BETHESDA, MD—Nearly a decade ago, the member states of the United Nations set eight international Millennium Development Goals (MDG) to achieve by 2015. These goals are designed to combat the most severe problems facing the developing world, including extreme poverty and child mortality. Number six on that list is “combating HIV/AIDS, malaria, and other diseases.” While a great deal of attention has been paid over the last decade to HIV and an increasing amount to malaria, there is a concern that the “other diseases” are falling by the wayside, despite contributing to a massive amount of pain and suffering worldwide.

“The MDG has helped generate an enormous amount of philanthropy for AIDS and malaria,” explained Peter Hotez, MD, PhD, to an audience of disease researchers at NIH last month. ’This is making a huge [difference] to the world’s poorest people. The problem is for those of us who work on what is called ‘the other diseases.’ We don’t see any individuals getting up and saying we need to take on these other diseases. We realized that we were on the outside looking in on this important progress going on in global health.”

The Bottom Billion

Hotez is an internationally recognized leader in what have become known as the neglected tropical diseases (NTDs)—those diseases that take a heavy toll on the poorest people in the world, or whom Hotez refers to as the ’bottom billion.”

“These are the 1.4 billion people who live on less than $1.25 a day. These are the [subsistence] farmers and urban slum dwellers of the world. [If you are one of them], you live in a place where there’s an element of hopelessness about life. Not only are you destined for poverty, but your children [are] destined for poverty, and your children’s children.”

This extreme poverty not only results in disease, but the effects of the disease promote poverty. These NTDs include ascariasis, trichuriasis, schistosomiasis, hookworm, lymphatic filariasis, trachoma, and onchocerciasis. Most NTDs are worm diseases and combined they affect more than 1 billion people in the world, with many having multiple infections. Most of the areas with infected populations are in South America, Africa, and Southeast Asia.

“And these diseases have more in common than not in common. They’re not acute infections; they’re chronic infections. People have these NTDs for decades; maybe their whole lives. They are chronic and disabling conditions.”

While the economic effects of these diseases are unknown for most countries, statistics from India show at least $1 billion in economic losses per year due to NTDs, with people working in rural India losing 20% of their productivity.

However, Hotez noted, these figures do not add up to much of a convincing sound bite to use when arguing for more attention or more funding. “We don’t have a sound bite; we don’t have an elevator speech; we don’t have an easy number.”

Unlike HIV/AIDS or malaria, there is no large number of deaths due to these diseases. But in terms of disability-adjusted life years (DALYs), NTDs result in the loss of 56.6 million DALYs—more than malaria or TB and two-thirds that of HIV.

The true impact of these diseases is not seen in the deaths of those afflicted, but in the loss of quality of life. Most of these diseases are disfiguring in one way or another—some of them grotesquely so.

“The psychological impact of these diseases is devastating,” Hotez said. “There’s a huge social stigma with these NTDs.” For young women especially, the effect of these diseases can be traumatic. In many countries, being afflicted with a disfiguring disease can keep a young woman from ever marrying, or is grounds for abandonment.

But it is the children that suffer the most from these diseases. Across the board, children are more likely to become infected. Researching children in Paquila, Guatemala, researchers found that almost all of the children were infected by ascariasis, with most having trichuriasis as well. ’And we can duplicate this result in any village [like it] in Guatemala,” Hotez said.

It has been found that infection with these diseases as a child can severely impact a child’s development. People with chronic infections through childhood can expect to be on the very low end of the growth scale, as well as have a lower IQ. “The more worms you have, the lower your IQ, the worse you’d do on tests of cognition, memory, [and the worse you do in] school performance and school attendance. It’s preventing children from growing to their full potential.”

Hotez asked his audience to put forward some hypothesis for why children are infected at a higher rate than adults and why infection by worms could lead to developmental problems. The notion that children expose themselves to more river water and mud was thrown out, as was the idea that worms leach nutrients and disrupt internal systems, which could impact development. Hotez admitted that both notions sounded plausible, but could not say whether either was true.

“Why are children wormier? Nobody knows. Why are worms suppressing growth? Nobody knows. This is the world’s leading endocrinopathy, and there’s not one published abstract on why worms are inhibiting growth.”

Innovative Solutions to Economic Hurdles

In the late 1960s, during the peak of the Cultural Revolution, China began a nationwide effort to treat lymphatic filariasis using diethylcarbamazine-fortified salt, becoming the first country to effectively eradicate the disease. They also showed the effectiveness of mass drug utilization using extremely cheap drugs—$4 per 1,000 tablets—on a population that has no money to spend on therapies.

Efforts in other countries followed, and after 30 years of mass drug administration, drugs for lymphatic filariasis are reaching about 42% of the people that need it. But for the most common NTDs, such as ascariasis, trichuriasis, hookworm, and intestinal helminthiasis, “we’re doing terribly,” Hotez declared.

One possible solution is a “rapid impact package” of multiple drugs that target all seven of the biggest NTDs. “We can get this package for 50 cents a person per year, because the cost is all just distribution.” The Global Network for NTDs, an advocacy group that Hotez co-founded in 2006, has launched the Just 50 Cents Campaign to help raise money and awareness about the solution.

As part of $3 billion in the FY 2011 budget being spent on global health concerns, President Obama announced in February that $155 million would be devoted to NTDs. Hotez is grateful that the US is making such a commitment, but is realistic when taking into account the big picture of NTD research money. “AIDS, malaria, and TB take up 73% of research and development funding for infectious disease worldwide. For all non-big three infectious diseases there is $750 million in R&D funding globally.”

The scientific hurdles are daunting, but the economic ones are larger. The greatest disease burden is in those countries that can’t afford to pay for even modestly-priced pharmaceuticals.

To overcome the economic hurdle, Hotez has helped create the Human Hookworm Vaccine Initiative (HHVI), a development partnership based at the Sabin Vaccine Institute and supported by the Bill and Melinda Gates Foundation. Because hookworm reinfection rates are so high, Hotez sees a vaccine as the best hope in seriously impacting the disease. With advice from vaccine experts at NIH and the Walter Reed Army Institute of Research, Hotez and his team have created a test vaccine that is managing to reduce the hookworm burden by about 60%.

After coming up with a viable vaccine, the researchers are finding that the challenge now lies in the problems of mass production and in finding low-cost expression vectors. ’If they cost more than $1 a dose, we might as well not be making them,” Hotez declared.

The HHVI has partnered with Instituto Butantan, a public sector vaccine manufacturer in Brazil that may eventually manufacture and distribute the vaccine. With 32 million of its citizens suffering from hookworm, Brazil has a vital stake in finding a vaccine.

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