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Targeting an Ancient Killer

A Deadly Worldwide Toll

Play this scene over tens of thousands of times in Africa and nearly 90 other devel- oping countries, and you start to appreciate the public burden posed by malaria today. The World Health Organization (WHO) estimates that in 2018 there were 219 million cases of malaria, and 435,000 people died of this disease.

Nirbhay Kumar, PhD, a professor of global health at Milken Institute SPH, has seen firsthand the devastation the disease can bring to African villages. There, a bite from a mosquito can represent much more than just an annoying itch. It can be a death sentence. Over the years of studying malaria, he has developed a passion aimed at stopping this disease.

“My goal is to eliminate malaria—a disease that kills nearly half a million people a year, the majority of them children living in Africa,” he says. “If we are successful, we will have a long lasting, effective vaccine to combat this ancient disease.”

Kumar, a survivor of malaria, grew up and was educated in India, began his quest to find a way to eliminate malaria back in 1982. He was a young postdoctoral scientist then working at the National Institutes of Health (NIH) in Bethesda, MD, and looking for ways to connect basic science to the public health goal of saving lives. He started researching ways to combat the disease, first at NIH and then at the Johns Hopkins Bloomberg School of Public Health. In 2010, he left Baltimore and continued his malaria vaccine research at the Tulane University School of Public Health and Tropical Medicine.

In September 2018, Kumar joined the faculty at Milken Institute SPH and immediately began to establish his lab and build a secure insectary on the seventh floor of the state- of-the-art GW Science and Engineering Hall. Kumar has assembled a team, and now they are forging ahead on a $1.9 million NIH-funded study to develop a combination vaccine capable of eliminating malaria.

Mosquitoes have been spreading the parasite that causes malaria since time immemorial. Yet, in the modern world, developed coun- tries have used recent scientific advances and strong public health systems to make great progress against this disease. Consider, if you will, a surge in malaria cases that occurred in Mexico in the 1990s.

Milken Institute SPH Global Health Professor Carlos Santos-Burgoa was on the frontlines of the effort to tamp down that surge, first as the dean of the School of Public Health of Mexico and then as the director general of the Health Environment and Work Institute. Santos- Burgoa helped spearhead a partnership in which public health officials, researchers and community members established an aggressive program that paired treat- ment with the elimination of the vector’s breeding grounds.

“It was a public health success story,” he says, pointing out that the number of cases of malaria dropped after the intervention and remains low to this day.

The Quest to Find a Vaccine

Yet, despite the advances against malaria in much of the developed world, progress has stalled in regions like Africa. According to the World Health Organization (WHO), the African continent continues to shoulder a dispro- portionately high share of the world’s malaria burden. In 2017, the region accounted for 92 percent of all malaria cases and 93 percent of malaria deaths.

Over the years, Kumar has developed a great appreciation for P lasmodium, a wily parasite that continues to evolve resistance to the most powerful anti-malarial drugs. Indeed, according to new reports published this summer in T he L ancet, malaria drugs are now failing at an alarming rate in Southeast Asia, and the worry is that the resistance will spread. In addition, while insecticide spraying and treated bed nets can help reduce malaria transmission, mosquitoes are increasingly impervious to DDT and other pesticides.

Kumar knew that in underdeveloped regions of the world like Africa, stamping out the disease would require more than the usual array of weapons that were currently being used. At Hopkins and then later at Tulane, Kumar focused on devel- oping extra firepower to deploy in this war.
He started working on a transmis- sion-blocking vaccine, or TBV, and created one aimed at stopping the transmission
of the parasite from infected people to mosquitoes.

But this vaccine does not directly protect people against malaria. Instead, it takes a community-based approach to malaria control. Healthy people would get the vaccine, and if they are bitten by an infected mosquito and develop malaria later on, the vaccine would prevent the parasites from being passed on to other mosquitoes. In turn, that block means that the disease is not passed on to other healthy people in the community.

With this strategy, fewer and fewer mosquitoes are infected with malaria If TBVs were 100 percent effective in blocking the spread of malaria, the battle would be over. However, in some cases, TBVs do not work effectively, and when the parasites are transmitted, the deadly cycle of new infections continues.

A Promising ‘Cocktail’ Approach

To close that gap, Kumar and his team are now adding another vaccine to the mix to create a combination approach—one that would prevent not just transmission from infected people to mosquitoes but the other way around as well. “Combining two vaccines in a cocktail could potentially stop the cycle that results in hundreds of millions of malaria cases every year,” Kumar says. He has already started testing this combination vaccine in mice and will know by the end of the year if it works.

Still the team is a long way off from the next step, an effective and safe combina- tion vaccine that can be given to people. Once the testing in animals is complete, the researchers will seek a partnership with a company to produce a vaccine for testing in clinical trials—a process that can take years.

The goal is to produce a safe and effective combination vaccine that can be ushered through the regulatory hurdles and on
to the clinic, where it can provide some protection to the young girl in Zambia and many others in Africa, India and other parts of the world where malaria still poses a threat. “There are more than 200 million cases of malaria today in countries around the world,” he says. “We want to bring that number down to the point where elimina- tion of malaria is within sight.”

Fighting Emerging Disease Threats From the Field to the Lab

Professor of Global Health Christopher Mores has a bag packed in case he must fly out to help contain a disease threat like the Ebola outbreak that in August of this year began spreading in the Democratic Republic of Congo (DRC). “When I’m not putting out fires, you can find me in the lab,” says Mores, who is on the frontlines of research to stop viruses that can cause epidemics like Ebola, chiku- ngunya and Zika.

Mores, who joined Milken Institute SPH in September 2018, previously served as a professor at the Louisiana State University in Baton Rouge and as department head of the Virology and Emerging Infections at the U.S. Naval Research Unit No. 6 in Lima, Peru. He responded to the 2014 Ebola crisis in Sierra Leone. Since arriving in DC, Mores has been setting up a state-of-the-art Biosafety Level 3 laboratory (BSL-3) on the seventh floor of the GW Science and Engineering Hall. It is the only such high-contain- ment laboratory at GW, and once it goes hot, Mores will kick off a study aimed at supporting a vaccine for Chikungunya, a mosquito-borne viral disease that first emerged in Tanzania but now infects people in more than 60 countries in Asia, Africa, Europe and the Americas.

Mores and his team are part of a larger effort supported in part by the Coalition for Epidemic Preparedness Innovations (CEPI) to develop and bring to market a vaccine that would protect people against chikungunya. Under the partnership agreement lead by the biotech company Themis Bioscience, CEPI will provide up to $21 million for Phase 3 clinical testing of the vaccine.

CEPI is targeting chikungunya and 11 other diseases, including Ebola, because they have the potential to trigger a world- wide pandemic. In the BSL-3, Mores and his team will give antibodies from human volunteers that received the experimental chikungunya vaccine to mice to see if it will protect them from infection, a key step in proving a vaccine is effective. At press time, Mores is also monitoring the rapidly moving situation in the DRC. In response to CDC requests, he has been in touch with public health workers fighting to contain the deadly outbreak of Ebola, which has now been classified as a global emergency by the World Health Organization. “If they need more boots on the ground, I’m ready,” he says.

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