1. Consultant Paediatric Gastroenterologist
Persistent Diarrhea
Dr. Shrish Bhatnagar
Consultant Paediatric Gastroenterologist
Eras’ Lucknow Medical College & Vivekananda Polyclinic and Institute of Medical Sciences, Lucknow.

3. WHO Definition Diarrhea Duration >/= 14 days acute in onset
following infective etiology
Definition excludes specific conditions like celiac disease, tropical sprue, or other congenital, biochemical or metabolic disorders
Bulletin of the World Health Organization, 1988, 66:709–717.

4. 80% associated with malnutrition
Burden of disease
80% associated with malnutrition
WHO CDD Programme; Indian J Med Res 1996;

5. Causes of Persistent diarrhea
Secondary
Lactose intolerance
Fungal
Super-infection
Diarrhea compounded by
Primary malnutrition……Enteropathy
UTI
SEPSIS
SIBO
Antibiotic- associated diarrhea

6. Natural history of diarrhea
Acute diarrhea: 70% resolve in 1 wk
Acute diarrhea : 90-95% resolve in 2 wk
5-10% become persistent
Majority
subsides in 4-6 weeks
If persistent beyond >6-8 weeks (small proportion)
Think of other causes
Ind J Gastroenterol 1993;12:

7. Further prolongation of diarrhea (>6-8 weeks)
Think of
Cow’s milk ± soya allergy
Immunodeficiency
Celiac disease
Lymphangiectasia
Cystic fibrosis
Anatomical causes
Refer to a specialist at the earliest

8. Risk factors of disease
Age <1 year
Malnutrition
Impaired immunity
Multiple antibiotics
Early introduction of animal milk
Occurrence of recent diarrheal episode
Reduced intake of breast milk

9. Risk factors of death 6 months of age or less Severe dehydration
Use of total parenteral nutrition
Systemic infection: most important
WHO Bulletin 1996

10. Stool Pathogens Shigella Salmonella
Isolation in stool : 55-70% Interpretation difficult: excreted in healthy
Shigella
Salmonella
E.coli (Enteropathogenic and enteroaggregative)
Giardia lamblia
Cryptosporidium
Entameba histiolytica
Ind J Gastroenterol 1993;12:

11. Management

12. Consequences of diarrhea
Principles
Consequences of diarrhea
Malnutrition
Infections

13. Effects: Secondary lactose intolerance
Prolonged Diarrhea
Malnutrition
Food allergies
(soy, bovine)
Compromised immunity
Persisting infections
Small bowel mucosal injury
Superadded infections (fungal)
Villous atrophy
Loss of brush border enzymes
Antibiotics
Effects: Secondary lactose intolerance
Malabsorption
Hypoalbuminemia
Bacterial overgrowth

14. Vicious cycle
Break!

15. Step 1: Resuscitation Fluid resuscitation: Correction of electrolytes
ORS or
Ringer lactate (I.V.)
Correction of electrolytes
Correction of hypoglycemia

16. Step 2: Identify infections
Look for infections quickly:
Respiratory, UTI, Sepsis
Examine perineum and oral cavity
TLC and DLC
Blood and urine culture
Chest X-Ray
Start appropriate antimicrobials

17. Stool examination No role of routine stool culture and isolation
of pathogen
Stool for fungus: budding yeasts and hyphae
Stool for C. difficile toxin in a clinical setting:
Antibiotic associated diarrhea
Stool for opportunistic infections if
immunodeficiency is suspected:
3 consecutive fresh samples

18. Indications for antibiotics
Blood in stools: Shigella
Systemic infections
Severe malnutrition
Concomitant UTI
<4mo age group
No Role of empirical Nitazoxanide for Cryptosporidium
Insufficient data to recommend the use of any kind of antibiotic in persistent diarrhoea of unknown cause or non-specific cause
BMC Infectious Diseases 2009,

19. Case I: 4 mo girl VPIMS Ofloxacin , racecadotril, probiotics Top fed
Bottle feeding
Intt. fever (1000F) 10 days
Acute onset, watery
15 times/day for 7 days dehydration
Persistent diarrhea 2 weeks
5-6 times/day, small quantities
Catheterized

20. Further course… Suspect UTI
Urine exmn: 15 WBC/ hpf
Urine culture: E.coli
USG-KUB: normal
H/O fever
Catheterization
Suspect UTI
Sensitive antibiotics (3rd gen cephalosporin) for 7 days
Afebrile
Formed stools
MCU/ DMSA scan at follow-up (8 weeks): normal

21. Case II: 9mo boy ELMCH Top fed Bottle feeding
No fever or urinary symptoms
Acute onset, watery
15 times/day for 7 days
Persistent diarrhea 2 weeks
5-6 times/day, small quantities
Cefixime 3 days
Ofloxacin 5 d
Norfloxacin-metranidazole 7 d

22. Satellite lesions around flexures, scrotum and penis
Examination
Oral thrush +
Soft abdomen
No hepatosplenomegaly
Other systems normal
Perianal erythema +
Satellite lesions around flexures, scrotum and penis
Curdy white lesions

23. Fungal diarrhea (super-infection)
Diagnosis
Fungal diarrhea (super-infection)
Stool
Budding yeast cells and hyphae ++
Opportunistic infections: no organism
C. difficile antigen: negative

24. Management Oral fluconazole 6mg/kg for 10 days Oral Clotrimazole paint
Supplements
Diarrhea resolved in 3 days
No recurrence

25. Step 3: Lactose intolerance
Load in diet
Glucose + Galactose
Absorbed
Lactase
Unabsorbed lactose
Acidic
Osmotic
stool
Colon
Hydrogen + Lactic acid

26. Persistent diarrhea 3 weeks
Case III: 11 mo boy
SPARSH
Explosive stools
On cow’s milk
Acute onset, watery
diarrhea for 5 days
Persistent diarrhea 3 weeks
10-14 times/day, explosive
Ofloxacin 7 days

27. Perianal erythema (widespread) Minimal lesion on scrotum
Examination
Soft abdomen
No hepatosplenomegaly
Other systems normal
Perianal erythema (widespread)
Minimal lesion on scrotum

28. Cornerstone of management
Step 4: Dietary therapy
Cornerstone of management

29. Diet algorithm ? Diet A: Low lactose diet failure
Diet B: Lactose-free diet
Diet C: Monosaccharide based diet ?
failure
May use
Green banana diet
Hydrolysed or
amino acid formulae
(Elemental diet)
Needs to be revisited in current era
failure
Total parenteral nutrition

30. Green banana formulation
Basis of use
Amylase resistant starch (ARS)
Not digested in human intestine
Delivered to colon
Increase salt, water absorption
Provide energy
Trophic effect
Colonic
Bacteria
Short chain
fatty acids
Gastroenterology 2001;121:554-60

31. Step 5: Nutritional supplements
Multivitamins: Twice RDA for 2-4 weeks
Iron: after cessation of the diarrhea
Folic acid: 1 mg/day for 2 weeks
Vitamin A: as per protocol
Potassium: 2-3 mEq/kg/day for 2 weeks
Magnesium sulphate: 0.2 mL/kg/d IM for 2-3d
Zinc: Can be given. No major role

32. Step 6: Monitoring the response
Successful treatment:
Diarrhoea: passive (<2 stools/day x 2 consec. days)
Adequate food intake
Documented weight gain
Target: Weight on day 7 > weight at admission
Weight gain should be documented on at least
3 successive days
Regular follow up

33. How long should we give Diet A or B?
Minimum 7 days trial each before failure is declared
If lactose intolerance: Lactose-free diet for at least 21 days

34. Additional drugs Antimotility drugs: Never
Antisecretory (racecadotril):
No role in persisted diarrhea
Probiotics (Lactobacilli, S. boulardii):
weak benefit

35. Case IV: 16 mo boy Sparsh Top fed Bottle feeding
No fever or urinary symptoms
Acute onset, watery
15 times/day for 7 days
Loose stools , occasional abdominal pain & bloating X 14 days
Cefixime 3 days
Ofloxacin 5 d
Norfloxacin-metranidazole 7 d

36. All Investigation Normal
Further course…
Lactulose hydrogen breath test which showed a rise in hydrogen suggestive of “Small intestinal bacterial overgrowth’’.
All Investigation Normal
Suspect SIBO
Substantially under-diagnosed & misdiagnosed entity
Frequently implicated as a cause of prolonged diarrhea & abdominal pain.
Characterised by an increased number and/or abnormal type of bacteria in the small intestine.

37. SIBO-Pathophysiology 9
SIBO significantly interferes with enzymatic, absorptive and metabolic actions of a macro-organism.
Due to injury of the brush-border of enterocytes, the activity of disaccharideses may be decreased.
Injured small intestinal mucosa can have undesirable consequences in increased intestinal permeability and/or protein-losing enteropathy.
Deficiency of vitamin B12 results from the consumption of this vitamin by anaerobic micro-organisms.
Bacteria may also utilise intraluminal protein in the small bowel, this may lead to protein deficiency for the macro-organism and excessive production of ammonia by bacteria.
Deconjugation of bile acids by bacteria results in malabsorption of fat and liposoluble vitamins.

38. SIBO Persistent Infectious diarrhoea diarrhea Summing up:-
Infectious diarrhoea can predispose to SIBO and SIBO inturn can lead to prolongation of the diarrhoea.
Persistent
diarrhea
Infectious diarrhoea
SIBO
Source : Giannattasio, Antonietta, Alfredo Guarino, and Andrea Lo Vecchio. “Management of Children with Prolonged Diarrhea.” F1000Research 5 (2016): F1000 Faculty Rev–206. PMC. Web. 10 May 2016.

39. SIBO-Diagnosis 9 Physical examination provides non specific findings.
Laboratory investigations
Complete blood count – anemia may be present
Low serum Vit. B12
Low serum prealbumin
Microbial investigation of jejunal aspirate obtained by endoscopy (gold standard but has low reproducibility & difficulty in identifying culture resistant organisms)
Hydrogen & methane breath analysis by chromatography following oral glucose /lactulose (most commonly used test): Early single peak following oral glucose or double peak after lactulose indicates a positive test.

40. SIBO-Treatment 9
Correction of the underlying cause (dietary/medical/surgical)
Nutritional support in patients with weight loss & nutritional deficiency.
- Supplementation of vitamin B12 , fat-soluble vitamins, calcium, Folic Acid
- Exclusion of lactose from diet.
- Reduction of simple sugars
- Energy needs conveyed by administering fat & medium chain triacylglyceroles
3) Antibiotics (mainstay of treatment) : A number of antibiotics have been tried for SIBO. Rifaximin appears promising.

41. Rifaximin-Dosing Dosing as per body weight
Dosage for adults and children older than 12 years is 10 to 15 mg/kg/day
Younger children a daily dose of 20 to 30 mg/kg/day (Treatment duration 7days)
Still not approved for <2 Years of age
Prescribing Information- Rifaximin
A Review of its Antibacterial Activity, Pharmacokinetic Properties and Therapeutic Potential in Conditions Mediated by Gastrointestinal Bacteria
Jane C. Gillis  Rex N. Brogden
March 1995, Volume 49, Issue 3, pp
First online: 24 October 2012

42. Rifaximin Pharmacokinetics & Safety profile
Unabsorbed from gut ->enables inhibition of enteric pathogens.
< 0.4% detected in blood & urine.
Undetected in bile, breast milk
Excreted unchanged in feces.
Half life – 6 hrs
No significant drug interactions.
Excellent safety profile.
Caution advocated in liver disease.
Safety in pregnancy not evaluated.

43. Rifaximin efficay & safety in children
Rifaximin being a non absorbable antibiotic with excellent tolerability in adults promises an ideal drug for use in children with Travelers Diarrhea & SIBO.
A meta-analysis of studies of Rifaximin in children was conducted by Fabio Capello et al. 11
Search Methods: All available publications related to use of rifaximin in children included
Results: Higher number of healed patients in the rifaximin groups at the end of the studies, with a reduction of the mean number of stool/day (-2,021; p<0,001); more formed stool (OR 4,31; p=0,001); a shorter Recovery Time when compared to control groups. The microbiological tests performed after treatment have shown the persistence of 54% of the potentially most dangerous pathogenic bacteria in the children treated with diet and rehydration alone, in comparison with 11.2% in children treated with rifaximin . (chi square 7.4; p= 0.02).
Conclusions: Use of rifaximin for bacterial diarrhea in children over 2 years may be fully justified in selected circumstances as in case of travelers' diarrhea, recurrent or relapsing diarrhea known or supposed to be caused by non-invasive Bacterial over growth

44. Summary Infections, malnutrition form vicious cycle
Persistent diarrhea > 14 days
Infections, malnutrition form vicious cycle
UTI, Fungal Infection ,Secondary lactose intolerance, SIBO are cause for prolongation
Home Based Dietary Management with correction of prolongation factor is the main stay of treatment
Rifaximin has a role in SIBO in children

45. Preparation of green banana diet
Raw, green banana
Remove skin
Take pulp, blend
Homogenized
100 g
Cook in boiling water
For 7-10 minutes +
Oil 25 g
Glucose 20 g
Nacl 01 g
± Egg white 80 g
Rice 10 g powder
Cook in one liter water +
Feed
Calories: 54/100ml