Welcome to the World Shared Practice Forum.
I'm Dr. Judith Palfrey, the director
of the Global Pediatrics Program at Boston Children's Hospital.
Our topic today is the treatment and prevention
of diarrhea diseases in children,
and we're very, very fortunate to have
with us Dr. Chris Duggan.
Dr. Duggan is the medical director
of the Center for Advanced Intestinal Rehabilitation.
He is also a Professor of Pediatrics
and Nutrition At the Harvard Medical School
and Professor of Nutrition at the Harvard
School of Public Health.
Chris, you've been doing work in diarrhea
for an awful long time.
How long have you been working on this?
Well, diarrheal disease got me into the field
of gastroenterology and nutrition, actually.
As a medical student, I spent a very important time
in my life working on an oral rehydration
solution on the Apache Indian reservation.
And it really opened my eyes to the important role
of diarrheal diseases and child health.
Now, I just was looking at some statistics,
and it looks as if diarrheal disease still
causes somewhere between 10% and 15% of childhood deaths
around the world.
Is that right?
It's unbelievable how common diarrheal disease is
and how commonly child death is related to diarrheal disease.
Diarrhea causes more childhood deaths than AIDS, tuberculosis,
and malaria combined, which is an amazing fact
that many people don't know.
Now, the good news is that deaths due to diarrheal disease
have been declining for many years now.
Several years ago, the total numbers
of childhood deaths due to diarrheal disease
was about 3 million.
And now it's less than 750,000.
So there have been important improvements
in how we manage children with diarrhea to reduce
their chances of dying.
So are these deaths happening in all the places
around the world in the same rates
or are there differences around the world?
There's huge disparities between when and where children
die from diarrheal diseases.
And it also matters where within a certain country you live
and whether you are a boy or a girl.
Sadly, girls have higher rates of death
due to diarrheal diseases as they
do to other causes of death, unfortunately.
Interestingly, of all the causes of diarrheal diseases
and childhood deaths, nearly 50% of all childhood deaths
are in only five countries of the world-- India, Nigeria,
the Democratic Republic of Congo, Pakistan, and China.
So kids get diarrhea all the time.
Why would you die of diarrhea?
Well, in settings where resources are poor
or adequate medical care is not available,
children can die from the acute episodes
of diarrhea because of electrolyte imbalances
and dehydration, or hypovolemic shock.
More chronic causes of death due to diarrheal disease
are related to the interaction between undernutrition
and chronic diarrhea or persistent diarrhea.
Those children won't die of acute dehydration,
but will die of their infectious complications
of undernutrition.
So we'll get back to that a little bit later.
But tell us now-- you've worked on oral rehydration
interventions.
You have some ideas about what to do when
you have a deathly ill child.
Tell us a little bit about that.
Well, the beauty of oral rehydration solution
is that it's an incredibly simple and straightforward
public health intervention.
Regardless of the age of the child, the age of the adult,
for that matter, the etiology of the diarrheal disease,
oral rehydration solutions can effectively treat dehydration
and prevent dehydration in almost all causes
of diarrheal disease.
So that's one of the major public health advantages.
If you have a simple solution that's
widely available and widely used,
you can prevent many of the deaths due to dehydration.
So tell us a little bit about the history.
How did this come about?
How did we learn-- because I think if you get diarrhea,
you put an IV in, right?
Well, the history of the development of oral rehydration
solution is fascinating.
Because unlike many of the high tech solutions in medicine,
which we think of as emanating from academic medical centers
in our country or in Europe, oral rehydration solutions
first were developed in the areas of the world
where cholera and other diarrheal diseases were
killing vast numbers of people.
And those included areas of India,
in Calcutta specifically, and what is now Dhaka, Bangladesh.
Those academic medical centers took observations
that people made in both animal models and at the bedside
and designed oral fluids that would adequately
replenish water and electrolytes for severe diarrhea.
Can you tell us a little bit about the most effective way
to treat diarrhea?
Well, I mentioned earlier that one
of the beauties of oral rehydration solution
is its simplicity.
And part of the simplicity and management
of a child with acute diarrhea and dehydration
is that with very well known parameters,
you can assess whether that child has
mild, moderate or severe dehydration.
And depending on how severely dehydrated they are,
that determines treatment options.
So can you tell us a little bit more what treatment you
would select for each of those?
Sure.
So children with mild to moderate dehydration
can be always managed with oral rehydration solutions.
And their symptoms of dehydration
are very predictable.
So a child with mild dehydration may only
have an increased heart rate or mild mucosal dryness
of the oral mucosa.
A child with moderate dehydration
may have a prolonged skinfold or perhaps some delayed capillary
refill.
And a child with severe dehydration
will have altered mental status and lack of responsiveness.
Those children are not candidates
for immediate oral rehydration solution,
but need intravenous rehydration to treat hypovolemic shock.
The next few slides will show, in a time-elapsed fashion,
the successful management of a child who
presented to a hospital I used to work at in Cairo, Egypt.
And at the beginning of the morning,
children would pour into this clinic,
having traveled all night on buses and trains
to be adequately treated for diarrhea and dehydration.
And as you can see at 9 o'clock, this young infant
has moderate dehydration.
In other words, if you felt his mouth, it would be very dry.
And you can see the top of his skull has a sunken fontanel.
His eyes are sunken as well.
But with adequate rehydration, namely 5mL of fluid
that is provided every minute or so,
this child will become increasingly rehydrated.
You can see at 9:15, he's increasingly thirsty.
At 10 o'clock, he looks much, much better.
He's getting an adequate amount of oral rehydration solution.
And by 12:00 noon, he's completely rehydrated
and has successfully avoided the complications of dehydration
due to diarrheal disease.
And at 1 o'clock, he's back nursing on his mother's breast.
As you know, human milk is the best form of infant nutrition,
especially for children who are recovering from diarrhea.
That's a pretty dramatic sequence.
So I'd like to turn now to our colleagues around the world.
Please remember to first state your city and country location.
The question is this-- Dr. Duggan
has presented mild, moderate and then the severe categories.
How are you all around the world making those distinctions?
What are the parameters that you're using?
Are you finding that looking at mild, moderate and severe
is helpful for you in your treatment decisions?
Now you keep talking about this ORS solution.
What is it?
How is it made?
How do I get hold of it if I'm a physican at the bedside?
Tell us a little bit more about this.
Well, oral rehydration, as I mentioned earlier,
was designed in areas of the world
where cholera was an important cause of deaths
due to diarrhea.
And as such, the original solutions
had the same amount of sodium that
were included in lost sodium due to cholera stools.
And so there was always this principle
of matching the sodium and water content that's
lost through diarrhea with what's
taken in from oral rehydration solutions.
And what if I can't measure the electrolytes?
What if I'm in a situation where I just don't have that--
Well, most people are in actually that situation.
And not only can they not measure stool electrolytes,
but they can't measure the child's electrolytes.
But again, many, many studies have
shown that oral rehydration solution, properly
administered, successfully corrects
hyponatremia and hypernatremia.
The newer solutions, however, have a slightly reduced amount
of sodium but therefore reduce the osmolarity of the solutions
and seem to work better to improve rehydration and have
less vomiting.
Don't you need some sugar?
You do.
So what you're pointing out is the important factor
of sodium glucose transport at that level
of the epithelial cell.
So as you see here, the concentration
of sodium in the stool output in three general types
of diarrheal disease-- cholera on the left, enterotoxogenic E.
coli in the middle and rotavirus diarrhea on the right.
And on the black bar, you can see concentration
of sodium milliequivalents per liter
and the yellow bar looks at stool output
in ccs per kilo per 8 hours.
And you can see a general trend where
sodium concentration and stool output
generally correlate together.
And this is an important take home message
of gastrointestinal physiology.
In other words, where sodium goes, water is sure to follow.
Taken at the level of the epithelial cell,
you can see that sodium and glucose get
co-transported from the lumen of the gastrointestinal tract
into the epithelial cell.
And from there, sodium is inserted into the blood vessel
by sodium potassium ATPase.
Sodium therefore goes from the lumen of the gut
through the enterocyte into the bloodstream
and water follows both through the enterocyte
and between the enterocytes.
The interesting thing about sodium glucose co-transport
is that's not the only mechanism through which sodium
can be co-transported through the epithelial cells.
There are sodium amino acid based
co-transporters that also effectively transport
sodium from the lumen of the gut into the bloodstream.
So are those amino acids included in the ORS?
Standard ORS only includes sodium and glucose
as the major co-trans molecules.
But any of these new ones have--
Some of the new ones have included some amino acids,
but it's important that the total osmolarity
of the solution still be maintained, that it's not
a hypertonic solution.
So since the ORS is coming through the GI tract,
are we at a little bit more safety
margin in terms of getting brain swelling and that type
of thing?
Oh, absolutely.
One of the major advantages of oral rehydration solution
is that unlike intravenous fluids, which
can be given at too rapid a rate and lead
to edema or overhydration, oral rehydration solutions
are therefore more physiologic when they're administered.
But you have said to us that there's a situation where
the child is so lethargic-- and really just cannot take
by mouth-- that we need to go to IV.
What do we do then?
Where we go with that?
Oh, absolutely.
Intravenous rehydration is clearly of critical importance
when you have a child with hypovolemic shock.
The beauty of ORS is that many children
if they're treated early, for instance at home,
before they seek medical attention,
some of that severe dehydration can perhaps be averted.
Now we see these lovely little packets of ORS.
How do people get them?
And in a minute I'm going to ask our friends
around the world about whether they have
any issues of getting them.
But tell us a little bit about how a hospital prepares
or a clinic prepares to have enough of the ORS solutions
to be available if there is a cholera epidemic
or there are problems.
Sure.
Those are great questions.
Oral rehydration salts are distributed in packets
throughout most of the world's countries.
And I've traveled to many different countries
and found them in rural shops, urban shops,
really wherever that there are people
and there are pharmacies and even small village stores.
They often carry these packets of oral rehydration salts.
In hospitals or academic medical centers
that take care of large number of patients,
obviously they don't use the packet so much
as premixed solutions.
So here at Boston Children's Hospital,
we use a commercial product that's
already mixed in a water form.
So maybe if I can turn to our colleagues around the world--
and again, please remember to state your city and country
location.
Question is this: are you able to get
hold of the oral rehydration salts and the IV solutions
that you need when children present
with this range of diarrhea?
Are there any situations where you're
finding yourself constrained by a supply chain or difficulties
getting the materials?
Let's just change gear a little bit.
You now have a child who's been treated.
They're doing a little bit better.
When do you start feeding them and how do you
get the continued feed going?
Treatment for diarrheal disease, although we've to this point
talked more about oral rehydration solution,
really does include both continued nutritional
management of the child while you're rehydrating them.
For many years in the 1950s and '60s,
prolonged gut rest was the recommended therapy
for children with diarrheal diseases.
And that's a natural response, because indeed,
if you starve a child with diarrhea,
they will have less stool output.
But the health of their enterocytes will suffer.
When you make a child NPO or nil per os,
they have enterocyte atrophy and their absorptive capacity
is worsened.
So for the past 15 or 20 years, we
have strongly recommended continued feeding
during diarrheal disease.
So as soon as a child is rehydrated,
they should be resumed with breast milk or their usual diet
that they had before they were sick with diarrhea.
When I was training, it was the BRAT diet-- Bananas,
Rice cereal, Applesauce, and Tea.
Anything to that, or is there something else
that you recommend now?
Well, the BRAT diet is in fact lacking
in several important nutrients.
There's inadequate protein, inadequate fat, and low amounts
of vitamin D and A. So it's not a good diet
to recommend for a prolonged period of time.
Having said that, diet modifications
are common across many different cultures.
And in fact, there are reasons to suggest
that some of the foods in the BRAT diet might be helpful.
Rice, for instance, might have some anti-secretory processes
and that's why rice-based oral rehydration
solution is helpful in patients with cholera.
But I think physicians and caretakers do a disservice
to their children when they overly restrict dietary intake.
The child should be encouraged to eat more when they're
recovering from diarrheal disease
to prevent untoward nutritional consequences.
And then what about probiotics?
Are we pushing the yogurt and things of this sort?
The probiotic literature is a very interesting one.
And there are some among us who feel
that probiotic supplementation with acute diarrhea
does reduce the duration of diarrhea.
However, if you look at the difference
in diarrheal duration, it's about on the order
of a half a day, or perhaps a day of illness,
which is somewhat marginal.
If you compare the cost of probiotics with the effect,
it's not clear to me at least that this
is an important intervention.
And you mentioned getting the child back onto breastfeeding.
But what about the situations where they're
no longer breastfeeding.
Is there a time to introduce the dairy products, any time
to hold off on that?
Sure the literature concerning both the combination
of lactose-containing foods as well as foods with cow's milk
protein is pretty clear cut.
One concern was that children with prolonged diarrhea
would have persistent lactose malabsorption.
But it turns out if you're a relatively well-nourished
child, the degree of lactose malabsorption
is relatively minor after an acute episode
of diarrheal disease.
So it is only in those children with a widespread enteropathy
or severe undernutrition do we recommend lactose-free feedings
after acute diarrhea.
The issue of cow's milk protein has also
been addressed because of the potential concern
that an acute enteritis might somehow
predispose a child to have an allergic response to cow's milk
protein.
But that does not seem to be the case either.
Well, now we've talked a lot about the various kinds
of feeding.
I'd love to turn back to our colleagues
and have them please remember to state their city and country
location.
Tell us a little bit about what you do in your practice
in terms of getting children back onto their regular diet,
if there are intermediate diets that you go to
and when you try to get them back
onto their regular feedings.
So that's a little bit of a segue into something
you seem to like to talk about.
What is from A to zinc?
Well, A to zinc corresponds to two important micronutrients.
And the literature from the 1990s and '80s
really pointed out the critical nature
of two important nutrients-- number one, vitamin A
and number two, mineral zinc.
So first off, for vitamin A, important studies
performed by a number of colleagues in the 1980s
suggested that vitamin A supplementation
was an important way to reduce all cause child
mortality in areas of the world where vitamin A was
a poor component of the diet.
And to this day, intermittent high dose administration
of vitamin A every six months or so to children under age two
has reduced deaths due to a variety
of infectious illnesses.
So that's an important child survival
story that has been told.
Certainly deaths due to diarrheal disease
have been prevented by widespread high dose vitamin
A supplementation as well.
How's that working?
Where is it working?
Well, there are some countries that
have rolled it out quite well and they've
shown impressive changes.
However, as the decades have passed on,
there is a school of thought that
suggests as diets have become more diverse,
they've questioned the role of weather high dose vitamin
A supplementation is still an important component.
And those are middle income countries
such as several countries in South America.
Countries in sub-Saharan Africa, South Asia still, I think,
show good evidence that intermittent periodic high dose
vitamin A supplementation is important.
So the mechanism of the vitamin A action-- what is that?
Well, vitamin A is an important nutrient
to maintain intestinal and other epithelial cell lining.
So one school of thought is that vitamin A deficient animals
or children might have increased permeability
and therefore are more susceptible
to infectious gastroenteritis as well as respiratory infections.
And then zinc-- where's is it working?
Tell us that story.
Well, zinc is also a critical nutrient
for both mucosal immune factors and systemic immunity.
And again, in areas of the world where
zinc components of the diet are not high in bioavailability,
children with low zinc stores don't grow as well.
They have stunting.
And they have higher rates of pneumonia and diarrheal
diseases.
Unlike vitamin A, high dose zinc supplementation is toxic.
High dose vitamin A is stored in the liver
and can be distributed to the body
as time goes on over the months after dosage.
But zinc actually has to be given pretty regularly
on a daily basis.
So that's hampered the public health's ability
to distribute zinc in an effective way
outside of capsules.
Well, again, around the world, please
remember to state your city and location.
I'd be very interested to learn whether you have programs
in vitamin A and zinc implementation
and how you're finding them working out.
So we've talked about treatment.
We've talked a little bit about prevention.
And are there other preventive things
that you'd like for the group to know?
Sure.
There are a number of important and new areas
of diarrheal prevention.
And they include, obviously, some
of the important virus and bacterial vaccines that
are being distributed.
So for instance, in the United States,
it's routine for children to receive the rotavirus vaccine.
That vaccine is now increasingly being
used in a number of countries in sub-Saharan Africa and South
Asia to reduce the burden of diarrheal disease.
So that's certainly an exciting innovation
that will come out as that vaccine is implemented
more widely.
There are vaccines on the horizon against other forms
of enteropathogenic an anterotoxigenic E. coli
infections that also contribute to the global burden
of diarrheal diseases.
But even before those vaccines are implemented and brought
out, there are important nutritional and child health
interventions that we can make.
Perhaps the strongest one is encouraging
exclusive breastfeeding for the first 6 months of life.
For many years, the World Health Organization
and other policymaking bodies have
suggested that is the most important nutritional component
of early childhood development.
So exclusive breastfeeding and delaying
the onset of complementary foods until six months of age
is an important component to reduce the burden
of diarrheal disease.
Hand washing is important.
Toilets are important.
Safe disposal of wastes is an important component
of reducing the burden of diarrheal disease.
So in your experience, what are some
of the management challenges or even management mistakes
that you'd like to point out to people?
Sure.
Well, one of the fundamental aspects
of accurate and adequate care for a child with dehydration
is shown in this slide.
And it's an important component that strict and accurate ins
and outs are measured.
So on the right, you can see a child
who's lying in a cholera cot.
And these are, as the name implies,
designed for children with high rates of purging.
And all of the stool output is measured in a bucket,
as shown on the left.
And by measuring exactly how much stool output comes out,
the physicians and nurses taking care of that child
can accurately provide exactly that amount of fluid
to replenish the child and treat,
as you can see, severe dehydration that's
occurring in this child.
So accurate measures of ins and outs
is really a cornerstone of successful therapy.
The adequacy of urine and tissue perfusion
is key to how appropriate and how adequate rehydration
has taken place.
Nonsensible losses can be estimated, as you know,
but a part of the management has to be ins and outs, so
all of the outputs and all the inputs.
The second cornerstone is continued feeding
to provide adequate nutritional support to a child who's
recovering from acute diarrhea.
So oftentimes, if we're in the throes of, let's say,
a rotavirus or a cholera epidemic,
there's just so many children coming to the clinic
or coming to the hospital.
Any tricks in terms of how to manage
large numbers of children with these kind of problems?
Sure.
The principles of medical triage occur
and can be applied in those situations,
just as they are on the battlefield.
And so you need to take advantage and take
great care of identifying those children who
have severe dehydration, very quickly
plug them into intravenous rehydration routes.
Those children with less severe dehydration
can be managed as outpatients with oral rehydration
solutions.
One of the beauties of oral rehydration solutions
is that mothers and fathers can be
taught how to administer this fluid at home
and prevent need for admission.
You've worked a lot with children with HIV.
Tell us about what happens when you
have a child with HIV who then has
a diarrhea episode like this.
Sure.
Well, those children can be, as you can imagine,
quite challenging to manage.
Because children with HIV infection
are at risk of developing not just acute diarrhea,
but persistent diarrhea.
And persistent diarrhea can cycle through
with undernutrition.
Turns out that undernutrition is a huge risk
factor for childhood death due to diarrheal diseases.
So with HIV infection and diffuse enteropathy
due to HIV infection and/or chronic gastrointestinal
infections, the management is very important
to do quite well.
Many of those children require inpatient hospitalization.
They need treatment of intercurrent infections.
They need to make sure that appropriate anti-viral therapy
is on board.
And they need appropriate and important nutritional
supplementation to get them through their infection.
So one last one-- talk to us just a little bit more
about the treatment of the children who
have persistent diarrhea.
Who are they, how do they get identified,
and how do we treat them?
Yes.
So persistent diarrhea has been defined by the World Health
Organization as diarrhea that lasts for more than 14 days.
And obviously, that's not a large number
of children around the world.
Most children recover from diarrheal disease
between 3-7 days.
But children with persistent diarrhea
are at high risk of subsequent death,
so they need to be highlighted as people
who need extra attention.
And with diarrhea that lasts for at least 14 days,
you can imagine that because of anorexia--
in other words, poor appetite-- and chronic malabsorption,
these are children at high risk of severe acute malnutrition,
chronic malnutrition, and a variety
of micronutrient deficiencies.
So persistent diarrhea, the importance
of nutritional management and providing adequate calories--
protein, fat, all the specific micronutrients--
is of vital importance.
And how many of those children actually
have, say, a superinfection with an invasive bacteria
of some sort?
They can have bacterial infections.
Cryptosporidium is an important component of diarrheal disease
that's persistent in nature.
That's what recent studies have shown.
Children with persistent diarrhea and malnutrition,
as you know, can also succumb to other non-gastrointestinal
infections, whether it's complicated by pneumonia
or malaria in those areas of the world where malaria is endemic.
So all physicians and nurses taking
care of children with persistent diarrhea
need to be tuned into all those possibilities.
So, thank you, Dr. Duggan.
This has been a wonderful review of the treatment
and the prevention of this incredibly important problem,
which is diarrhea in children around the world.
Thanks so much.
Thank you.
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