Andrew Carnegie once wrote that to die rich was to die in disgrace. Like the 19th-century Pennsylvania steel magnate, Microsoft founder Bill Gates seems determined not to let that happen.

Mr. Gates has promised to give away 95 per cent of his personal fortune, currently valued at $46 billion. He has already endowed the Bill and Melinda Gates Foundation, created to help fight disease and improve education worldwide, with $24 billion; since its inception in 2000, the foundation has distributed more than $6.2 billion. And just this week, during his and his wife's three-nation tour of Southern Africa, Gates committed an unprecedented $168 million in private money to fight malaria.

While the Gateses embrace old-style charity, their methods are thoroughly 21st century. Much of their money goes to finding scientific solutions to the world's health problems - like the development of malaria vaccines and new AIDS -prevention techniques. Health workers in Africa say that the world's richest couple are profoundly affecting the direction of research and aid, and creating new hope for tackling some of the most difficult problems here.

"I think it's been quite remarkable the influence they've had in revitalizing and revolutionizing the global health agenda," says Peggy Morrow, vice president of the Program for Appropriate Technology in Health in Seattle, which is working with the Gates Foundation on a variety of issues, including developing a malaria vaccine and developing new screening techniques to prevent cervical cancer in developing countries. "They have changed our priorities, as well as some of the ways in which we work."

An example in Mozambique

Observers say the size and scope of their grants have enabled the Gateses to highlight issues the world has forgotten about. The grant for malaria research, announced Sunday at a rural clinic in Mozambique, is a prime example. Although malaria strikes more than 300 million people every year and kills more than 1.1 million, most of them children and most of them in Africa, it has received just a fraction of the attention and spending of AIDS.

Efforts to create a vaccine have been in development for at least 15 years, but lack of money slowed progress. The Gates Foundation, in partnership with GlaxoSmithKline Biologicals and others, is now funding vaccine trials in rural Manhica, Mozambique, and Gambia. If successful, a malaria vaccine could be available in less than 10 years - still a long way off, but closer than if no Gates funding were provided.

"Even two or three years ago, let alone 15 years ago, we couldn't have imagined that private funding would come available," says Anne Walsh, director of global communications for GlaxoSmithKline Biologicals. "Without the funding, it would have been a lot more difficult and a lot slower."

The development of new prevention methods like vaccines and microbicides hold great appeal to the Gateses, who see them as a long-term investment with potentially high rewards. But they're also working to improve the use of existing technology, and particularly to increase the rate of child immunizations in poor countries.

Despite decades of work by organizations like the World Health Organization(WHO), which helped eradicate smallpox, more than 30 million children around the world still do not receive basic immunizations, and many new vaccinations have yet to reach most of the developing world.

In 1999, the Gateses donated $750 million to found the Global Alliance for Vaccines and Immunization (GAVI), an organization aimed at improving access to immunization. Since GAVI's founding, an additional 8 million children have received basic vaccination and 30 million have received new vaccinations that were previously unavailable.

"[Bill Gates] became interested in vaccines because, first of all, he saw that this was something his own children were getting but children in other countries were not," says Tore Godal, executive secretary of GAVI. "But also, I think he saw it as analogous to software development. Difficult to develop, but easy to use."

When Gates first started becoming involved in African health issues, there was initial skepticism of his approach.

"There was some criticism at first, that he was very American to look at short technological solutions to complex issues," says Lisa Jacobs, spokeswoman for GAVI.

But officials at GAVI say those fears were quickly put to rest. Now, because of the Gates's donations, GAVI, which brought together private donors, international organizations like UNICEF, national governments, and pharmaceutical companies, has become a model for funding large public-health projects and an inspiration for the United Nations Global Fund to Fight AIDS, Tuberculosis, and Malaria.

"There is a recognition that the traditional way of doing this wasn't working," says Dr. Godal, who says the Global Fund and other groups have now borrowed GAVI's way of requiring countries to apply for funding from a central fund. "We needed a new approach that would be innovative and risk taking."

Ordinary family, extraordinary wealth

In addition to the large new donation to fight this week, the Gateses checked on the progress of research into microbicides in Johannesburg - new AIDS-prevention methods for women to which they've donated $60 million. They also met with Botswana's President Festus Mogae about that country's program to give free antiretrovirals to people with HIV, to which the Gateses have donated $50 million.

To date, the Gates Foundation has sent half its money to improve health in the world's poorest countries. In addition to higher-profile diseases like AIDS and malaria, it also contributes to fighting lesser-known problems, such as the Guinea Worm Disease.

For Mrs. Gates, philanthropy is a responsibility of privilege. She describes her family as an ordinary one - with extraordinary wealth.

"When we're back at home, we don't sit around the dinner table among ourselves, talking about the enormous change that we're going to make across the continent," she said in Mozambique. "But we do try and share with our children some of the needs of children around the world, because we do want to instill in our children a responsibility."

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