Research Article: The Role of Research in Viral Disease Eradication and Elimination Programs: Lessons for Malaria Eradication

Date Published: January 25, 2011

Publisher: Public Library of Science

Author(s): Joel G. Breman, Ciro A. de Quadros, Walter R. Dowdle, William H. Foege, Donald A. Henderson, T. Jacob John, Myron M. Levine

Abstract: Using their experiences from, and analysis of, global campaigns to eradicate smallpox, poliomyelitis, and measles, Myron Levine and colleagues derive lessons for malaria eradication.

Partial Text: Despite a previous global eradication campaign (1955–1969), malaria continues to be a major public health problem. Faced with hundreds of millions of malaria cases annually and nearly a million deaths, the international community is renewing efforts to eradicate this disease. But, initiatives for national or regional elimination or global eradication of any disease represent complex efforts that consume vast financial, health services, and infrastructural resources and require decades of commitment. Such programs demand sound scientific underpinnings and management structures that can adapt to changing epidemiologic scenes and can learn from the experiences of previous programs. Herein we describe three viral disease elimination/eradication efforts whose research agendas offer lessons for malaria scientists and public health program managers. The disease elimination programs we consider are smallpox (the one human infectious disease successfully eradicated), poliomyelitis (transmission of wild-type 2 poliovirus was interrupted globally since 1999, although transmission of types 1 and 3 continues in several countries), and measles (whose transmission has been eliminated in the Americas and in several countries worldwide). Each author has participated in one or more of these eradication/elimination initiatives and some also have experience in malaria research.

The foremost lesson learned from eradication/elimination efforts for viral diseases is that a flexible research agenda must be initiated early, prior to or concomitant with the launch of eradication interventions.

A feature common to smallpox, poliomyelitis, measles, and Plasmodium falciparum and Plasmodium vivax malaria is that humans constitute the sole reservoir of these pathogens; one need not worry about animal or environmental reservoirs as sources of reintroduction into human populations.

A theme common to the smallpox, polio, and measles eradication/elimination programs is the critical role that surveillance has played in every phase, including quantification of the burden at the onset of the program; monitoring progress of the program at local, national, and global levels; intensive searches for the last cases and infected persons; and documentation of the interruption of transmission. The critical role of surveillance necessitated research to develop new epidemiologic surveillance systems for all three diseases and, for measles and polio, sero-epidemiologic methods, tests to identify asymptomatic carriers, and molecular methods to establish the geographic source and relatedness of isolates from outbreaks and clusters over different time periods. This lesson is directly applicable to the Malaria Eradication Program, which will need to assure that adequate surveillance methods and techniques are in place to monitor the effectiveness of the program.

Research fostered by the viral disease eradication/elimination programs has shown how molecular tools add precision to surveillance. The molecular epidemiologic evaluation of plasmodial parasites will be similarly helpful, particularly in the later stages of a Malaria Eradication Program; research in this area should be encouraged.

The eradication of smallpox and of type 2 poliovirus infection globally, and the elimination of polio and measles from various regions and countries was achieved using vaccines as the primary intervention tool. As malaria transmission diminishes, other interventions (e.g., vector control, insecticide-impregnated bednets, new drugs, etc.) will surely play critical roles, but the lesson from the viral disease programs is that vaccines that interrupt transmission could play a critical role in helping to eradicate malaria.

Smallpox and measles viruses are transmitted by the respiratory route (droplets/aerosol), while polio is mainly transmitted by the fecal-oral route in developing countries. Although modeling played no role in smallpox eradication, it has been extremely useful in the GPEI as a valuable epidemiologic research tool, for addressing economic issues, and for providing insight into future programmatic options [25]. Modeling research is currently addressing the risks of virulent vaccine-derived poliovirus that may be chronically shed by immunodeficient individuals and from circulating vaccine-derived poliovirus, after OPV is withdrawn posteradication [70]. Similarly, measles was one of the first infectious diseases studied with models, and models are now being used to elucidate better the epidemiologic behaviour of measles and predict the effect of interventions [71],[72]. Although the ability to generalize from models is debated [73], there is consensus that the quality of input data is steadily improving, even as the epidemiology of measles is changing globally.

Another lesson for malaria from the viral eradication/elimination programs is the important role that socio-cultural, religious, and local political factors play in public perception of the disease and of the main intervention tools of the eradication program; these factors can accelerate or impede eradication efforts. It is prudent to support research on these issues and on improving ways to communicate effectively with local populations. In this area of research, one size does not fit all.

A cross-cutting theme among the smallpox, polio, and measles eradication/elimination programs is that interruption of the last vestiges of transmission in a country or region is problematic and requires the allocation of as many resources as the early stages that achieved a 90%–99% reduction in incidence. Therefore, interventions often need to be modified, sometimes drastically, to complete the job of elimination.

The final lesson learned from the viral disease eradication programs is that discussion of posteradication scenarios, problems, and potential solutions must begin at the onset of the programs. Focused research can find early solutions for some posteradication issues. In the case of smallpox, affirmation of the eradication of smallpox was followed by a discontinuation of routine vaccination globally. The only way that smallpox disease can occur anew is if nefarious individuals with access to virus undertake a deliberate bioterror release. In the case of polio, however, since 2005, GPEI has been grappling with posteradication questions of use of OPV, the quandary of vaccine-derived poliovirus persistence, laboratory destruction and containment of poliovirus stocks, surveillance needs, vaccine compositions, and response strategies. These questions have become the drivers of a research agenda [78]. For measles, the major posteradication dilemma will be whether to continue routine immunization with the live measles vaccine. Given that in some industrialized countries, certain groups in the population view measles vaccine with more suspicion than the wild virus, it might be necessary to develop and utilize an alternative nonliving type of measles vaccine [36].

Nine cross cutting lessons have been provided by these three vaccine-dependent eradication and elimination programs of viral diseases in which research was integral to guide program activities. These lessons will be useful to the revitalized Malaria Eradication Initiative. Research played a critical role in the Smallpox Eradication Program and is still contributing critically to the GPEI and measles elimination and mortality control programs. Despite having tools for primary prevention, considerable research has been essential to address geographic variations in the force of transmission of smallpox, polio, and measles and to adjust the tactical use of the preventive tools.



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