Of Pathogens and Poverty
Microbial Solutions
Regina Kelder

Of Pathogens and Poverty

How are we faring in the global fight against neglected tropical diseases? A Q&A with Peter Hotez.

Neglected tropical diseases (NTDs) are a key reason why many of the world's poorest can't escape the chains of poverty. Almost everyone in the so-called "bottom billion" suffers from at least one NTD, a medical diverse group of infections spread by bacteria, viruses, protozoa and helminths. One of the most common is dengue fever, a viral disease transmitted by Aedes mosquitoes that infects 400 million people yearly. In December, three tropical hotspots—Mexico, the Philippines and Brazil—approved the first vaccine to fight this global scourge, a major advance in controlling dengue's spread. Unfortunately, developing novel therapeutics, vaccines and diagnostics for other NTDs, such as hookworm or Chagas disease, continues to be both a scientific and financial challenge, notes Peter Hotez, president of the Sabin Vaccine Institute in Houston, Texas and Washington, D.C., and a leading advocate for the treatment and prevention of NTDs. The Rockefeller, Cornell, and Massachusetts General-trained biochemist and pediatrician said the global public health community has gotten some things right. About 10 years ago Dr. Hotez worked with the US Congress and the White House to establish an NTD Program through US Agency for International Development (USAID) to supply low cost rapid-impact packages of essential drugs aimed at five NTDs. The program has since helped bring vital medicines to 450 million people in the developing world, with the assistance of pharmaceutical companies that donate the medicines free-of-charge. Where the global public health community has been less successful, he says, is figuring out a way to develop and finance new technologies, therapeutics and vaccines for NTDs—an Ebola vaccine being a prime example.

The world's 20 largest economies also aren't giving adequate attention to the NTDs occurring in their own countries, a topic of Hotez's upcoming book, tentatively titled Blue Marble Health: Diseases of the Poor Amid Wealth (Johns Hopkins University Press) due out this summer. Along with his work at Sabin, a non-profit dedicated to eliminating the seven most common NTDs (ascariasis, hookworm infection, trichuriasis, schistosomiasis, lymphatic filariasis, onchocerciasis, and trachoma), Hotez is dean of the National School of Tropical Medicine at Baylor College of Medicine and Endowed Chair in Tropical Pediatrics at Texas Children's Hospital in Houston. In December 2014, he was one of four scientists named as US Science Envoy by the White House; Hotez's focus is Saudia Arabia, Tunisia, and Morocco. Eureka caught up with Dr. Hotez to talk about the significance of the dengue vaccine and where the world stands on other NTDs. Here are his edited responses.

Dr. Peter HotezQ: How do you get governments excited about diseases that, let's face it, aren't household terms?

PH: I try to make it clear that these aren't rare diseases but the most common afflictions of humans living in extreme poverty. As I often say, these are the "stealth reasons" why people cannot escape poverty. They can have a deleterious impact on child growth and development, worker productivity and pregnancy outcomes, and because they can destabilize whole populations or communities NTDs are a global security issue as well.

Q: Are we moving the needle in getting people to care about NTDs?

PH: We have had some success. Getting Congress to appropriate money for rapid-impact packages was a significant achievement. We've finally figured out that these are big problems in sub-Saharan Africa and the poorest parts of Latin America and Southeast Asia. Yet we have failed to see the high burden these poverty-related diseases are having among poor people living in wealthy countries. At least half of the world's NTDs are among the poor living in G20 countries. This includes the US, where I estimate there are 12 million Americans living in poverty with at least one parasitic tropical disease. I thought this would generate interest and attention, but quite the opposite has happened.

Q: What diseases are we talking about?

PH: Chagas disease is one example. Another is toxocariasis, a parasitic worm infection of the brain. I estimate that 2.8 million African Americans living in poverty are infected with it.

Q: How do you get it?

PH: Toxocariasis is from stray dogs and cats in degraded urban environments defecating indiscriminately. The eggs are shed in the environment. Chagas is transmitted by kissing bugs.

Q: Where else are we falling behind?

PH: We haven't done enough with innovations for new technologies. A good example is the Ebola vaccine. That technology was published in 2003, but it sat there for 11 years because nobody cared about it. The model says you develop it at a research institute, in this case the NIH or an academic lab, and then you wait for a multinational pharmaceutical company to come along and license it. Well, they have minimal interests in licensing innovations for these diseases. It was only when things got dire in West Africa that the US government, through BARDA [Biomedical Advanced Research and Development Authority] put up around $100 million, and then Merck, Glaxo, Crucell developed it in record time. By the time the vaccine was available Ebola was gone. So it was an absolute failure of the system. We have a related problem at the Sabin Vaccine Institute. We need financing to advance these vaccine studies beyond Phase 1. Our product development partnership at Sabin represents an additional actor. We can't wait for the multinationals. It's not that they are bad guys, in fact the entire USAID NTD Program relies on their generous donations, but we can't rely exclusively on them for next generation innovations.

Q: Is most of the NTD research occurring on the prevention side or the therapeutic side?

PH: If you look at the 20 or so PDPs [Product Development Partnerships], most are developing small molecule therapeutics. Vaccines tend to take a lot longer to develop and pose greater challenges for an investor. If it is a preventive vaccine immunizing small children the safety bar is set pretty high, and rightfully so. The complexity of manufacturing is also higher for vaccines than for small molecule drugs.

Q: So, then, what drew Big Pharma to develop a dengue vaccine?

PH: Well, this is one of the few diseases where Big Pharma is actually competing. You might ask why. It is widely occurring among wealthy and middle class populations around the world—it's become a huge problem in Singapore, Rio de Janiero, Sao Paulo, all over Jakarta—and so the market is not as depleted as it would be for hookworm schistosomiasis. The latest numbers coming out of Simon Hay's group, who used to be at the University of Oxford, estimates 390 million cases of dengue annually. We are in the midst of a dengue explosion, a pandemic, though some of my colleagues don't like me to use that term.

Q: There was also an outbreak of dengue recently in Hawaii.

PH: Yes, and you have Aedes mosquitoes in the US Gulf Coast, as well. And it's not only dengue now. We are also seeing an influx in the US of several arboviruses, the two latest being the Chikungunya virus and the Zika virus. Zika is rapidly spreading across Latin America and the Caribbean where it is going to pose huge maternal-child health risks, as well as damaging the region economically.

Q: What specific design challenges are there in making a dengue vaccine?

PH: With dengue you have four serotypes. The severe form, which causes dengue shock syndrome or dengue hemorrhagic fever, often happens when you get exposed to one of the serotypes previously and you get a second one on top of it. What this means is that in a vaccine you have to get equal immunity to all four serotypes at the same time. That has been a challenge scientifically.

Q: In general, is it harder developing vaccines for tropical diseases due to the nature of the pathogens?

PH: It can be. Getting the immune system to combat an animal, which is basically what a worm is, can be very challenging. But we are making progress. Our hookworm vaccine candidate is in clinical trials in Brazil and Africa. And our vaccine for schistosomiasis is also in clinical trials.

Q: What do you do as US Science Envoy?

PH: We're looking at building vaccine capacity in the Middle East and North Africa. The next wave of epidemic infections could arise out of ISIS-occupied areas. All of the things that caused Ebola to break out in Liberia, Sierra Leone, are now in place in conflict areas of Syria, Iraq, Libya, Yemen. Southern Europe has also become a big global hot spot.

Q: What's occurring in Southern Europe?

PH: We have seen a re-emergence of malaria in Greece, dengue in Portugal and West Nile virus in Spain and Italy, and schistosomiasis in Corsica. Is it because of diseases coming over from the Mediterranean or from the Middle East? Is it climate change? If you talk to climate change scientists, they say next to the Arctic, Southern Europe is the next shoe to drop. Or is it the economic downturns in Southern Europe? Or a combination of these forces?

Q: Finally, any reactions to President Obama's reference to malaria at the SOTU?

PH: Our last two US Presidents, both President George W Bush and President Obama, have been really strong on combating global infectious diseases. It is one of the few global issues where there is wide agreement on both sides of the aisle. From my 11 years in Washington DC when I was chair of microbiology at George Washington University I learned that bipartisan support is about the only way to accomplish big things in the US Government. And the results have paid off in terms of public health. A 2015 Lancet paper from the Global Burden of Disease Study found that through US Government initiatives, together with the Global Fund to Fight AIDS, TB, and malaria, we're turning the corner of HIV/AIDS in Africa and decreased malaria cases and deaths by about one-third. We also made big strides towards eliminating some of the NTDs such as lymphatic filariasis and trachoma. We're talking about hundreds of thousands of lives saved annually. There's also a return on investment, as these diseases hinder economic development. All of this should be better highlighted as a source of pride for all Americans!

(Photos credit: Baylor College of Medicine)

How to cite:

McEnery, Regina. Of Pathogens and Poverty. Eureka blog. Jan 20, 2016. Available: https://eureka.criver.com/of-pathogens-and-poverty/