In Brazil, Field Trials To Treat World's Poor

George Washington University professor Jeff Bethony, center, and researcher Ricardo Fujiwara confer at a Brazilian lab on the hookworm project.
George Washington University professor Jeff Bethony, center, and researcher Ricardo Fujiwara confer at a Brazilian lab on the hookworm project. (By Monte Reel -- The Washington Post)
By Monte Reel
Washington Post Foreign Service
Wednesday, October 11, 2006

BELO HORIZONTE, Brazil -- Adriana Pereira da Silva's family and friends are a weary lot who spend their days coaxing whatever crops they can from the red dirt that surrounds their thatch-roofed shacks.

It's a tough life, which Pereira da Silva assumed was why so many people seemed perpetually worn out. But another explanation hides in the dirt itself: Up to 80 percent of the people in her village are infected with hookworm, a vitality-sapping parasite that crawls up from the ground, penetrates the skin and settles in the intestines.

"People seem tired all the time, and they never eat," said Pereira da Silva, a nurse who lives in Americanias, a small village here in Minas Gerais state, in eastern Brazil. "They don't know what's wrong with them."

The global health community has known for a long time about the wide-ranging complications that hookworm causes, but pharmaceutical companies have had little incentive to develop a vaccine: Most of those infected are too poor ever to pay for medicine, so recovering expensive development costs would be a long shot.

But now the medical ghetto of neglected diseases -- the field concerned with ailments affecting the 2.7 billion people who live on less than $2 a day -- is undergoing a transformation, thanks to an influx of cash from wealthy philanthropists and an emerging development model that promotes public-private partnerships.

That transformation has allowed Pereira da Silva, who staffs a rural public health outpost that is little more than a desk and a stethoscope, to become part of a well-equipped field team testing a vaccine for hookworm -- a venture researchers had been vainly trying to sell to pharmaceutical companies for years.

If successful, the vaccine could help eliminate such hookworm-related ills as increased child mortality, stunted learning capacity and reduced economic production.

The project has been made possible with grants totaling more than $53 million from the Bill and Melinda Gates Foundation, which, along with other donors such as the Rockefeller Foundation and Doctors Without Borders, has in recent years provided the financial incentive to get several such ventures off the ground.

The effects of the funding are hard to miss: Since 1975, only 13 drugs targeting neglected diseases have been launched, according to a study published this year by the London School of Economics and Political Science. But at the end of 2004 alone, 63 projects to develop such drugs were underway, according to the study, and standard attrition rates indicate that eight or nine of those would reach the market.

Although sub-Saharan Africa is generally hit hardest by neglected diseases, Brazil has emerged as an important testing ground for the approach. In addition to the hookworm trial, tests across the country are targeting diseases such as leishmaniasis and schistosomiasis.

"The idea is to partner with public-sector vaccine manufacturers in what we call 'innovative developing countries' -- places like Brazil that may not perform so well economically but have somehow managed to overachieve in their ability to make health products," said Peter Hotez, head of microbiology at George Washington University, who is developing the hookworm vaccine in partnership with Brazilian scientists and the Sabin Vaccine Institute in Washington.

The benefits of the newfound interest might be felt first in places such as Pereira da Silva's village. Along with other field researchers, the nurse has begun treating infected villagers with existing medicines that can kill the worms -- the first step in the field trials.

In the United States, hookworm was eliminated after World War II by treatment and education. In places such as rural Brazil, the extent of the poverty means those approaches won't be enough. Wearing flip-flop sandals, for example, is considered a luxury, and most of the villagers simply get reinfected when they walk barefoot in the fields or bend down to cultivate a manioc, or cassava, root. Because most houses don't have toilets, the worms are constantly reintroduced into the ground.

Researchers hope the vaccine they will soon begin to test will have a permanent impact, setting off a chain reaction that could transform such communities literally from the ground up. If villagers are healthier, they'll be better able to work, and if they can work, they can help build local economies.

"Even after the first treatments, people started telling us they were feeling better, and that got them planting more crops," said Renata Diniz, coordinator of the hookworm project's field team.

When it funded the hookworm project, the Gates Foundation evaluated such economic effects, said Regina Rabinovich, head of the foundation's infectious diseases program. The foundation was also drawn to the project because Hotez's group saw a way to manufacture the new drug by going around the pharmaceutical companies and teaming with Brazil's state-run Butantan Institute, which makes 85 percent of the vaccines distributed nationally.

The institute has built a new production facility in its Sao Paulo headquarters, and scientists are already strategizing about how they can produce a vaccine that public health institutions could afford to distribute. The goal is to eliminate dependence on wealthy donors.

It's a way of thinking that hasn't been widespread under the corporate model, said researcher Isaias Raw, who leads Butantan.

"The whole model had to be modified, and it is beginning -- slowly -- to happen now," Raw said. "When you start developing a product, you tool yourself for the prices that your market can afford. You can say, 'I'm going to make an efficient product that costs very little,' or you can say, 'I'm going to make a very sophisticated product with a fancy box that only the wealthy can afford.' That is what happens, in general, with someone looking at profit as the goal."

Getting governments worldwide to that point will not happen overnight. The hookworm vaccine trials alone will take years.

"There's no precedent for this in the contemporary era of science," said Jeff Bethony, a George Washington University microbiologist who leads the laboratory team in Brazil working on the hookworm trials. "But interest is really building. People go where there's money: If you build it, they will come."

Most of the money poured into neglected disease research in recent years has come from the Gates Foundation, which estimates that it has given about $595 million to the specialty. In addition to the fieldwork, its funds have helped launch a medical journal dedicated to diseases that had gone largely disregarded.

"The money has transformed the environment surrounding these diseases, and if they suddenly pulled out all of that money, the environment would remain transformed," said Richard E. Chaisson of Johns Hopkins University's Bloomberg School of Public Health, who oversees testing of new tuberculosis medications in Brazil. "People now view this field completely differently. That's not going to go away."

© 2006 The Washington Post Company