of countrywide comprehensive 1955-Mexico decides to undertake malaria age to limited epidemiologically oriented eradication and appeals to UNICEF for programs directed toward the containment of assistance. malaria-especially in of intense transmis- -UNICEF/WHO Joint Committee sion." (Scholtens et al. 1972). Intensified sup- Health Policy approved the inclusion of pression had been replaced by array of malaria eradication among supported tive containment efforts (Spielman & Rossignol programs. 1984). -VIII World Health Assembly autho- rized the WHO to implement "a pro- gramme having its ultimate objective A Chronology the world-wide eradication of malaria; The following sequence of events summarizes the events that mark the creation and termination 1956-Decision of U.S. government to sponsor of the global malaria eradication campaign: programs of PAHO and WHO. Trans- 1945-UNRRA assists Italy and Greece in formation of all control projects sup- laria eradication. ported by ICA (AID) to eradication 1944-1945-DDT trials performed in Italy. campaigns. 1946-Missiroli outlines plan for the eradi- -UNICEF declares that it would cation of malaria in Italy. longer support malaria control but only -Vector eradication is attempted in Sar- eradication. dinia. -IDAB report to ICA recommending -UNRRA proposes malaria control pro- conversion of all control programs to gram to WHO Interim Commission. eradication programs. 1947-Commitment of PAS Organization (Pan 1957-Section 420 of the Mutual Security Act American Sanitary bureau) to eradica- passed. tion ofAe. aegypti.. -Malaria programs administered 1948-Pampana supports malaria eradication trally within ICA and specific budgets reasonable goal. submitted to Congress. 1950-At the 13th Pan American Sanitary Con- 1958-U.S. congressional support for malaria ference (PASC), Soper proposes eradication laria eradication international 1961-Programs administered by regional bu- health program. Pan American Sanitary within AID and budgets Bureau (PASB) adopts general princi- longer submitted to Congress. (AID ples and "recommends that the PASB places ICA). stimulate and coordinate anti-malaria 1963-U.S. congressional support ends. AID programs and arrange economic assis- employs 80 technical malaria advisors. tance to individual countries, in order 1965-AID requests that the USPHS adminis- to achieve continental eradication of ter its antimalaria programs, malaria." (Anonymous 1961) 1966-USPHS responsibility for pro- -13th FASC approves continental pro- grams "after AID made firm commit- gram for smallpox eradication, ment to support the then ongoing 15 -Haiti countrywide anti-yaws campaign country programs to completion." is executed. -An agreement signed 3 March in -13th PASC approved continental pro- which the USPHS agreed to furnish gram of yaws eradication. ident advisors; 39 AID direct-hire 1951-Emergence of insecticide resistance in laria advisors continuing in the program anophelines in Greece (Scholtens et al. transferred to PHS. Policy deter- 1972). mination and programming support 1954-14th PASC declares malaria eradication mained with AID'S regional bureaus. emergency need- and demands that 1968-AID notified PHS that antimalaria PASB carry out its 1950 resolution. funding would be reduced (July). January 1993 SPIELMAN RESEARCH WORLDWIDE MALABIA ERADICATION 15

1969-AID multilateralizes. CDC then had 64 This will necessitate reorientation of the Americans working malaria malaria eradication efforts from that of and 22 in Atlanta. countrywide comprehensive coverage to 1970-A memorandum of understanding be- limited epidemiologically oriented tween AID and USPHS stated that all programs directed toward the containment bilateral technical malaria services of malaria-especially in of intense would be phased out. transmission.--(Scholtens et al. 1972) -AID that it will assist WHO In many tropical endemic sites, locally to full responsibility for multi- controlled integrated malaria management laterialization. programs may lead to maintainable gradual -Airgram "AID Policy for Malaria Erad- suppression oftransmission of malaria.-- ication Multilateralization of Technical (Kitron & Spielman 1989) Services" (AIDTO Circular A 1727, 8 August 1970) set out roles for WHO, UNICEF. AID, and USPHS. Message Research restated in AIDTO Circular A-733 Malariological research had place in the dated 3 July 1973. AID eradication effort of 1958-1963. While the 1972-PHS notified AID that the operation proceeded in time-limited eradica- dum of understanding of August 1970 tion mode, any meaningful research program would be terminated June 30. seemed superfluous. Why study something that 1976-AID Audit Report finds that malaria is is about to disappear? Do lack any necessary heavily resurgent and recommends for- techniques? Indeed the original Mutual Security mation of strategy. Act contained research provisions, and the 1978-WHO decides primary health AID administrators of the program in those years and H-2000. deliberately excluded this function. Research ad- 1982-GAO reports that $989 million had been vocacy subversive. spent failed program. Only few lamented the demise ofmalariolog- 1983-AID Strategy Workshop recommends ical research: "... there should not have been tactical flexibility and long-term anti- de-emphasis of basic research and training in all malaria interventions. aspects ofmalariology including control but that, The following quotations illustrate the rise and instead, the efforts towards accelerated at- fall ofthe concept ofmalaria eradication (see also tempt at eradication should have been added to Kitron 1987)-. these efforts." (Huff 1964). Their voices In Europe, having regard to the present largely ignored: "However, to voice such doubts state of knowledge, the correct anti-malaria has become tantamount to being the devil's ad- vocate to being against virtue. To the few practice is to endeavor to reduce the inci- voices which have been raised the dence and severity of the disease. Mea- questioning advisability of using this effort and designed to accomplish than quick final solution have not been heard in the din of that (particularly aiming at 'erad- shouting about initial successes." (Huff 1964). wise and ication') not proposition Interestingly, $2 million research fund be justified only in very exceptional cir- established by Congress in 1959 for the purpose cumstances.--(League of Nations Ma- of developing programs for other diseases. The laria Commission 1927) stated objective "to determine the feasibility The concept of malaria eradication of future intensive programs for reduction, born in the United States, but its growth trol, eradication of disease problems of inter- slow. It had to the dictum national importance." (Section VI of Public Law that while malaria could be controlled, 86-108 of 24 July 1959). These funds, presum- eradication should not be attempted.... In ably; would not have been appropriate for malar- 1943 the concept of eradication iological research. cepted, but its terminology not. Too Organized malariological research programs many years had been spent in emphasizing began to resurface, however, after the time- control in the belief that eradication limited nature of the eradication program had unjustified because of the certainty of rein- been abandoned in 1963. The rationale, fection.--(Williams 1958) then, could be paraphrased "Yes, intensive of killing chemicals cannot be continued This to be health programme pre- without limit of time because the target popula- senting many features of military tion will ultimately adapt. Scientific research ef- paign, and whose aim not merely forts, therefore, will be used to provide sustain- the surrender, but the extermination of the ability. Appropriate funding, deriving from tax enemy.--(WHO 1960) the operational budget, will provide contin- 16 JOURNAL OF MEDICAL ENTOMOLOGY Vol. 30,

series of replacement intervention technol- National Institutes ofAllergy and Infectious Dis- ogies.*' One of the most influential supporters of (NIAID)) and the WHO associated TDK the eradication concept, George Macdonald, (more than $10 million). knowledged in 1965 that malariological research Although this research effort has registered im- had become appropriate with the words, "Re- pressive successes, chain of DDT-substitutes search is needed, although always in parallel to has materialized. Even now, residual operational schemes. Never, happened too of- insecticide matches the effectiveness, safety, du- ten in the past, should it consist of preliminary ration of residual effect and economy of DDT; studies which indefinitely delay the start of antimalaria drug compares with the effec- activity and have real prospect of solving op- tiveness, lack of nontarget toxicity and low cost erational programs. No preliminary exper- of chloroquine; antimalaria vaccine appears iments required... The principle of eradica- close to the point of application. Bacillus thu- tion in contrast with control derives largely from ringiensis israelensis (BTI) is the main Soper. He has the goal of eradication well ful product deriving from this biological control advanced, and there valid why effort, microbial insecticide that may help he should not it reached." Research had duce the abundance of vector anophelines under gained legitimacy certain circumstances. Instead, DDT and chloro- Thereafter, research assumed increasingly quine well diverse other antimalaria prominent place in the eradication programs of agents have progressively lost effectiveness AID and WHO. Indeed, the U.S. Congress began throughout much of the world's tropics. "In Au- the intensified 1958-1963 eradication project gust of 1984, [AID] announced major break- with the clear understanding that the required through in the development of vaccine [and it] intervention technique, indoor residual applica- should be ready for around the world, espe- tion of DDT, already at hand. As early cially in developing countries, within five years August 1960, however, the ICA Expert Panel (Brady in Anonymous 1985). This misguided but Malaria acknowledged that "A number of tech- enduring optimism by the senior assistant ad- nical problems have appeared which complicate ministrator for science and technology of AID is malaria eradication. These include insecticide reflected in repeated rounds of requests for pro- resistance of the mosquito vector, drug resis- posals for vaccine-development, the most recent tance of the malaria parasite, variability and carried deadline of October 1992. A useful im- modification in the type and construction of munogen has yet to be developed, in spite of dwelling to be sprayed, nomadism and pop- quarter century of intensive effort. We still ulation movement, and unusual habits of the "Waiting for the vaccine" (Targett 1991). mosquito vector. Experience shows that early This program of antimalaria vaccine research and continuing epidemiological evaluation and directed mainly toward immunogens simu- entomological research required to recognize lating epitopes the sporozoite stage of the and solve these problems where they exist." pathogen, objective that peculiarly in- Originally the malariological research objec- appropriate for permanent residents of tive adopted by the various agencies mainly malarious regions. If such people to be intended to produce endless chain of vaccinated successfully, they would become pro- insecticides. Each newly devised insecticide, gressively naive against the stages of the patho- unfortunately, became incrementally gen that directly disease. In the pensive and generally less effective than the pre- event that protection less than lifelong (as vious chemical. When DDT replaced by likely), any failure to revaccinate would organophosphate (malathion), the incremental increase the burden that malaria places pop- increase approached factor of 3.5 (Wright et al. ulations. This "visitor's vaccine" (Clyde 1987) 1972). The next increment, for the carbamate could have effect the force of transmission propoxur, approached multiple of 8.5. Econom- of malaria. Although the effect would be less ics formed the rock which this ship of faith in dramatic, certain disease-modifying vaccines science collided. Other speculative promising (Mendis 1991). Conflict search modes established, including pro- and accusations of dishonesty have surrounded gram for biological control of vectors, drug this vaccine program (Marshall 1988). screening program and vaccine program, The focus of research optimism to have By 1982, AID had devoted $170.1 to research, shifted recently from vaccine development mainly focusing vaccine and drug develop- toward molecular entomology (James 1992, ment (Anonymous 1982). Some $125 million had Miller 1992). Advocates of these sophisticated accumulated in designated research fund due research activities promote studies designed to to 5% tax operational efforts. These expen- genetically transform vector anophelines such ditures channeled through academic that they cannot support the development of the network administered directly by AID ($26.5 malaria pathogen. Malaria oocysts would be mel- million), the U.S. Army ($69 million), Navy ($6 anized before sporozoites could develop. Such million), USPHS (>$10 million to the CDC and "designer gene" mosquitoes would then be January 1993 SPIELMAN RESEARCH WORLDWIDE MALARIA ERADICATION 17

leased in endemic sites where they would feed analysis of the history of the open-ended global harmlessly (?) people. These beneficial program of 1955 through 1969 does not consider quitoes expected to replace the native vector the closely reasoned and intensive world- mosquitoes through unstated mode. Invad- wide program of 1958-1963. ing transposable elements may provide vehicle A decade after its inception, the architect of for such displacement (Kidwell & Ribeiro 1993). the IDAB Report reviewed the outcome of the But, because such transposon has been dem- program that he helped create (Russell 1968). onstrated in mosquitoes, malariological studies After listing its and failures. Russell this possibility conducted fruit- concluded his retrospective with the words "the flies. Even if such speculative competitive dis- credits greatly overshadow the debits. Noth- placement effective, few knowledgeable ing in the history ofpublic health, it to me, residents of malaria-endemic sites would toler- equals in determination, accomplishment, and ate deliberate infestations of anthropophagous generosity, the performance of the United States mosquitoes placed their homes, however in its fight against malaria at home and abroad." "beneficial." Any expectation of widespread al- After another decade, memoir written by of truistic sacrifice in one's "backyard" the leaders of this AID effort emphasized the misplaced. The "cutting edge" of malariological role of WHO and enumerated "Some 37 research appears to have turned into the deep tries have been certified by WHO hav- laboratory, [that] ing achieved eradication of malaria. However, A balanced statement of the malariological this leaves nearly 50 other countries search problem presented by Brad- which at- recently and ley (1991). A "great range of imperfect tools for tempted eradication did not succeed." (Smith 1977). AID and WHO eradication efforts malaria control" already exist, and these be applied locally, with good effect. He cites produced mixed results. Blake's admonition that "He who would do good Antimalaria strategies became transformed by must do it in minute particulars; the general the 1980s. The AID program specified that good is the cry of the charlatan." Incremental "country requesting assistance in controlling its local gains likely to be sustainable than malaria problem [must] make commitment of general global victories. long-term support of the proposed program." (Anonymous 1983). The tactical nature of the in- tervention should be designed in spirit of Conclusions "maximum flexibility." Research and training Huffs "great gamble" shadows any intensified "the keys to long-term success." Most strik- program directed against vector-borne infec- ingly, eradication redefined ending tion. "Untimely proposals for eradication of such "when certain [prevalence] requirements diseases onchocerciasis [or of guinea met" rather than at predetermined time. worm]. only lead to disappointments...." The recommendations pointed toward the idea (Jeffery 1976). The consequences of failure of sustainability well afibrdability and at- quire careful consideration. tempted to comply with the Declaration of Alma Although support for world-wide malaria erad- Ata (Health for All by the Year 2000) by intro- ication discontinued by the U.S. Congress ducing primary health and the idea of scheduled, in 1963, its short-term accomplish- munity participation into the antimalaria ments contained many ofthe elements of major mentarium. Thus, programs horizontalized victory (Johnson 1973). Health had improved from the eradicationist vertical mode of admin- greatly; many millions of malaria infections had istration. Research, particularly aiming toward been prevented and uncounted lives saved. In- vaccine development, became high priority. tolerable human suffering would have followed AID established research efforts under the Office any cessation ofantimalaria activities. It became of the Science Advisor and in the Bureau of Sci- unarguable that antimalaria activities must be and Technology in Health and TDR Pro- continued; the then nonimmune residents of gramme established at the main offices of these regions could not have been abandoned to WHO. A series of future-oriented programs of malaria's inevitable return. The admirable logic research thereby to replace the that ruled the original 1958-1963 intervention, mediately beneficial goal of time-limited inter- however, abandoned. ventions. Gramiccia & Beales' (1988) review of "the Despite these conceptual changes, many local cent history of malaria control and eradication" antimalaria programs remain locked in the mode presents detailed analysis of WHO antimalaria of the late 1960s- Prevalence estimates for the expenditures, but omits mention of the vastly previous and for the current year displayed greater U.S. congressional expenditure the prominently for visitors' inspection. Progress is massive force of technical personnel required for measured 2-yr span, and failure of reduc- its conduct. "Dr. P. Russell of the USA, consult- tion of the annual parasite index is attributed ant to WHO" is mentioned in passing. Their to inadequate indoor residual spray coverage. 18 JOURNAL OF MEDICAL ENTOMOLOGY Vol. 30,

However misleading, simplicity renders this the ICA expert panel malaria, 1960. Am. J. Trop. doctrine attractive. Med. Hyg. 10; 451-502. The unified antimalaria tactic of indoor resid- 1963. Report development ofmalaria eradication ual spraying longer is applicable. Because programme. Provisional agenda for the 33 Session, insecticide resistance tends to hinder inter- Executive Board, WHO. EB33/4. 1976. Audit Report: malaria eradication vention efforts, and because drug resistance im- programs. Auditor General. Report May 1976. and therapy, ability to 76-348, AID. pedes prophylaxis Washington, DC. intervene has diminished. De- against outbreaks 1979. Plan of operation for malaria control pro- spite periodic episodes of fascination with gramme in Sri Lanka. U.S. AID Document Proj- array of intervention technologies (alternative in- SRL MPD 001. secticides, medicated salt, drug administra- 1981. Zanzibar malaria control (621-0163): Project tion, genetic control, biological control, anti- paper. U.S. AID Document No. 621-U-026. malaria vaccines, impregnated bednets, and 1982. Malaria control in developing countries: transgenic vector mosquitoes), antimalaria where does it stand? What is the U.S. role? Report panacea should be expected. Instead, series of to the Administrator, Agency for International De- paradigms has been devised to encourage local velopment, 26 April 1982. ID-82-27. General Ac- agencies to adapt integrated package of tech- counting Office, Washington, DC. nologies to their antimalaria needs (Oaks et 1983. AID strategy workshop. June 7-10,1983. Co- al. lumbia, Maryland. Contract DPE-1179-C-2073-0, 1991). Agency for International Development, Washing- The closer antimalaria program progresses ton, DC.70pp. toward eradication, the greater the chance that 1985.' Malaria: meeting the global challenge. A.I.D. ultimate failure may damage the public health. Science and Technology in Development Series, Sustainable interventions, therefore, would be Agency for International Development. Oelge- those that most conservative. They should schlager, Gunn & Hain, Boston. limited region rather than geopolitical Bradley, D, J. 1991. Malaria-whence and whither, entity, help promote the general economy of the pp. 11-29. In G.A.T. Targett [ed.l, Waiting for the local population such that program responsibility vaccine. Wiley, Chichester, U.K. devolve ultimately indigenous agencies. Breeland, S. G., H. C, Gutierrez, P. O'Connor & J. 0. Ideally, such interventions would be applied Stivers. 1987. Evaluation report: Malaria control (Project 518-0049). AR-043 Vec- casionally in time and in place; global project/Ecuador irregularly Biology & Control, Arlington, VA. tend Although solutions to be most dangerous. Clyde, D. F. 1987. Recent trends in the epidemiol- powerful and useful of intervention ogy and control of malaria. Epidemiol. Rev. 9: 219- already at hand, vigorous research efforts 243. quired to increase this armamentarium. The op- Gabatdon, A. 1956. The time required reach portunity lies in interpreting rich store of eradication in relation malaria constitution. Am. antimalaria experience and in devising novel J. Trop. Med. Hyg. 5: 966-976. strategies and administrative structures that Gramiccia, G. & P. F. Beales. 1988. The recent his- appropriate to particular local situations. These tory of malaria control and eradication, pp. 1355- 1378. W. H, Wemsdorfer I. considerations persuade to seek small gains. In & McGregor [eds.], Malaria-principles and practice of malariology. Churchill Livingstone, Edinburgh. Hagen, W. A. 1958. The control and eradication of Acknowledgments animal diseases in the United States. Annu. Rev. We gratefully acknowledge the assistance of Liz Microbiol. 12: 127-144. Campbell and Don Johnson (Atlanta, GA) and A. A. Hoffman, F. L. 1917. A plea and plan for the erad- Shaper (Louisville, KY). This article supported in ication of malaria throughout the western hemi- part by the Vector Biology and Control Project, Arling- sphere. Prudential, Newark, NJ. ton VA. Huff, C. G. 1964. Unfinished business. Am. J. Trop. Med. Hyg. 13-. 243-247. James, A. A. 1992. Mosquito molecular genetics: References Cited the hands that feed bite back. Science 257: 37. Jeffery, G. M. 1976. Malaria control in the twentieth Andrews, J. M., G. E. Quinby & A. D. Langmuir. century. Am. J. Trop. Med. Hyg. 25: 361-371. 1950. Malaria eradication the United States. Johnson, D. R. 1973. Recent developments in Am. J. Pub. Health 40: 1405-1411. quito-borne diseases: malaria. Mosquito News 33: Anonymous. ;1956a. Malaria eradication: report and 341-347. recommendations of the International Develop- Johnson, D. R. & P. G. Kesavalu. 1987. Report of Advisory Board, April 13, 1956. ICA, Wash- the final assessment: Timor malaria control project, ington, DC. Indonesia, August 31-September 28,1987. AR-054. 1956b. Expert Committee Malaria, Sixth report, Vector Biology and Control, Arlington, VA. Athens, 20-28 June 1956. WHO/Mal/180, 28 June Karefa-Smart, J. 1963. The challenge of unfinished 1956. tasks. Ind. Trop. Health 5: 13-16. 1957. Sixth report of the WHO Expert Committee Kenniston, K. 1989. Living with AIDS. Introduc- Malaria. WHO Tech. Rep. Ser. 123. tion to the issue. Daedalus 118: 9-32. 1961. Report and recommendations malaria of Kidwell, M. G. & J.M.C. Bibeiro. 1992. Can January 1993 SPIELMAN ET AL.: RESEAKCH WORLDWIDE MALARIA ERADICATION 19

posable elements be used drive disease refracto- indigenous species, pp. 850-857. In Proceedings, riness genes into vector populations? Parasitol. 4th International Congress Tropical Medicine Today 8: 32M29. 4th Mal., Washington, DC., May 10-18. Kitron, U.' .1987. Malaria, agriculture and develop- 1951. Nationwide malaria-eradication projects in lessons from past campaigns. Int. Jour. the Americas. V. General principles of the eradica- Health Serv. 17: 295-326. tion programs in the western Hemisphere. J. Nat. Kitron, U.^& A. Spielman. 1989. Suppression ofma- Mal. Soc. 10;183-194. laria transmission through reduction: anti- 19S8. International health in the Americas, 1954- anopheline used in Israel, U.S.A. and 1957; director's review. PASB Offic. Doc. 25: 1-20. Italy. Revs. Infect. Dis. 1-1: 391-405. 1965. Rehabilitation of the eradication concept ^Logan, J.,A. 19S3. The Sardinian Project: exper- prevention of communicable diseases. Pub. Health iment in the eradication of indigenous malarious Rep.80;855-869. John Hopkins Press, Baltimore, MD. 1977. Ventures in world health. Pan. Am. Health Macdonald, G. 1965. Eradication of Malaria. Pub. Org.Sci.Pnbl.355. HIth. Rep. 80: 870-879. Soper, F. L. & D. B. Wilson. 1943. Anopheles gam- E. 1988. Crisis in AID malaria network. Marshall, hiw in Brazil, 1930 1940. Rockefeller Founda- Science 24: 521-S23. tion, New York. K. N. 1991. Malaria vaccine research, pp. Mendis, 1944. Species eradication: practical goal of spe- 183-186. In G.A.T. Targett [ed.], Waiting for the cies reduction in the control of mosquito-borne dis- vaccine. Wiley, Chichester, U.K. Nat. Mal. Soc. 1: 5-24. Miller, L. H. 1992. The challenge of malaria. Sci- J. 257: 36. Spielman, A. & P. A. Rossignol. 1984. Insect 167-183. In K. S. Warren & A. F. Mahmoud Mountin, J. W. 1944. A program for the eradication tors, pp. of malaria from continental United States. J. Natl. [eds.], Tropical and geographic medicine. McGraw Mal. Soc. 3; 69-73. Hill, New York. Oaks, S. C, Jr., V. S. Mitchell, G. W. Pearson & C. J. Targett, G.A.T. 1991. Waiting for the vaccine. Carpenter. 1991. Malaria: obstacles and oppor- Wiley, Chichester, U.K. tunities. National Academy of Sciences, Washing- Williams, C. L. 1957. Excerpts from by ton, DC. Charles L. Williams, Jr. M.D. Acting Chief, Public Pampana, E. J. 1948. Malaria problem for the Health Division, International Cooperation Admin- World Health Organization. Proc. 4th Int'l Cong. istration, malaria eradication, before the Senate Trop. Med. Mal., pp. 940-946, Washington, DC., Appropriations Committee. Congr. Rec. Senate, May 10-18, 1948. Aug. 27, 16039-16043. Bussell, P. F. 1968. The United States and malaria: Williams, L. L. 1945. The extended malaria control ^debits and credits. Bull. N.Y. Acad. Med. 44; 623- program. Pub. Health Rep. 60: 464-469. 653. 1958. Malaria eradication-growth of the concept Rockefeller Foundation. 1915. Annual report. Rock- and its applications. Am. J. Trop. Med. Hyg. 7: 259- efeller Foundation, New York. 267. Scholtens, B., L. Cowper, N. G. Gratz, G. Hashim & W. World Health Organization (WHO). 1958. Official Dijk. 19i)0. Report of external review of records, 90. WHO, New York. the Pakistan Malaria Control Program. Vector Biol- 1959. Official records, 98. WHO, New York. ogy and Control, Arlington, VA. 1960. Malaria. Special Issue of World Health, Scholtens, K. G., L. Kaiser Sc A. D. Langmuir. March/April 1960, pp. 8-12. 1972, An epidemiologic examination of the 1962. Official records, 116. WHO, New York. egy of malaria eradication. Int. J. Epidemiol. 1: 15- 1970. Official records, 176. WHO, New York. 24. - Wright, J. W, B. S. Fritz & J. Howarth. 1972. Smith, E. A. 1977. Malaria control: pesticides Changing concepts of vector control in malaria the comprehensive approach. Calif. Mosq. Vec- eradication. Annn. Rev. Entomol. 17: 75-102. Cont. Assoc. 45; 1-5. Soper, F. L. 1948. Species Sanitation applied Receivedfor publication 70ctoberl992; accepted}) the eradication of (a) invading species, (b) October 7992. ARTICLES Plague (Yersinia pestis) in Cats: Description of Experimentally Induced Disease

PETER W. GASPER,1 ALLAN M. BARNES,2-3 THOMAS ]. QUAN,2 JACQUELINE P. BENZIGER,1 LEON G. CARTER,2 MALA L. BEARD,2 GARY 0. MAUPIN2

J. Med. Entomol. 30(1): 20-26 (1993) ABSTRACT Sixteen healthy fed 6-wk-old laboratory that had died of experimentally induced Yersinia pestis infection (strain NM77-538), simulate oral exposure plague. The closely monitored after ingestion. Physical performed and vital signs recorded daily. Plague antibody titers and cultures of blood, throat, and oral cavity performed daily. Complete blood counts and biochem- istry panels performed d. Complete necropsies performed any that died. Cats exhibited ofthree responses following ingestion of plague-infected they either died (6/16 38%), developed transient illness and recovered (7/16 44%) showed signs of illness (3/16 19%). A continual fever greater >40C associated with poor prognosis. The highest antibody titers developed in the group that shed the plague bacillus extended period of time. Blood, throat, and oral cavity cultures positive in 100% of the fatal Throat cultures positive 75% of the exposed In contrast other carnivores, infected with Y. pestis exhibit bubo formation and pneumonic lesions similar to those in people with plague. Because of the potential transmission o(Y. pestis from cats to people, development of plague vaccine for may be warranted.

KEY WORDS plague, Yersinia pestis,

WILD RODENTS, most notably squirrels, and their (27%) occurred in veterinarians their fleas the primary of human plague sistants (CDC, unpublished data). infection in the western United States. In recent Domestic cats have long been known to be years it has become apparent that domestic cats ceptible to plague and to suffer mortality from the provide important link between plague infec- disease (Simpson 1905). The feline response is in tion in its usual hosts and humans (Thomton et al. contrast to raptors and other birds; wild carnivores, 1975, Poland & Barnes 1979, California Depart- including black bears, coyotes, badgers, skunks, ment of Health Services 1980, Kaufmann et al. and raccoons; and domestic dogs, which 1981, Barnes 1982, Werner et al. 1984, Weniger et markably resistant to Y. pestis infection. Current al. 1984, Eidson et al. 1988, Eidson et al. 1991). At information concerning responses of cats to infec- least 15 human plague known to have tion is based observations of pet cats in clinical originated by direct contact with infectious body situations from epidemiological investigations fluids excretions from plague-infected cats (Kilonzo 1980, Eidson, et al. 1988, Eidson, et al. (CDC 1979, CDC, unpublished data). Another 1991). Except for limited study involving only five strongly suspected to have origi- four cats (Bust et al. 1971), experimental studies nated in the Seven ofthe 15 proven represented in the literature. (46%) and 2 of the suspect cat-acquired The objectives of this study to character- (40%) fatal. Four ofthe 15 (27%) ize the pathogenesis of plague in domestic cats> acquired primary plague pneumonia by inhala- clarify their actual and potential role(s) in the tion ofY. pesfzs-infected droplets expelled by cats epidemiology and epizootiolqgy of plague- with secondary plague pneumonia. Four ofthe 15 including the risk of infection transmitted from them to cat and veterinarians-and to evaluate the humoral immune response of cats Pathology Department, Colorado University, Fort exposed to Y. pestis. Collins, CO 80523. Division of Vector-Eome Bacterial Zoonoses, Center for Infectious Diseases, Centers for Disease Control, Public Materials and Methods Health Service, U.S. Department of Health and Human Serv- ices. 2087, Fort Collins, 80532. Facilities. Experiments conducted at the Deceased. Painter Center for Laboratory Animal Research,

0022-258S/93/0020-0026S02.00/0 1993 Entomological Society of