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.
Throughout this article we use the following terms to denote progressive decreases in the extent of human disease and transmission of agent, as a result of deliberate interventions 
. “Control” is the reduction of incidence of a disease to an arbitrary level whereupon it is no longer a public health priority. “Elimination” is the interruption of transmission of the pathogen when disease incidence becomes zero in a population within a large defined geographic area (e.g., one or more countries). A caveat in measles and polio elimination initiatives is that imported cases may appear in a country without indigenous transmission, i.e., a country that has achieved elimination. Elimination is considered to remain intact, so long as the importations are contained and do not ignite anew extended indigenous transmission. Finally, “eradication” signifies the interruption of transmission of a pathogen worldwide and a reduction in disease incidence to zero; this assumes that surveillance systems could detect transmission, if any. Theoretically, eradication should obviate the need for further control measures other than surveillance (as with smallpox).
Aside from the common requirements for adequate resource commitment, broad advocacy and political will relevant to all disease eradication initiatives, there are biologic and epidemiologic factors that specifically affect the feasibility of eradication of smallpox, polio, measles, and malaria. summarizes these salient factors. provides illustrative examples in which research played an important role in the eradication of smallpox, the near-eradication of polio, and the elimination of measles from the Americas and some other countries. From these experiences, lessons were learned that are applicable to the Malaria Eradication Program and that should, we believe, be incorporated in the Malaria Eradication Research Agenda (malERA) described in this Supplement.
A comparison of the inherent salient features of smallpox, polio, measles, and malaria infections that favour or impede elimination of the disease and the most effective past and current interventions.
Research outputs that contributed to the eradication of smallpox and the regional elimination of polio and measles (or outputs that are still undergoing evaluation or development): Lessons for the rejuvenated Malaria Eradication Program.