A new vaccine candidate could vanquish a major cause of deadly diarrheal disease as thousands of cases of explosive diarrhea linked to Cyclospora from tainted lettuce have spread across the United States this summer, with the first two deaths from the outbreak confirmed in Michigan. The outbreak is the immediate face of a system that lets contaminated food move through the country until people start getting sick and dying. The people at the bottom pay first.
NPR said over 1 million people die from diarrheal illness such as dysentery every year, nearly half of them children under age 5, and that Chad has the highest rate of childhood deaths, with roughly 1 in 140 children under 5 dying each year. Those numbers sit under the polite language of public health, but they point straight at the same old hierarchy: some places get clean water, labs, antibiotics, and clinics, while others get the leftovers and the funerals.
Who Pays for the System
The vaccine candidate 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, showed it was 89% effective at preventing shigellosis, one of the leading causes of diarrheal deaths. The study recruited 108 adults. Half received the vaccine, a weakened version of the shigella bacteria suspended in a liquid, almost like a yogurt, in a dose a tad less than a shot-glass worth taken twice a month apart. The other half got doses of salt water.
Dr. Robert Frenck, a professor of pediatrics at Cincinnati Children's and director of its Center for Vaccine Research, co-led the trial and said the weakened bacteria is strong enough to bring on an immune reaction but shouldn't make anyone really sick. Dr. Kawsar Talaat, an infectious disease physician and vaccine scientist at the Johns Hopkins Bloomberg School of Public Health, said the trial's deliberate exposure made the result hard to dismiss. She said 81% of the placebo group got sick, experiencing diarrhea and fever in some cases before receiving antibiotics. Talaat said, "So the fact that the vaccine prevented almost 90% of the illness is really remarkable." She added, "It's the best efficacy we've ever seen."
The trial itself shows how medicine often works inside the same unequal order it claims to fix. The volunteers were paid about $250 a day for roughly a week and took a quiz to ensure they knew the risks. Frenck said their commitment made a swift and efficient trial possible. The people taking the risk were compensated for a few days; the disease, meanwhile, keeps chewing through children across the world.
What the Clinics See
Frenck said, "Throughout the world, diarrheal illness is the second leading cause of death of children," and, "And Shigella is one of the more common causes of bacterial diarrhea." It spreads through contaminated food and water and is more common where sanitation is poor. That’s the real map here: not just germs, but infrastructure, neglect, and the unequal distribution of safety.
Dr. Jahangir Hossain of the Gambia Medical Research Council Unit at the London School of Hygiene & Tropical Medicine said children who get Shigella often slip off their growth curves and never fully recover. He said, "If somebody develops Shigella, then they develop prolonged diarrhea, more hospitalization, more malnutrition and cognitive impairment." He said the peak risk arrives between 12 and 23 months of age. Hossain said he has battled shigellosis since the 1990s, first in Bangladesh and now in West Africa, and recalled that at the International Centre for Diarrhoeal Disease Research in Dhaka, sometimes 800 diarrheal patients would come in a day. He said, "A Shigella patient comes with bloody diarrhea. They develop fever, and abdominal pain," and, "Definitely it is emotional for every doctor facing a patient coming with Shigella and malnutrition." He said families often travel one to three hours to reach a clinic and that diagnostic labs common in American hospitals mostly are not there. Treatment is antibiotics, but resistance has reached over 80% for some antibiotics in some regions.
No Shigella vaccine has ever been licensed despite more than 100 years of research. Prior candidates topped out below WRSs2's efficacy: one had 74% in young adults but no protection in younger children, an Israeli vaccine managed 28% overall, and WRSs1 had 40% and more side effects. Hossain said, "It is very good efficacy," and added, "Usually WHO wants 60% efficacy and then it is fine — but it is 89% efficacy. It is a good hope." He cautioned that it was a small trial and only in adults.
What They Call a Solution
Hossain said increasing antibiotic resistance makes a vaccine especially important. He said, "The biggest problem is antimicrobial resistance," and listed ciprofloxacin, azithromycin and ceftriaxone as antibiotics that are sometimes ineffective. Talaat said, "As these organisms become harder and harder to treat, the need for a vaccine also increases," and added, "We saw it with typhoid — there's some typhoid that's almost impossible to treat with antibiotics now." She said vaccines could reduce antibiotic use and therefore resistant strains.
The vaccine was not side-effect free. Over half of recipients reported a headache and about 45% had some diarrhea after their dose, but no one was hospitalized. The authors called the safety profile acceptable while noting more work is needed to balance safety and efficacy. WRSs2 protects against a single species, Shigella sonnei. Frenck said, "The holy grail — the thing that would be perfect — would be a vaccine that would control ETEC [enterotoxigenic E. coli], Campylobacter and Shigella," and said that would allow prevention with one or two administrations. He said a combination vaccine could also help because kids get a lot of vaccines. Talaat said it is easier to add one combination vaccine than several into the schedule, like MMR or Tdap. Hossain said, "Combination is good — if it's possible to make it in a realistic way," but warned that combining many serotypes and pathogens could be practically difficult. He said, "We cannot delay — we need something immediately."
All agreed the next step is testing in children. The paper and Hossain called for trials in places where poor sanitation contributes to high rates of diarrheal disease, especially among young children. Talaat said, "The most important population for a potential Shigella vaccine would be children under 5," and added, "We want a vaccine that's safe and effective in children as young as one year of age, or even younger." Frenck said vaccines are needed to achieve his goal of "really reducing deaths of children in the world."