More than one billion people in the world are currently afflicted by one of the seventeen diseases classified as Neglected Tropical Diseases (NTDs), 500 million of which are children. In Texas alone, more than one million families with children are affected by NTDs. The Texas Children’s Hospital Center for Vaccine Development is the first center in the world dedicated primarily to the discovery and development of vaccines against NTDs, and is making new strides every day.
Established in collaboration with Texas Children’s Hospital, the Sabin Vaccine Institute, and Baylor College of Medicine, the Center moved from Washington D.C. to Houston, TX three years ago. After the development of vaccines against hookworm and schistosomiasis, currently in clinical trials, the center is now focused on leishmaniasis, Chagas disease, and Severe Acute Respiratory Syndrome (SARS).
“We have a pretty diverse portfolio of diseases that we are developing vaccines and a set of new interventions for,” said Associate Dean of the National School of Tropical Medicine, Dr. Maria Bottazzi to BioNews Texas. “We are the only organization that is primarily dedicated to the development of vaccines for NTDs, so most likely you won’t find anybody else who is doing this.”
Why Pediatric Neglected Tropical Diseases?
Despite the fact that most NTD patients are adults, researchers have turned their focus to developing vaccines and therapies for children, since NTDs strike the population very early in their lives. Some NTDs can affect babies that are just weeks old and even fetuses through their infected mothers. “Even when you are infected as a kid, you will continue to suffer from it throughout your life. It will most likely persist until adulthood,” explained Dr. Bottazzi.
If a person is infected with an NTD as a child, the disease will most likely impact that person’s entire life, starting with the growth, learning, and intellectual capabilities of the individual, as well their transition into adulthood. According to the Center, an NTD patient who carries a disease from the time they are a child is highly unlikely to become a productive or healthy adult.
“Usually you have little kids that if you don’t treat, or if you don’t prevent these diseases early, they are stunted kids, diminished compared to healthy kids, and they actually don’t do good in school, so their intellectual capacities are all so vastly reduced, ” said Bottazzi. “And this eventually leads to a low capacity of being a worker or having a productive adult life.”
NTDs are chronic and debilitating conditions that are not only caused by poor environmental conditions, but also lead to perpetual poverty, thus creating a vicious cycle that is difficult to break without medical intervention. “NTDs have a common set of characteristics in addition to their link with poverty because of their long term effects on child development, worker productivity and the health of girls and women,” said Dr. Peter Hotez, the founding dean of the NSTM, President of the Sabin Vaccine Institute, Texas Children’s Hospital Endowed Chair in Tropical Pediatrics, and world-renowned advocate and researcher of Neglected Tropical Diseases.
NTDs disproportionately affect the female demographic and women are by far the most affected gender. Some diseases classified as an NTD can get progressively worse during a pregnancy or be congenitally transmitted, Chagas disease being an example. “When you develop a vaccine, there’s a very specific process, so you need to make a lot of evaluations using the adult population,” explained Dr. Bottazzi. “But the intention is that some of the disease vaccines are not only for pediatric use, but also for the entire community.”
Depending on the purpose of the vaccine, it will typically be designed for different kinds of patients. For example, the Chagas disease vaccine currently under development is meant for adults that already show signs of cardiomyopathy, which means that the goal is to treat the cardiac condition. In this case, the choice for developing a therapeutic vaccine is based on the degree to which the disease and its symptoms are hard to identify and prevent, “so it is better to give them tools that can be complemented and that can be able to cure them.”
In cases of preventative vaccines, such as for Schistosomiasis, the idea is to reach the population as early as possible. After performing Phase 1 clinical trials for safety in both the United States and Brazil, the Schistosomiasis vaccine will enter its next testing phase before the end of the year, becoming the fourth vaccine developed within the Center’s partnership. New trials are planned to begin in Africa as well.
When Prevention is No Longer an Option
In addition to efforts focused on disease prevention, the NSTM is also engaged in the treatment of NTDs in currently diagnosed patients, a reality for more than one billion people throughout the world. The first step is to raise awareness and increase general knowledge among both the general population and medical community as well.
“We have four missions, including extramural support for our vaccine development program and program on epidemiology and diagnostics, but also a new diploma in tropical medicine for physicians to teach them about these diseases and how to recognize them, as well as a Summer Tropical Medicine Institute,” said Dr. Hotez. “We also have a Tropical Medicine Clinic for residents of Harris County, who often acquire these diseases in Houston and a NTD Policy Program with the Baker Institute at Rice University.”
Dr. Bottazzi believes that most physicians know how to treat children for NTDs, since some of the diseases cannot be treated until a certain age, for example, or among pregnant women who cannot be treated until a certain trimester in their pregnancy. “But the reality is that the course of treatments available right now don’t have a real impact on these populations because you need to be very cautious and physicians need to be mindful of the individuals that they are treating because some drugs also don’t work if people are already chronically infected,” Dr. Bottazzi said.
As a result, Bottazzi believes the only way to increase successful treatment of NTDs is to create new interventions in order to complement the current courses of treatment already available. The main purpose of NSTM is to engage in an integrated set of interventions, which in turn will allow for a greater chance of reaching the population. “A single strategy is usually not successful. That is why you need to look for alternatives and to work on an integrated manner.”
One of the ways to succeed is to create “programs of mass drug administration to target NTD, while simultaneously developing new drugs and vaccines,” as Dr. Hotez believes. This strategy defined by the NSTM calls for a better understanding within communities of which diseases pose the most significant threat, including its symptoms, risks, and markers, as well as more investment in research and development, in order to develop better interventions.
“So certainly the influx of new funding to address these diseases reached what we call the 10-90 gap, meaning that usually 10 percent of the world’s diseases is where we see most of the research and development funding, while the other 90 percent are the diseases that most impact the world population and are the ones that are receiving the least amount of research and development funding. I think it must be a better balance in how much funding has to be injected into discoveries that have a global and public health impact,” explained Dr. Bottazzi.
While tropical diseases are indeed neglected, “they are not rare diseases,” notes Dr. Hotez. And while they are in fact driven by poverty, they can also be found in rich, developed countries as well. “Somewhat paradoxically, we have found that many of these highest disease burden NTDs occur predominantly in the largest emerging market economies that comprise the group of 20 nations (G20), in addition to Nigeria, which also has one of the world’s largest economies.”
More than the climate or any other factor, poverty is determinant to the dissemination of NTDs. Both developing and first-world nations alike — the United States included — have not been able to eradicate poverty.
“We have 20 million Americans living in extreme poverty, one-half of the U.S. poverty level, and around 4 to 5 million Americans living on less than $2 per day, a global benchmark. They are mostly in Texas and the Gulf Coast and include Chagas disease, cysticercosis, congenital CMV infection, toxocariasis, toxoplasmosis, trichomoniasis and dengue/WNV,” explained Dr. Hotez.
More than one million families are afflicted by an NTD in Texas, one of the reasons why the Center has been dedicated to finding widespread NTDs in Houston and other Gulf Coast Areas. According to Dr. Bottazzi, this is a new phenomenon. However, traditionally, scientists were not looking for NTDs in countries such as the U.S., and instead regarded NTDs as a set of diseases found in other countries and focusing their resources in locations such as Sub-Saharan Africa.
The solution outlined by Dr. Hotez lies in the concept and policy framework of “blue marble health,” which consists of a dialogue between the G20 countries synthesizing health goals with economic, environmental, and social priorities in order to accelerate poverty reduction efforts and focus on NTD. He believes that if all of the G20 countries engage in the goal, the world’s NTD would be reduced to one-half or, in some cases, may even be eliminated.
“Blue marble health connects countries worldwide by recognizing that extreme poverty is a fundamental underlying factor for NTD, regardless of where they occur,” said Hotez, the concept’s author. “G20 countries have an exceptional opportunity to embrace NTD control as a cross-cutting strategy and achieve long-lasting, inclusive prosperity within their societies and lower-income countries.”
Breaking with the Paradigm
Besides the efforts to revolutionize the treatment and prevention of NTDs and being the main institution to focus on these types of conditions in children, the NTSM is also engaged in the purpose of changing the way in which medical research is performed. “We basically take this integrated approach in conjunction with hospitals and product development partnerships models and policy makers and we can address these diseases into an integrated manner,” Dr. Bottazzi explained.
The product development partnership between Texas Children’s Hospital and the Sabin Vaccine Institute “is the model of what you call translational medicine, which is bringing a discovery all the way to the clinic.” What the scientists are trying to accomplish is to open the process of research to the community.
The goal is to learn from each other and see every stage of development of the intervention in development through open access and public publishing. The researchers share the intellectual property so that all areas of studies can advance in order to increase the speed and reach the population earlier and better.
“Is not very easy to accomplish — the usual traditional model is that academics develop discoveries and then biotechnology or biopharmaceutical companies buy the intellectual property and you really don’t hear or see information on how the development is done. Our major achievement is that we are filling a gap that is very hard to actually have people do, especially in this model of academic partnership, from the bench discovery all the way to the clinic.”
The model also relies on involving government and the community on early stages of the process, so that they can have an accelerator, which is the global access. By sharing information, the researchers expect that it will take less time to convince policy makers or public health practitioners to accept an intervention and “that’s why we do a lot of advocacy and policy.”
In this way, the NTSM, which employs approximately 50 scientists and staff members as well as other research teams from national partners, aims to focus their talent and resources on addressing and eventually eliminating NTDs globally. Although they are the only institution primarily dedicated to the development of vaccines for NTDs, the NTSM is one key piece of a larger ongoing effort around the world that will continue to require advocacy, funding, partnership, and research among leaders in science, government, business, and education in order to eliminate the suffering and socio-economic malaise caused by tropical diseases.