lect 1 Acute intestinal infections.pptx infectious

Infectious disease

1. Lecture 1 Topic: Acute Intestinal Infections in Children Lecture plan: Classification of diarrhea in children Dysentery in children Salmonellosis Acute intestinal infections caused by opportunistic enterobacteria Viral diarrheas Treatment of AII Infectious diseases department

2. There are 3 clinical types of diarrhea: acute watery diarrhea – lasts several hours or days and includes cholera acute bloody diarrhea – also called dysentery persistent diarrhea – lasts 14 days or longer. Diarrhea is frequent loose or watery bowel movements that deviate from a child’s normal pattern. Diarrhea may be accompanied by anorexia, vomiting, acute weight loss, abdominal pain, fever, or passage of blood. If diarrhea is severe or prolonged, dehydration is likely. Even in the absence of dehydration, chronic diarrhea usually results in weight loss or failure to gain weight. Diarrhea is a very common pediatric concern, and diarrhea and dehydration cause about 1.5 to 2.5 million deaths/year worldwide. It accounts for about 9% of hospitalizations in the US among children < 5 years of age. 1. Diarrhea in children Definition Classification

3. There are 1.7 billion cases of childhood diarrhea every year, and diarrhea is the second leading cause of mortality in children under five years old, with about 525,000 childhood deaths annually. Most of this mortality is preventable through access to care and rehydration therapy. Complications such as ensuing malabsorption can be seen that impact child growth after recovery from the immediate illness. There are an estimated 5.2 million cases of bacterial diarrhea in the U.S. annually, with 80% of infections resulting from foodborne contamination. Global estimates for the prevalence of specific types of bacterial diarrhea among all diarrheal causes include  E.coli  10% to 25%,  Shigella  10%,  Salmonella  3%,  Campylobacter  3 to 6%. A nd bacterial diarrhea in the U.S. was estimated to be approximately 31% of all diarrheas. The proportion of bacterial pathogens resulting in foodborne diarrheal illness in the U.S. is estimated to be:  Salmonella  15.4%,  Campylobacter  11.8%,   Shigella   4.6 %,  Shiga-toxin producing E. coli  (STEC) around 3%. https://www.ncbi.nlm.nih.gov/books/NBK551643/ Epidemiology

4. Etiology of Diarrhea in Children The causes and significance of diarrhea differ depending on whether it is acute (< 2 weeks) or chronic (> 2 weeks). Most cases of diarrhea are acute. Acute diarrhea  usually is caused by Gastroenteritis Antibiotic use Food allergies Food poisoning Most gastroenteritis is caused by a virus; however, any enteric pathogen can cause acute diarrhea. Chronic diarrhea  usually is caused by Dietary factors Infection Celiac disease Inflammatory bowel disease Chronic diarrhea can also be caused by anatomic disorders and disorders that interfere with absorption or digestion. https://www.msdmanuals.com/professional/multimedia/table/some-causes-of-diarrhea Etiology of Diarrhea

5. Etiology of Diarrhea

6. Pathophysiology of Diarrhea in Children Mechanisms of diarrhea may include the following: Osmotic Secretory Inflammatory Malabsorptive Osmotic diarrhea  results from the presence of non-absorbable solutes in the gastrointestinal tract, as with  lactose intolerance . Fasting for 2 to 3 days stops osmotic diarrhea. Secretory diarrhea  results from substances ( eg , bacterial toxins) that increase secretion of chloride ions and water into the intestinal lumen. Secretory diarrhea does not stop with fasting. Inflammatory diarrhea  is associated with conditions that cause inflammation or ulceration of the intestinal mucosa ( eg ,  Crohn disease ,  ulcerative colitis ). The resultant outpouring of plasma, serum proteins, blood, and mucus increases fecal bulk and fluid content. Malabsorption  may result from osmotic or secretory mechanisms or conditions that lead to less surface area in the bowel. Conditions such as pancreatic insufficiency and  short bowel syndrome  and conditions that speed up transit time cause diarrhea due to decreased absorption. physiology of Diarrhea in Children

7. 2. Dysentry in children (Shigellosis) Definition Acute diarrhea associated with blood, mucus and pus cells (WBCs) in the stool, is called dysentery. The term bacillary dysentery is used to describe dysentery caused by Shigellae spp.

8. Etiology

9. Shigellosis is common disease occurring primarily in children between 1-10 years of age. Fecal-oral transmission is more common in this age group. Infection in the first months of age is rare especially in breast-fed babies. Humans are the major reservoir of infection. Contaminated food and water supplies are common source of spread. Incubation period is from 1-7 days (average 2-4 days). infected patients, especially who are not receiving antibiotic therapy, may shed organisms up to month. Epidemiology

10. Shigellae are invasive p athogens that destroy the superficial epithelial cells, producing inflammation, edema, micro-abscesses, and ulceration with bleeding. The colon is selectively affected. Pathogenesis Development of disease and form of disease depends characteristic pathogenic bacteria (toxicity, invasiveness) and also depends on the conditions of host (macro organism). Shigellae enter the host through the mouth. Death of Shigella causes to release (liberation) of endotoxin, which enters in blood and development of intoxication.

11. Pathogenesis

12. By types : 1 . typical – colitis 2 . atypical : - hyper toxic form; - food poisoning; - dyspeptic form; - obliterated form; - subclinical form (bacterial carrier). II. By severity: mild, moderate, severe. III. By course of disease: - With complication; - With out complication; - Acute (before 1, 5 months); - Prolong ((before 3 months) ; - Chronic – more than 3 months Classification of clinical forms of dysentery Clinical manifestation Dysentery is characterized by an incubation period of 1-7 days (at the average 2-3 days, max 17 )

13. There are 2 syndromes: intoxication and colitis. The onset of disease is acute. We can see increase temperature to 40 C, anorexia, headache, vomiting. In young children may be convulsions present. Diarrhea is characterized by the frequent passage of small liquid stools that contain blood, mucus and pus. Abdominal pain and tenesmus (unproductive, painful straining) are common. Most patients initially have a watery diarrhea that over the subsequent 1 or 2 days evolves into a more typical invasive syndrome. Dysentery is a syndrome characterized by frequent (usually 10 to 30 times per day) of small-volume stool consisting of blood, mucus, and pus. This diarrhea is accompanied by severe abdominal cramps and tenesmus – the painful straining with stooling, it may lead to rectal prolapse (especially in young children). Typical form – colitis :

14. Onset may be abrupt. Child may have crampy abdominal pain, urgency, tenesmus, malaise, and non-localized tower abdominal tenderness. Temperature is usually up to 104°F (40°C) lasting for 1- days. Due to vomiting and diarrhea, there is dehydration. Watery and mucoid stools contain blood. Shigellosis may present like CNS disease such as meningitis , particularly when high-grade fever is associated with seizures, lethargy , and neck rigidity. Seizures occur in 30% of children with S higella gastroenteritis and are more common if the temperature rises up to 104°F. Symptoms generally last 3-7 days Onset may be abrupt. Child may have crampy abdominal pain, urgency, tenesmus, malaise, and non-localized tower abdominal tenderness. Temperature is usually up to 104°F (40°C) lasting for 1- days. Due to vomiting and diarrhea, there is dehydration. Watery and mucoid stools contain blood . Shigellosis may present like CNS disease such as meningitis , particularly when high-grade fever is associated with seizures, lethargy, and neck rigidity. Seizures occur in 30% of children with Shigella gastroenteritis and are more common if the temperature rises up to 104°F. Symptoms generally last 3-7 days . Clinical manifestation

15. Dehydration Acidosis Shock and renal failure Bacteremia metastatic infections Febrile seizures Rectal prolapse Hemolytic-uremic syndrome (HUS) Complications: Investigations: https://emedicine.medscape.com/article/968773-workup?form=fpf Stool examination should reveal leukocytes (pus cells) and red blood cells. Complete blood count may show leukocytosis with shift to left. In children who appear to be toxic, blood culture may be positive. Diagnosis is confirmed by isolating the S higellae by stool culture. Specimens should be plated lightly onto MacConkey , xylose-lysine- deoxycholate , Hektoen enteric, or  Salmonella- Shigella ,  or eosin-methylene blue agars.

16. Fluid and electrolyte replacement by using oral rehydration solution (ORS). Nutrition is key concern. high-protein and high caloric diet. A single large dose of vitamin (200,000 IU) decreases the severity of shigellosis. Zinc supplementation (20 mg elemental zinc for 14 days} decreases the duration of diarrhea, improves weight gain and immune response, and decreases diarrheal disease in the next months in malnourished children. Antibiotics not only cure the disease but also decrease further intestinal shedding of the organisms and further transmission of infection to others. Choice of antibiotics depends upon recent local stool culture reports. Effective antibiotics are: N alidixic acid, ceftriaxone, ciprofloxacin, cefixime , chloramphenicol and azithromycin. Treatment Encourage prolonged breastfeeding, Hand washing especially after defecation and before food preparation and consumption should be done. Proper water and sewage treatment should be ensured Prevention:

17. 3. Salmonellosis in children (non- typhoidal ) Salmonellosis is an acute infectious disease. Salmonellosis ranges clinically from the common Salmonella gastroenteritis (diarrhea, abdominal cramps, and fever) to enteric fevers (including typhoid fever) which are life-threatening febrile systemic illness requiring prompt antibiotic therapy. Focal infections and an asymptomatic carrier state occur. The most common form of salmonellosis is a self-limited, uncomplicated gastroenteritis Definition Worldwide anthropozoonotic infection. The source of infections is human with salmonellosis disease, bacterial carrier and animals. The transmission way is fecal-oral usually by contaminated food and water and person to person contact . Epidemiology

18. Salmonella  species are thought to be part of the normal microbiota of an animal’s gut or gallbladder, these animals may also play a role in the pathogen’s indirect or direct transmission to humans. The sources of  Salmonella  infection include Poultry and poultry products, which are considered the primary source of  Salmonella  infection in humans. Meat contamination occurs generally as a result of improper handling of the infected organs, such as the gut and liver, during carcass processing  Epidemiology

19. Pathogenesis

20. Clinical manifestation The incubation period is from some hours (12-24) to 3 days. Classification: I. By type 1. The typical forms include: Gastritis Enteritis Colitis Gastroenteritis Enterocolitis Gastroenterocolitis 2. The atypical forms: Septic form. Dyspeptic form Carrier Subclinical form Typhoid form II. By severity: mild, moderate, severe. III. By course of disease: - With complication; - Without complication;

21. Clinical manifestation

22. Gastroenteritis Is one of the most common forms of salmonellosis (96-98% of cases) Acute onset. The body temperature rises (in severe forms to 39°C and above) accompanied by general weakness, headache, chills, nausea, vomiting, pain in the epigastric and umbilical areas, followed by diarrhea Some patients initially have only a fever and some signs of intoxication, and then they experience changes in the gastrointestinal tract

23. Symptoms of salmonellosis are relatively mild and patients will make a recovery without specific treatment in most cases. However, in some cases, particularly in children and elderly patients, the associated dehydration can become severe and life-threatening. Although large  Salmonella  outbreaks usually attract media attention, 60–80% of all salmonellosis cases are not recognized as part of a known outbreak and are classified as sporadic cases, or are not diagnosed as such at all. profuse watery liquid stool , fetid, greenish in color , with pieces of undigested food, mixed with mucus.

24. Enterocolitis T his form arises in children of early age by contact way of transmission. Acute onset of disease: increase of temperature to 38 C – 40C C, symptom of intoxication: patient with high temperature for 5-7 days, loss of appetite and sleep impairment, vomiting, abdominal pain, increased watery stools of dark green color with contains of mucus and blood. The diarrhea is usually characterized by the presence of white and red cells in the stool. There is a voluminous diarrhea with gross blood and pus in the stool. The stool is green and includes mucus. Gastrointestinal syndrome is characterized by frequent (about 10 to 30 times per day) big-volume stool.

25. Atypical forms: Typhoid form. This form is characterized by acute onset of disease with increase of body temperature up to high grade, intensive symptoms of intoxication: headache, vomiting, stupor and loss of consciousness, pale color of the skin, meteorism , abdominal pain, watery stool, not much content of mucus, green color, hepatospleenomegaly . Septic form. It is a severe form, with acute onset of disease. It is characterized by increase temperature to 40 C degrees, there are severe intoxication symptoms, mostly associated with neurological symptoms. Secondary septic foci may be internal organs (osteomyelitis, purulent lymphadenitis and other), mostly this form does not involve intestinal form. There is sometimes occurrence of watery stool with mucus and green color, this form has characteristic long duration and may ends with lethal outcome (death). Diagnosis is based on isolation of salmonella from secondary purulent foci or blood. Subclinical form. Salmonellosis appears in children of any age, the clinical symptoms are absent, there is a positive bacteriology analysis.

26. Complications Specific complications: intestinal dysbiosis , intestinal bleeding, perforation of intestine and peritonitis . Nonspecific complications: severe malnutrition, anemia, meningitis, osteomyelitis, abscess, pyelonephritis, otitis, pneumonia and other.

27. Laboratory findings Routine examinations: WBC - is normal or increased. Bacteriological examinations: Stool cultures Blood culture Serological tests(Vidal test): Antibody reaction appear during first week

28. Ceftriaxone (50 mg/kg/24 hours as single daily dose lV or IM). Cephalosporin - C efixime (8 mg/kg/24 hours divided every 12-24 hours). Azithromycin (12 mg/kg/24 hours orally for the 1* day, followed by mg/kg/24 hours for the next 5 days). Ciprofloxacin (20-30 mg/kg/24 hours divided into 2 doses) Treatment and prevention

29. 4. Acute intestinal infections caused by opportunistic enterobacteria The most frequently identified organisms causing bacterial diarrhea are  Escherichia coli  (most common worldwide ), Campylobacter  (most common in children), Yersinia, Clostridium spp., Klebsiella , Proteus, Yesinia, Staphylococcus and other). Traveler's diarrhea can be most commonly the result of  Shiga-toxin producing E. coli (STEC),  as well as   Shigella , Salmonella, Entamoeba histolytic, Giardia, Cryptosporidium, Cyclospora , and enteric viruses.

30. Escherichia coli (E. coli ) bacteria normally live in the intestines of healthy people and animals . Most types of  E. coli   are harmless or cause relatively brief diarrhea . But a few strains , such as  E. coli  O157:H7, can cause severe stomach cramps , bloody diarrhea and vomiting . Human may be exposed to  E. coli   from contaminated water or food — especially raw vegetables and undercooked ground beef . Healthy adults usually recover from infection with  E. coli  O157:H7 within a week . Young children and older adults have a greater risk of developing a life-threatening form of kidney failure . Most types of  E. coli  are harmless and even help keep GIT healthy. But some strains can cause severe   diarrhea or food poisoning   due to contaminated food or polluted  water . Escherichi osis Definition https://www.ncbi.nlm.nih.gov/books/NBK564298/

31. Etiology Escherichia coli  results in intestinal illness as well as infection outside of the intestine. Intestinal illness caused by  E. coli  is caused by one of five subtypes, and they are identified according to their O and H antigens. The O antigen is determined by a repeating polysaccharide chain present in the lipopolysaccharide (LPS) outer membrane, and the flagellum determines the H antigen.

32. Epidemiology Person-to-person contact is an important mode of transmission through the oral- faecal route. An asymptomatic carrier state has been reported, where individuals show no clinical signs of disease but are capable of infecting others . The World Health Organization reports there are roughly 2.8 million cases of EHEC/STEC infections globally as of 2014 .  According to the CDC, there were reportedly 3,127 cases in the United States in 2019 .  While the number of reported cases of O157:H7 declined in the United States in 2019, the number of non-O157:H7 EHEC/STEC cases rose by 35% compared to the previous year. This is likely due to more readily available PCR-based assays to identify organisms that allow laboratories to distinguish  E. coli  O157:H7 from non-O157:H7 strains. EHEC/STEC infections are common across all age groups, but hemolytic uremic syndrome (HUS) resulting from EHEC/STEC infections is most common in children less than five years old and adults greater than 60 years old.

33. Pathophysiology ETEC: Colonizing fimbriae expressed by ETEC enable the bacteria to attach to the intestinal wall. Once connected, ETEC expresses a heat-labile toxin (LT) and/or heat-stable toxin (ST), which are secretory toxins encoded on plasmids. LT stimulates adenylate cyclase leading to increased intracellular cyclic adenosine monophosphate ( cAMP ) and the subsequent chloride secretion from intestinal crypt cells. This mechanism also inhibits intestinal villi from absorbing sodium chloride. This process leads to free water secretion into the intestinal lumen, thus producing watery diarrhea. ST stimulates guanylate cyclase leading to increased intracellular cyclic guanosine monophosphate (cGMP) and the subsequent chloride secretion and inhibition of sodium chloride absorption, thus producing watery diarrhea

34. Pathophysiology EHEC/STEC: EHEC/STEC produces bloody diarrhea due to its ability to express Shiga toxin 1 (Stx1) and or Shiga toxin 2 (Stx2).Stx1 and Stx2 are closely related to Shiga toxin ( Stx ) produced by  Shigella dysenteriae . EHEC/STEC, which expresses Stx2, results in bloody diarrhea and may also express Stx1, while bacteria that do not express Stx2 do not induce bloody diarrhea. The Stxs are a group of bacterial AB protein toxins composed of one A subunit and five identical B subunits capable of inhibiting protein synthesis through their ability to target eukaryotic ribosomes. The A subunit is responsible for inhibiting protein synthesis while the B pentamer binds glycosphingolipid Gb3, a cellular receptor on endothelial cells. The inhibition of protein synthesis results in enterocyte cell death and subsequent inflammatory colitis. The EHEC/STEC genome also encodes intimin , which is its primary adhesin , and EHEC/STEC possesses a plasmid (pO157) that expresses a pore-forming toxin termed EHEC- hemolysin.Once EHEC/STEC attach and produce localized intestinal damage, the Stx toxins enter the host and travel to target organ epithelial cells. Glomerular epithelial cells undergo similar damage as enterocytes, and as a result of cell death, detach from the glomerular membrane. This inflammatory state results in thrombosis and activation of the coagulation cascade yielding subsequent thrombocytopenia, anemia, and renal damage, the HUS triad. EHEC/STEC is also known for its ability to induce hemolytic uremic syndrome (HUS). HUS is characterized by the triad of microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and renal insufficiency.

35. EPEC: A bundle-forming pilus (BFP) is encoded by the plasmid ( pEAF ), enabling EPEC to form a localized attachment to enterocytes in the small intestine. Once bound, the outer membrane protein colonization factor, intimin , facilitates enhanced adherence. Intimin is an outer membrane protein colonization factor encoded on the eae gene within the locus of enterocyte effacement (LEE) chromosomal island. The LEE chromosomal island elaborates approximately 20 secretory toxins that are injected in the enterocyte by a type III injectisome . These toxins result in a series of events, ultimately leading to the characteristic effacement of microvilli, increased permeability of tight junctions, and alterations in water and electrolyte secretion and absorption. EspF is a LEE-secreted protein that is not involved with attaching and effacing. It appears to disrupt the intestinal barrier function by increasing monolayer permeability via alteration of electrical resistance. EspF has several protein-protein interaction domains that may function by interacting with endocytic regulation. Two other secreted proteins, EspG and EspG2, inhibit luminal membrane chloride absorption by decreasing surface expression of the Cl-/OH-exchanger via disruption of microtubules. Pathophysiology

36. EPEC: A bundle-forming pilus (BFP) is encoded by the plasmid ( pEAF ), enabling EPEC to form a localized attachment to enterocytes in the small intestine. Once bound, the outer membrane protein colonization factor, intimin , facilitates enhanced adherence. Intimin is an outer membrane protein colonization factor encoded on the eae gene within the locus of enterocyte effacement (LEE) chromosomal island. The LEE chromosomal island elaborates approximately 20 secretory toxins that are injected in the enterocyte by a type III injectisome . These toxins result in a series of events, ultimately leading to the characteristic effacement of microvilli, increased permeability of tight junctions, and alterations in water and electrolyte secretion and absorption. EspF is a LEE-secreted protein that is not involved with attaching and effacing. It appears to disrupt the intestinal barrier function by increasing monolayer permeability via alteration of electrical resistance. EspF has several protein-protein interaction domains that may function by interacting with endocytic regulation. Two other secreted proteins, EspG and EspG2, inhibit luminal membrane chloride absorption by decreasing surface expression of the Cl-/OH-exchanger via disruption of microtubules Pathophysiology

37. Pathophysiology EAEC: EAEC exhibits a stacked brick pattern of adherence to epithelial cells. The virulence plasmid encodes the transcriptional activator AggR which activates several virulence factors, although scientific understanding of this process is not complete.AggR likely induces aggregative adherence fimbriae (AAF/I-III), adhesin , surface protein dispersin , and the enterotoxins Pet, EAST-1, ShET1, and ShET2. Dispersin likely promotes AAF-mediated colonization.

38. Pathophysiology EIEC: Like EHEC, enterotoxins induce secretory diarrhea. Subsequent colonization and invasion of colonic mucosa, replication, cell-to-cell spread result in inflammatory colitis. Extraintestinal infections caused by  E. coli  are generally the result of the translocation of commensal  E. coli  outside of the intestine. The urinary tract is the most common extraintestinal site of infection caused by  E. coli . UTIs are a significant reason for ambulatory care visits in the US and is the second most common cause of hospitalization after pneumonia. Urinary tract infections from  E. coli  result from bacteria ascending the urethra and are more common in women than men, given the proximity of the urethra. Community-acquired pneumonia (CAP) caused by  E. coli  is common, but ventilator-associated pneumonia (VAP) is more common. Hospitalized patients, particularly those on mechanical ventilation, are at an increased risk of aspirating gastric contents.  E. coli  bacteremia is often the result of a primary  E. coli  infection at another site. Community-acquired  E. coli  bacteremia is most frequently the result of urinary tract infections in older adults, while hospitalized patients likely develop bacteremia as a result of lower respiratory tract infection

39. Classification of clinical forms of Escherichiosis I. By types : 1. Typical. 2. Atypical forms: coli-sepsis form; obliterated form; subclinical form (bacterial carrier). II. By severity: mild, moderate, severe. III. By course of disease: With complication; without complication; Acute; Prolong (more than 1, 5 months).

40. Enteropathogenic E. coli (This stereotypes O26, O41, O44, O55, O75, O86, O111, O119, O125, O126, O127, O142, O153, O408), Primarily affects infants. Rapid spread person to person may occur. Symptoms develop after a incubation period from 1 to 2 days. Acute onset of disease, increase temperature from 38C, general weakness, vomiting, and anorexia. Frequent watery stools with contents of mucus, flatulency (at palpation distended abdomen), paresis of colon. Dehydration i s common Symptoms end within usually 5 to 15 days. Enteroinvasive E. coli (This stereotypes O124, O151, rarely O28, O29, O32, O112, O129, O 135, O 139, O143, O 144, O152 and O164) Causes a form of diarrhea similar to Shigella infection. The incubation period is usually 1 to 3 days. There are 2 syndromes: intoxication + enterocolitis . The onset of disease is acute, increase of temperature 38-40 C, vomiting, abdominal cramps, and tenesmus. Stools often contain blood and leukocytes. Symptoms are usually self-limited within 7-10 days. Enterotoxigenic E. coli ( This stereotypes O6, O7, rarely O8, O9, O15, O20, O25, O 27, O 63, O73, O 78, O80, O 85, O115, O128, O 139, O148, and O159) Diarrhea is watery and ranges from mild to severe. Children experience several episodes of during the first 3 years of life. Incubation period is 1-3 days, followed by the sudden onset of watery diarrhea without blood, mucus. Vomiting may occur, but most patients have no fever. Infection usually is self-limited and persists less than 5 days.

41. Enterohemorrhagic E. coli ( E. coli O157, O 145) The disease ranges from mild watery diarrhea to severe hemorrhagic colitis and may be followed by haemolytic uraemia syndrome (HUS consists of the triad of microangiopathic hemolytic anemia, thrombocytopenia and renal insufficiency) HUS typically develops in the second week of illness (range 2-14 d), often after the diarrhea has resolved. Patients present with pallor, weakness, irritability, and oliguria or anuria. Following an incubation period of 3-4 days, watery diarrhea develops, often accompanied by abdominal cramping and vomiting. Diarrhea becomes bloody in 1-2 days in most patients but usually is not associated with fecal leukocytes. Fever is present in about a third of cases. Illness duration typically is 4-10 days. Enteroaggregative E. coli cause watery diarrhea. Little data are available regarding their mechanisms of pathogenesis. _____________________________________________ For patients with extraintestinal illness, culturing blood, urine, or sputum will identify  E. coli . Many gram-negative bacilli have developed antibiotic resistance genes, and  E. coli  is no exception. Extended-spectrum beta-lactamase (ESBL) -producing  E. coli  confer resistance to most beta-lactamase antibiotics (e.g., cephalosporins , monobactams , etc.). In contrast, carbapenemase -producing  E. coli  strains possess genes conferring resistance to carbapenems (e.g., imipenem , ertapenem , and meropenem ).

42. Summary E. coli - Gram-negative bacilli, non-spore-forming, flagellated, facultatively anaerobic Ferments lactose (grows on MacConkey agar) Catalase positive Oxidase negative  ETEC - Culture: MacConkey agar, indole producing Molecular diagnosis: LT or ST genes EHEC/STEC - CultureO157:H7: Sorbitol- MacConkey agar, indole producing Non-0157:H7: MacConkey agar Molecular diagnosis: NAAT of Stx1 and Stx2 EIEC - Culture: MacConkey agar (glucose and xylose), indole producing Molecular: NAAT of lacY EPEC - Culture: MacConkey agar, indole producing Molecular diagnosis: pEAF plasmid or BFP factor EAEC - Culture: MacConkey agar, indole producing Molecular diagnosis: AggR regulon Investigations: Stool cultures Blood culture WBC - is normal or increased Hb – decreased Er – decreased Plt – decreased ESR - increased   Urine output- oliguria, anuria Creatinine – increased Diagnostics

43. Treatment Watery Diarrhea: Rehydration: Oral fluids, if tolerated IV fluids if oral fluids not tolerated Invasive diarrhea: Antibiotics Ceftriaxone 50-100 mg/kg/day IV or IM, BID 3-5 days Ciprofloxacin 20-30 mg/kg/day PO BIDfor 7-10 days Ampicillin PO, IV 50-100 mg/kg/day QID for7 days Azithromycin: 10 mg/kg on day 1 st , 8mg/kg on days 2 and 3 (5 th ) Rifaximin : - Children 3 to 11 years: Limited data available: Oral: 100 mg 4 times daily for up to 5 days to treat infectious diarrhea. - Children ≥12 years and Adolescents: Oral: 200 mg 3 times daily for 3 days.

44. Differential diagnosis

45. 5. Viral diarrhea Viruses are the leading causative agent of acute infectious gastroenteritis within the United States and worldwide. They are responsible for most diagnosed cases of acute community-acquired diarrhea. Acute diarrhea is characterized by the sudden passage of watery or loose stools that occur frequently—more than 3 times within 24 hours or totaling at least 200 grams of stool per day. In addition, the duration of the condition is limited to 14 or fewer days. The additional symptoms that may occur include nausea, vomiting, fever, abdominal pain, and other constitutional discomfort. Furthermore, one may experience respiratory symptoms, fatigue, and weight loss. Definition

46. Etiology The most frequently studied human pathogens are rotavirus, enteric adenovirus, astrovirus , and the genera  Norovirus  and  Sapovirus  in the Caliciviridae family. Certain members of the Picornaviridae family, such as aichivirus , are believed to cause gastroenteritis, while the origins of other viral sources of diarrhea remain unidentified. Norovirus , a member of the Caliciviridae family, is a small, non-enveloped, and single-stranded RNA virus that is the most common cause of acute viral gastroenteritis. This virus can lead to substantial outbreaks, often from contaminated water or food and through person-to-person transmission. Other significant virus outbreaks may occur in schools, cruise ships, and other highly populated areas. Rotavirus, of the Reoviridae family, is a non-enveloped and double-stranded RNA virus. On the other hand, enteric adenovirus is a non-enveloped and double-stranded DNA virus, with types 40 and 41 primarily responsible for causing gastroenteritis, commonly observed in children younger than 2 years old

47. Diarrhea may be caused by several mechanisms including ( i ) malabsorption that occurs secondary to the destruction of enterocytes, (ii) villus ischemia and activation of the enteric nervous system that may be evoked by release of a vasoactive agent from infected epithelial cells in the absence of significant pathologic lesions or enterocyte damage, and (iii) intestinal secretion stimulated by the intracellular or extracellular action of the rotavirus non-structural protein, NSP4, a novel enterotoxin and secretory agonist with pleiotropic properties. Pathogenesis

48. Symptoms linked to acute viral gastroenteritis typically manifest following an incubation period of 24 to 60 hours, with the expected duration ranging from 12 to 60 hours. Vomiting occurs frequently. The duration of diarrheal symptoms can differ among various viral pathogens. In rotavirus infections, vomiting frequently marks the onset of the illness, followed by acute watery diarrhea. In addition, fever is present in approximately one-third of cases and may accompany these symptoms. The illness usually lasts between 5 and 7 days. Norovirus symptoms commonly include nausea, vomiting, and diarrhea. However, a smaller subset of children might experience only vomiting, whereas older adults may manifest solely diarrhea. The incubation period ranges from 12 to 48 hours, and symptoms typically persist for 1 to 3 days. Conversely, enteric adenovirus infection has an extended incubation period of 8 to 10 days, and the associated illnesses might endure for up to 2 weeks. Patients often experience mild, diffuse abdominal pain upon palpation during a physical examination. Although voluntary guarding might be observable, the abdomen usually maintains a soft texture. Fever between 101 °F and 102 °F is observed in approximately half of all cases. Instances of moderate-to-severe dehydration are relatively infrequent Clinical manifestation

49. Diagnosing acute viral gastroenteritis primarily relies on clinical evaluation, rendering laboratory tests and stool studies unnecessary for diagnosis and treatment. Stool studies are usually negative results for leukocytes and blood. However, stool studies should be conducted in cases of persistent fever and dehydration or to detect the presence of blood or pus in the stool. If signs of dehydration are not present, it is not required to measure serum electrolytes. Assessing the complete blood count does not reliably assist in differentiating between viral and bacterial gastroenteritis. Reverse transcriptase–polymerase chain reaction (RT-PCR) of stool is the most frequently used laboratory test to diagnose viral gastroenteritis. Rapid diagnostic tests are available for detecting rotavirus antigens and adenoviruses in fecal samples using monoclonal antibody-based enzyme immunoassay (EIA), latex agglutination, or nucleic acid amplification techniques (NAATs).  Diagnostics

50. Treatment There's no specific treatment for a rotavirus infection. Antibiotics and antivirals won't help a rotavirus infection. Usually, the infection resolves within 3 to 7 days. Preventing dehydration is the biggest concern. To prevent dehydration while the virus runs its course, drink plenty of fluids.

51. The best way to protect against  rotavirus  disease is to get the rotavirus vaccine. Children who are not vaccinated usually have more severe symptoms the first time they get rotavirus disease. Vaccinated children are less likely to get sick from rotavirus. Available vaccines There are two rotavirus vaccines licensed for use in infants in the United States. Both available rotavirus vaccines are given by putting drops in the infant's mouth. Your child's doctor can help you choose which rotavirus vaccine to use. RotaTeq ® (RV5) Rotarix ® (RV1) Rotavirus vaccine can be safely given during the same doctor’s visit with DTaP vaccine; Hib vaccine; polio vaccine; hepatitis B vaccine; and pneumococcal conjugate vaccine. RotaTeq ®  (RV5)  is given as 3 doses. 2 months old: 1st dose 4 months old: 2nd dose 6 months old: 3rd dose Rotarix ®  (RV1)  given as 2 doses. 2 months old: 1st dose 4 months old: 2nd dose Prevention

52. There are four main approaches to the treatment of infectious diarrhea. Supportive therapy— proper diet, fluid and electrolyte replacement. Anti- diarrhal symptomatic treatment to reduce stool frequency and any other symptoms such as abdominal pain. Anti-secretory drug therapy aimed at reducing fecal losses. Specific therapy such as antimicrobial chemotherapy to reduce duration and severity of the illness. 6. Treatment 0f Acute Intestinal Infections

53. Indications for medical evaluation of children with acute diarrhea include the following: Younger than 3 months Weight of less than 8 kg History of premature birth, chronic medical conditions, or concurrent illness Fever of 38ºC or higher in infants younger than 3 months or 39ºC or higher in children aged 3-36 months Visible blood in the stool High-output diarrhea Persistent emesis Signs of dehydration as reported by caregiver, including sunken eyes, decreased tears, dry mucous membranes, and decreased urine output Mental status changes Inadequate responses to oral rehydration therapy (ORT) or caregiver unable to administer ORT The report also includes information on assessment of dehydration and what steps should be taken to adequately treat acute diarrhea.

54. Management of Diarrhea

55. Signs of Dehydration

56. Treat the dehydration – motion frequently the hydration status Treatment plan A Treatment plan B Treatment plan C Give ORS solution Give ORS solution 75 ml/kg Give IV fluids (Ringer lactate) 100 ml/kg After each stool: <24 months: 50-100 ml (1/4-1/2 cup) between 2 and 9 years:100-200ml(1/2-1cup) >10 years: as much as wanted In the first 4 hours: <4 months, <5 kg: 200-400 ml 4-11 months, 5-7,9 kg: 400-600 ml 12-23 months, 8-10,9 kg:600-800 ml 2-4 years, 11-15,9 kg: 800-1200 ml 5-14 years, 16-29,9 kg:1200-2200 ml >15 years, >30 kg: 2200-4000 ml Children <1 year: 100 ml/kg in 6 hours Start rapidly: 30 ml/kg within the first hour and then slow down Children >1 year and adults: 100 ml/kg in 3 hours Start rapidly: 30 ml/kg within the first 30 min and then slow down

57. Treatment Watery Diarrhea: Rehydration: Oral fluids, if tolerated IV fluids if oral fluids not tolerated Invasive diarrhea: Antibiotics Ceftriaxone 50-100 mg/kg/day IV or IM, BID 3-5 days Ciprofloxacin 20-30 mg/kg/day PO BID for 7-10 days Ampicillin PO, IV 50-100 mg/kg/day QID for7 days Azithromycin: 10 mg/kg on day 1 st , 8mg/kg on days 2 and 3 (5 th ) Antibiotics are of no value when a viral infection is the cause of gastroenteritis.  Antidiarrheal medications such as  L operamide  should not be given to children under 18 years of age.

58. Give Zinc supplements (20 mg in 1 tablet ) - Up to 6 months : 1/2 tablet daily for 14 days - 6 months or more : 1 tablet daily for 14 days - Infants : dissolve tablet in a small amount of expressed breast milk , ORS or clean water in a cup - Older children : tablets can be chewed or dissolved in a small amount of clean water in a cup . Probiotics Probiotics are organisms such as bacteria that are naturally found in the body and promote the growth of good bacteria. They are also in foods and can be taken as supplements. Probiotics, such as lactobacillus (typically present in yogurt), may slightly shorten the duration of diarrhea (perhaps by a day) if people begin taking them soon after the illness starts. However, probiotics probably do not prevent more serious consequences of gastroenteritis, such as the need for intravenous fluids or for hospitalization.

59. Prevention Key measures to prevent diarrhea include: access to safe drinking-water use of improved sanitation hand washing with soap exclusive breastfeeding for the first 6 months of life good personal and food hygiene health education about how infections spread rotavirus vaccination

60. Differential Diagnosis Bacterial diarrhea is part of the differential diagnosis for systemic illness with acute onset of diarrhea, including the following: Viral systemic diseases including viral gastroenteritis, or multi-system viral infections including adenovirus , enterovirus Protozoal diarrhea, such as  Giardia  or  Cryptosporidium,  can also present similarly. In endemic areas, consideration of arboviral syndromes or malaria may also be necessary . Non-infectious causes should also be excluded, such as: inflammatory bowel disease (IBD ), irritable bowel syndrome (IBS ), malabsorption syndromes (celiac disease, Whipple's disease), cystic fibrosis, carcinoid tumor, lactose intolerance, hyperthyroidism, and antibiotic-induced diarrhea

61. Refferences : 1 .https :// www . cdc . gov / disasters / disease / diarrheaguidelines . html   2. https ://www.ncbi.nlm.nih.gov/books/NBK564298 / 3. https://www.msdmanuals.com/professional/pediatrics/symptoms-in-infants-and-children/diarrhea-in-children 4. https://www.who.int/news-room/fact-sheets/detail/diarrhoeal-disease#:~:text=There%20are%203%20clinical%20types,lasts%2014%20days%20or%20longer . 5. https://www.ncbi.nlm.nih.gov/books/NBK143745/ 6. https://www.google.com/url?sa=i&url=https 7. https://ecampusontario.pressbooks.pub/app/uploads/sites/159/2018/07/OSC_Microbio_24_03_DisProTbl1-794x1024.jpg 8. https://emedicine.medscape.com/article/968773-workup?form=fpf 9. chrome-extension:// efaidnbmnnnibpcajpcglclefindmkaj /https://www.childrens.health.qld.gov.au/__data/assets/pdf_file/0025/176902/gdl-63001.pdf 10. https://www.cambridge.org/core/journals/epidemiology-and-infection/article/hospitalisations-due-to-bacterial-gastroenteritis-a-comparison-of-surveillance-and-hospital-discharge-data/E06909E818D7AD6FF726EB 8A7324F135 11. https://www.mdpi.com/2079-6382/13/1/76 12. https://www.ncbi.nlm.nih.gov/books/NBK8435/ 13. https://pubmed.ncbi.nlm.nih.gov/3364075/ 14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7152102/ 15. https://www.intechopen.com/chapters/71420 16. https://www.who.int/news-room/fact-sheets/detail/e-coli 17. https://www.ncbi.nlm.nih.gov/books/NBK470525/ 18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7128947/ 19. https://www.cdc.gov/pinkbook/hcp/table-of-contents/chapter-19-rotavirus.html

62. Minimal or no dehydration Rehydration therapy - Not applicable Replacement of losses Less than 10 kg body weight - 60-120 mL oral rehydration solution for each diarrhea stool or vomiting episode More than 10 kg body weight - 120-140 mL oral rehydration solution for each diarrhea stool or vomiting episode   Mild-to-moderate dehydration Rehydration therapy - Oral rehydration solution (50-100 mL/kg over 3-4 h) Replacement of losses Less than 10 kg body weight - 60-120 mL oral rehydration solution for each diarrhea stool or vomiting episode More than 10 kg body weight - 120-140 mL oral rehydration solution for each diarrhea stool or vomiting episode     Severe dehydration Rehydration therapy - Intravenous lactated Ringer solution or normal saline (20 mL/kg until perfusion and mental status improve), followed by 100 mL/kg oral rehydration solution over 4 hours or 5% dextrose (half normal saline) intravenously at twice maintenance fluid rates Replacement of losses Less than 10 kg body weight - 60-120 mL oral rehydration solution for each diarrhea stool or vomiting episode More than 10 kg body weight - 120-140 mL oral rehydration solution for each diarrhea stool or vomiting episode If unable to drink, administer through nasogastric tube or intravenously administer 5% dextrose (one fourth normal saline) with 20 mEq /L potassium chloride     Severe dehydration Rehydration therapy - Intravenous lactated Ringer solution or normal saline (20 mL/kg until perfusion and mental status improve), followed by 100 mL/kg oral rehydration solution over 4 hours or 5% dextrose (half normal saline) intravenously at twice maintenance fluid rates Replacement of losses Less than 10 kg body weight - 60-120 mL oral rehydration solution for each diarrhea stool or vomiting episode More than 10 kg body weight - 120-140 mL oral rehydration solution for each diarrhea stool or vomiting episode If unable to drink, administer through nasogastric tube or intravenously administer 5% dextrose (one fourth normal saline) with 20 mEq /L potassium chloride