A ONCE-VANQUISHED KILLER RE-EMERGES

• Malaria kills more than two million adults and children annually, a death toll comparable to that of AIDS.
• Children are especially vulnerable. Malaria kills more children globally than any other disease: A child dies every 12 seconds.
• Once on the brink of elimination, malaria has come back with a vengeance. From 300 to 500 million new cases arise each year, according to the World Health Organization.
• Ninety percent of the transmission of malaria occurs in rural Africa. Ninety percent of deaths due to the disease occur in sub-Saharan Africa.
• In some areas, malaria sufferers occupy more than one-third of all hospital beds. The direct and indirect costs of malaria drain an estimated $2 billion from sub-Saharan nations every year.

The Ancient Scourge of Malaria
Malaria, an ancient scourge that once seemed on the brink of total elimination, has come back with a vengeance. The number of new cases of the disease has quadrupled in the past five years, and the World Health Organization estimates that between 300 and 500 million new cases occur each year. In addition to causing untold suffering and disability, malaria ranks as one of the world's major killers, costing two million people their lives annually, a death toll comparable to that of AIDS. Children are especially vulnerable: year after year, ore children die from malaria than any other single disease.

Making a bad situation worse, this resurgence of malaria has overwhelmed the world's means for combating the disease. The search for a vaccine continues, as it must, but so far the history of malaria vaccine research is one of alternating chapters: hopes raised, hopes dashed.

That leaves effective treatment drugs as the only thing standing between good health and life and disease and dying for millions of malaria-afflicted people. But a crisis looms: the mosquito-borne parasite that causes malaria is becoming increasingly resistant to all known treatment drugs. Today, "multidrug-resistant" malaria is disabling and killing tens of thousands of people all over Southeast Asia. Large parts of the world may soon be without any effective antimalarial drug and therefore vulnerable to devastating epidemics of malaria.

The emergence of drug resistance is a problem with other infectious diseases:  tuberculosis and HIV are just two prominent examples. With malaria, the situation is especially grave because so few compounds have been identified as being potentially useful in the development of new drugs.

Current research spending on antimalarial drugs is dwarfed by the enormity of the problem. At present, the total public-sector spending on malaria research is about $85 million, which is only about two cents for every reported case. In the private sector, as the pharmaceutical industry has consolidated and become more competitive, the few companies that supported antimalarial drug discovery and development have either discontinued their programs or significantly cut them back.

The Harvard Response
Recognizing the growing threat of malaria and the structural and economic problems hampering research, the Harvard School of Public Health has launched the Harvard Malaria Initiative. The Initiative is designed to discover, develop, and test drugs that will defeat drug-resistant malaria. Researchers at the School will work at the basic science level, using their knowledge of the genomic, molecular, and cellular mechanisms underlying multidrug resistance. They will map conceptual pathways to effective drugs as well as identify possible compounds. Collaborating with drug companies, they will then use these discoveries to screen and synthesize new antimalarial drugs and put them through the appropriate lab tests. Once the most promising candidates have been identified, Harvard malaria scientists, in close consultation with drug company scientists and experts, will work with long-standing collaborators in Africa, Asia, and South America to field test the drugs.

By enlisting and combining the strengths of academic and industry science, the Harvard Malaria Initiative will be greater than the sum of its parts, bringing new efficiency and much-needed resources to the antimalarial drug discovery.   Harvard researchers are in an especially advantageous position, having both the basic research resources and working relationships with teams of collaborators around the world. Pharmaceutical scientists will contribute pharmacological expertise as well as product development equipment and skills.