milestones in public health: chapter 1

8/14/2019 Milestones in Public Health: Chapter 1

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Ch:lpterVaccines and theEradication of SmallpoxLooking Back

"Ring :lrollnd the rosy I A po cket full of posies I Ashes,:lshes I We :111 f.111 down!"Who isn't f.1rnili:lr with thi s c hildh oo d so ng? M:lny pe op lemi ght be surprised that this verse (i'om the 1600s refers toan outbre:lk of the plague th:lt dev:lst:lted mu ch of westernEurope, Hu m :lns :Ire still vulnerable to infecti ou s dise:lsesthat through history have run rampant and killed V:lstntllubers of people ,The plague and smallpox did just th:ltthrough 1llu ch of the Dark and Middle Ages. Ne w virusessuch as HI V and SAltS threaten humans in this ce ntur y.The development of v:lccincs, th erefo re, is one of man's

greatest achievements. Vacc ines protect peo p le frolll f.1taldiseases, incre:lse life expect:lncy and spare co ulltlessmillions from p:lin :lnd sutTerin g.Th\! word I/{/(Cill(' comes fronl "vaca," Lat in for cow. In1796 in Clollcestershin.:, Engbnd, ])1'. Edwa rd Jenne r


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discovered the first va cci ne for slll:lllpox. Jenner used Illatcri:l.l from a skin pustu le which contained live III1Crillil1 Ilints, avi rus be lieved to be spread by cows to milk1mids, ca usi ngcowpox. Milkmaids who contrac ted cowpox, a mild diseasein humans , seemed to be inHllune to smallpox, a virulents e a s t ~ in humans. Jenn er inoculated 24 children with the

vllaillia virus and, like the milkmaids, they became immuneto smal1pox. Despite its success, the smallpox vaccine neverbecame widespread enough to fully COll trol the diseaseuntil late ill the 20th century. It was especially problelllaticin the tropics, where slispensions eQuId Ilot be kept coolenough to be effective.In 1895, Loui s Pasteur developed the second vaccillt!, thisone for rabies, a groundbrc:l.kin g achievement. As the firstexample of a pathogen being altered for a therapeuticpurpose, Pasteur's success opened the door to the fieldof imlllunobiology. That same year, Emil von l3 ehring ofMarburg Univt!l"sity in Germ:lI1 y introduced the diphthe riavaccim:. Three other vaccines - for typhoid, chole ra andplague - were also developed late in the 19th century, burtheir use was not widespread at the beginning of the 20 thcentury. Too many impoverished countries Iud no pllblichealth infrastructure, and the cos tS of vacci ne distributionwere prohibitive.Although smallpox was still widely prevalent in the UnitedStates at the beginning of the 20th centur y, it was by 110means the onl y infeCtious disease to affect the Americanpop ulation. In 1920, for example, 469,924 cases of measlesresul ted in 7,575 deaths. That same year, nearly 148,000diphth eri:l. cases resulted in more than 13,000 deaths and107,473 pertuss is cases resulted in more than 5,000 deaths.The development of the polio vaccine in 1955 had aradical imp act on the use of vacci nes in the United States.Parents were eager to protect their chi ldren from the "ironlung" disease, and Cong ress appropriated funds to inoculateschool children with the polio vaccine.The U.S. governmentthen began a major push to promote the use of vacci nes .Today, most Americans don't think twice about vaccination.Children routinely undergo a series of vacc inations frombirth through e:uly childhood. Th ese include vacci nltionsagainst diphtheria, pertussis. tetanus, poliomyel itis, measles,mumps, rubella, chicken pox and H fll'lIIopllilrl s illjlIlW'::fI(,

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Toxoid Vaccine. This type of vaccine llses protein tOXIllSthat have been secreted by pat hogenic bacteria bur areinactivated. Th ese vaccin es also require several injections; diphtheria and tetanus vaccines are examples.

Since 1900, vacc ines have been developed and licensedagainst 21 other diseases, wi th ten limited to selectedpopulations at high risk accord in g to residence, age,medical condition or risk behaviors. At the start of the21st century, the vaccine-delivery system in the UmtedStates has evolved into a collaboration of a l l l e v e l ~ ofgovernment (federal, state, local) and public and privatehealth care providers. The system continues to harnessthe latest technological advances. [)


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,Hi storians saythat smallpoxmade the Spanishconquest ofMexico possiblewhen Cor tes andhis (ollqllisladl>rSintroduced it tothe Aztec popula-tion in Techotitlanin 1520.

Case StudyEradication of SmallpoxThe story of vaccincs begins with smallpox . Overthou sa nds of years, hundreds of millions of peoplecontracted the disease. Th e Illummified body of PharaohRamcsses V of Egypt, who died in 1157 Be, shows apustular rash, the earliest physical ev idence of sm:dlpox.During the next thousand years, traders carried the dis-C:lSt' from Egypt to India, and from there it swept intoChim. It re:tched Japan by the 6th century ;llld Europeby the [ [th century, spread by recurnillg crusaders. In the20th century alone, an estim:lted 300 million people :Irebelieved co h:lVe died from it. Although sJllallpox wasdeclared eradicated in 1980, the threat that it might bedistributed by a terrorist has created fear.Smallpox was particularly c a and deadly inpopulations exposed for the first time to explore rs fi'olllEurope. It paved the way for Spanish conquests in LatinAmerica. Historians say that smallpox ll1ade theSp:lt1ish conquest of Mexico possiblt when Cortes andhis c/lllqllis/adors unintentionally introduced it to the Aztecpopulation in Techotitlan in 1520. Sm:lllpox rav:lged theAztecs, who had no natural immunity. CorteS and his menthen proceeded to co nquer a vas tly weakened Aztecem pire. During the French :lnd Indian War, Lord JeffreyAmherst deliberately infected blankets with smallpox anddistributed them to Ind ians ou tside Fort Ticonderog:l , thefirst known eX:lTllpl e of germ warfare.Smallpox afft"cts only humans. Transmission occurs whenthe II(/r;o/a "ims (an orrlwpoxllirus) is inhaled in dropletsor aerosols from the respir:ltory tract. Transmission alsooccurs through cOntact wi th skin lesions of infectedpatients or their bedding or clothing.The lIlcubationperiod laStS St"ven to 17 days, with an average of 12 d:lYs.Th e dise:lsc presents first with feve r for two to four days,followed by a rash lasting for w ~ e k s . The rash evolvesslowly from papules to vesicles, then pustules and finallyscabs, all at the samc stage in any onc arca" Transmission


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occurs mainly during the rash phJse Jnd diminishes as thelesions sClb. Historica lly, Jbout 50 percent of ullvJ cc inaccdfunily members became infected. T he mortality rate was20 percent to 30 percent in unvaccinated populations, butlllany survivors were left with severe sca rring and so mewith blindness .Noting that survivors enjoyed lifelong immunity from anyrecurrence of the disease, physicians in China and IndiJ inthe 10th century began to experiment with inoculation.[ n a process called variola/ion, these physicians introducedpm from smallpox pustules on infected people into non-infected peopl e. Usually, the person who was 1I10culatedwould develop only a few pustules and a fever. However,111 up to twO percent of the cases , J virulent or aggress iveform of the dis ease developed, causing death. Nonetheless,the odds were great that an inoculated person would survive and, thereafter, enjoy lifelong immunity.Th e idea ofvario/ario1l spreJd to Europe. [n a i:1motls case in1721, Lady Mary Wortley Montagu, a smallpox survivorleft with unsightly pockmarks, lea rned of ImriolaliOIl whileher husband was posted to Constantinople as the Britishamb assador. She inoculated her children and persuadedthe Princess ofW;des to do the same. In f:1ct, Edwardjenner, the discoverer of the smallpox vaccine, had beenso inoculated.In 1796, Dr. j enner vacc inated 24 children with pus hehad extracted from a milkmaid's cowpox pustule. First,he experimented with james Phipps, an eight-year-oldboy, by int roducing the cowpox strain through :I cut inthe arm. After purposely exposing the young boy tosmallpox, Je nner followed the boy's status closely andconcluded that the introduced vaccillia lIirlls confe rredillllllLllllty from smallpox. Next,jenner inoculated hi sown 11 -month-old son with the same result.The cowpoxvaccine proved effec tive with all 24 children, co nfer ringli felo ng immunity from smallpox. By tod:ly's standards,Jenne r 's experiments on human subjects would not beconsidered ethical. Fortunately, the fact dut his cowpoxvaccine worked is not in di spute, and hi s discove ry wouldprotect millions of lives in the future.

,.

In 172I,smallpoxsurvivor, LadyMomagu, learnedof variolation whilein Constantinople.She inoculatedher children andpersuaded thePrincess ofWalesto do the same.


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Sm:t!lpox continued to appel!" in outb reaks throughout[ht' world into the 20th century. In fact, a deadly smallpoxoutbreak in the United States between 1900 and 1904caused an average of 48 , 164 cases in each of those yearsand resulted in an av(::rage of 1,528 deaths annually. Dueto improved tracking and containment, outbreaks of thesevere form of the disease (va rio/I! " ldjOT) ended abruptlyin 1929 in the U.S.; outbreaks of I!ario/a III;I/(Ir, the milderform , declined in the 1940s with the last U.S. case report-ed in 1949.Om,' scare in Ne w York City in 1947 re sulted in thecity vacc Lnating more than six 1l1l11ion residents. AMexican busi nessman who traveled by bus to the city,Un:lware that he was incubating smallpox, spread thcdisease to 12 people, two ofw ho LTl dicd, including him.

N e l l l ~ ) r k e r s Ii"e IIp Ior iIlO(U/lllioll iu 1947.Fearing the worst in the densely populated city, healthatLthOflties took no chances and ordered the mass vacc i-nation, which took place within one month at hundrcdsof stations iLl hosp itals, police stations and firehouses .A resolution proposcd by a delegate from the forllLaUSSR at the 11th World Health Assembly in 1958 and


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passed by the assembly ill [959 paved the way for aworldwide etTort to eradicate smallpox. In 1966 atthe 19th World Hea lth Assembly. the World HealthOrganization (WHO) called upon all the world's govern-ments to suppor t and give financial backing to a newlycreated Global Smallpox Eradication Campaign.Why did sm allpox, of all diseases, become a c:mdidare forwo rld w id e e radica tion? All important reason was that itrema in ed a powerful kill er throughout the world . In theyear prior to the start of the WHO eradication program,an estimated 15 million people coml


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... and the worldbegan to understand that promptdetection andcontainmentcould lead to theeradicat ion of thedisease.

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in Iran, Iraq and Syria, cases we re imported, and epidemicsoccu rred. However, by la te 1973 outbreaks had beencontained except in Bangladesh. That year, Intensifiedcampaigns began in the five countries with remainingendem ic cases - Bangladesh, India, Nepal, Pakistan andEthiopia. India alone reported 64 percent of the caseswo rldwide.By 1976, only Ethiop ia remained with smallpox, andall attention turned to it. Th e milder strain, variolalIIillor, spread tenaciously across a vast, sparsely settledregion made destitute by civ il war. Th e last outbreak wasfinally contained in the Ogaden Desert in August 1976.

However, an affec ted nomad population had alreadymigrated into Somalia, and it was there that the lastknow n outbreak occurred on October 26, 1977.[n 1980, th e W HO declared smallpox eradicated. Th esteps taken to get to that pOlllt illustrated how the surveillance and co ntainment programs could be adapted toindividual countr ies to allow teams to succeed in ve rydifferent populations. Th e combination of a persistent,coordinated international effort, spearheaded by theWHO, :md innovative approaches at local levels led tosuccess. Lessons learned from the eradication camp aignare relevant in the 21 st century as th e threat of weapon-ized smallpox forces the public health community toconfron t a scourge it hoped had been co nqu ered. D

,However, anaffected nomadpopulation hadalready migratedinto Somalia, andit was there thatthe last knownoutbreak occurredon October 26,1977.


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16 Mllc>wllcs Chaplcr I Vaccmes Lookmg A h ~ a d

Looking AheadAdvances in Vaccine ResearchThe need for new vaccines and new vaccine technologieshas never been gre:tter II I light of the events of SeptemberII, 200 I. Vaccines arc likely to be the only practical meansof protection in the event that biological weapons of massdestruction are unleashed on an unsuspecting population.Weapons that use diseases to kill la rge Ilumbers of people,that can be readily transmitted person to person - anthrax,smallpox. and plague being the foremost threats - ca ll fornew types of second-generation vaccines to be developedand stockpiled .Currently, only small amounts of anthrax vaccine are produced in the U nited States with use limited to those in themilitary. Planning is in progress, however, to produce largequantities of a more modern vacclI1e that cou ld be used inthe gene ral population in case of a serious threat or attack .[11 August 2003, D.A. H enderson, wh o now serves as ase lllor adv iser at the Center for Biosecurity, Universityof Pittsburgh Medical Center, and Dean Emeritus at theBloomberg School of Public Health at Johns HopkinsUniversity, addressed the issue of preparedness to deal witha possible small pox rdease. "Preparedness is mllch bette rthan it was at 9/11," he said. "We have ample vaccine andneedles, a better-educated public health and medical COIll-mllnity, most hospitals have negative pressure examinationrooms and some areas are prepared for large-scale vaccination should that be necessary. In all, 700,000 in the militaryand some 40,000 civilian health workers have now beenvaccinated, far fewer in the Civilian sector than we believedesi rable. Work remains to done, bu t progress in movingtoward a full prepa redness has been gr:ltifying."[n the United States, . . :111 estimated 11,000 birthseach day place stress on the vaccine-delivery system. Eachnewborn currently requires a se ries of between 15 and 19vaccine doses in the first 18 months of life . Ne w combination vacc ines may reduce that number to 11, but as additional vaccines are developed, the numbe r of doses maywell rise again. Parents tend to value immunization, a signof public trust that all successful vaccine programs co unt

,... an es timated11 ,000 births eachday place stresson the vaccinedelivery system.


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,Vaccines havesaved more livesthan any surgicaltechnique orany medication,includingantibiotics.

all. Adverse results, although rare, still occur, however. :l.l1dsurveillance to detect these events l11ust continue, alongwith research im o possible risk f:,ctors and their manageIllent. For each new vaccine program, an accompanyingpublic-inform:ltioll campaign is essential. Professional andadvocacy groups must be kept informed every step of theway, as Illust legislators, educators and the media.[n 1998, an article in Tflr uw(el suggested dlat theMMR (measles, mumps, rubella) vaccine might be linkedto inc rC:lscs in autism. As D.A. Henderson points Ollt, how eve r, " I, for one, am fully pe rsuaded by several studies thatdemonstrate conclusively there is no relationship betweenMMI"t and autisl11 .TIle problem: poor science in the firstplace and a press eage r to publicize the spect3cular.Regrettable." After the Lwrc/ article, some parents refusedthe MM R vaccine for their children, and this eventuallyresulted In measles outbreaks that would h:lVe been prevented. Concerns over adverse events must be b:llancedwith the knowledge ell:lt v:lccines avert misery. Many agr:lndp:lrent owes a long life no t just to cle:lll W:lter. bu talso to remarkable advances in v:lccines . Vaccineshave saved Illore lives than any surgical technique or anymedic:ltioll, including ant ibiotics.Despite th e success of smallpox eradic:ltiol1, many diseasesthat vaccines prevent still persist, especi:llly in developingcountries. Polio, measles and rubella are still threats tomillions of children and adults worldwide. According tothe W HO, infectious diseases were the leading causesof death worldwide in 1996, with 17 million deaths :lIlnually compa red to tell million from heart disease and sevenmillion fiom cancer. Even ill the United States and otherindustrialized coulltries, infectious diseases caused 18percent of deaths.The world has seen infectious diseases both old and ne wcontinue to emerge rather tlun decline as it enters the21 st century. Mabria has risen dramatically. thanks in partto resistant strains, as has gonorrhea, tuberculosis andtyphoid - diseases that had been previously controlledwith standard antimicrob ial therapy. Devastating diseasessuch as Ebola hacmorrhagic fever, hepatitis C, H IV/ Al DS,Lyme, monkeypox. SAI"tS and West Nile virus, havt':lppe:1red suddenly. Un til there are effective vacei ncs, these


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18 M t l ~ 5 1 O n e , Clur!er J Vaccmes Lookmg Ahead

unexpected diseases will continue to affect variouspopulations around the wo rld.Vaccines now in development to fight infect ious diseasesinclude vaccines against additional serotypes of pneumo-coccal and meningococca l infections, influenza, parain -fluenza and respiratory sy ncytial virus (RSV ). Anotherexciting area of research is therapeutic vacc ines aga in stnoninfectious diseases, such as cance r. Experimental vac-cines to fight cervi cal cancer caused by human papillornavirus and other cancers are cu rrently being researched inclinical trials. Othe r promising vaccines in deve lopmencinclude those to fight autoimmune diseases, gastric ulcers,and rheumatic heart disease as a result of Group A strepto-coccal infec tioll. Tr ials arc also llllder way for vaccines toprevent H IV infect ion , the cause of acqui red immunod efi -ciency syndrome (AIDS). ... Hopeful developments maysoon make trials possible for vaccines to fight Al zheimer'sand breast ca ncer, two devastating diseases that affect largenumbers of people.Tht" reccnt declarat ion by the WHO to eradicate polioglobally by 2005 prom ises relief for a large part of theworld's population. While polio was eliminated fr0111th e Western Hemi sph ere through vaccination in 1991 ,the disease is still endemic in three countries of Asia :l.Ildfour Others In Afn ca, but all have mounted vaccinationcampaigns to stop the disease. By 2010, vaccines againstseveral types of meningitis , pneumonia, as well as rotavirus-caused diarrhea and human papilloma vi rus (the cause ofcervical cancer) should be introduced. In the future, vac-cines against AIDS, malaria and pulmonary tuberculosismay begin saving lives, and measles should be contro lledthroughout the globe as well. Thanks to advances in vac-cine technology, inf.l1lts may well be protected th roughouttheir lives against many of the pathogens that threaten the irhealth today. Developments under way promise on e day toprovide lmmllllologic protect ion against conditions suchas as thma , multiple sclerosis and diabetes.In the last quarter of the 20th century alone, new vaccine-delivery techno logy made ra pid strides. Modern biotechnol-ogy gave rise to conjugate vaccines, live vector vaccines, new

,Hopeful deve lo p-ments may soonmake ttials possi-ble fo r vacc ines tofight Alzhe imer'sand bre ast cancer,two devastatingdiseases that affectlarge numbers orpeople.


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milestones in public health: chapter 1

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