Pivotal strategies in smallpox eradication

Issue: July 2013

ByD.A Henderson, MD, MPH

We celebrate the 35th year without smallpox, once the most serious pestilence known to mankind. The achievement was the product of a global eradication program that was launched in 1967 with a 10-year time target. The last case occurred in October 1977. The total cost of the program was estimated to be about $300 million, one-third of which constituted international contributions. The achievement has been lauded as one of the most important of the 20th century. However, the decision by the 1966 World Health Assembly to undertake this campaign had been controversial. At the time, a global malaria eradication program, then in its 12th year, was failing. Many argued that it was technically impossible to eradicate any disease and questioned the judgment of WHO and professional public health. The decision to proceed was decided by a margin of only two votes.

A dedicated staff with heroic efforts and perceptive insights was the heart of the effort. Two specific features were critical: 1) a disease surveillance-containment strategy; and 2) a heat-stable, quality-assured vaccine conferring protection with a single inoculation.

A new strategy

The WHO director-general’s proposed strategy, as described in his report to the 1966 Assembly, called for a two-part strategy to be pursued from the beginning of the program in every country: 1) a vaccination campaign to assure an 80% level of vaccination immunity; and 2) a surveillance program to obtain weekly reports of cases from all health units and, in response, a “2- or 3-day intensive mass program of vaccination in the immediate area.”

At the time the eradication effort began, vaccination in most countries was sporadic with limited campaigns to stem epidemics; reporting of cases was so grossly incomplete as to be meaningless. “Surveillance-containment” was a new concept to all countries. It had been introduced at CDC in 1949 by Alex D. Langmuir, MD. It called for health units to report promptly the occurrence of cases; for continuing epidemiological analyses of data; and for implementation of control measures based on these data. It was invaluable in deciding strategies and in monitoring program progress. Having served as chief of CDC’s Surveillance Branch for the preceding 5 years, I appreciated its value; being co-author of the director-general’s report permitted the early incorporation of the concept.

D.A. Henderson

In the first months of the global program, William H. Foege, MD, MPH, along with local staff, investigated and contained outbreaks in eastern Nigeria. It was part of an 18-country USAID/CDC effort. They discovered that smallpox was much less contagious than many believed. Limited containment measures could contain reported outbreaks rapidly and hasten smallpox elimination over large areas. This was confirmed in contemporary studies in Pakistan and later studies in India and Brazil.

Some asserted that surveillance containment was so effective and essential that mass vaccination programs should be stopped and all resources turned to surveillance. In fact, there were arguments to the contrary. Before the 1967 global eradication campaign began, many nations had eliminated smallpox, despite having no surveillance activity, and vaccination that relied on a liquid lymph vaccine that was not heat-stable and deteriorated within a few days.

We eventually confirmed that countries of North America and most of South America, Europe, China and the Soviet Union had already eliminated smallpox. In temperate climates and with even a modest infrastructure extending beyond urban areas, smallpox could be eliminated even with the fragile liquid vaccine and an inadequate reporting network. A vaccine that was stable in tropical climates could open new vistas.

A new smallpox vaccine

A timely breakthrough in smallpox vaccine production occurred in the 1950s. Leslie Collier, MD, of the Lister Institute in England, perfected a method for the large-scale production of freeze-dried vaccine. The resultant vaccine withstood temperatures of 100°F for more than a month. As the program began, a newly invented device for vaccination became available — the bifurcated needle. It greatly simplified vaccination technique, permitting vaccinators with little training to achieve successful vaccinations nearly 100% of the time and with only one-quarter as much vaccine.

Initially, we estimated a need for 300 million doses of vaccine per year. The United States and the Soviet Union promised 75 million doses per year; most of the rest would have to be provided by endemic country producers. Laboratories in the Netherlands and Canada agreed to test lots of vaccine from all countries. It was soon discovered that less than 10% met acceptable standards. An urgent meeting of vaccine producers produced a detailed manual for the production of freeze-dried vaccine; consultants then visited and worked with country laboratories. Within 5 years, all vaccine in use was freeze-dried and all lots met international standards; more than 80% was produced in developing countries.

With a disease that spread so slowly as smallpox and vaccine that provided protection with a single inoculation, eradication was clearly an achievable goal. Edward Jenner, FRS, who discovered smallpox vaccine, wrote in 1801: “It now becomes too manifest to admit of controversy, that the annihilation of the Small Pox … must be the final result of this practice.” It required more than 115 years.

Three months after smallpox eradication was declared, in May 1980, a meeting was convened with the theme, “What next do we eradicate?” Ebullient enthusiasm prevailed as candidates of every type were proposed ranging from hunger to urban rabies. Neither I nor my colleagues who had fought the major smallpox battles shared this optimism. There was more to smallpox eradication than vaccination and corralling outbreaks. Floods, famines, assassinations, civil wars, hundreds of thousands of refugees, kidnapped teams, tortuous and stubborn bureaucracies, deficient funds and fatigue were fresh memories. As were several instances in which the possible collapse of the program hinged on political events wholly out of our control. We had defeated a lethal enemy that was far more susceptible to eradication than any other disease — but by a very narrow margin. The ultimate difference was a highly antigenic heat-stable vaccine abetted by surveillance-containment programs.

Future eradication targets

As we look to the possibility of other eradication targets, we need to bear in mind the disastrous consequences of the collapse of the failed malaria eradication campaign. Support for international health programs slumped and the proposal for a smallpox eradication program was itself almost rejected. We need to think carefully before making other commitments that, as with malaria and polio, may cost many times what had been anticipated and with adverse consequences to other health programs. At the 1980 meeting, I offered the view that I knew of no other human disease for which we now have the essential conditions and tools to anticipate eradication in the foreseeable future.

More than 30 years later, I still fail to identify a plausible disease eradication program with the necessary attributes which could succeed in weathering the storms — natural and bureaucratic — that such an effort would have to endure. Polio eradication could be an exception, but the effort still required is dauntingly formidable.

References:

De Quadros CC. Bull World Health Organ. 1972;46:165-171.
Fenner F. Smallpox and Its Eradication, WHO;Geneva:1988.
Foege WH. Am J Epidemiol. 1971;94:311-315.
Langmuir AD. Proc R Soc Med. 1971;64:681-684.
Mack TM. J Infect Dis. 1970;122:479-488.

For more information:

D. A. Henderson, MD, MPH, is a distinguished scholar at the UPMC Center for Health Security in Baltimore, as well as a Johns Hopkins University Distinguished Scholar. He also is a professor of medicine and public health at the University of Pittsburgh. He can be reached at UPMC Center for Health Security, 621 E. Pratt St. Suite 210, Baltimore, MD 21202.

Disclosure: Henderson reports no relevant  financial disclosures.