- Cholera affects 3
million to 5 million people globally every year, leading to over 100,000
- Severity of cholera
infection and related deaths is more in persons with blood group O.
- Diarrhea and
dehydration in cholera are
mediated via a signaling molecule in the intestinal cells.
- Cholera toxin
causes excessive levels of this molecule in O blood group persons, leading to
more severe disease.
up To The Study
long it has been known that blood group O
suffer from severe cholera, more likely to be hospitalized
and sadly more likely to die from the disease too. Though Public Health
specialists (epidemiologists) first made this observation nearly four decades
ago, the reasons for that have remained a mystery.
at the Washington University School of Medicine in St. Louis, led by James
Fleckenstein, MD, an associate professor of medicine and molecular
microbiology, attempt in this study to explain why.
‘Mystery of increased cholera deaths in O blood group persons unraveled.’
Stem Cells - The Target Cells of This Study
antigens - A, B, AB and O - are mainly present on the surface
of red blood cells, they also occur on the surface of many other cell types,
including the lining cells of the intestine.
determine the effect of cholera
toxin on intestinal cells carrying different
blood group antigens, Fleckenstein, F. Matthew Kuhlmann, MD, Matthew Ciorba,
MD, and colleagues used clusters of
intestinal epithelial stem cells, called enteroids
, that could be
cultivated in the lab and are capable of differentiating into mature intestinal
University is one of the leading centers to have built a bio bank of intestinal
epithelial stem cells
(enteroids), derived from patients for the purpose of research. Since these clusters of stem cells are derived from
normal intestinal cells from several individuals
, they are better than traditional cell lines
, which are derived from
cancer cells from a single person and may contain mutations that cause them to
behave differently compared to normal cells.
Details of The Study
researchers treated four groups of
enteroids with cholera toxin
- two obtained from people with blood group A and two from people with blood group
O. They then measured the amounts of a
key signaling molecule within the intestinal cells
. Enteroids from the
other two blood types - B and AB were unavailable at the time of the study.
found that levels of the signaling
molecule were roughly twice as high in the cells with the 'O' antigen
in the cells with the 'A' antigen, suggesting that people with group O antigen
who were exposed to cholera toxin would probably suffer more severe diarrhea
have shown that blood type influences how strongly cholera toxin activates
intestinal cells, leading to diarrhea
," said James Fleckenstein, MD, the
study's senior author and an associate professor of medicine and molecular
is well-established that high levels of this molecule lead to diarrhea, so
we're making the assumption that higher levels lead to even more diarrhea,"
said Kuhlmann, an instructor in medicine and the lead author on the study.
"Unfortunately, we have no way directly to link the responses to the volume of
diarrhea and, therefore, the severity of disease."
Validation of The
scientists re-confirmed their original results in an intestinal cell line
originally derived from a person with blood group A. The cell line was modified
to produce the 'O' antigen instead.
found that cholera toxin induced almost double the amount of the key signaling
molecule in cells with O antigen than in the intestinal cells with A antigen.
isn't sure why intestinal cells with different blood group antigens on their
surface respond differently to the cholera toxin.
cholera toxin is known to bind weakly to the ABO antigens, so they may be
acting as decoys to draw the toxin away from its true target," Fleckenstein
said. "It may be that the type O antigen just isn't as good of a decoy as the
type A antigen."
is a bacterial infection caused by Vibrio cholerae,
affecting the small
intestine. The organism releases a toxin, the cholera toxin, that causes
infected intestinal cells to secrete huge quantities of water and salt into the intestinal lumen, leading to severe diarrhea and dehydration that may result in shock, and even death in severe cases.
fluid and electrolyte replacement, and control of infection are critical to management.
Epidemiology of Cholera
is transmitted via the fecal-oral
route by ingestion of contaminated food or water.
affects between 3 to 5 million people around the world annually, leading to
100,000 to 120,000 deaths. The disease has been endemic in the Indian
subcontinent for centuries, and also sees the most number of cholera related
cholera epidemic has persisted in Haiti since 2010, brought by United
Nations (UN) workers from Nepal. These workers had come to Haiti as part of the
UN team to help rebuild the country following a massive earthquake earlier.
From The Study
the Ganges River delta region of India and Bangladesh, where cholera is highly
endemic, blood group O is less common than in the rest of the world. Only 37
percent of Indians and 33 percent of Bangladeshis have blood group O, as
compared to 45 percent of people around the world, according to published
research. It is believed that the deadliness
of the disease made having the type O antigen a liability, causing nature to
reduce the proportion of type O people in endemic regions
study also shows that enteroids, or
clusters of intestinal stem cells that were developed only recently, could be
an important tool for studying infectious diseases
of the gut.
beautiful thing about this research is that we've taken intestinal cells from
people here in Missouri and used them to understand the pathophysiology of a
disease that affects people worldwide," said Ciorba, an assistant professor of
medicine and one of the study's authors.
this particular situation, we knew that the epidemiologists thought that blood
type mattered, but using enteroids, we're actually able to see those
differences in different people. It's a proof of principle that this system can
answer questions of global impact."
the long term point of view, a safe water supply, better sanitation, food
safety and creating community awareness are the best means to control cholera
and other diarrhoeal illnesses.
WHO is also studying the use of latest tools to complement these traditional
measures. Oral cholera vaccines proven to be safe and effective have recently
become available for commercial use. Some countries have already tried using
oral cholera vaccines to immunize populations considered to be at high risk for
present, two oral cholera vaccines
are available, namely
Dukoral ( made by SBL Vaccines) and ShanChol (made by Shantha Biotec in India),
which are World Health Organization (WHO) prequalified.
the vaccines are two-dose vaccines, many weeks can elapse before people getting
vaccinated are protected. Vaccines give only incomplete protection. Therefore,
vaccination should not replace standard prevention and control measures.
gained following the use of oral cholera vaccines is now available for
analysis. Work is in progress
to determine the role of mass vaccination as a public health strategy to
protect at risk populations against cholera. References:
- Study may explain why some people with type O blood more likely to die of cholera - (https://medicine.wustl.edu/news/study-may-explain-people-type-o-blood-likely-die-cholera/)
- Information on Cholera - (https://en.wikipedia.org/wiki/Cholera#Epidemiology)
- Cholera Vaccines - (http://www.who.int/topics/cholera/vaccines/en/)