62. Control and Eradication

Disease-specific Case Studies

In this section, we apply the reasoning developed previously to provide an empirical analysis of the three most recent eradication programs—smallpox and the two ongoing programs, poliomyelitis and dracunculiasis.

Smallpox

As noted before, smallpox eradication was achieved in October 1977, 11 years after the intensified program began. Following implementation of a rigorous certification procedure, the WHA declared smallpox eradicated in 1980.

Fenner and others (1988) have estimated the annual benefits of smallpox eradication to developing and industrial countries (see table 62.1). These aggregate estimates, obtained by prorating estimates of the benefits of eradication for India and the United States to all developing and industrial countries, respectively, suggest that developing countries benefited more from smallpox eradication than industrial countries. Qualitatively, a consistent picture emerges: smallpox eradication was not only an extraordinary investment for the world; it was also an investment that benefited every country, rich and poor alike.

When the eradication effort began, smallpox was no longer endemic in most industrial countries. Nonetheless, these countries needed to maintain populationwide immunity under the threat of possible imported cases from endemic countries. They would gain from eradication not only through the cessation of vaccination and its associated costs but also by being able to decrease the number of quarantine inspectors at ports of entry and by averting costs of care related to the adverse events from this live vaccine.

The still-endemic countries would also save vaccination costs, although most were vaccinating only a comparatively small proportion of their populations. The greater benefit to them was the avoided cost of disease, including the extraordinary death toll. A number of developing countries had accorded smallpox prevention a high priority, as was evidenced by the number that succeeded in interrupting transmission without international assistance. This list includes China, which was not a member of WHO at the time the eradication effort commenced.

Indeed, and as shown in table 62.1, the still-endemic countries contributed an estimated two-thirds of the US$298 million cost of eradication. International sources funded the balance. If the latter cost is interpreted as the incremental cost of achieving eradication, the benefit-cost ratio of global smallpox eradication was over 450:1, a singularly high figure. Even including the expenditure by endemic countries, the benefit of eradication exceeded the cost by an unusually large amount.

Brilliant (1985) calculated the annual costs of the smallpox eradication campaign for India to be about US$17 million per year, including indirect costs (lost productivity caused by adverse reactions to vaccination) and opportunity costs (health workers being diverted from other programs). These costs were only a fraction of the annual benefits of eradication to India, which, by Brilliant's calculations, were US$150 million. The benefit estimates by Fenner and others (1988) are much larger, and those of Ramaiah (1976) are smaller, but all three studies draw the same (qualitative) conclusion: smallpox eradication was a good investment for India. Basu, Jezek, and Ward (1979, 312) present estimates identical to those in Ramaiah (1976), but without giving attribution.

Originally, India had decided to undertake a smallpox program just one month after the WHA voted to eradicate the disease globally in 1959. The attempt failed, however, largely for administrative reasons (Basu, Jezek, and Ward 1979; Brilliant 1985; Fenner and others 1988). Essentially, India had an economic incentive to control smallpox on its own (Brilliant 1985, 33) but lacked organizational capacity and an effective strategy for achieving this goal. Note, however, that India had other health priorities, including family planning. According to Brilliant (1985, 33), "for India's health planners, occupied then by emergencies and competing political demands on scarce resources, the long-term benefits from disease eradication were not a great motivation. Health planners are sensitive to immediate political realities, and the benefits of smallpox eradication would be realized only at some future time when the $3 million annual expenditures for smallpox could be applied to other health problems. In the meantime, however, the cost of putting so many scarce resources into one program rather than into many health needs was high."

Table 62.2 provides estimates of the benefits of smallpox eradication to the United States. The total benefit of eradication to the United States is about the same order of magnitude as India's, but the breakdown is different. Whereas India benefited mainly from avoided infections, the United States benefited mainly from avoided vaccinations. By the time the eradication program was launched, the United States had already interrupted smallpox transmission, but vaccination was costly, both in economic and human health terms (a small number of people died every year from infections arising from the live vaccine). Defending the nation from imported infections imposed additional costs.

In health terms, smallpox eradication saved millions of lives; in economic terms, it yielded a benefit many times greater than the cost. Identifying another investment that has yielded comparable returns and has benefited every country is difficult. One reason that the economics of smallpox eradication were so favorable is that all countries had strong incentives to join in the eradication of the disease. A huge organizational effort, but only a relatively small incremental cost, was needed to achieve eradication. The specter of global terrorism has recently caused some countries to prepare themselves for a possible smallpox attack by stockpiling vaccine. Although such actions reduce the benefits of eradication, the economics remain favorable.

Smallpox, however, was a special case. Many attributes of the disease and the vaccine favored eradication. The vaccine was heat stable and required only a single dose to protect a person for a period of at least 5 to 10 years. Vaccination was easily performed and protected immediately on application. Every individual who became infected exhibited a typical, easily recognized rash, thus permitting accurate surveillance without recourse to laboratory diagnosis. The disease spread slowly so that transmission could readily be stopped by isolating the patient and vaccinating contacts within the area.

Poliomyelitis

The polio eradication program, launched by the WHA in 1988, has made substantial progress (CDC 2003a, 2003b, 2003c, 2004a, 2004c, 2004e, 2004g, 2005). The incidence of paralytic poliomyelitis in children fell by more than 99 percent, from an estimated 1,000 cases per day worldwide in 1988 to fewer than 4 cases per day in 2003. The number of poliomyelitis-endemic countries also fell, from 125 in 1988 to just 6 by 2003 (Afghanistan, the Arab Republic of Egypt, India, Niger, Nigeria, and Pakistan). This laudable reduction was the result of repetitive vaccination campaigns with easily administered oral polio vaccine to whole regions, to nations, and to large sub-populations.

During 2004, however, polio immunization activities in northern Nigeria were halted for an extended period for fear of tainted vaccines, and this permitted the development of epidemics extending throughout the country. The disease spread as well to 10 other African countries and to Saudi Arabia, Yemen, and Indonesia. Transmission has again been reestablished in several African countries (Burkina Faso, Central African Republic, Chad, Cote d'Ivoire, and Sudan). Heroic efforts are being made to control these outbreaks by large-scale immunization, but in countries such as these, where health services are stressed and the health, communication, and transportation infrastructures are weak, disease transmission is difficult to interrupt. Meanwhile, other countries throughout the world that appear to be polio free are continuing their vaccination programs but finding it increasingly difficult to maintain a momentum of interest, effort, and financing.

The difficulties of maintaining credible surveillance systems throughout the developing countries were vividly demonstrated by the discovery of polio in Sudan in May 2004, more than three years after the last case had been reported (CDC 2005). In the interim, specimens from 75 to 90 percent of such cases were processed in the laboratory, and measures of surveillance for acute flaccid paralysis cases were reported to have been entirely satisfactory. At first, the Sudanese cases were considered to have resulted from importations from Nigeria, and, indeed, some cases were. However, from more detailed laboratory studies, it was determined that type 1 wild virus had been circulating undetected for more than three years and type 3 virus for nearly five years.

Clearly, stopping the continuing transmission of wild poliovirus is itself a formidable challenge, the success of which is by no means certain. A problematic discovery since the global eradication program began was the finding that individuals with particular immunologic disorders shed polio vaccine virus for many months to years, thus serving as a reservoir for this virus. The virus, in turn, can revert to a neurovirulent form, which is capable of causing outbreaks of disease (Bellmunt and others 1999). Such individuals may be wholly without symptoms and impossible to identify except through fecal cultures. Moreover, no treatment is known to stop them from shedding virus. They pose an all but insurmountable challenge to the current poliomyelitis eradication effort.

The program is further hampered by the tool that has provided so much success—oral poliovirus vaccine (OPV). In resource-poor environments, poliomyelitis is best controlled with the inexpensive, live, and easily administered oral vaccine. The live vaccine is excreted and can infect other susceptible contacts. The ability of OPV to immunize others indirectly makes it an ideal vaccine for achieving high levels of population-based immunity, especially in lower socioeconomic populations that are the most difficult to reach. However, the excreted virus occasionally reverts to a pathologic state, causing not only cases but outbreaks of vaccine-associated paralytic polio, which may not emerge until months or even years after the vaccine has been administered (Kew and others 2004). Unfortunately, the alternative inactivated polio vaccine (IPV) is not immediately an option in many nations, not least because global manufacturing capacity could not begin to meet demand. Other problems include the current cost differential between OPV and IPV, the increased difficulty of administering the vaccine by syringe and needle, and the need to achieve higher coverage rates with IPV because it does not spread from person to person as does OPV.

Tragically, if OPV use were discontinued, in the absence of alternative immunity, polioviruses would likely circulate silently (Eichner and Dietz 1996) and reemerge. Preliminary results from a model presented by WHO indicate a greater than 60 percent chance of an outbreak within two years of the possible global cessation of OPV (WHO 2004) because of continuous circulation of undetected live vaccine viruses that can revert. Outbreaks have already been observed in several regions where decreasing use of live vaccine has left pockets of susceptible persons who eventually have been exposed to vaccine-derived pathogenic viruses (Kew and others 2002). Such an outbreak could occur with disastrous speed because the polio virus is far more contagious than that of smallpox. In developing countries, virtually all cases of polio occurred among those under five years of age, older persons having been protected by the natural immunity of earlier infection. Within five years after vaccination ceased, therefore, the population immunity level in the developing countries would be no better than it was before vaccination was introduced. With this is mind, it seems questionable as to whether all health ministers could be persuaded to call for a country-wide cessation of poliomyelitis vaccination itself, given the uncertainties of virus detection in so many remote and inaccessible areas of the world.

By definition, eradication implies certifying cessation of virus transmission and the absence of reservoirs so that control interventions can cease. As noted earlier in this chapter, it is only for this reason that eradication yields a dividend. Although the interruption of wild poliomyelitis virus transmission is theoretically feasible, the obstacles to achieving and maintaining this goal are formidable. At this time, it is difficult to foresee a future that does not envisage a continuing vaccination program, perhaps with IPV use in countries that can afford the substantial additional costs entailed and with OPV use in all other countries.

The polio eradication initiative, like that for smallpox, has had to rely primarily on voluntary donations provided both to WHO and bilaterally. Playing an especially important role have been the Rotary International Foundation and the Bill & Melinda Gates Foundation. From 1988 to 2004, more than US$3 billion was spent on the effort (WHO 2003).

What are the economics of polio eradication? Bart, Foulds, and Patriarca (1996) developed the first global cost-benefit analysis of polio eradication, beginning with the costs incurred since 1986, the year that the Pan American Health Organization launched a regional eradication effort, and extending to 2040. They assumed that eradication would be achieved in 2005, using OPV, and that vaccination would cease after eradication had been certified. Benefits (like costs, discounted at 6 percent) reflect the avoided costs of acute care and avoided vaccination costs after certification. Their analysis showed that the initiative would break even by 2007 and yield a net benefit to the world of more than US$13 billion by 2040—an encouraging result, but it was based on the assumption that all vaccination would stop abruptly in 2005.

Khan and Ehreth (2003) developed a similar analysis but provided regional detail. They estimated the costs and medical costs avoided of polio immunization and eradication over the period 1970 to 2050, assuming that vaccination could cease after 2010. As table 62.3 shows, Khan and Ehreth estimated that polio immunization and eradication would entail a negative net cost overall, with Europe and the Americas saving the most and with other regions incurring a positive net cost. Compared with other health interventions, this cost to developing countries may still be comparatively cost-effective. However, Khan and Ehreth comment that the cost per disability-adjusted life year (DALY) saved is high for developing countries (see table 62.3). As they explain (Khan and Ehreth 2003, 705), "This implies that without the financial support from developed countries of the world many developing countries would not have opted for polio interventions for implementation. From the developed countries' point of view, providing support for the polio program is not simply helping the poor and the disadvantaged, it actually represents a good economic investment."

Unfortunately, both of these cost-benefit studies have substantial limitations. First, both show that eradication is economically attractive if one incorporates all costs and benefits from the inception of this program. Because eradication has not yet been achieved, this approach mixes retrospective evaluation and prospective analysis (historical expenditures and benefits are sunk and so are irrelevant to the current situation). Second, benefits and costs are calculated in both studies relative to a world without immunization. A better approach would be to calculate the net benefits of eradication compared with the alternative of an optimal control program. The choice is not between doing nothing and eradication. It is between an optimal level of control and eradication. Finally, both studies assume that vaccination can cease in 2005 or 2010. As explained previously, this possibility is highly unlikely.

A more recent analysis by Sangrujee, Caceres, and Cochi (2004) calculates the costs for 15 years following the goal of certification of eradication in 2005 for three different scenarios: continued use of OPV, OPV cessation with optional use of the killed or inactivated polio vaccine, and OPV cessation with universal IPV. Table 62.4 shows their results.

The respective cost to middle- and high-income countries is the same for all three scenarios, reflecting the assumption that the high-income countries will switch to IPV by 2005 and middle-income countries will do so between 2006 and 2008. The scenarios differ only for the low-income countries. In the first scenario, these countries are expected to continue routine immunization using OPV; in the second, immunization ceases in 2011, followed by a system of surveillance and response. In the third scenario, the low-income countries join the others in switching to IPV between 2008 and 2010. Of these three scenarios, the second comes closest to the 2005 post-eradication strategy now advocated by the polio eradication program leadership.

Unfortunately, this analysis is also deficient. First, interruption of transmission will not occur before 2006, and certification will take an additional three years. Hence, analysis of post-eradication costs should begin in 2009 at the earliest, with the costs of continuing immunization needing to be borne up until that time. Second, the analysis assumes a capacity to supply IPV that exceeds current estimates. It is not obvious that this scenario is feasible or, if it were, if the costs of scaling up production are adequately reflected in the calculations. Third, and most importantly, Table 62.4 indicates that only low income countries would benefit from polio eradication over this 15 year time scale—and yet the table does not include any estimate of the risk these countries would bear of a possible outbreak.

Although this analysis suggests that the discontinued use of OPV promises the greatest return to eradication, this assumes that circulating vaccine-derived polioviruses could be contained if and when they emerged. However, preparing for this possibility would require a far more effective global surveillance system than now exists, maintenance of a laboratory infrastructure, and stockpiles of OPV. In addition, controlling outbreaks with OPV without the risk of viruses reverting to virulence will be exceedingly difficult in the setting of an accelerating proportion of immunologic-naive individuals. The use of OPV in this scenario could very well cause poliomyelitis to again become endemic. In any case, the estimated cost of any of the strategies exceeds $20 billion.

The economics of polio eradication are thus not as favorable as concluded by either Bart, Foulds, and Patriarca (1996) or Khan and Ehreth (2003). Both studies assume that vaccination can cease without IPV being used as a substitute anywhere, both exclude the costs of maintaining a response capacity, and neither accounts for the real threat of reemergence. Sangrujee, Caceres, and Cochi (2004) take account of two of these considerations, but their analysis calculates only the costs for 15 years, ignoring both the risk of reemergence and the benefits of eradication. Hence, each study provides only a partial glimpse of the economics of polio eradication and does not adequately address the fundamental difficulty (inability) of stopping vaccination and maintaining eradication.

In conclusion, although the economics of polio eradication may have been thought to be favorable by some (Aylward and others 2003), they are far less favorable than were the economics of smallpox eradication, even assuming that polio vaccination could cease.

Dracunculiasis

Dracunculiasis, or guinea worm disease, is a nematode infection, which is controlled not by vaccination but by education of the affected population, provision of nematode-free water through wells or filtration, and treatment of cases. It is not a global disease but found only in the rural areas of a few very poor tropical countries. This last difference is especially important from an economics perspective. It means that international financing of a guinea worm eradication program needs to rely more heavily on development assistance rather than on the self-interest of donor countries.

Thus far, the eradication program has been successful in reducing the number of cases of guinea worm 99 percent from the 1986 level (Carter Center 2004). The geographic range of the disease has also been reduced from 20 to just 12 countries. Although this achievement is important, eradication remains elusive many years beyond 1995, the year that the WHA set for eradication in 1991 (Cairncross, Muller, and Zagaria 2002, 232).

Only one cost-benefit study of the guinea worm eradication program has been published (Kim, Tandon, and Ruiz-Tiben 1997), and it is unfortunately flawed in a number of respects. First, as indicated previously, eradication costs should be compared with those associated with an alternative optimal control program. Second, the cost-benefit analysis applies to the period 1987 to 1998 and thus is backward looking. The analysis can reveal whether the money spent previously yielded a benefit in excess of the cost (it did), but it cannot reveal whether eradication was worth pursuing at the time that this study was undertaken. Finally, it takes no account of the investment decision of eradication—the main reason for pursuing the eradication goal in the first place.

This last omission is especially relevant to the study's analysis of the eradication program in Sudan. The study projected that, by 1998, infections would cease everywhere except Sudan. (Plainly, this prediction was wrong, although Sudan is the largest problem for the program, mainly because of the ongoing civil war, which has limited accessibility to endemic areas; see Hopkins and others 2002.) It then calculates the net present value of eliminating the disease there. The results are not promising. They show that eradication is attractive only if the disease can be eliminated in Sudan within five years. However, this analysis ignores the dividend that eradication would earn Sudan. It also disregards the most important feature of eradication—that if the disease were certified to have been eliminated from its last stronghold, it would yield a benefit to all potentially vulnerable countries. Thus, the economics of eliminating dracunculiasis from Sudan, if that is where the disease makes its last stand, will be much more attractive than suggested by this analysis.