62. Control and Eradication

Frameworks for Eradication

Numerous issues need to be considered in planning expanded control measures that lead, possibly, to regional cessation of transmission or global eradication of disease. These complex issues will be further examined in the chapter.

Scientific Considerations

Scientific considerations include the nature of potential reservoirs for disease-causing microbes or their vectors, technologies available for interrupting disease transmission, changes in host capabilities to deter infections and disease, and satisfactory containment of organisms in laboratories.

Geographic and Environmental Controls

The limit of endemicity for microbes and their associated diseases is determined in part by their ability to exist in nature outside the human host. Both geographic and temporal variations determine the ecological niche of microbes, resulting in variable annual incidence rates throughout the world. This niche limitation is further extended to intermediary vectors and hosts in complex biological systems. Natural environmental barriers also may isolate the habitats of helminths. Infectious agents that are not limited to an environmentally restricted intermediary host or those that have longer latent periods, thereby allowing translocation, may have a global pattern of distribution. Examples include the highly transmissible viral agents such as measles, rubella, influenza, and varicella. Although these agents are not geographically constrained, their transmission patterns are directly and indirectly influenced by seasonal environmental factors and population-based immunity.

Potential Reservoirs

A microbe and associated disease can not be eradicated if the microbe is capable of persisting and multiplying in a reservoir. Microbes that thrive in nonhuman species may reemerge if control efforts cease, thus leaving human populations susceptible. Similarly, if the infectiousness of a human is long lived or could lead to potential recrudescence, surveillance efforts would have to continue as long as the last individual remained potentially capable of transmitting infection, as would be the case with tuberculosis or hepatitis B infection.

Transmissibility

The inherent rate of a microbe's ability to cause secondary infections is defined by an organism's reproductive rate in a fully susceptible (R₀) and partially susceptible (R) population. The reproductive rate of organisms that infect individuals only once because of durable immunity is inversely proportional to the average age of infection in an endemic area. Agents that cause childhood infections, such as viral respiratory agents, are far more transmissible than helminths and subsequently require more intensive control efforts to interrupt transmission.

Natural Resistance to Reinfection

Many natural infections induce long-lived immunity to reinfection. Although the most commonly used vaccines have been available for fewer than 50 years—less than the lifetime of an individual—they, too, are assumed to offer long-lasting immunity. Because eradication depends on reducing susceptible populations in potentially endemic areas, long-lived protection through immunization or natural disease is important to successful programs.

Laboratory Containment

Laboratory specimens containing the organism targeted for eradication could serve as reservoirs. Considerable effort may be necessary to ensure their maximum security. That these microbes may be inconspicuous in specimens collected for other purposes poses special challenges. This situation is especially true for the poliomyelitis virus, which may be found in many stool specimens collected for studies completely unrelated to current poliomyelitis eradication efforts.

Operational Considerations

Optimization of control requires a fundamental appreciation of the biological systems that govern the ecology of microbes and their intermediary and human hosts. The reproductive rate, R, is influenced by many local factors, including population density (of vectors, intermediary hosts, and humans) and other environmentally determined conditions, all highly variable throughout the world. For a disease to be controlled to stop transmission, the intervention-altered reproductive rate must be maintained below 1.0. At the same time, all reservoirs of the responsible microbe must be controlled.

Three main components of possible eradication programs are

• surveillance, including environmental sampling where appropriate and clinical testing

• interventions, including vaccination and chemotherapy or chemoprophylaxis or both

• environmental controls and certification of eradication.

Each of these components must be undertaken at local, community, national, regional, and global levels. Eradication differs from control in that it is expected to be permanent. Success depends on having adequate surveillance to identify potentially infectious persons and on stopping transmission before infection of a new cohort of susceptible persons arises as a result of births, migration, or the waning effectiveness of prophylactic measures.

Disease Surveillance

Effective surveillance requires a sensitive system to detect the presence of microbes within the environment, intermediary hosts, and clinical cases. Surveillance and response systems need to be more efficient than the rate of transmission of the targeted agent. As eradication progresses, the sensitivity of detection systems must be steadily enhanced to detect all existing foci. Nonclinical or latent infections pose formidable barriers to eradication efforts. Operationally, the need for near-perfect sensitivity comes at the expense of lower specificity. Thousands of skin lesions from suspected smallpox patients were tested in reference laboratories during confirmation of smallpox eradication, and tens of thousands of stool specimens are being examined for poliovirus. Highly sensitive systems used to detect measles cases in theAmericas began to identify a greater proportion of rubella and parvovirus infections because of the nonspecific surveillance of rash illness. Such findings are important because the identification of other diseases that mimic the targeted disease can lead to a misdirection of resources. However, the ability to detect such similar clinical cases can serve as a proxy measure for the adequacy of surveillance. For example, identification of a minimum incidence of cases of acute flaccid paralysis that is not related to polio has served as an indicator of adequate efforts of case finding for polio.

Interventions

Interventions to block transmission of the targeted infectious agent should be easy to deploy and adaptable to diverse conditions, given the global goal of eradication. Cost considerations and local acceptance of the required sacrifices (both short and long term) are crucial for success. Interventions may be designed for environmental control of microbes, isolation (quarantine) of clinically infectious individuals to limit their contacts with susceptible persons, treatment of clinical cases to limit the duration of infectiousness, or reduction in the infected pool of individuals through immuno-or chemoprophylaxis.

Certification

The last tool for eradication is a certification process whereby independent, respected parties certify the absence of disease transmission or the existence of any specific microbe in an uncontrolled reservoir, including laboratories (Breman and Arita 1980). Although certification can be implemented on a regional basis, it must ultimately be done globally. Certification is one of the greatest challenges in any eradication effort, given the exceedingly great difficulty of verifying a negative finding in a reasonably short period of time. When certification is completed, curtailment of control measures should be possible.

Strengthening control efforts sufficiently to achieve eradication is a difficult and expensive task. It requires that scaling up of such efforts occur over a wide area—at the community, national, regional, and global levels. Its efficacy depends heavily on the adequacy of local financial and human resources, as well as on a broad range of logistical factors.

Economic Considerations

Control and eradication programs have many economic dimensions: private versus social net benefits, short-term versus long-term net benefits, and local versus international net benefits. Such interventions also have implications for existing public health programs.

Private versus Social Net Benefits

Individuals have private incentives to protect themselves from disease—by means of vaccination, for example. But when individuals protect themselves—when they elect to be vaccinated—they offer a measure of protection to others by helping limit the spread of infection. In brief, the social benefit of vaccination is greater than the private benefit alone. As more people become vaccinated, the marginal private and social benefit of vaccination—that is, the benefit of vaccinating an additional susceptible person—declines. The marginal private benefit is likely to fall because, as more people are vaccinated, the probability of a susceptible person becoming infected falls. The marginal social benefit is likely to fall for the same reason and for one other: as more people become protected, the total number of susceptible persons falls. The marginal social benefit of vaccination falls sharply at the critical level of immunization—the level at which herd immunity is conferred on all susceptible persons. When a population is immunized to this level, a disease ceases to be endemic, and imported infections cannot spark an epidemic.

This level is determined by the epidemiology of a disease, but whether it pays to vaccinate to this level depends on the economics, and the economics depend in turn on the social costs and not only the social benefits of vaccination. These costs consist of the direct costs of producing, distributing, and administering a vaccine. The economics depend also on the costs borne by the individuals who are vaccinated, such as those incurred by individuals who experience vaccine complications. The proportionate costs of reaching people who live in remote areas and those who are at special risk, such as migrants and the homeless, increase as the fraction of the population vaccinated increases.

The economics of varying levels of disease control depend on the relationship between the marginal social benefits and the marginal social costs of vaccination. As vaccination levels increase, the marginal social benefits of vaccination fall, whereas the marginal social costs rise. Social welfare is maximized where these two relations intersect, which might be called the "optimal" level of vaccination—a level that may or may not achieve cessation of transmission or eradication.

Short-Term versus Long-Term Net Benefits

Control programs require ongoing intervention. Sustaining a given level of protection requires that, over time, a certain proportion of new susceptible persons be vaccinated. Eradication differs from control in being permanent. The economics of eradication must therefore take account of long-term benefits as well as short-term costs.

The long-term benefits of eradication consist of avoided future infections and vaccination costs—a dividend. To calculate this benefit, one projects future infection and vaccination levels in the absence of eradication, attaches values to these, and discounts them. If this sum exceeds the costs of eradication, then eradication enhances social well-being, and it therefore should be undertaken.

In deciding on the benefits of eradication, the cost of future infections and vaccination should ideally be compared with the best alternative to eradication: the level of optimal control (Barrett and Hoel 2003).

The costs of eradication must also take into account ongoing surveillance requirements, laboratory containment, and perhaps the maintenance of stockpiles of vaccine in the chance event of disease reemergence. From an economic perspective, attractive candidates for eradication are those diseases that some countries have themselves targeted for interruption of transmission nationally or regionally.

Local versus International Net Benefits

Control differs from eradication in another important way. Control refers to location-specific interventions. Eradication, by contrast, is global. In economic terms, eradication is a global public good. No country can be excluded from the benefit of eradication, and no country's consumption of that benefit diminishes the amounts available to other countries. Control, by contrast, supplies only a local public good.

Eradication requires a global effort. A disease can be eradicated only if microbe transmission ceases everywhere. This spatial dimension to eradication is of fundamental importance because no world government can implement an eradication policy; the WHA can declare its support for eradication, but WHO does not have the power to enforce the execution of a national program in support of that goal. The outcome experienced by any country depends not only on whether the country itself eliminates the disease within its borders but also on whether all other countries do so. Indeed, eradication is a weakest-link public good.

Whether eradication is achieved depends on the level of control adopted by the country that undertakes the least control. In practical terms, any country in which disease is endemic can prevent eradication from being achieved. In 2004, the global polio eradication initiative, after investing more than US$3 billion and involving some 20 million volunteers over a period of 16 years, was placed at risk of failure by the actions of one local administration. In the Kano state of Nigeria, local leaders claimed that the polio vaccine was tainted with the AIDS virus and sterility drugs and declined to participate in a national immunization day program. The European Union then declined to pay for the national program in Nigeria, believing the money would be wasted (Roberts 2004). One consequence was the subsequent spread of polio to nine formerly polio-free countries. Concerted efforts by WHO later persuaded local leaders in Nigeria to rejoin global efforts, but special vaccination programs had to be launched over a population area of more than 300 million persons. This situation dramatically illustrated the vulnerabilities inherent in a weakest-link public good.

What are the incentives for states to participate in an eradication effort? To begin, assume that countries are symmetric, meaning that all countries have the same benefits and costs of control. Assume as well that eradication is feasible. Four possible situations then exist (Barrett 2003):

• First, the global net benefit of eradication may be negative—the cumulative programmatic costs outweigh the net present value of the cumulative benefits. In this case, elimination would also yield a negative net benefit to every country, and so no country would eliminate the disease.

• Second, the global net benefit of eradication may be so large that each country would choose to eliminate the disease even if others did not. In this case, all countries would eliminate the disease, and the disease would therefore be eradicated. In these two cases, no need exists for an international policy.

• Third, each country may have an incentive to eliminate a disease only if all other countries have eliminated it. In this case, achieving global eradication requires coordination. Here a role exists for international policy, but all that is required is for each country to be assured that all others will eliminate the disease.

• Finally, and noting that the "last" country to eliminate a disease would get just a fraction of the global dividend from eradication, under some circumstances no incentive may exists for this country to eliminate the disease—even if all other countries have done so and even if the entire world would be better off if it did. This case is the most worrisome, because implementation of the efficient outcome would likely require enforcement.

All this hypothesizing assumes that countries are symmetric, and of course they are not. Some countries gain less from control and would gain less from eradication than others. Some are unable to implement an elimination program, even if they would very much like it to succeed. In these situations, achieving an eradication goal will require international financing and technical assistance, with the countries that benefit most from eradication compensating the other countries for the costs of eradicating the disease. National and international reproach are often expressed if a country lags in its eradication efforts. International financing has been a key element in all eradication programs.

We have thus far looked at eradication from the perspective of only the self-interests of states. But eradication also has implications for development. In particular, eradication has two advantages over control programs. The first is that the rich countries may gain directly if the goal is achieved, giving them a vested interest in ensuring that the goal is achieved. The second is that eradication is permanent, making an investment in eradication financially sustainable. This second advantage is important because financial sustainability has proved to be a key problem for disease control programs in developing countries (Kremer and Miguel 2004).

Vertical versus Horizontal Programs

Control and eradication programs cannot be viewed in isolation. All programs have implications for the delivery of comprehensive primary care services. An important question is whether targeted, or so-called vertical, programs draw critical resources away from other health care programs or whether they serve instead to augment competence and capacity. The evidence is mixed.

Evidence suggests that disease-specific systems can serve to expand polyvalent services (Aylward and others 1998). Smallpox eradication, for example, gave many national governments the confidence to introduce the Expanded Program on Immunization, with the ability to deliver vaccines and micronutrients in routine schedules and through national campaigns. However, other evidence suggests that some vaccination programs have adversely affected primary health services (Steinglass 2001; Taylor, Cutts, and Taylor 1997) and may have even increased costs. Implementation of international initiatives can also expose conflicts of priorities. The polio eradication initiative, for example, has successfully vaccinated children in the poorest of countries against this disease, but in some of these countries it has failed to timely include the co-administration of measles and other common childhood vaccines, which would have had a much greater effect on child mortality.