2. INTRODUCTION Leading cause of childhood morbidity & mortality in
developing countries
Important cause of malnutrition
80% of deaths due to diarrhoea occur in the first two
years of life.
Children <3 years of age in developing countries
experience around three episodes of diarrhoea each year.
4. Epidemiologic features of Diarrhea
2 billion cases of diarrheal disease every year
Greatest burden seen in children under the age of 5 years
About 5000 deaths in children every day
Incidence and risk of mortality are highest in this age group
About 78% occur in the South-East Asian & African
regions
An average of 3 episodes of acute diarrhoea every year
5. Diarrhea in India
Accounts for 20% of all paediatric deaths in India
2nd leading cause of child mortality after acute respiratory
infections (30%)
25.2 % is the Prevalence rate among children under age 5 Yrs
49.1% : Highest in the age group of 6–11 months
15.7% : Lowest among children aged 48–59 months
Prevalence of Diarrhoeal Disease, its Seasonal and Age Variation in
Kashmir, India. Int J Health Sci . Jul 2008; 2(2): 126–133.
6. Clinical Types
Acute watery diarrhoea (including cholera):
Lasts several hours or days
Main danger is dehydration
Weight loss occurs if feeding is not continued;
Acute bloody diarrhoea:
Also called dysentery
Main dangers - damage of the intestinal mucosa,
sepsis and malnutrition
Other complications : dehydration , HUS
7. Persistent diarrhoea :
Lasts 14 days or longer a/w malnutrition
Main danger - malnutrition & serious non-intestinal
infection
Other complications : dehydration
Diarrhoea with severe malnutrition :
Main dangers - severe systemic infection ,
dehydration,
heart failure and vitamin and mineral deficiency.
10. Pathophysiology of acute diarrhea
Increased secretion of fluid and electrolytes
Decreased digestion and absortion of nutrients
Abnormal transit due to aberrations of intestinal
motility
11. Dehydration
During diarrhoea there is an increased loss of water
and electrolytes (Na, Cl , K , and HCO3 ) in the liquid
stool.
Dehydration occurs when these losses are not
replaced adequately and a deficit of water and
electrolytes develops.
12. Diarrheal Disease
Current Management
Bacterial
diarrhea
ORS Zinc Probiotics Antibiotics
Ofloxacin
Ofloxacin +
ImidazleOfloxacin : Not recommended in children
Amoebic infections are to the tune of 5% in children < 5yrs
Limitations of Prescribing antibiotic in Diarrhea / Dysentry
Ofloxacin : Toxicity and risk of cartilage damage
Ofloxacin / Imidazoles : Bitter taste, Palatability, Nausea
5-8 days of lengthy treatment
Recovery time is 4-5 days after treatment
No effect on improvement of stool consistency
Emerging resistance, not recommened in < 8yrs of age
irrational combinations as H1/2 is different quinolones (12hrs)
Metronidazole(8hrs)
Limitation
s
13. Treatment Plan A: home therapy to
prevent dehydration and malnutrition
Children with no signs of dehydration need extra
fluids and salt to replace their losses of water and
electrolytes due to diarrhoea. If these are not given,
signs of dehydration may develop.
14. four rules of
Treatment Plan A:
Rule 1: give the child more fluids than usual
Suitable fluids : two groups:
Fluids that contain salt :
• ORS solution
• Salted drinks (e.G. Salted rice water or a salted yoghurt drink)
• Vegetable or chicken soup with salt.
Fluids that do not contain salt, such as:
• Plain water
• Water in which a cereal has been cooked
• Unsalted soup
• Yoghurt drinks without salt
• Green coconut water
• Weak tea (unsweetened)
• Unsweetened fresh fruit juice.
15. Unsuitable fluids
Drinkssweetened with sugar, which can cause
osmotic diarrhoea and hypernatraemia.
Some examples are:
• Commercial carbonated beverages
• Commercial fruit juices
• Sweetened tea.
With stimulant, diuretic or purgative effects, for
example:
• Coffee
• Some medicinal teas or infusions.
16. How much fluid to give
The general rule is: give as much fluid as the child or adult
wants until diarrhoea stops.
• Children under 2 years of age: 50-100 ml (a quarter to
half a large cup) of fluid;
• Children aged 2 up to 10 years: 100-200 ml (a half to one
large cup);
• Older children and adults: as much fluid as they want.
17. Rule 2: Give supplemental zinc (10 - 20 mg) to
the child, every day for 10 to 14 days
Dose : infant – 0.5 mg/kg/day
<6 mth – 10 mg/day
>6 mth – 20 mg/day
Preparations : zinconia 20mg/5ml
zincovit 10mg/5ml
18. Rule 3: Continue to feed the child, to prevent
malnutrition
Food should never be withheld
Breastfeeding should always be continued.
Aim - give as much nutrient rich food as the child
will accept.
19. Rule 4: take the child to a health worker if
there are warningsigns of dehydration or
other problems
• Starts to pass many watery stools;
• Has repeated vomiting;
• Becomes very thirsty;
• Is eating or drinking poorly;
• Develops a fever;
• Has blood in the stool; or
• The child does not get better in three days.
24. ORAL REHYDRATON SOLUTION
ORS -special combination of dry salts that, when
properly mixed with clean water, can help rehydrate
the body when a lot of fluid has been lost due to
diarrhoea.
Basis of ORS – Glucose linked absorption of sodium
remains intact irrespective of etiology of diarrhoea.
25. TYPES OF ORS FORMULATIONS
Glucose based ORS
Rice based ORS
Low osmolarity ORS
Home available ORS
Mineral based ORS(zinc)
28. NORMAL BACTERIAL FLORA OF THE
GI TRACT
Aerobic and anaerobic bacteria, yeast and fungi live into the GI tract
which has more than 400 m2 of surface area.
There are more than 2000 species of commensal bacterial organisms
within our bodies, the vast majority in the gut.
The several species of microorganisms in the adult human gut are
known as the microbiota which may contain nearly 100 times the
number of genes contained within the human genome.
The genome of these collective organisms is called the microbiome.
The longitudinal distribution of intestinal microorganisms increases in
density progressing from the small bowel to colon.
Therapeutical use of probiotic formulations in clinical practice. Clinical Nutrition 29 (2010) 701e725
29. Therapeutical use of probiotic formulations in clinical practice. Clinical Nutrition 29 (2010) 701e725
31. Mechanisms of probiotic/host interaction.
World Gastroenterology Organisation Practice Guideline Probiotics and prebiotics.
www.worldgastroenterology.org/.../guidelines/19_probiotics_prebiotics
32. Probiotics
Probiotics are “live microorganisms, which when administered in
adequate amounts, confer a health benefit on the host.
Probiotics are generally recommended to help strengthen host
system and assist in recovery from certain diseases.
There are several challenges in choosing the appropriate
probiotic; including the wide diversity of probiotic strains,
quality control of commercially-available probiotic products and
the degree of evidence-based trials for each disease and
probiotic.
McFarland LV. Systematic review and meta-analysis of Saccharomyces boulardii in adult patients. World J Gastroenterol
2010 May 14; 16 (18):2202-2222
33. Probiotics
The ability of an organism to be an effective probiotic has been
found to be strain-specific and microbial organisms are defined
by their genus, species and strain.
Probiotic products are available in various forms: capsules of
freeze-dried or lyophilized cultures, heat-dried culture
supernatants mixed in dairy food or other foods.
McFarland LV. Systematicv review and meta-analysis of Saccharomyces boulardii in adult patients. World J
Gastroenterol 2010 May 14; 16 (18):2202-2222
34.
35. Saccharomyces boulardii
Saccharomyces boulardii was discovered by a French microbiologist, Henri
Boulard in 1920 when he was in Indo-China searching for new strains of
yeast that could be used in fermenting processes.
Saccharomyces boulardii (S. boulardii) is a yeast isolated from the skin of
Lychees grown in Indo-china and belongs to the same species as
Saccharomyces cerevisiae (S. cerevisiae), although it definitively has
different taxonomy, physiological, metabolic and genetic characteristics.
It is a non-pathogenic thermotolerant yeast that grows optimally at 370C.
It is a live yeast that is available as a lyophilized preparation for adults as a
250 mg capsule.
Prajapati P, Patel M, Krishnamurthy R. Saccharomyces boulardii- a probiotic of choice. CIBTech Journal of
Biotechnology. 2013 Vol. 2 (2) April-June, pp.1-6
36. Properties of S boulardii
Organisms need to survive at body temperature, be resistant to stomach
acids and bile acids, and exist in the competitive milieu of the intestinal
tract to show their effect.
Probiotic strains of Saccharomyces have been shown to have these abilities.
Although the optimal temperature for most strains of Saccharomyces range
from 22-30 c, S. boulardii survives best at 37 c, giving it a unique advantage
of being one of the few yeasts that do best at human body temperatures.
These studies indicate that S. boulardii is a safe and effective
biotherapeutic agent for the treatment of gastrointestinal disease.
Prajapati P, Patel M, Krishnamurthy R. Saccharomyces boulardii- a probiotic of choice.
CIBTech Journal of Biotechnology. 2013 Vol. 2 (2) April-June, pp.1-6
37. Pharmacokinetics
S. boulardii, when given orally, achieves steady-state concentrations
within three days and is cleared within 3-5 d after it is discontinued.
Blehaut et al gave eight healthy volunteers S Boulardii (oral dose of 5
X109) for six days and followed them for time to clearance.
They determined that S boulardii has a half life of 6 hours, fecal steady
state concentration (2 × 107/g) were reached by day 3 and the yeast was
cleared after four days after administration.
Elmer et al found that some types of fiber (psyllium) increased S
boulardii levels by 22%, while other type of fiber (pectin) showed no
effect.
McFarland LV. Systematicv review and meta-analysis of Saccharomyces boulardii in adult patients. World J
Gastroenterol 2010 May 14; 16 (18):2202-2222
38. Stability of S boulardii
Probiotic product manufacturing may affect its shelf-life. Probiotics
may be available as lyophilized or heat-dried preparations.
Lyophilized preparations of S boulardii are stable over one year at room
temperature, as long as it is protected from moisture.
Daily administration of lyophilized S. boulardii at standard doses
results in detectable levels of live yeast throughout the GI tract.
S. boulardii does not attach to the mucosa of the intestine
Prajapati P, Patel M, Krishnamurthy R. Saccharomyces boulardii- a probiotic of choice. CIBTech
Journal of Biotechnology. 2013 Vol. 2 (2) April-June, pp.1-6
39.
40. Anti-Microbial Action – Direct Anti-
Toxin Effect
The anti-toxin action elicited by S boulardii is mainly due to small
peptides produced by the yeast.
A 54kDa serine protease is able to inhibit enterotoxin and cytotoxic
activities of C. difficile by degradation of toxin A and B and receptors
sites of toxin A on the enterocyte cell surface.
S. boulardii has several different types of mechanisms of action. which
may be classified into three main areas: luminal action, trophic action
and mucosal-anti-inflammatory signaling effects.
S. boulardii may interfere with pathogenic toxins, preserve cellular
physiology, interfere with pathogen attachment, interact with normal
microbiota or assist in reestablishing short chain fatty acid levels.
Prajapati P, Patel M, Krishnamurthy R. Saccharomyces boulardii- a probiotic of choice. CIBTech
Journal of Biotechnology. 2013 Vol. 2 (2) April-June, pp.1-6
41. Inhibition of Growth and Invasion
of Pathogen
In vitro, S boulardii directly inhibits the growth of several pathogens
(Candida albicans, E. coli, Shigella, Pseudomonas aeruginosa,
Staphylococcus aureus, Entamoeba hystolitica), and cell invasion by
Salmonella typhimurium.
This mode of action is most likely important for the prevention and
therapy of infectious diseases but also for the treatment of (chronic)
inflammation of the digestive tract or parts thereof.
In addition, this probiotic action could be important for the
eradication of neoplastic host cells.
Prajapati P, Patel M, Krishnamurthy R. Saccharomyces boulardii- a probiotic of choice. CIBTech Journal of
Biotechnology. 2013 Vol. 2 (2) April-June, pp.1-6
42. Trophic and Immune System Effects
S boulardii can reduce mucositis, restore fluid transport pathways,
stimulate protein and energy production or act through trophic effect
by releasing spermine and spermidine or other brush border enzymes
that aid in the maturation of enterocytes.
S boulardii may also regulate immune responses, either acting as an
immune stimulant or by reducing pro-inflammatory responses.
S. boulardii may cause an increase in secretory IgA levels in the
intestine. It has also been found associated with higher levels of serum
IgG to C. difficile toxins A and B.
McFarland LV. Systematic review and meta-analysis of Saccharomyces boulardii in adult patients. World J
Gastroenterol 2010 May 14; 16 (18):2202-2222
43. Trophic and Immune System Effects
S. boulardii may also interfere with NF-κB-mediated signal
transduction pathways, which stimulate pro-inflammatory
cytokine production.
S. boulardii has also been shown to cause the trapping of T
helper cells into mesenteric lymph nodes, thereby reducing
inflammation.
McFarland LV. Systematic review and meta-analysis of Saccharomyces boulardii in adult patients. World J Gastroenterol
2010 May 14; 16 (18):2202-2222
44. Mechanism of Action
McFarland LV. Systematic review and meta-analysis of Saccharomyces boulardii in adult patients. World J
Gastroenterol 2010 May 14; 16 (18):2202-2222
45. The normal microbiota and probiotics interact with the
host in metabolic activities and immune function and
prevent colonization of opportunistic and pathogenic
microorganisms
World Gastroenterology Organisation Practice Guideline Probiotics and prebiotics.
www.worldgastroenterology.org/.../guidelines/19_probiotics_prebiotics
46. Commercially used probiotic strains.
Therapeutical use of probiotic formulations in clinical practice. Clinical Nutrition 29 (2010) 701e725
47. Bifidobacteria benefits on human health.
Therapeutical use of probiotic formulations in clinical practice. Clinical Nutrition 29 (2010) 701e725
48. Main therapeutic and nutritional effects of Lactobacilli.
Therapeutical use of probiotic formulations in clinical practice. Clinical Nutrition 29 (2010) 701e725
Notes de l'éditeur
Cryptosporidium (HR 2·3; 1·3–4·3) in toddlers aged 12–23 months
In fact the mammalian gut is considered one of the most densely
populated ecosystems on Earth with a bacterial load in the region of
1012 organisms/g of fecal material in the large intestine.
Anaerobic
bacteria benefit the host by performing metabolic functions
including fermentation, providing short-chain fatty acids (SCFAs),
producing vitamins, adding to the trophic action of the epithelium
and aiding in the development of the immune system.