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A medical illustration depicts the Shigella bacteria, a leading cause of diarrheal disease.
Smith Collection/Gado via Getty Images
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Smith Collection/Gado via Getty Images
This summer, diarrhea made headlines in the United States with thousands of cases linked to Cyclospora from contaminated lettuce, resulting in the first two confirmed deaths in Michigan. Globally, diarrhea remains a persistent and deadly threat. Each year, over 1 million people succumb to diarrheal diseases like dysentery, with nearly half of the victims being children under five. Chad records the highest rate of childhood deaths, with approximately 1 in 140 children under five dying annually.
Despite its impact, diarrhea often receives inadequate attention in public health discussions due to the “poo taboo”—a reluctance to discuss the topic openly.
However, a new vaccine candidate brings hope.
“Rigorous” trial, “remarkable” response
The WRSs2 vaccine, developed by the Walter Reed Army Institute of Research, underwent trials at Cincinnati Children’s Hospital Medical Center and the Emory Vaccine Center’s Hope Clinic in Atlanta. This summer, The Lancet Infectious Diseases published the results, showing 89% efficacy against shigellosis, a leading cause of diarrheal deaths.
The study involved 108 adults, with half receiving the vaccine—a weakened form of the shigella bacteria in a liquid form, similar to yogurt. The dose, slightly less than a shot glass, was administered twice a month apart. The other half received salt water.
According to Dr. Robert Frenck, a professor of pediatrics at Cincinnati Children’s and co-leader of the trial, the weakened bacteria is designed to trigger an immune response without causing illness.
Dr. Kawsar Talaat, an infectious disease specialist at the Johns Hopkins Bloomberg School of Public Health, noted that despite the small number of participants, the trial’s rigorous design makes the 89% efficacy difficult to dismiss. In this trial, 81% of those in the placebo group fell ill, experiencing diarrhea and fever before receiving antibiotics.
“The fact that the vaccine prevented almost 90% of the illness is truly remarkable,” Talaat commented. “It’s the best efficacy we’ve ever seen.” Talaat was not involved in this trial.
Dr. Frenck expressed gratitude to the trial volunteers, who were compensated about $250 a day for a week and took a quiz to ensure they understood the risks. Their involvement allowed for a rapid and efficient trial, eliminating the need to wait for natural infections in a larger group.
A scourge for children
Dr. Frenck highlighted the global impact of diarrheal illnesses as the second leading cause of death in children, with Shigella being a common bacterial cause. The disease spreads through contaminated food and water, particularly in areas with poor sanitation.
Children who survive Shigella often do not fully recover, falling behind on growth curves.
Dr. Jahangir Hossain from the Gambia Medical Research Council Unit noted that children aged 12 to 23 months face the highest risk. Hossain, who has worked on shigellosis cases since the 1990s, described the emotional toll on doctors treating patients with Shigella and malnutrition.
At the International Centre for Diarrhoeal Disease Research in Dhaka, Hossain observed days when up to 800 diarrheal patients sought treatment. The lack of diagnostic labs in some regions, combined with antibiotic resistance, complicates treatment.
No Shigella vaccine has been licensed despite over a century of research. Previous candidates achieved lower efficacy levels than WRSs2, which reached 89%. An earlier candidate achieved 74% efficacy in young adults but failed to protect younger children, while an Israeli vaccine showed a 28% overall efficacy. WRSs2’s precursor, WRSs1, had a 40% efficacy and more side effects.
“The efficacy is very good,” Hossain remarked, noting that the WHO considers 60% efficacy acceptable. However, he cautioned that the trial was small and only involved adults, calling for larger trials in children.
A timely trial
Dr. Hossain emphasized the urgency of a vaccine due to rising antibiotic resistance in shigellosis treatment. “The biggest problem is antimicrobial resistance,” he said. In some regions, even ceftriaxone is ineffective against resistant Shigella strains, leading to longer illnesses and higher mortality risks.
Talaat echoed these concerns, pointing to typhoid as an example of how vaccines can reduce antibiotic use and, consequently, resistant strains.
While the vaccine is not without side effects—over half reported headaches and 45% experienced some diarrhea—no hospitalizations were linked to the vaccine. The researchers deemed the safety profile acceptable but acknowledged the need for further work to optimize the balance between safety and efficacy.
What’s next
WRSs2 targets a single Shigella species, Shigella sonnei, which is among the most common causes of diarrheal deaths. Dr. Frenck envisioned a combination vaccine to protect against other major bacterial causes of diarrhea, such as ETEC and Campylobacter, though not cyclosporiasis.
Talaat noted the practicality of a combination vaccine, as it could be incorporated into existing schedules like the MMR or Tdap vaccines. However, Hossain expressed caution, citing the challenges of combining multiple pathogens into one vaccine.
Despite these challenges, all agree that the next step is to test the vaccine in children, particularly those in regions with poor sanitation, where diarrheal diseases are prevalent. “The most important population for a potential Shigella vaccine would be children under 5,” Talaat said. “We want a vaccine that’s safe and effective in children as young as one year of age, or even younger.”
For Dr. Frenck, the ultimate goal is clear: reducing child mortality worldwide through effective vaccines.

