WHAT'S NEW THIS SATURDAY: A DOZEN CLASSICS IN EPIDEMIOLOGY AND PUBLIC HEALTH

Saturday, 30th of March 2013

WHAT'S NEW THIS SATURDAY: A DOZEN CLASSICS IN EPIDEMIOLOGY AND PUBLIC HEALTH

A few hardy perennials, for your reading pleasure.

Note that several of the authors, such as Joseph Goldberger and D. A. Henderson, had a rough ride getting their views accepted by their colleagues. Doll and Hill got early acceptance of their views on smoking and cancer, but the battle continues 60 years later between public health and Big Tobacco.

Some of these items are out of the archives. The piece on measles co-authored by the late, great Bob Keegan is new, and worth a look at http://www.childsurvival.net/?content=com_articles&artid=1828

Bob Davis

FLORENCE NIGHTINGALE ON NURSING

A revolutionary in her day, Nightingale is best known for her work in the Crimean War. She also turned to statistics later in her career. According to her biography in Wikipedia, she was a pioneer in the presentation of information and visual graphics.

Notes on Nursing: What is, and what is is not

At http://www.deltaomega.org/documents/nurse1.pdf

ROBERT KOCH ON THE ETIOLOGY OF TUBERCULOSIS

Robert Koch started out as a country doctor, but grew to prominence as the co-founder, with Louis Pasteur, of the germ theory of disease, which replaced the miasma theory. In French, M. tuberculosis is colloquially known as “Koch’s bacillus.”

http://www.deltaomega.org/documents/RkochAetiologyTB.pdf

THE CHADWICK REPORT

Report of the Sanitary Condition of the Labouring Population and on the Means of its Improvement.

Presented to both Houses of Parliament, by Command of Her Majesty, July 1842.

http://pds.lib.harvard.edu/pds/view/7418570?n=5&imagesize=1200&jp2Res=.25&printThumbnails=no

SNOW ON CHOLERA

See below, from The New Yorker magazine, a book review by Steven Shapin on cholera, with special reference to the work of John Snow, who showed during the 1854 London cholera outbreak that cholera is a waterborne disease. Those interested in Snow’s original publications should go to http://www.uic.edu/sph/prepare/courses/chsc400/resources/snowcase1.htm

Excerpt from The New Yorker, 6 November 2006, full text at http://www.newyorker.com/archive/2006/11/06/061106crbo_books

Hepatitis B Vaccine

PANUM ON MEASLES IN THE FAROE ISLANDS

Peter Panum's classic Observations Made During The Epidemic of Measles on The Faroe Islands inThe Year 1846 describes in detail a virgin soil outbreak of the kind often seen as late as the 20th century, absent vaccination, in islands and archipelagos. Panum calculated the incubation period and estimated the case fatality rate (just under 2 percent). He also showed, notably, that virgin soil epidemics of measles infect nearly all susceptibles, and that natural infection confers lifelong immunity. He showed that measles struck all age groups. Of the 7864 population, 6100 contracted the disease, and 170 died, for a case fatality of 2.8 percent. Panum’s precise observations permitted him to determine the incubation period of measles.

The miasma theory was still popular in the 19th century. Here is Panum’s observation.

‘Experience in regard to the fact that measles is not miasmatic but purely contagious in character has been so dearly bought on the Faroe Islands that the people there will probably agree with us hereafter that it is correct, at least in practice, to consider measles as a contagious and not as a miasmatic nor miasmatic-contagious disease. It is another question whether measles can arise spontaneously. This did not happen on the Faroes, and although from a theoretical point of view, in analogy with typhus and the like, the possibility cannot be denied, yet with respect to regulations that might be instituted against the spread of the disease, especially under conditions such as those on the Fame Islands, Iceland, and other isolated places, if spontaneous origin ever occurs, the occasions are so rare that they cannot he taken into consideration.’

Full text with tables is at http://www.deltaomega.org/PanumFaroeIslands.pdf

PASTEUR AND RABIES

It is hard to choose a single topic from all of Pasteur’s work. Not all of it is available in English. See below a description of his work on rabies and the rabies vaccine.

Pasteur biographies are on Wikipedia both in French, http://fr.wikipedia.org/wiki/Louis_Pasteur and, concisely, in English, at

http://en.wikipedia.org/wiki/Louis_Pasteur

Volume VI of his Works, in French, covering vaccines and viral diseases, is athttp://gallica.bnf.fr/ark:/12148/bpt6k73613

Good reading.

Journal of Neurology Neurosurgery and Psychiatry 2002;73:82

HISTORICAL NOTE

‘Louis Pasteur and Rabies: a brief note’

JMS Pearce, 304 Beverley Road, Anlaby, Hull HU10 7BG, UK; jmspearce@freenet.co.uk

The almost universal fatality in victims of untreated human rabies surrounds the disease with understandable terror. The word comes from the Latin rabere to rage or rave. It was known as canine madness, or hydrophobia that produces paralysis or a vicious excitability and in man fatal encephalitis with throat spasms on swallowing.

A variety of meningoencephalitis rabies presents as a "hydrophobic" or "spastic" form and a "tranquil" or "paralytic" (rabies without hydrophobia) form, the latter with an ascending paralysis of Landry type, terminating in bulbar, respiratory, and encephalitic symptoms. The history of dog bite is often unclear if it has occurred some months earlier. Symptoms usually develop, however, 10 to 50 days after exposure; death ensues within about 10 days. In Great Britain rigid quarantine laws on the importation of all livestock led to its virtual eradication.

In 1804, Georg Gottfried Zinke first transmitted rabies1 from a rabid dog to a normal one, and from dog to a rabbit and a hen, by injection of saliva. This proved that the disease was infectious. By 1826, Franz Christian Karl Krugelstein (1779–1864) wrote a full account of rabies, with a bibliography of 300 items.2

But the species susceptibility was unclear until Victor Galtier demonstrated the transmission from dog to rabbit to rabbit, in series.3 He then immunised sheep by inoculating rabid saliva intravenously. This did not produce the disease but interestingly, protected the animals from the effects of a further inoculation.4

His work aroused the interest of Louis Pasteur who with C Chamberland, PPE Roux, and T Thuillier wrote the first of their papers in 1881,5 heralding the beginning of Pasteur's studies on rabies. In further work,6 they showed indications of the rabies virus in the blood.

"It first lodges and multiplies in the spinal cord and brain".

He reported: When passed from dog to monkey and then from monkey to monkey, the virulence diminishes with each transmission, and then if inoculated back into dogs, rabbits, or guinea pigs, it remains attenuated. However, virulence was serially increased when passed from rabbit to rabbit, or from guinea pig to guinea pig. He was thus able to produce the virus in various degrees of virulence. Sections of rabid spinal cord from a highly virulent strain after serial passage through many rabbits were suspended in dry air; the virulence gradually diminished with time. Thus, Pasteur produced an attenuated vaccine, and successfully immunised 50 inoculated dogs.7

On Monday 6 July 1885, Joseph Meister, aged nine, was brought to him from Alsace having been bitten by a rabid dog on 4 July. With some reluctance, Pasteur was persuaded by Drs Vulpian and Grancher of the Académie de Médecine to give Dr Grancher the emulsion from the cord of a rabbit that had died of rabies on 21 June, and had been kept in dry air for 15 days. The child was given 13 further inoculations in 10 days with portions of the cord that were progressively fresher (more virulent), until after three months and three days he announced that the child's life was now out of danger and his health appeared excellent. On 20 October, he successfully treated another patient infected by a mad dog six days earlier. By 1886, he had treated 350 patients from all over Europe, Russia, and America.8

This is considered his greatest triumph. Microscopic diagnosis was later made possible by Aldechi Negri's discovery of the Negri body (1903–5). Fermi used phenol treatment of rabid tissue to prepare the Fermi vaccine in 1908. Webster and Clow first grew the virus in tissue culture in 1936, which led to human cell culture vaccine,9 and diploid cell vaccine in 1978.

A French chemist, Louis Pasteur (1822–95), is often called the founder of microbiology.10 In 1863, the Emperor Napoleon III instructed him to investigate diseases affecting wines. He successfully investigated pébrine and flacherie, diseases of silkworms in the 1860s and by enforcing isolation of infected silkworms controlled the illness that was destroying silk production.

His early studies on fermentation that showed that yeast acts as microorganisms that converts sugar into alcohol and not as chemical enzymes, as was believed by Liebig and others. He also claimed a specific ferment that sours milk. Just as a specific microorganism, or "germ" causes each type of fermentation, many diseases are also caused by specific ferments (Memoire sur la fermentation appelee lactique, 1858). Fermentation resembled the observed putrefaction of wounds. The (invisible) germs or ferments were in the air, a notion that caused disdain amongst critics of his germ theory of disease. His proof that diseases could be caused by "germs" was a novel and major discovery.8 Pasteur showed that the virulence of infected blood was dependent on temperature and oxygen, so that fowl with their high body temperature resisted inoculation with anthrax. Following Koch's work on anthrax spores in 1876, Pasteur established that a culture grown at high temperature was less virulent and induced only a mild illness in sheep: an attenuated "anthrax vaccine". This was akin to Edward Jenner's vaccination with cowpox to immunise against smallpox.

In 1854, he became professor of chemistry and was elected as a member of the French Academy of Medicine, a singular honour. The University of Bonn conferred the MD, honoris causa in 1868, which he returned in 1871. In his own time, Pasteur achieved great celebrity culminating in a public subscription of two and a half million francs that made feasible the creation of the Pasteur Institut, in Paris. Despite a stroke at the age of 46, he continued researches undaunted until 1888. He died on 28 September 1895 at Garches, Seine-et-Oise.8

References

1. Zinke GG. Neue Ansichten der Hundswuth, ihrer Ursachen und Folgen, nebst einer sichern Behandlungsart der von tollen Thieren gebissenen Menschen. Jena: CE Gabler, 1804.

2. Krugelstein FCK. Die Geschichte der Hundswuth und der Wasserscheu und deren Behandlung. Gotha, In der Hennings'schen Buchhandlung, 1826.

3. Galtier V. Études sur la rage. Ann Med Vet 1879;28:627–39.

4. Galtier V. Les injections de virus rabique dans le torrent circulatoire ne provoquent pas léclosion de la rage et semblant conférer limmunité. La rage peut être transmise par l'ingestion de la matiére rabique. C R Acad Sci (Paris) 1881;93:284–5.

5. Pasteur L et al. Sur la rage. C R Acad Sci (Paris) 1881;92:1259–60. English translation in: R Suzor. Hydrophobia: an account of M. Pasteur's system. London, 1887.

6. Pasteur L, Chamberland C, Roux PPE. Nouvelle communication sur la rage. C R Acad Sci (Paris) 1884;98:457–63, 1229–31. English translation in: R Suzor. Hydrophobia: an account of M. Pasteur's system. London, 1887:159–97.

7. Pasteur L. Méthode pour prévenir la rage aprés morsure. C R Acad Sci (Paris) 1885;101:765–74; 1886;102:459–69, 835–38; 1887;103:777–85. English translation of first part (1885) in: Bibel. Milestones in immunology (1988). Madison: Science Tech: Berlin Springer Verlag (See no. 2541).

8. Nicolle J. Louis Pasteur. A master of scientific enquiry. London: The Scientific Book Guild, 1962. (Among several biographies, this provides one of the best, detailed accounts of Pasteur's major experimental work and reasoning.)

9. Wiktor TJ. Human cell culture rabies vaccine. JAMA 1973;224:1170–1.[Medline]

10. Singer C. A short history of medicine. Oxford: Clarendon Press, 1928:225–34, 261.

GOLDBERGER ON PELLAGRA / FAO GUIDELINES ON PELLAGRA

The proof that pellagra is a nutritional disease came from South Carolina studies published by Dr. Joseph Goldberger in 1915. Whether the experiments he performed on himself and his assistant would pass a bioethics committee today is an open question.

The following is from the homepage of the NIH. After the NIH text, the FAO guidelines on pellagra.

http://history.nih.gov/exhibits/Goldberger/index.html

Dr. Joseph Goldberger & the War on Pellagra

Pellagra no longer stalks the nation as it once did. But during the early part of the 20th century, pellagra, a disease that results from a diet deficient in niacin, killed many poor Southerners. Dr. Joseph Goldberger, a physician in the U.S. government's Hygienic Laboratory, the predecessor of the National Institutes of Health, discovered the
cause of pellagra and stepped on a number of medical toes when his research experiments showed that diet and not germs (the currently held medical theory) caused the disease. He also stepped on Southern pride when he linked the poverty of Southern sharecroppers, tenant
farmers, and mill workers to the deficient diet that caused pellagra.

Joseph Goldberger's theory on pellagra contradicted commonly-held medical opinions. The work of Italian investigators as well as Goldberger's own observations in mental hospitals, orphanages, and cotton mill towns, convinced him that germs did not cause the disease.
In such institutions, inmates contracted the disease, but staff never did. Goldberger knew from his years of experience working on infectious diseases that germs did not distinguish between inmates and employees. Lombroso had speculated that spoiled maize caused pellagra.

Goldberger found no evidence for that hypothesis, but diet certainly seemed the crucial factor. Shipments of food that Goldberger had requested from Washington were provided to children in two Mississippi orphanages and to inmates at the Georgia State Asylum. Results were dramatic; those fed a diet of fresh meat, milk and vegetables instead of a com-based diet recovered from pellagra. Those without the disease who ate the new diet did not contract pellagra.

Critics, many unable to part from the germ theory of pellagra, raised doubts. Goldberger hoped to squelch those reservations by demonstrating the existence of a particular substance that when removed from the diet of healthy individuals resulted in pellagra.
With the cooperation of Mississippi's progressive governor, Earl Brewer, Goldberger experimented on eleven healthy volunteer prisoners at the Rankin State Prison Farm in 1915. Offered pardons in return for their participation, the volunteers ate a corn-based diet. Six of the eleven showed pellagra rashes after five months.

Expert dermatologists made the actual diagnosis of pellagra to avoid the appearance of a conflict of interest on Goldberger's part.
Although many scientific colleagues sang Goldberger's praises, even mentioning a Nobel nomination, others still doubted. In the pages of the Journal of the American Medical Association, critic W.J. MacNeal challenged the results. One Birmingham physician referred to the experiment as "half-baked." Still others thought the whole experiment a fraud.

Angry and frustrated, Goldberger would not give up trying to persuade his critics that pellagra was a dietary disorder, not an infectious disease. He hoped that one final dramatic experiment would convince his critics. On April 26, 1916 he injected five cubic centimeters of a pellagrin's blood into the arm of his assistant, Dr. George Wheeler.
Wheeler shot six centimeters of such blood into Goldberger. Then they swabbed out the secretions of a pellagrin's nose and throat and rubbed them into their own noses and throats. They swallowed capsules containing scabs of pellagrins' rashes. Others joined what Goldberger called his "filth parties," including Mary Goldberger. None of the volunteers got pellagra. Despite Goldberger's heroic efforts, a few physicians remained staunch opponents of the dietary theory of pellagra.

Goldberger vs. The South

If poor diet resulting from poverty among Southern tenant farmers and mill workers was the root cause of pellagra, then the only real cure was social reform, especially changes in the land tenure system. A dramatic drop in cotton prices in 1920 and the attendant decrease in
the income of many Southerners occasioned a spike in the number of reported pellagra cases. Goldberger publicly predicted dire public health consequences for 1921 when there might be as many as 100,000 pellagra cases including 10,000 deaths and even worse for 1922.

Newspaper headlines warning of famine and plague in the South caught the eye of President Warren G. Harding, who asked Surgeon General Hugh Cumming for a report and was supportive of PHS appeals for an increased budget for hospitalization and supplies. The Public Health Service called upon Southerners to provide local relief for the poor.
However, the response of many in the South was the opposite of grateful and magnanimous. Enraged Southerners, led by South Carolina Congressman Jimmy Byrnes, denounced the negative characterization of their region and feared that it would discourage economic investment and tourism in the South. They believed that Southern pride and
Southern prosperity were on the line.

Goldberger proved correct. There was a dramatic increase in pellagra and in the number of deaths, although not quite as many as he had predicted. The land reform that Goldberger believed necessary to eliminate pellagra was accomplished not by scientific reasoning but by
the invasion of boll weevils. The insect destroyed cotton fields and forced Southerners to diversify their crops. By growing more food crops, Southerners improved their diets and suffered less from pellagra.

The Great Mississippi Flood

During the 1920s, Goldberger continued research to identify what he called the "pellagra preventive factor." He learned that small amount of dried brewer's yeast prevented the disease as effectively and more cheaply than fresh, lean meat, milk, and vegetables. He also began laboratory experiments on dogs after learning that black tongue disease was the canine equivalent of pellagra. When the Mississippi River overflowed its banks in 1927, Goldberger returned to the field with PHS statistician Edgar Sydenstricker. Together they traveled the Mississippi valley collecting statistical data on every aspect of
Southern life for their epidemiological studies while delivering jeremiads against the system that left the poor too destitute to eat a healthy diet. The message was unwelcome and unheeded.

From the FAO Guidelines on Pellagra,
http://www.fao.org/DOCREP/W0073e/w0073e05.htm#P4008_468640

LANGMUIR ON THE EPIDEMIC INTELLIGENCE SERVICE, CDC

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1422746/pdf/pubhealthrep00127-0062.pdf

HENDERSON ON SMALLPOX

In the mid-60s, the global smallpox eradication strategy moved from mass vaccination of populations to identification of smallpox foci and their focal containment. Surveillance became the partner of vaccination. Two articles on SEP set out the lessons learned:

1) ‘Principles and Lessons from the Smallpox Eradication Programme,’ Bulletin of the World Health Organization, 1987, 65:4, the last reference at http://whqlibdoc.who.int/bulletin/1987/Vol65-No4/

2) ‘Smallpox Eradication’, Public Health Reports, 1980, September-October 1980, Vol. 95 No. 5 423, full text below.

In what can only be described as vintage Henderson, he states in the latter article

'I have no idea what "health for all by the year 2000" means, and I know of no one who expects to achieve it. "Primary health care" is a term which means all things to all people and is useless as an operational concept. So-called "vertical programs" are now regarded as passe. The key phrase today is "horizontal programs." My own view of a "vertical" program is one for which clear objectives are decided, surveillance and assessment systems are developed to monitor progress, and, in brief, it is one in which a management structure is established. The "horizontal programs" that I have seen best describe the sleeping postures of the workers.'

D. A. HENDERSON, MD, MPH

DOLL AND HILL ON SMOKING AND LUNG CANCER

Rarely has a ten page article caused such an impact as 'Smoking and Carcinoma of the Lung: Preliminary Report,' published by Richard Doll and A. B. Hill in the British Medical Journal in September 1950. The authors carefully review, and demolish, the alternative explanations to a causal relationship between smoking and lung cancer.

'Consideration has been given to the possibility that the results could have been produced by the selection of an unsuitable group of control patients, by patients with respiratory disease exaggerating their smoking habits, or by bias on the part of the interviewers. Reasons are given for excluding all these possibilities, and it is concluded that smoking is an important factor in the cause of carcinoma of the lung.’ (see full text available at http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=14772469 ).

Giving credit where due, Doll and Hill reference in 1950 the earlier work of German and American researchers on the same subject. Knowing that their analysis of hospital records would draw criticism, they followed this 'preliminary report' with a prospective study of comparative mortality in smoking and nonsmoking British physicians. This confirmatory study, published in 1954, is at http://www.bmj.com/cgi/reprint/328/7455/1529

Before his death, Doll gave an interview to Cancer World, accessible at www.cancerworld.org/CancerWorld/getStaticModFile.aspx?id=269

Herewith, excerpts from the interview:

'Sir Harold Himsworth, the Secretary of the Medical Research Council (MRC), who had commissioned the study, accepted the results straight off. But most cancer research workers did not accept it, and in fact they advised the Department of Health that they shouldn’t take any action because they were uncertain about what it meant.

'It wasn’t until 1957, when the Government asked the MRC for a formal opinion as to whether our conclusion was correct or not, that the MRC formally considered it and said it was correct and advised the Government to that effect. The result was that the Minister of Health in 1957 called a press conference to announce the results of the MRC consultation.

'He announced that the MRC had advised them that smoking was the cause of the great increase in lung cancer. While he was reporting this to the media, he was smoking a cigarette himself!'

. . . 'The tobacco industry in America . . . tried to get a colleague of mine, Ernst Wynder, sacked from his job with the Sloan-Kettering. They put pressure on the Director not to allow Wynder to publish anything that claimed smoking caused disease, and the Director did try to suppress his studies. Wynder, however, responded by setting up his own organisation and getting support from somebody else to carry on doing the research. So when he published his results, they didn’t have the Sloan-Kettering stamp. Sloan-Kettering came out of it very badly. However, despite this sort of pressure, the leading epidemiologists in America all got together fairly early on – in the late 1950s – and said they regarded it as proved that smoking causes disease. The trouble was the American law courts. The industry made it so expensive to sue them that it wasn’t for some years that you got very wealthy groups of lawyers who were prepared to take them on. The industry could make it so expensive by raising objections and making it last a very long time.'

Reviewing, in the Bulletin of the World Health Organization, the early reactions to tobacco research,

Michael Thun, of the American Cancer Society, wrote about 'when the truth is unwelcome' at

http://www.scielosp.org/scielo.php?pid=S0042-96862005000200015&script=sci_arttext&tlng=en

· ANDREWS AND LANGMUIR, THE PHILOSOPHY OF DISEASE ERADICATION

http://ajph.aphapublications.org/doi/pdf/10.2105/AJPH.53.1.1

KEEGAN AND COLLEAGUES: COMPARING MEASLES WITH PREVIOUS ERADICATION PROGRAMS: ENABLING AND CONSTRAINING FACTORS

Robert Keegan 1, Alya Dabbagh 2, Peter M. Strebel 2 and Stephen L. Cochi 3

The Journal of Infectious Diseases, Volume 204, Issue suppl 1,Pp. S54-S61

J Infect Dis. (2011) 204 (suppl 1): S54-S61. doi: 10.1093/infdis/jir119 This article appears in: Global Progress Toward Measles Eradication and Prevention of Rubella and Congenital Rubella Syndrome

+ Author Affiliations

1Independent consultant, Atlanta, Georgia

2Department of Immunization, Vaccines and Biologicals, World Health Organization, Geneva, Switzerland

3Global Immunization Division, Centers for Disease Control and Prevention, Department of Health and Human Services, Atlanta, Georgia

Correspondence: Peter M. Strebel, MBChB, MPH, IVB/EPI, World Health Organization, 20 Ave Appia, CH-1211 Geneva 27, Switzerland (strebelp@who.int).

Abstract below; best viewed at http://jid.oxfordjournals.org/content/204/suppl_1/S54.long

Background. Five major disease eradication initiatives were initiated during the second half of the 20th century. The enabling and constraining factors—political, social, economic, and other—for these previous and current eradication programs can inform decision making regarding a proposed measles eradication initiative.

Methods. We reviewed the literature on the yaws, malaria, smallpox, guinea worm, and polio eradication programs and compared enabling and constraining factors for each of these programs with the same factors as they relate to a possible measles eradication initiative.

Results. A potential measles eradication program would enjoy distinct advantages in comparison with earlier eradication programs, including strong political and societal support, economic analyses demonstrating a high level of cost-effectiveness, and a rigorous upfront process, compared with previous eradication initiatives, that has validated the feasibility of achieving measles eradication. However, increasing population density, urbanization, and wars/civil conflicts will pose serious challenges.

Conclusions. Measles eradication will be very challenging but probably not as difficult to achieve as polio eradication. Measles eradication should be undertaken only if the commitments and resources will be adequate to meet the political, social, economic, and technical challenges.

More than 22 years have passed since the launching of the polio eradication initiative by the World Health Assembly (WHA) in 1988, the last of 5 global eradication activities initiated in the second half of the 20th century. Given that only 1 of these disease eradication programs has been completed successfully (smallpox), serious consideration of a global measles eradication initiative merits a comparison of the enabling and constraining political, social, economic, and technical factors involved in measles eradication with those of the previous and current eradication programs. This analysis may be helpful to decision-makers weighing the evidence for or against the establishment of a measles eradication initiative. Also, it may illuminate opportunities to build on factors that facilitate success and to mitigate factors that might threaten success if a global measles eradication initiative is launched at a future date.

The malaria, smallpox, and polio eradication initiatives were formally launched by the World Health Assembly in 1955, 1959, and 1988, respectively [1, 2] (Table 1). The yaws eradication program also had its formal beginning in 1955 at the Second International Conference on the Control of Yaws, although it was never formally launched as an eradication initiative by the World Health Organization (WHO) (ie, no WHA resolution was ever passed) [3, 4]. In 1986, the WHA resolved to eliminate Guinea worm (dracunculiasis) and passed a resolution for eradication in 1991 [5]. Other large public health programs launched in the twentieth century and continuing today, including programs to eliminate neonatal tetanus and tuberculosis, do not have eradication as the objective and are not considered in this paper.