Have you ever heard of human challenge studies (where people are intentionally infected with pathogens to test drugs and vaccines)? I hadn’t either but the practice has a long history and in the past few decades, its become much more mainstream.
“Human challenges date back to the 18th century and the first vaccine, when English physician Edward Jenner attempted to persuade the world that infecting a person with harmless cowpox could prevent disease from its dreaded cousin, smallpox. Jenner scraped “matter” taken from a cowpox sore on a dairymaid’s hand into the skin of 8-year-old James Phipps, the son of his occasional gardener, and then repeatedly tried to infect him with smallpox. “Poor Phipps,” as Jenner later referred to the boy, never came down with smallpox. Jenner reported that some 6000 other people were vaccinated and then the “far greater part of them” were challenged with smallpox. Two centuries later, the vaccine Jenner pioneered eradicated the virus from the human population.”
Thankfully, there are now stricter safety procedures and new ways to weaken pathogens so the risks are reduced. This is giving new life to human challenge trials at universities and at the government level as researchers feel they are a powerful tool for studying diseases and potential therapies. In fact, hVIVO in London now specializes in human challenges. Currently, there are challenge studies where people are being deliberately infected with malaria, influenza, shigella, dengue, norovirus, tuberculosis, rhinovirus, Escherichia coli, typhoid, giardia, and campylobacter.
More from the article:
“The risks are obvious: Otherwise healthy people can suffer harm and, if the disease is contagious, potentially sicken others. But if done right, the benefits are compelling, a growing number of researchers say. The standard pharmaceutical development path for products that target pathogens moves slowly from studying safety, dosing, and biological responses in hundreds of people to an expensive efficacy trial with thousands of participants at high risk of becoming naturally infected. Human challenge studies, which only involve a few dozen volunteers, speed the process of deciding whether to scrap or pursue a promising lead, saving time and money. And tests that intentionally infect people can quickly and efficiently flag potential side effects, advocates say. “You certainly can’t do a $100 million study for every candidate vaccine that appears safe and immunogenic,” says Mark Mulligan, a molecular virologist who heads the vaccine center at Emory University in Atlanta and does human challenges with norovirus and tuberculosis.”
Insights from human challenges go far beyond drugs and vaccine development and are sometimes the only way to answer critical questions:
- In 1974 the U.S. National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland, awarded the University of Maryland a half-million dollars to create a new vaccine testing center, headed by Levine, that would recruit volunteers from colleges and church groups. The center began with influenza challenges, which were conducted in refurbished rooms at the University of Maryland Hospital that had bunk beds for 22 people and an isolated air system. The researchers had little trouble recruiting volunteers, who received the same fee as jurors ($20 a day), which the researchers deemed fair but not coercive. Volunteers had to take a written test to prove that they understood the risks.
- Two years later, at the request of NIAID’s Cholera Panel, Levine’s group added challenges with V. cholerae to test cholera vaccines. The cholera studies led to the scuttling of a leading vaccine candidate, a finer understanding of effective immune responses, and, ultimately, compelling evidence that a different cholera vaccine worked. In June, the U.S. Food and Drug Administration (FDA) will consider licensing a cholera vaccine for travelers based largely on Levine’s work. This is the most influential role the human challenge model has ever played in the FDA approval process.
- In 1985, a team led by Ripley Ballou began human challenges with malaria at the Walter Reed Army Institute of Research (WRAIR) in Silver Spring, Maryland. That program pioneered advances that have lowered the risks of human malaria challenges and increased the benefits, opening the way to the trials flourishing today in several places.
- Ballou, the head of vaccine R&D in the United States at GlaxoSmithKline (GSK), and his team bred mosquitoes in an insectary, and then fed them on human blood infected with the malaria parasite Plasmodium falciparum. He and five other Army colleagues each took a candidate malaria vaccine and then let five infected mosquitoes—which their group had determined was the number needed to reliably transmit the parasite—lunch on their arms.
- In the 1980s and 1990s, Frederick Hayden of the University of Virginia School of Medicine in Charlottesville conducted challenge studies with influenza that helped speed the development of Tamiflu and Relenza, drugs that have become the mainstays of treatment.
- In June 2013, Anna Durbin of Johns Hopkins Bloomberg School of Public Health in Baltimore, began challenging volunteers who had received a dengue vaccine made by NIAID. Instead of using wild-type dengue virus, Durbin and her Hopkins team infected people with a naturally weak isolate of the virus that had been further attenuated in the lab. As she and her group reported online on 16 March in Science Translational Medicine, none of the 21 people who received the vaccine became infected after the challenge, but all 20 controls had the virus in their blood, and 16 developed a rash. Based in part on these results, the Butantan Institute in São Paulo, Brazil, this year launched an efficacy trial of the vaccine that plans to enroll 17,000 people.
Since the mid-1990s, when the FDA deemed organisms used in challenge studies to be experimental medicines, the trials have face greater regulatory scrutiny. Researchers must submit Investigational New Drug applications before conducting trials, institutional reviews have intensified, and safety measures are much stricter, too.
Intentionally infecting people is an odd pursuit for a doctor. Would you sign up to allow someone to purposely infect you with Dengue fever? Or influenza? I’m a healthy girl, but I can’t imagine sequestering myself in a hotel, even on someone else’s dime, for 9 days after being exposed to something like malaria.
What are your thoughts?
Via HealthNut News