Acute gastroenteritis (AGE) Common condition in childhood 5 million deaths per year <5 yo in developing countries 2 million deaths annually worldwide Rotavirus is the most important cause but other intestinal viruses such as norwalk, noroviruses and enteroviruses, bacteria (Salmonella, Shigella) and Vibrio cholerae, protoza (such as criyptosporidium) are also important causes

AGE The hallmark is diarrhea Change in bowel habit resulting in substantially more frequent and/or looser stools Diarrhea may be associated with vomiting Two important clinical suggestions: -diarrhea and/or vomiting can be non-specific presenting signs in children with systemic sepsis e.g meningococcal infection, septicemia and urinary tract infection. Assess each child carefully -if a child has vomiting alone consider the possibility of other diagnoses e.g intestinal obstruction, diabetes or meningitis

Degree of dehydration in AGE Clinical signs become apparent at 3-4% Minimal or no dehydration if <3% Mild to moderate if 3-8% dehydrated Severely dehydrated if >9%

Assessment of degree of dehydration and recommended management Minimal or no deydration (<3%): no signs -manage at home generally -normal fluids, continue breast-feeding, normal diet -admit if very young, diagnosis in doubt, or large losses

Assessment of degree of dehydration and recommended management Mild to moderate dehydration (3-8%) -general appearance abnormal (looks unwell) - dry oral mucosa -absent tears -sunken eyes -diminished skin turgor (skin recoil after pinching skin>2s, capillary return >2s) -Manage in hospital with ORS -if ORS not tolerated, may require NG tube feeds or IV fluids -resume normal diet when tolerated

Assessment of degree of dehydration and recommended management Severe dehydration (>9%): -signs from mild to moderate +deep acidotic breathing -altered neurological status(drowsiness, irritability) -decreased peripheral perfusion -circulatory collapse -measure BUN, electrolytes, acid-base balance -resuscitate with IV bolus if shocked -rehydrate IV over 2-6 hrs with regular clinical and lab review

Assessment of degree of dehydration and recommended management Fluid requirement calculated as: volume needed to replace the deficit + maintenance fluids ongoing losses

Daily maintenance fluid requirement (MFR) Weight of the child MFR First 10 kg 100ml/kg Second 10 kg 50 ml/kg Subsequent 20 ml/kg Example: if the child weighs 8 kg MFR is 800ml İf the child weighs 12 kg MFR is(10x100)+(2x50):1100 ml İf the child weihgs 23 kg MFR is (10x100)+(10x50)+(3x20):1560 ml

Route of rehydration Question: is oral rehydration as effective and safe as IV rehydration? Compared to children treated with IV rehydration children treated with oral rehydration has significantly fewer major adverse events including death or seizures and significant reduction in lenght of hospital stay Fonseca BK, Holdgate A. Arch Pediatr Adolesc Med 2004;158:483-90 (meta analysis , 16 trials 1545 children)

Route of rehydration A cochrane review of 17 trials, 1811 participants, all poor to moderate quality More treatment failures with ORT No significant differences in weight gain, hyponatremia, hypernatremia, duration of diarrhea or total fluid intake ORT group stayed in the hospital for 1.2 days less Phlebitis occured more often in the IVT group and paralytic ileus in the ORT group Six deaths occured in the IVT and two in the ORT group For every 25 children treated with ORT one would fail and require IVT Hartling L, Bellemare S et al The Cochrane Database of Systematic Reviews 2006;(3) Art no CD004390

Route of rehydration Both oral and IV rehydration are safe and effective In developing countries where mothers nurse their infants and give frequent oral feeds, ORT is preferred In industrialized countries, ORT is cheaper and with fewer adverse effects Parents and nursing staff should be encouraged to give ORT and be informed that if they do so the child will avoid IV line and get home quicker

Route of rehydration Rapid IV rehydration over 4 hrs was advocated by WHO in 1980s for children in developing countries for moderate to severe dehydration In industrialized countries the practice of rapid IVT to rehydrate children over 1-3 hrs and send them home if they can tolerate oral fluids has been found to be safe and effective The main potential danger is fluid overload and/or electrolyte imbalance especially if the degree of dehydration is overestimated which is common. There is also risk of sending home some children who are in need of hospital care

Route of rehydration Severe dehydration (>9%) is life threatining and there is consensus that one should rehydrate severely dehydrated children using IV fluids

Choice of ORS Since 1980s the WHO has recommended a standart ORS with relatively high Na and glucose content (90 mmol/L Na, 111mmol/L glucose, total osmolality 311mmol/L) A number of studies compared standart ORS with reduced osmolality ORS (rORS) (total osmolality 250 mmol/L) rORS Has been found to be associated with fewer unscheduled IV infusions, lower stool output and less vomiting. No additional risk of hyponatremia was found The WHO now recommends rORS for non-cholera diarrhea

Mode of delivery of ORS Giving ORS by a NG tube is increasingly common in some industrialized countries NG tube feeds have the advantage of getting fluid in if a child refuses to drink or is vomiting frequently They are far less invasive, cheaper and less traumatic then IV fluids On the other hand they are more invasive then oral feeds, unpleasant and have not been shown to have any advantage over oral rehydration

Choice of IV fluids In many industrialized countries N/2 or N/4 saline are chosen for IV fluids and they are made isotonic by adding dextrose But as dextrose is rapidly metabolized the fluid becomes rapidly hypotonic The use of low Na fluids has recently been questioned following episodes of catastrophic hyponatremia associated with IV rehydration for AGE

Choice of IV fluids Hyponatremia is particularly likely to develop in children who concurrently have the syndrome of inappropriate ADH secretion (SIADH) Dehydration, vomiting and stress are potential causes of SIADH and occur commonly in AGE Investigations showed that for resuscitation of children with severe GE using IV fluids, normal saline with or without added dextrose is recommended

Antibiotics and AGE Antibiotics are not routinely recommended for AGE Most episodes of AGE are caused by viruses Most episodes are self-limiting, including those caused by bacteria and antibiotic use is likely to select for antibiotic resistance Antibiotics might increase gastrointestinal motility and cause bacterial overgrowth and thus worsen diarrhea

Antiemetics in AGE Ondansetron and metoclopramide reduces the number of episodes of vomiting in AGE in children compared to placebo but increases the incidence of diarrhea Use of antiemetics is not recommended in childhood AGE

Diet in AGE There is widespread consensus that breast-fed babies with dehydration from AGE should be rehydrated orally or IV but continue breast feeding Breast milk contains as much lactose as formula feeds. Despite this, many people advocate low lactose or lactose-free formulas, supposedly because of risk of lactose intolerance secondary to AGE

Diet in AGE A meta analysis of 29 trials (2215 patients) found no advantage of lactose-free formulas over lactose-containing formulas for the majority of infants, although infants with malnutrition or severe dehydration recovered more quickly when given lactose-free formula Brown KH, Peerson JM et al. Pediatrics 1994;93:17-2 Using diluted food in children recovering from AGE is not recommended because it is unnecessary and also prolongs symptoms and delays nutritional recovery

Diet in AGE Formulas containing soy fiber has been reported to reduce liquid stools without changing the stool output. This might reduce diaper rash and encourage early resumption of normal diet, but the benefits are probably insufficient to merit its use as a standard of care

Diet in AGE Children receiving semisolid or solid foods should continue to receive their usual diet. Routinely witholding food is inappropriate. Early feeding reduces changes in intestinal permeability caused by infection, reduces the duration of illness, and improves nutrition

Zinc in diarrheal disease Severe zinc deficiency is associated with diarrhea (acrodermatitis enteropathica) In developing countries, prophylactic dietary oral zinc supplementation reduces the incidence and severity of acute diarrheal disease in childhood The WHO recommends that oral zinc is given to children in developing countries at the onset of diarrhea

Probiotics in AGE Probiotics are live microorganisms in fermented foods or components of microbial cells that have a beneficial effect on the health and well-being of the host No serious adverse effects of probiotics have been reported in well people, but infections have been reported in people with impaired immune systems

Probiotics in AGE In one systematic review, probiotics reduce the risk of diarrhea lasting 3 or more days by 60% and reduce the duration of diarrhea by 18 hrs A cochrane review on 1917 adult and pediatric patients showed that probiotics reduced the risk of diarrhea at 3 days by 34% and the main duration of diarrhea by 30.5 hrs There is great variability among probiotics, further research is needed to to determine the optimal type, dosage and regimen Their routine use is not recommended in AGE in children but it is likely that their benefit outweighs their harm

Antibiotic associated diarrhea In most cases no pathogen is identified Toxin producing C. difficile is responsible for a minority Stopping antibiotics usually relieves the problem Dietary manipulation may help If it is not possible to stop the antibiotic, it is recommended to change to a regimen less likely to cause diarrhea Amoxicillin, broad-spectrum cephalosporins, quinolones are the antibiotics most commonly associated with diarrhea When C. difficile is identified, metronidazole 10 mg/kg (max 400 mg) orally 8 hourly for 7-10 days

Campylobacter enteritis Usually self-limited Antibiotics have relatively little clinical benefit and because of the risk of resistance are not routinely indicated Antibiotherapy is indicated only when there is high fever or severe illness suggesting septicemia , usually in infants. If antibiotics are indicated: eryhtromycin 10mg/kg PO q6hrs or azitromycin 10 mg/kg PO daily For bacteriemia gentamicin <10y 7.5mg/kg IV daily; >10 y 6mg/kg IV or ciprofloxacin 10mg/kg (max400mg) IV q12hrs

cholera Rehydration is the basis of treatment and can usually be achieved orally Standart ORS or rice-based ORS is recommended Antibiotic therapy reduces the volume and duration of diarrhea Azitromycin 20mg/kg POI as a single dose or doxycycline child>8yrs:2.5mg/kg (max100mg) PO q12h x3d or ciprofloxacin 25 mg/kg (max 1 g) PO as a single dose or erythromycin 12.5 mg/kg (max 500mg) PO q6hx3d

EHEC enteritis Infection with some EHEC strains e.g 0157:H7 and 0111:H8 can lead to development of HUS and TTP The use of antibiotics is controversial because they increase the release of shiga-like toxin and increase the incidence of HUS and TTP in humans Studies do not show any benefit of antibiotic use and some associate antibiotics with a higher risk of HUS and/or longer duration of diarrhea

EPEC enteritis Most EPEC infections occur in developing countries and organism is never cultured If serotype 0111:B4 is cultured mecillinam (extd spectrum penicillin) showed a clinical cure 79%, trimethoprim-sulfamethoxazole 73% and placebo only 7% The main significance is for traveler’s diarrhea

Non-typhoid Salmonella enteritis(NTS) NTS infections are food-borne Extraintestinal complications such as septicemia, meningitis and osteomyelitis are rare Outbreaks are associated especially with infected meat or eggs, cattle or pigs In developing countries, particularly tropical Africa, NTS are important cause of invasive extraintestinal disease

Non-typhoid Salmonella enteritis(NTS) Antibiotics result more negative stool cultures during the 1st week but cause more frequent clinical relapses and prolongation of detection of salmonella in stools after 3 wks Adverse drug reactions are more common with antibiotics Antibiotics are not indicated for asymptomatic short-term carriers Antibiotics are indicated for suspected or proven septicemia (infants<3m , malnourished infants or immunocompromised children with bloody diarrhea and fever and /or Salmonella isolated from feces

Non-typhoid Salmonella enteritis(NTS) Antibiotics are also recommended for Salmonella infection occurring in association with chronic gastrointestinal disease, malignant neoplasms, hemoglobinopathies or severe colitis Amoxicillin is preferred if the organism is susceptible For empiric therapy ciprofloxacin 10 mg/kg POq12h OR azithromycin 20mg/kgPO 1st day and 10mg/kg daily If PO not tolerated ciprofloxacin 10 mg/kg (max 400mg)IV q12h OR ceftriaxone 50mg/kg (max 2g) IV daily

Typhoid and paratyphoid fevers S. typhi and S, paratyphi are endemic in many developing countries. Almost all infection in industrialzed countries are acquired by travelers It is a septicemic illness rather then diarrheal illness Fever, hepatomegaly, abdominal pain, diarrhea, vomiting, cough, malaise and headache are prominent findings. Rose spots and bradycardia are rare in children Febrile convulsions, jaundice, ileus, perforation and impaired consciousness are other manifestations Hematologic abnormalities include neutropenia, leucopenia and thrombocytopenia

Typhoid and paratyphoid fevers For antibiotherapy: ciprofloxacin 15mg/kg (max500mg) PO q12hx 7-10d OR Azithromycin 20mg/kg (max1g)x5d If PO not tolerated ciprofloxacin 10mg/kg (max400mg) IV q12hx 7-10d OR Azithromycin 20mg/kg (max1g) IVx5d If clinical response delayed ceftriaxone 50mg/kg (max 2g) IV daily

Shigellosis Antibiotic therapy is recommended for children with shigella dysentery, even if mild, for public health reasons because a very low inoculum causes infection Effective antibiotics, if the organism is sensitive include quinolones, ceftriaxone, azithromycin, cefixime, and cotrimoxazole ciprofloxacin 15mg/kg (max500mg) PO q12hx 3d OR Azithromycin 20mg/kg (max1g)x5d OR Cotrimoxazole 4+20mg/kg PO q12hx5d

Traveler’s diarrhea At least 11 million people develop traveler’s diarrhea worldwide Passage 3 or more unformed stools over 24h with symptoms sterting during or shortly after a foreign travel, nausea, vomiting, abdominal pain, fever, tanesmus, and blood or mucus in stools About 85% are bacteria and ETEC is the most common one, campylobacter jejuni is responsible in 30% of cases, salmonella and shigella each accounts for 15% 2/3 of ETEC produce a heat-labile toxin similar to cholera toxin which induces secretory diarrhea For prevention boil it, cook it, peel it or forget it. Avoid drinking local water, consider tap water and ice cubes as contaminated. Bottled water is not always safe. Swimming pool is also a potential risk

Traveler’s diarrhea Althogh there are no efficacy data in children, an oral, killed, recombinant B-sub-unit, whole-cell vaccine against cholera and ETEC is available. Two doses given at least one week apart create immunization one week after the second dose Vaccine is licenced in only a few countries including Sweden and Canada Prophylactic antibiotics are recommended only in immunucompromised child traveling for a short period of time, in which case ciprofloxacin may be the antibiotic of chioce

Traveler’s diarrhea All trials reported a significant reduction in duration of diarrhea in participants treated with antibiotics compared with placebo The most effective antibiotics for empiric therapy from trials are quinolones, azithromycin, and rifaximin All patients should take fluids and electrolytes. Rehydration with ORS is particularly important for young children Antimotility drugs, such as loperamide, should be avoided in children, because of the danger of causing paralytic ileus. Mild cases do not usually need antibiotics For moderate to severe disease, azithromycin 20 mg/kg (max 1 g) orally, as a single dose OR ciprofloxacin 20 mg/kg (max 750 mg) orally, as a single dose OR norfloxacin 20 mg/kg (max 800 mg) orally, as a single dose OR trimethoprim+sulfamethoxazole 4+20 mg/kg (max 160+800 mg) orally, 12-hourly for 3 days OR rifaximin 10 mg/kg orally, 12-hourly for 3 days

Amebiasis E. histolytica infection can cause non-invasive intestinal infection, which can be symptomatic or cause amebic dysentery or colitis, ameboma, and/or liver abscess Passage of Entamoeba cysts or trophozoites in the absence of acute dysenteric illness does not warrant antimicrobial therapy Patients with amebic colitis characteristically present with dysenteric symptoms of bloody diarrhea, abdominal pain, and tenderness. Children can have rectal bleeding without diarrhea. The onset can be gradual, with several weeks of symptoms: often multiple, small volume, mucoid stools, but sometimes profuse, watery diarrhea

Amebiasis Toxic megacolon complicates amebic colitis in about 0.5% of patients Amebomas are localized inflammatory, annular masses of the cecum or ascending colon which can cause obstruction and be confused with carcinomas The diagnosis of amebic colitis rests on the demonstration of E. histolytica in the stool or colonic mucosa of patients with diarrhea. Commercially available ELISA assays are more sensitive and less user-dependent than microscopy

Amebiasis Serum antibodies against amebae are detected by indirect hemagglutination in >70% of patients with symptomatic E. histolytica infection and are particularly sensitive (>94%) in amebic liver abscess For acute amebic dysentery, the nitroimidazoles (metronidazole, tinidazole, ornidazole) are >90% effective metronidazole 15 mg/kg (max 600 mg) orally, 8-ourly for 7–10 days OR tinidazole 50 mg/kg (max 2 g) orally, daily for 3 days

Cryptosporidium Cryptosporidium parvum infection causes frequent, watery diarrhea, without blood in immunocompetent children. Other prominent symptoms include crampy abdominal pain, fever, and vomiting. Asymptomatic infection is rare. Infections are often waterborne; the cysts are resistant to chlorine, and contaminated water and swimming pools have been the source of large outbreaks. In immunocompetent children, infection usually resolves after 10 days (range 1–20) and requires no specific treatment. In contrast, Cryptosporidium infection can be life-threatening in immunocompromised children. To treat Cryptosporidium infection in immunocompromised children, nitazoxanide 1–3 years: 100 mg 12-hourly; 4–11 years: 200 mg 12-hourly; 12 years or older: 500 mg orally 12-hourly, for 3 days

Giardiasis Giardia lamblia is a flagellate protozoan parasite with a worldwide distribution. Infection is primarily waterborne, and although humans are the main reservoir of infection, animals such as dogs and cats can contaminate water with infectious cysts. Infection can be asymptomatic, can be acute with watery diarrhea and abdominal pain, or protracted with chronic or intermittent foul-smelling stools, abdominal distension, flatulence, and anorexia

Giardiasis Diagnosis is by detecting cysts in stool. Although ELISA tests on stool are slightly more sensitive than direct microscopy for ova and parasites, one study suggested that both tests need to be performed to achieve a sensitivity >90%. Diagnosis in difficult cases may require examination of aspirated duodenal fluid. Most authorities agree that treatment of patients with asymptomatic passage of Giardia cysts is unwarranted. The traditional treatment of symptomatic patients is with metronidazole 5 mg/kg (max 250 mg) orally, 8-hourly for 5 days, which is 80–95%effective For immunocompetent children who fail therapy, it is usual to repeat the original course while investigating whether reinfection may have occurred from a family member or water source