Global Health
A new vaccine could vanquish a major cause of deadly diarrheal disease
August 7, 20267:36 AM ET
Joseph Kim
A medical illustration depicts the Shigella bacteria, a leading cause of diarrheal disease.
Smith Collection/Gado
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Smith Collection/Gado via Getty Images
Diarrhea has been a headline story in the United States this summer, with thousands of cases of explosive diarrhea traced to Cyclospora from tainted lettuce –- and the first two deaths from the outbreak now confirmed in Michigan
In other parts of the world, diarrhea is a constant — and deadly — threat. Over 1 million people die from diarrheal illness such as dysentery every year. Nearly half of them are children under age 5. Chad has the highest rate of childhood deaths: roughly 1 in 140 children under 5 die each year.Â
In the world of public health, however, the disease often does not get the attention it deserves. It’s because of what researchers call the “poo taboo” –- people just aren’t comfortable talking about diarrhea
Now a vaccine candidate offers a new hope
“Rigorous” trial, “remarkable” response
The vaccine is called WRSs2 –- named after the Walter Reed Army Institute of Research. It was tested jointly at Cincinnati Children’s Hospital Medical Center and the Emory Vaccine Center’s Hope Clinic in Atlanta. The results, published in The Lancet Infectious Diseases this summer: It was 89% effective at preventing one of the leading causes of diarrheal deaths, shigellosis
The study recruited 108 adults. Half received the vaccine — a weakened version of the shigella bacteria suspended in a liquid — almost like a yogurt. The dose is a tad less than a shot-glass worth taken twice a month apart. The other half got doses of salt water
The weakened bacteria is strong enough to bring on an immune reaction but shouldn’t make anyone really sick, says Dr. Robert Frenck, a professor of pediatrics at Cincinnati Children’s and director of its Center for Vaccine Research, who co-led the trial
Even though the number of trial participants were relatively small, that “rigorous” setup also makes the 89% figure harder to shrug off, says Dr. Kawsar Talaat, an infectious disease physician and vaccine scientist at the Johns Hopkins Bloomberg School of Public Health. Deliberate exposure is a brutal test — in this trial, 81% of the placebo group got sick, experiencing diarrhea and fever in some cases before receiving antibiotics
“So the fact that the vaccine prevented almost 90% of the illness is really remarkable.” she says. “It’s the best efficacy we’ve ever seen.”
Talaat runs studies of her own but was not involved in this trial
Frenck thanks the volunteers who contributed to the study. He says they were paid about $250 a day for roughly a week for the trial, and took a quiz ensuring they knew the risks. While it might not be for everyone, he says the volunteers made a swift and efficient trial possible rather than enrolling thousands and waiting for them to naturally get infected — and he notes their commitment is critical to the vaccine effort
A scourge for children
“Throughout the world, diarrheal illness is the second leading cause of death of children,” Frenck says. “And Shigella is one of the more common causes of bacterial diarrhea.” It’s spread through contaminated food and water. Cases are more common in areas with poor sanitation
The children who survive don’t always recover fully. Kids who get Shigella often slip off their growth curves and never quite catch up
“If somebody develops Shigella, then they develop prolonged diarrhea, more hospitalization, more malnutrition and cognitive impairment,” says Dr. Jahangir Hossain of the Gambia Medical Research Council Unit at the London School of Hygiene & Tropical Medicine. The peak of risk, he says, arrives between 12 and 23 months of age
Hossain has spent his career battling shigellosis cases since the 1990s, first in Bangladesh and now in West Africa. At the International Centre for Diarrhoeal Disease Research in Dhaka, where he started out, sometimes 800 diarrheal patients would come in a day, he says
“A Shigella patient comes with bloody diarrhea. They develop fever, and abdominal pain,” he says. “Definitely it is emotional for every doctor facing a patient coming with Shigella and malnutrition.” Families often travel one to three hours to reach a clinic, he says, and the diagnostic labs that American hospitals take for granted mostly aren’t there. The treatment is antibiotics, but with resistance reaching over 80% for some antibiotics in some regions, efficacy can vary widely
No Shigella vaccine has ever been licensed, despite more than 100 years of research. Prior candidates topped out well below WRSs2’s efficacy: one had 74% in young adults but no protection in younger children; an Israeli vaccine managed 28% overall; WRSs2’s precursor, WRSs1 had 40% and more side effects
“It is very good efficacy,” Hossain says. “Usually WHO wants 60% efficacy and then it is fine — but it is 89% efficacy. It is a good hope.”
But he sounds a cautionary note about the study: “It is a small trial, and it is only the adult age group.” Hossain wants to see larger trials happen and see if it works in young children
A timely trial
Dr. Hossain notes that the prospect of a vaccine is especially critical because increasing antibiotic resistance has complicated shigellosis treatment
“The biggest problem is antimicrobial resistance,” Hossain says. “Usually we give antibiotics — ciprofloxacin, then azithromycin, and ceftriaxone — but sometimes it does not work. In some countries, especially in South Asia, even ceftriaxone is resistant.” Patients infected with antibiotic resistant Shigella, therefore, are often sick longer and are at higher risk of dying
Talaat sees the same trend and highlights a precedent for what a vaccine can do about it. “As these organisms become harder and harder to treat, the need for a vaccine also increases,” she says. “We saw it with typhoid — there’s some typhoid that’s almost impossible to treat with antibiotics now.” She says if vaccines were to prevent the infection themselves, less antibiotics will be used which will in turn decrease the amount of resistant strains
The vaccine is not side-effect free. Over half reported a headache and about 45% of recipients had some diarrhea after their dose. But no one was hospitalized from the vaccine. The authors called the safety profile acceptable while noting more work will be done to hone the vaccine’s safety-efficacy balance — vaccines often have a tradeoff of more side-effects with a higher dose for a stronger efficacy
What’s next
WRSs2 is protective against a single species, Shigella sonnei. While one of the most common causes of diarrheal deaths, it’s part of a group of triggering bacteria
“The holy grail — the thing that would be perfect — would be a vaccine that would control ETEC [enterotoxigenic E. coli], Campylobacter and Shigella,” Frenck says. “Then you’d be able to prevent all these with one or two administrations.”
Frenck imagines a combination vaccine that would protect against all the major bacterial causes of diarrheal deaths, albeit likely not cyclosporiasis
There’s a practical reason for making it a combination vaccine too, Talaat says. “Kids get a lot of vaccines,” so Talaat says it’s easier to add one combination vaccine rather than several into the schedule — like the MMR or Tdap vaccine
Hossain is more cautious about whether making it a combination will impede vaccine development
“Combination is good — if it’s possible to make it in a realistic way,” he says. But he notes these vaccine trials have been ongoing for decades and worries if researchers “combine many serotypes and many pathogens together, it might be practically difficult.”
“We cannot delay — we need something immediately,” Hossain says
Regardless of whether it is a combination vaccine or not, all agree the next step is making sure it works in children. The people who die of and are affected by shigellosis are overwhelmingly small children in the global south, who, the authors say, have poorer immunity than well-developed and nourished children. The paper — like Hossain — calls for trials in places where poor sanitation is a factor in high rates of diarrheal disease, targeting particularly young children next
“The most important population for a potential Shigella vaccine would be children under 5,” Talaat says. “We want a vaccine that’s safe and effective in children as young as one year of age, or even younger.”
For Frenck, that’s the whole point. He says that vaccines are needed to achieve his goal of “really reducing deaths of children in the world.”
- diarrhea
