The World Health Organization is in the process of deciding how to prioritize vaccines for kids in low- and middle-income countries.
In the middle of the 20th century, an estimated 4.5 million children under the age of five per year perished from diarrhoea. Although oral rehydration therapy saved lives, it does not stop infection.
Millions of children in low- and middle-income nations continue to have frequent episodes of diarrhoea, which weakens their bodies and makes them more susceptible to malnutrition, stunted growth, and a variety of illnesses.
In tests using human cells and mice, scientists at Washington University School of Medicine in St. Louis have figured out how some forms of diarrhea-causing Escherichia coli (E. coli) bacteria harm the intestines to induce malnutrition and stunting. Additionally, they’ve demonstrated that immunisation against an E. coli toxin protects young mice from intestinal injury.
According to the research, a vaccine against this strain of E. coli could support efforts made around the world to ensure that all children not only survive until age 5, but also thrive.
The study can be found in Nature Communications online.
Fleckenstein researches the impact of enterotoxigenic E. coli (ETEC) on kids who live in areas where the bacteria are common. Although E. coli is a prevalent cause of diarrhoea throughout the world, strains found in high-income nations like the United States often don’t carry the same toxins as those in low- and middle-income nations. And that might be the deciding factor.
One of the two ETEC toxins, heat-labile toxin, was found to do more than just cause a case of the runs, according to a study done in 2020 by Fleckenstein and Alaullah Sheikh, Ph.D. Additionally, the toxin alters the gut’s gene expression by turning on more genes that aid in the bacteria’s attachment to the gut wall.
The toxin suppresses a wide range of genes connected to the lining of the intestines, where nutrients are absorbed, according to research by Fleckenstein and Sheikh. Microvilli, which resemble the bristles on a brush, are firmly packed together to form the intestine’s so-called brush border.
The brush boundary broke down when Fleckenstein and Sheikh exposed clusters of human intestinal cells to the toxin.They are short, floppy, and sparse instead of nice and tight and upright with thousands of microvilli per cell, similar as if you had pulled out most of the bristles and what was left was sort of raggedy, said Sheikh. The body’s capacity to absorb nutrients would suffer just from that.
However in addition, researchers discovered that genes involved in the absorption of particular vitamins and minerals were also downregulated. That might account for some of the micronutrient shortages we observe in kids who are exposed to these bacteria frequently.
Children in low- and middle-income nations frequently have diarrhoea, which increases the risk of stunting and malnutrition.
Researchers observed that one infection with E. coli that produces toxins was enough to harm the brush boundary when they studied young mice. On the other hand, recurrent infections caused severe intestine damage and slowed growth. Puppies infected with an E. coli strain devoid of the toxin did not exhibit any intestinal damage or stunting.
Fleckenstein and Sheikh reasoned that if the toxin is the issue, an immune response that neutralises the poison may stop the long-term damage. They administered the toxin vaccination to nursing mice moms to find out.
Although suckling mice are too young to get an immunisation, their immunised mothers create antibodies that are passed on to the pups through breast milk. Infant mice whose moms had received vaccinations looked to have healthy intestines, according to the researchers. This implies that immunisation can guard against intestinal damage that causes malnutrition.
This is support for creating a vaccination against this particular strain of E. coli, according to Fleckenstein.
The effects of being infected repeatedly as a youngster are lifetime.
Children may be shielded from the long-term impacts and have a higher chance of living long, healthy lives if vaccination is combined with initiatives to improve sanitation and access to clean water.