Diarrhoea update 1

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  • 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.
  • Diarrhoea update 1

    1. 1. DR. RAKES SHAHM.D.(PEDIATRICS) PANTH CHILDREN HOSPITAL HATKESHWAR
    2. 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.
    3. 3. Definition  Diarrhoea is the passage of loose or watery stools at least three times in 24 hour .
    4. 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. 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. 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. 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.
    8. 8. ETIOLOGY OF ACUTE DIARRHOEA Viral : Rota Virus  Adenovirus Norwalk Agent Bacterial :  V. Cholera  ETEC, EIEC  Salmonella  Shigella CampylobacterFungal :  Candida
    9. 9. Parasitic Infection :  Giardia Lamblia  Cryptosporidium  Entamoeba Histolytica Drugs :  Laxatives  Sorbitol  Antacids  Lactulose  Theophylline  Antibiotics  Quinidine Diet : Food Poisoning Food allergy
    10. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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.
    20. 20. ROLE OF ANTIBIOTICS
    21. 21. Bacteria Antibiotic Salmonella typhi, Salmonella paratyphi Ampicillin,† chloramphenicol,† TMP-SMZ, cefotaxime, ciprofloxacin‡ Nontyphoidal Salmonella Usually none (if ≥ 3 months old); ampicillin, cefotaxime, ciprofloxacin‡ Shigella ( Dysentery ) Children: Third-generation cephalosporin, TMP-SMZ Nalidixic acid Adults: fluoroquinolones‡ Escherichia coli Enterotoxigenic Usually none if endemic; TMP-SMZ or ciprofloxacin for traveler's diarrhea Enteroinvasive TMP-SMZ, ampicillin if susceptible Enteropathogenic TMP-SMZ or an aminoglycoside Enterohemorrhagic Usually none Enteroaggregative TMP-SMZ or an aminoglycoside Campylobacter jejuni Mild disease needs no treatment; erythromycin or azithromycin for diarrhea; aminoglycoside,
    22. 22. Bacteria Antibiotic Yersinia enterocolitica None for uncomplicated diarrhea; TMP-SMZ; gentamicin or cefotaxime for extraintestinal disease Vibrio cholerae Tetracycline, doxycycline, TMP- SMZ Clostridium difficile Oral metronidazole,§ oral vancomycin Entamoeba histolytica Metronidazole§ followed by iodoquinol to treat luminal infection Giardia lamblia Metronidazole,§ quinacrine, furazolidone, others Cryptosporidium parvum None; azithromycin or paromomycin and octreotide in
    23. 23. Complications 1) DEHYDRATION 2) DYSELECTROLYTAEMIA 3) PPT. OF MALNUTRITION 4) PERSISTENT DIARRHOEA 5) TOXIC ILEUS 6) HUS 7) DIC 8) CORTICAL VIEN THROMBOSIS.
    24. 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. 25. TYPES OF ORS FORMULATIONS  Glucose based ORS  Rice based ORS  Low osmolarity ORS  Home available ORS  Mineral based ORS(zinc)
    26. 26. 15th Aug. 2013 US FDA Announcement - Fluroquinolones
    27. 27. 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
    28. 28. Therapeutical use of probiotic formulations in clinical practice. Clinical Nutrition 29 (2010) 701e725
    29. 29. GI flora components Therapeutical use of probiotic formulations in clinical practice. Clinical Nutrition 29 (2010) 701e725
    30. 30. Mechanisms of probiotic/host interaction. World Gastroenterology Organisation Practice Guideline Probiotics and prebiotics. www.worldgastroenterology.org/.../guidelines/19_probiotics_prebiotics
    31. 31. 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
    32. 32. 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
    33. 33. 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
    34. 34. 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
    35. 35. 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
    36. 36. 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
    37. 37. 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
    38. 38. 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
    39. 39. 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
    40. 40. 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
    41. 41. 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
    42. 42. 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
    43. 43. Commercially used probiotic strains. Therapeutical use of probiotic formulations in clinical practice. Clinical Nutrition 29 (2010) 701e725
    44. 44. Bifidobacteria benefits on human health. Therapeutical use of probiotic formulations in clinical practice. Clinical Nutrition 29 (2010) 701e725
    45. 45. Main therapeutic and nutritional effects of Lactobacilli. Therapeutical use of probiotic formulations in clinical practice. Clinical Nutrition 29 (2010) 701e725

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