Gastroenteritis

Overview

Epidemiology

• The 2nd leading cause of morbidity Morbidity The proportion of patients with a particular disease during a given year per given unit of population. Measures of Health Status and mortality Mortality All deaths reported in a given population. Measures of Health Status worldwide
• 3 million deaths annually (> 8,400 per day)
• Mostly affects young children in developing countries
• International travelers are particularly susceptible.
• In the United States:
  • 179 million cases per year (17 million cases are foodborne)
  • Approximately 2 million hospitalizations per year

Etiology

• Viral:
  • Norovirus Norovirus Norovirus is a nonenveloped, single-stranded, positive-sense RNA virus belonging to the Caliciviridae family. Norovirus infections are transmitted via the fecal-oral route or by aerosols from vomiting. The virus is one of the most common causes of nonbacterial gastroenteritis epidemic worldwide. Symptoms include watery and nonbloody diarrhea, nausea, vomiting, and low-grade fever. Norovirus (common)
  • Rotavirus Rotavirus A genus of Reoviridae, causing acute gastroenteritis in birds and mammals, including humans. Transmission is horizontal and by environmental contamination. Seven species (rotaviruses A through G) are recognized. Rotavirus (common)
  • Enteric adenovirus Adenovirus Adenovirus (member of the family Adenoviridae) is a nonenveloped, double-stranded DNA virus. Adenovirus is transmitted in a variety of ways, and it can have various presentations based on the site of entry. Presentation can include febrile pharyngitis, conjunctivitis, acute respiratory disease, atypical pneumonia, and gastroenteritis. Adenovirus
  • Astrovirus
  • Immunocompromised patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship:
    • Cytomegalovirus Cytomegalovirus CMV is a ubiquitous double-stranded DNA virus belonging to the Herpesviridae family. CMV infections can be transmitted in bodily fluids, such as blood, saliva, urine, semen, and breast milk. The initial infection is usually asymptomatic in the immunocompetent host, or it can present with symptoms of mononucleosis. Cytomegalovirus
    • Enterovirus Enterovirus A genus of the family picornaviridae whose members preferentially inhabit the intestinal tract of a variety of hosts. The genus contains many species. Newly described members of human enteroviruses are assigned continuous numbers with the species designated ‘human enterovirus’. Coxsackievirus
• Bacterial:
  • Salmonella Salmonella Salmonellae are gram-negative bacilli of the family Enterobacteriaceae. Salmonellae are flagellated, non-lactose-fermenting, and hydrogen sulfide-producing microbes. Salmonella enterica, the most common disease-causing species in humans, is further classified based on serotype as typhoidal (S. typhi and paratyphi) and nontyphoidal (S. enteritidis and typhimurium). Salmonella (common)
  • Campylobacter Campylobacter Campylobacter (“curved bacteria”) is a genus of thermophilic, S-shaped, gram-negative bacilli. There are many species of Campylobacter, with C. jejuni and C. coli most commonly implicated in human disease. Campylobacter (common)
  • Shigella Shigella Shigella is a genus of gram-negative, non-lactose-fermenting facultative intracellular bacilli. Infection spreads most commonly via person-to-person contact or through contaminated food and water. Humans are the only known reservoir. Shigella
  • Escherichia coli Escherichia coli The gram-negative bacterium Escherichia coli is a key component of the human gut microbiota. Most strains of E. coli are avirulent, but occasionally they escape the GI tract, infecting the urinary tract and other sites. Less common strains of E. coli are able to cause disease within the GI tract, most commonly presenting as abdominal pain and diarrhea. Escherichia coli (E. coli)
  • Clostridium
  • Yersinia Yersinia Yersinia is a genus of bacteria characterized as gram-negative bacilli that are facultative anaerobic with bipolar staining. There are 2 enteropathogenic species that cause yersiniosis, Y. enterocolitica and Y. pseudotuberculosis. Infections are manifested as pseudoappendicitis or mesenteric lymphadenitis, and enterocolitis. Yersinia spp./Yersiniosis
• Parasitic:
  • Giardia Giardia A genus of flagellate intestinal eukaryotes parasitic in various vertebrates, including humans. Characteristics include the presence of four pairs of flagella arising from a complicated system of axonemes and cysts that are ellipsoidal to ovoidal in shape. Nitroimidazoles lamblia
  • Entamoeba histolytica Entamoeba Histolytica A species of parasitic protozoa causing entamoebiasis and amebic dysentery (dysentery, amebic). Characteristics include a single nucleus containing a small central karyosome and peripheral chromatin that is finely and regularly beaded. Amebicides
  • Cryptosporidium Cryptosporidium A genus of coccidian parasites of the family cryptosporidiidae, found in the intestinal epithelium of many vertebrates including humans. Hyper-IgM Syndrome
  • Cyclospora Cyclospora Cyclospora is a genus within the Coccidia subclass of protozoans. They are single-celled, obligate intracellular parasites that cause intestinal infections in humans. Humans are the only host for these species, and they are both transmitted through the fecal-oral route. The symptoms of cyclosporiasis are watery diarrhea, abdominal pain, and fever. Cystoisospora/Cystoisosporiasis and Cyclospora/Cyclosporiasis

Pathogenesis

• Modes of infection:
  • Foodborne (toxin accumulation in food products)
  • Fecal-oral (bacterial contamination)
  • Direct or indirect animal transmission
• Mechanism of diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea, associated findings, and etiology are described in the table below.

Clinical presentation

• Common symptoms:
  • Abdominal pain Abdominal Pain Acute Abdomen and cramps Cramps Ion Channel Myopathy
  • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea (watery, mucoid, or bloody)
  • Vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia 
  • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
  • Anorexia Anorexia The lack or loss of appetite accompanied by an aversion to food and the inability to eat. It is the defining characteristic of the disorder anorexia nervosa. Anorexia Nervosa
  • Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess
  • Myalgia Myalgia Painful sensation in the muscles. Ion Channel Myopathy
• Evidence of severe dehydration Severe Dehydration Fluid Replacement Therapy in Children: 
  • Tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children
  • Hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension

Diagnosis

• Stool testing:
  • Most patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship do not require stool testing.
  • Guided by clinical history and findings:
    • Blood or pus in the stool
    • Persistent fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
    • Severe symptoms
    • Prolonged course
    • High-risk patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
  • Fecal leukocytes Leukocytes White blood cells. These include granular leukocytes (basophils; eosinophils; and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). White Myeloid Cells: Histology or lactoferrin → inflammatory diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
  • Stool culture and polymerase chain reaction Polymerase chain reaction Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) ( PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR)) panel
  • Stool ova and parasites 
  • Direct viral antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination (rarely indicated)
  • C. difficile toxin enzyme immunoassay Enzyme immunoassay HIV Infection and AIDS
• General testing:
  • Generally only done in severe disease with evidence of dehydration Dehydration The condition that results from excessive loss of water from a living organism. Volume Depletion and Dehydration
  • Basic metabolic panel Basic Metabolic Panel Primary vs Secondary Headaches → assesses for acute kidney injury Acute Kidney Injury Acute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine. Acute Kidney Injury and electrolyte abnormalities
  • Complete blood count → leukocytosis Leukocytosis A transient increase in the number of leukocytes in a body fluid. West Nile Virus may be seen; eosinophilia Eosinophilia Abnormal increase of eosinophils in the blood, tissues or organs. Autosomal Dominant Hyperimmunoglobulin E Syndrome may signal a parasitic infection

The following algorithm summarizes the workup of gastroenteritis:

Management

• Supportive care:
  • Most infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease are self-limiting Self-Limiting Meningitis in Children and only require oral rehydration Rehydration Dengue Virus therapy.
  • Intravenous (IV) fluid hydration may be required for severe disease.
  • Oral and IV solutions should contain replacement electrolytes Electrolytes Electrolytes are mineral salts that dissolve in water and dissociate into charged particles called ions, which can be either be positively (cations) or negatively (anions) charged. Electrolytes are distributed in the extracellular and intracellular compartments in different concentrations. Electrolytes are essential for various basic life-sustaining functions. Electrolytes.
• Antidiarrheal Antidiarrheal Antidiarrheal agents include several drug classes, including opioid agonists, somatostatin analogues, adsorbents, and bile acid sequestrants. These medications mainly work through antimotility and/or antisecretory effects. Antidiarrheal Drugs agents ( loperamide Loperamide One of the long-acting synthetic antidiarrheals; it is not significantly absorbed from the gut, and has no effect on the adrenergic system or central nervous system, but may antagonize histamine and interfere with acetylcholine release locally. Antidiarrheal Drugs, bismuth salicylate): 
  • Reduce the duration of diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
  • Can delay the excretion of the causative pathogens or toxins, and are contraindicated in:
    • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea with fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
    • Bloody or mucoid stool
    • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea caused by C. difficile and Shigella Shigella Shigella is a genus of gram-negative, non-lactose-fermenting facultative intracellular bacilli. Infection spreads most commonly via person-to-person contact or through contaminated food and water. Humans are the only known reservoir. Shigella
• Antibiotic therapy:
  • Not routinely used
  • The decision to use antibiotics is often empirical, because enteric pathogen testing is not always expedient.
  • Possible indications: 
    • Dysentery (passage of bloody stools)
    • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever > 38°C (100.4°F)
    • Severe symptoms and hospitalization Hospitalization The confinement of a patient in a hospital. Delirium
    • High-risk population group (infants, elderly, immunocompromised, patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with comorbidities Comorbidities The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. St. Louis Encephalitis Virus)
    • C. difficile infection
  • Contraindicated if Shiga toxin Shiga toxin A class of toxins that inhibit protein synthesis by blocking the interaction of ribosomal RNA; with peptide elongation factors. They include shiga toxin which is produced by Shigella dysenteriae and a variety of shiga-like toxins that are produced by pathologic strains of Escherichia coli such as Escherichia coli o157. Diarrheagenic E. coli–producing E. coli is suspected (risk of hemolytic-uremic syndrome ( HUS HUS Hemolytic uremic syndrome (HUS) is a clinical phenomenon most commonly seen in children that consists of a classic triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Hemolytic uremic syndrome is a major cause of acute kidney injury in children and is most commonly associated with a prodrome of diarrheal illness caused by shiga-like toxin-producing bacteria. Hemolytic Uremic Syndrome))
  • Frequently used antibiotics:
    • Fluoroquinolones Fluoroquinolones Fluoroquinolones are a group of broad-spectrum, bactericidal antibiotics inhibiting bacterial DNA replication. Fluoroquinolones cover gram-negative, anaerobic, and atypical organisms, as well as some gram-positive and multidrug-resistant (MDR) organisms. Fluoroquinolones
    • Azithromycin Azithromycin A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. Macrolides and Ketolides
    • Trimethoprim-sulfamethoxazole (TMP-SMX)
    • 3rd-generation cephalosporins Cephalosporins Cephalosporins are a group of bactericidal beta-lactam antibiotics (similar to penicillins) that exert their effects by preventing bacteria from producing their cell walls, ultimately leading to cell death. Cephalosporins are categorized by generation and all drug names begin with “cef-” or “ceph-.” Cephalosporins

Complications

• During the infection:
  • Hypovolemic shock Hypovolemic Shock Types of Shock
  • Severe dehydration Severe Dehydration Fluid Replacement Therapy in Children
  • Acute kidney injury Acute Kidney Injury Acute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine. Acute Kidney Injury 
  • Metabolic acidosis Acidosis A pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up. Respiratory Acidosis
  • Electrolyte imbalances
  • Death
• Post-diarrheal complications are summarized in the table below:

Campylobacter

Pathogen

• Campylobacter jejuni Campylobacter jejuni A species of bacteria that resemble small tightly coiled spirals. Its organisms are known to cause abortion in sheep and fever and enteritis in man and may be associated with enteric diseases of calves, lambs, and other animals. Campylobacter are curved, gram-negative, oxidase-positive rods with polar flagella Polar flagella Campylobacter.
• Distinguishing features: 
  • Require a CO₂-rich environment
  • Grow at 42.0°C (107.6°F)
  • May appear S-shaped or like seagull wings due to their helical Helical Computed tomography where there is continuous x-ray exposure to the patient while being transported in a spiral or helical pattern through the beam of irradiation. This provides improved three-dimensional contrast and spatial resolution compared to conventional computed tomography, where data is obtained and computed from individual sequential exposures. Computed Tomography (CT) structure
• The most common pathogen responsible for foodborne gastroenteritis in the United States
• Highly contagious

Transmission

• Fecal-oral
• Foodborne (undercooked poultry and unpasteurized milk) and contaminated water
• Direct contact with infected animals Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, animalia was one of the kingdoms. Under the modern three domain model, animalia represents one of the many groups in the domain eukaryota. Cell Types: Eukaryotic versus Prokaryotic (cats, dogs, pigs) or animal products

Pathogenesis

• Invades the mucosa of the intestines → produces endotoxins Endotoxins Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. Bacteriology, enterotoxins, and cytotoxins Cytotoxins Substances that are toxic to cells; they may be involved in immunity or may be contained in venoms. These are distinguished from cytostatic agents in degree of effect. Some of them are used as cytotoxic antibiotics. The mechanism of action of many of these are as alkylating agents or mitosis modulators. Helicobacter → destroys mucosal surfaces → blood and pus in stools (inflammatory diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea)
• Rarely penetrates to cause septicemia

Clinical presentation

• Acute watery and bloody diarrhea Bloody diarrhea Diarrhea
• Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
• Severe right lower quadrant Right lower quadrant Anterior Abdominal Wall: Anatomy abdominal pain Abdominal Pain Acute Abdomen resembling appendicitis Appendicitis Appendicitis is the acute inflammation of the vermiform appendix and the most common abdominal surgical emergency globally. The condition has a lifetime risk of 8%. Characteristic features include periumbilical abdominal pain that migrates to the right lower quadrant, fever, anorexia, nausea, and vomiting. Appendicitis (“ pseudoappendicitis Pseudoappendicitis Inflammation of lymph nodes in the mesentery. Yersinia spp./Yersiniosis”)
• Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess
• Myalgias Myalgias Painful sensation in the muscles. Tick-borne Encephalitis Virus

Management

• Most cases will have a spontaneous resolution.
• Macrolides Macrolides Macrolides and ketolides are antibiotics that inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit and blocking transpeptidation. These antibiotics have a broad spectrum of antimicrobial activity but are best known for their coverage of atypical microorganisms. Macrolides and Ketolides and fluoroquinolones Fluoroquinolones Fluoroquinolones are a group of broad-spectrum, bactericidal antibiotics inhibiting bacterial DNA replication. Fluoroquinolones cover gram-negative, anaerobic, and atypical organisms, as well as some gram-positive and multidrug-resistant (MDR) organisms. Fluoroquinolones
• A 3rd-generation cephalosporin Cephalosporin Multidrug-resistant Organisms and Nosocomial Infections, imipenem Imipenem Semisynthetic thienamycin that has a wide spectrum of antibacterial activity against gram-negative and gram-positive aerobic and anaerobic bacteria, including many multiresistant strains. It is stable to beta-lactamases. Clinical studies have demonstrated high efficacy in the treatment of infections of various body systems. Its effectiveness is enhanced when it is administered in combination with cilastatin, a renal dipeptidase inhibitor. Carbapenems and Aztreonam, ampicillin Ampicillin Semi-synthetic derivative of penicillin that functions as an orally active broad-spectrum antibiotic. Penicillins, or gentamicin Gentamicin Aminoglycosides can be given for extraintestinal infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease.

Complications

• Guillain-Barré syndrome Guillain-Barré syndrome Guillain-Barré syndrome (GBS), once thought to be a single disease process, is a family of immune-mediated polyneuropathies that occur after infections (e.g., with Campylobacter jejuni). Guillain-Barré Syndrome (cross-reaction between C. jejuni antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions and human gangliosides)
• Reactive arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis (in HLA-B27–positive patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship)
• Hemolytic anemia Hemolytic Anemia Hemolytic anemia (HA) is the term given to a large group of anemias that are caused by the premature destruction/hemolysis of circulating red blood cells (RBCs). Hemolysis can occur within (intravascular hemolysis) or outside the blood vessels (extravascular hemolysis). Hemolytic Anemia
• Endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis and myopericarditis Myopericarditis Coxsackievirus
• Meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis

Non-typhoidal Salmonella

Pathogen

• S. enteritidis S. enteritidis A serotype of Salmonella enterica which is an etiologic agent of gastroenteritis in man and other animals. Salmonella and S. typhimurium S. typhimurium A serotype of Salmonella enterica that is a frequent agent of Salmonella gastroenteritis in humans. It also causes paratyphoid fever. Salmonella are gram-negative, non–lactose fermenting bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology.
• Produce hydrogen sulfide Hydrogen sulfide A flammable, poisonous gas with a characteristic odor of rotten eggs. It is used in the manufacture of chemicals, in metallurgy, and as an analytical reagent. Salmonella and are motile (unlike Shigella Shigella Shigella is a genus of gram-negative, non-lactose-fermenting facultative intracellular bacilli. Infection spreads most commonly via person-to-person contact or through contaminated food and water. Humans are the only known reservoir. Shigella)
• The 2nd most common pathogen responsible for bacterial foodborne gastroenteritis

Transmission

• Foodborne bacterial infection (poultry, raw eggs, milk)
• Reservoir Reservoir Animate or inanimate sources which normally harbor disease-causing organisms and thus serve as potential sources of disease outbreaks. Reservoirs are distinguished from vectors (disease vectors) and carriers, which are agents of disease transmission rather than continuing sources of potential disease outbreaks. Humans may serve both as disease reservoirs and carriers. Escherichia coli: enteric tracts of humans and domestic animals Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, animalia was one of the kingdoms. Under the modern three domain model, animalia represents one of the many groups in the domain eukaryota. Cell Types: Eukaryotic versus Prokaryotic (turtles, reptiles, chickens)
• Salmonella Salmonella Salmonellae are gram-negative bacilli of the family Enterobacteriaceae. Salmonellae are flagellated, non-lactose-fermenting, and hydrogen sulfide-producing microbes. Salmonella enterica, the most common disease-causing species in humans, is further classified based on serotype as typhoidal (S. typhi and paratyphi) and nontyphoidal (S. enteritidis and typhimurium). Salmonella is sensitive to stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy acid. Lowered stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy acidity (antacids or gastrectomy) increases the risk for infection.
• Other risk factors: 
  • Hemolytic conditions ( sickle cell anemia Sickle cell anemia A disease characterized by chronic hemolytic anemia, episodic painful crises, and pathologic involvement of many organs. It is the clinical expression of homozygosity for hemoglobin S. Sickle Cell Disease, malaria Malaria Malaria is an infectious parasitic disease affecting humans and other animals. Most commonly transmitted via the bite of a female Anopheles mosquito infected with microorganisms of the Plasmodium genus. Patients present with fever, chills, myalgia, headache, and diaphoresis. Plasmodium/Malaria)
  • Splenectomy Splenectomy Surgical procedure involving either partial or entire removal of the spleen. Rupture of the Spleen
  • Cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis
  • Leukemia and lymphoma Lymphoma A general term for various neoplastic diseases of the lymphoid tissue. Imaging of the Mediastinum
  • HIV HIV Anti-HIV Drugs infection

Pathogenesis

• Bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology invade the mucosa in the ileocecal region and are released into the lamina propria Lamina propria Whipple’s Disease → influx of neutrophils Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. Innate Immunity: Phagocytes and Antigen Presentation → inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation → ↑ prostaglandins Prostaglandins A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. Eicosanoids and cAMP cAMP An adenine nucleotide containing one phosphate group which is esterified to both the 3′- and 5′-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and acth. Phosphodiesterase Inhibitors → loose diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea and necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage of the upper mucosa
• Septicemia is not common (< 5%) with S. enteritidis S. enteritidis A serotype of Salmonella enterica which is an etiologic agent of gastroenteritis in man and other animals. Salmonella, but may occur with other subtypes.

Clinical presentation

• Incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus period of 8–72 hours, lasts 3–7 days
• Inflammatory watery diarrhea Watery diarrhea Rotavirus (occasionally bloody) 
• Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, chills Chills The sudden sensation of being cold. It may be accompanied by shivering. Fever
• Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess
• Myalgias Myalgias Painful sensation in the muscles. Tick-borne Encephalitis Virus
• Severe vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia 
• Abdominal cramping Abdominal cramping Norovirus

Management

• Supportive care
• Antibiotics:
  • Not required for most uncomplicated cases
  • Prolongs fecal excretion of the pathogen
  • Only indicated for systemic manifestations or severe diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea:
    • Fluoroquinolones Fluoroquinolones Fluoroquinolones are a group of broad-spectrum, bactericidal antibiotics inhibiting bacterial DNA replication. Fluoroquinolones cover gram-negative, anaerobic, and atypical organisms, as well as some gram-positive and multidrug-resistant (MDR) organisms. Fluoroquinolones ( ciprofloxacin Ciprofloxacin A broad-spectrum antimicrobial carboxyfluoroquinoline. Fluoroquinolones) 
    • TMP-SMX 
    • Azithromycin Azithromycin A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. Macrolides and Ketolides
    • 3rd-generation cephalosporins Cephalosporins Cephalosporins are a group of bactericidal beta-lactam antibiotics (similar to penicillins) that exert their effects by preventing bacteria from producing their cell walls, ultimately leading to cell death. Cephalosporins are categorized by generation and all drug names begin with “cef-” or “ceph-.” Cephalosporins ( ceftriaxone Ceftriaxone A broad-spectrum cephalosporin antibiotic and cefotaxime derivative with a very long half-life and high penetrability to meninges, eyes and inner ears. Cephalosporins)

Complications

• Bacteremia Bacteremia The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. Glycopeptides
• Reactive arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis
• Osteomyelitis Osteomyelitis Osteomyelitis is an infection of the bone that results from the spread of microorganisms from the blood (hematogenous), nearby infected tissue, or open wounds (non-hematogenous). Infections are most commonly caused by Staphylococcus aureus. Osteomyelitis (particularly in sickle cell patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship)
• Meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis 
• Myocarditis Myocarditis Myocarditis is an inflammatory disease of the myocardium, which may occur alone or in association with a systemic process. There are numerous etiologies of myocarditis, but all lead to inflammation and myocyte injury, most often leading to signs and symptoms of heart failure. Myocarditis, endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis

Shigella

Shigella Shigella Shigella is a genus of gram-negative, non-lactose-fermenting facultative intracellular bacilli. Infection spreads most commonly via person-to-person contact or through contaminated food and water. Humans are the only known reservoir. Shigella causes bacillary dysentery, also known as shigellosis Shigellosis Shigella.

Pathogen

• S. dysenteriae S. dysenteriae A species of gram-negative, facultatively anaerobic, rod-shaped bacteria that is extremely pathogenic and causes severe dysentery. Infection with this organism often leads to ulceration of the intestinal epithelium. Shigella, S. flexneri S. flexneri A bacterium which is one of the etiologic agents of bacillary dysentery and sometimes of infantile gastroenteritis. Shigella, S. sonnei S. sonnei A lactose-fermenting bacterium causing dysentery. Shigella, and S. boydii S. boydii One of the shigella species that produces bacillary dysentery. Shigella are gram-negative rods.
• Gastric acid resistant Acid resistant Echovirus
• S. dysenteriae S. dysenteriae A species of gram-negative, facultatively anaerobic, rod-shaped bacteria that is extremely pathogenic and causes severe dysentery. Infection with this organism often leads to ulceration of the intestinal epithelium. Shigella type 1 Type 1 Spinal Muscular Atrophy produces Shiga toxin Shiga toxin A class of toxins that inhibit protein synthesis by blocking the interaction of ribosomal RNA; with peptide elongation factors. They include shiga toxin which is produced by Shigella dysenteriae and a variety of shiga-like toxins that are produced by pathologic strains of Escherichia coli such as Escherichia coli o157. Diarrheagenic E. coli ( enterotoxin Enterotoxin Substances that are toxic to the intestinal tract causing vomiting, diarrhea, etc. ; most common enterotoxins are produced by bacteria. Diarrhea).

Transmission

• Fecal-oral
• Humans are the only natural reservoir Reservoir Animate or inanimate sources which normally harbor disease-causing organisms and thus serve as potential sources of disease outbreaks. Reservoirs are distinguished from vectors (disease vectors) and carriers, which are agents of disease transmission rather than continuing sources of potential disease outbreaks. Humans may serve both as disease reservoirs and carriers. Escherichia coli.
• Flies are vectors.
• Foodborne (unpasteurized milk products and raw, unwashed vegetables)
• Contaminated water
• Highly contagious

Pathogenesis

• Shigella Shigella Shigella is a genus of gram-negative, non-lactose-fermenting facultative intracellular bacilli. Infection spreads most commonly via person-to-person contact or through contaminated food and water. Humans are the only known reservoir. Shigella invades M cells M cells Salmonella through macropinocytosis → taken up by macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation → escapes its phagosome → reaches epithelial cytoplasm and replicates → induces inflammatory response → epithelial and immune cell death Cell death Injurious stimuli trigger the process of cellular adaptation, whereby cells respond to withstand the harmful changes in their environment. Overwhelmed adaptive mechanisms lead to cell injury. Mild stimuli produce reversible injury. If the stimulus is severe or persistent, injury becomes irreversible. Apoptosis is programmed cell death, a mechanism with both physiologic and pathologic effects. Cell Injury and Death
• Polymerized actin Actin Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or f-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or g-actin. In conjunction with myosins, actin is responsible for the contraction and relaxation of muscle. Skeletal Muscle Contraction filaments are used to spread cell-to-cell without needing to re-enter the extracellular milieu.
• Shiga toxin Shiga toxin A class of toxins that inhibit protein synthesis by blocking the interaction of ribosomal RNA; with peptide elongation factors. They include shiga toxin which is produced by Shigella dysenteriae and a variety of shiga-like toxins that are produced by pathologic strains of Escherichia coli such as Escherichia coli o157. Diarrheagenic E. coli release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology by S. dysenteriae S. dysenteriae A species of gram-negative, facultatively anaerobic, rod-shaped bacteria that is extremely pathogenic and causes severe dysentery. Infection with this organism often leads to ulceration of the intestinal epithelium. Shigella:
  • Has 3 properties: neurotoxic, cytotoxic Cytotoxic Parvovirus B19, enterotoxic
  • Causes intestinal secretion Secretion Coagulation Studies of solutes and water
  • Can induce HUS HUS Hemolytic uremic syndrome (HUS) is a clinical phenomenon most commonly seen in children that consists of a classic triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Hemolytic uremic syndrome is a major cause of acute kidney injury in children and is most commonly associated with a prodrome of diarrheal illness caused by shiga-like toxin-producing bacteria. Hemolytic Uremic Syndrome
• Resulting effects:
  • Watery diarrhea Watery diarrhea Rotavirus
  • Mucus secretion Secretion Coagulation Studies
  • Leukocyte infiltration 
  • Superficial ulcers 
  • Rarely causes invasion of blood vessels

Clinical presentation

• Incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus period of 0–48 hours, lasts 2–7 days
• Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
• Abdominal cramping Abdominal cramping Norovirus
• Tenesmus (urgency to defecate)
• Inflammatory diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea with mucus, pus, and blood

Antibiotics

• Usually resolves spontaneously
• Rehydration Rehydration Dengue Virus and electrolyte replacement may be needed.
• Antibiotics shorten the duration of symptoms and pathogen shedding in the stool:
  • Fluoroquinolones Fluoroquinolones Fluoroquinolones are a group of broad-spectrum, bactericidal antibiotics inhibiting bacterial DNA replication. Fluoroquinolones cover gram-negative, anaerobic, and atypical organisms, as well as some gram-positive and multidrug-resistant (MDR) organisms. Fluoroquinolones
  • Azithromycin Azithromycin A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. Macrolides and Ketolides
  • 3rd-generation cephalosporins Cephalosporins Cephalosporins are a group of bactericidal beta-lactam antibiotics (similar to penicillins) that exert their effects by preventing bacteria from producing their cell walls, ultimately leading to cell death. Cephalosporins are categorized by generation and all drug names begin with “cef-” or “ceph-.” Cephalosporins
• Avoid antimotility medications, because they can worsen symptoms and may lead to toxic megacolon Toxic megacolon An acute form of megacolon, severe pathological dilatation of the colon. It is associated with clinical conditions such as ulcerative colitis; Crohn disease; amebic dysentery; or Clostridium enterocolitis. Megacolon.

Complications

• HUS HUS Hemolytic uremic syndrome (HUS) is a clinical phenomenon most commonly seen in children that consists of a classic triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Hemolytic uremic syndrome is a major cause of acute kidney injury in children and is most commonly associated with a prodrome of diarrheal illness caused by shiga-like toxin-producing bacteria. Hemolytic Uremic Syndrome → due to Shiga toxin Shiga toxin A class of toxins that inhibit protein synthesis by blocking the interaction of ribosomal RNA; with peptide elongation factors. They include shiga toxin which is produced by Shigella dysenteriae and a variety of shiga-like toxins that are produced by pathologic strains of Escherichia coli such as Escherichia coli o157. Diarrheagenic E. coli, often seen in children
• Acute blood loss → mucosal ulcerations
• Intestinal complications: 
  • Toxic megacolon Toxic megacolon An acute form of megacolon, severe pathological dilatation of the colon. It is associated with clinical conditions such as ulcerative colitis; Crohn disease; amebic dysentery; or Clostridium enterocolitis. Megacolon
  • Colonic perforation Perforation A pathological hole in an organ, blood vessel or other soft part of the body, occurring in the absence of external force. Esophagitis
  • Intestinal obstruction Intestinal obstruction Any impairment, arrest, or reversal of the normal flow of intestinal contents toward the anal canal. Ascaris/Ascariasis 
  • Proctitis Proctitis Inflammation of the mucous membrane of the rectum, the distal end of the large intestine. Chronic Granulomatous Disease
  • Rectal prolapse Rectal prolapse Rectal prolapse, also known as rectal procidentia, is the protrusion of rectal tissue through the anus. The tissue may include just the mucosa or the full thickness of the rectal wall. Common risk factors include chronic straining, constipation, bowel motility disorders, and weakening of the pelvic floor muscles. Rectal Prolapse → due to tenesmus
• Reactive arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis 
• Though invasive, Shigella Shigella Shigella is a genus of gram-negative, non-lactose-fermenting facultative intracellular bacilli. Infection spreads most commonly via person-to-person contact or through contaminated food and water. Humans are the only known reservoir. Shigella only rarely causes septicemia.

Vibrio

Cholera Cholera An acute diarrheal disease endemic in india and southeast Asia whose causative agent is Vibrio cholerae. This condition can lead to severe dehydration in a matter of hours unless quickly treated. Vibrio is a severe form of gastroenteritis caused by Vibrio cholerae Vibrio cholerae The etiologic agent of cholera. Vibrio (V. cholerae).

Pathogen

• V. cholerae is a gram-negative, oxidase-positive, curved rod with polar flagella Polar flagella Campylobacter.
• Grows on alkaline media
• Distinguishing feature: “shooting star” motility Motility The motor activity of the gastrointestinal tract. Gastrointestinal Motility inactivated by specific serum
• Produces the cholera Cholera An acute diarrheal disease endemic in india and southeast Asia whose causative agent is Vibrio cholerae. This condition can lead to severe dehydration in a matter of hours unless quickly treated. Vibrio toxin

Transmission

• Inhabitant of coastal estuarine waters
• Fecal-oral spread
• Undercooked seafood or contaminated water
• Sensitive to stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy acid; requires a high dose for infection
• Outbreaks Outbreaks Sudden increase in the incidence of a disease. The concept includes epidemics and pandemics. Influenza Viruses/Influenza tend to occur during warm months.
• Endemic in areas of Asia ASIA Spinal Cord Injuries, Africa, the Middle East, Central and South America, and the U.S. Gulf Coast
• Susceptibility is increased in:
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with type O blood
  • Antacid, antihistamine, or proton pump Pump ACES and RUSH: Resuscitation Ultrasound Protocols inhibitor use

Pathogenesis

• Motility Motility The motor activity of the gastrointestinal tract. Gastrointestinal Motility, mucinase Mucinase An enzyme that catalyzes the random hydrolysis of 1, 4-linkages between N-acetyl-beta-D-glucosamine and D-glucuronate residues in hyaluronate. There has been use as antineoplastic agents to limit neoplasm metastasis. Helicobacter, and toxin-coregulated pili Pili Filamentous or elongated proteinaceous structures which extend from the cell surface in gram-negative bacteria that contain certain types of conjugative plasmid. These pili are the organs associated with genetic transfer and have essential roles in conjugation. Normally, only one or a few pili occur on a given donor cell. This preferred use of ‘pili’ refers to the sexual appendage, to be distinguished from bacterial fimbriae, also known as common pili, which are usually concerned with adhesion. Salmonella (TCP) aid in attachment to the intestinal mucosa Intestinal Mucosa Lining of the intestines, consisting of an inner epithelium, a middle lamina propria, and an outer muscularis mucosae. In the small intestine, the mucosa is characterized by a series of folds and abundance of absorptive cells (enterocytes) with microvilli. Small Intestine: Anatomy.
• Leads to colonization Colonization Bacteriology of the intestinal lining without invasion of the intestinal wall
• Cholera Cholera An acute diarrheal disease endemic in india and southeast Asia whose causative agent is Vibrio cholerae. This condition can lead to severe dehydration in a matter of hours unless quickly treated. Vibrio enterotoxin Enterotoxin Substances that are toxic to the intestinal tract causing vomiting, diarrhea, etc. ; most common enterotoxins are produced by bacteria. Diarrhea is released: activates adenylate cyclase → ↑ cAMP cAMP An adenine nucleotide containing one phosphate group which is esterified to both the 3′- and 5′-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and acth. Phosphodiesterase Inhibitors → efflux of electrolytes Electrolytes Electrolytes are mineral salts that dissolve in water and dissociate into charged particles called ions, which can be either be positively (cations) or negatively (anions) charged. Electrolytes are distributed in the extracellular and intracellular compartments in different concentrations. Electrolytes are essential for various basic life-sustaining functions. Electrolytes and water by the small bowel Small bowel The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy mucosa in the duodenum Duodenum The shortest and widest portion of the small intestine adjacent to the pylorus of the stomach. It is named for having the length equal to about the width of 12 fingers. Small Intestine: Anatomy and jejunum Jejunum The middle portion of the small intestine, between duodenum and ileum. It represents about 2/5 of the remaining portion of the small intestine below duodenum. Small Intestine: Anatomy

Clinical presentation

• Incubation period is 1–3 days.
• Some patients may be asymptomatic or have only mild symptoms.
• Profuse “rice-water” stools 
• Abdominal pain Abdominal Pain Acute Abdomen and nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics are less prominent than other forms of gastroenteritis.
• Can quickly lead to severe dehydration Severe Dehydration Fluid Replacement Therapy in Children and electrolyte depletion within hours:
  • Thirst
  • Oliguria Oliguria Decreased urine output that is below the normal range. Oliguria can be defined as urine output of less than or equal to 0. 5 or 1 ml/kg/hr depending on the age. Renal Potassium Regulation
  • Muscle cramping
  • ↓ skin turgor Skin turgor Malnutrition in children in resource-limited countries
• Severe cases can lead to altered mental status Altered Mental Status Sepsis in Children, renal tubular necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage, and circulatory collapse.

Management

• Urgent fluid and electrolyte replacement is the 1st priority.
• Antibiotics are used for severe disease, and can decrease diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea and shedding:
  • Doxycycline
  • Azithromycin Azithromycin A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. Macrolides and Ketolides ( erythromycin Erythromycin A bacteriostatic antibiotic macrolide produced by streptomyces erythreus. Erythromycin a is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50s ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. Macrolides and Ketolides in children)
  • Ciprofloxacin Ciprofloxacin A broad-spectrum antimicrobial carboxyfluoroquinoline. Fluoroquinolones

Complications

• Severe dehydration Severe Dehydration Fluid Replacement Therapy in Children
• Renal failure Renal failure Conditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate. Crush Syndrome
• Hypovolemic shock Hypovolemic Shock Types of Shock

Non-cholera Vibrio Vibrio Vibrio is a genus of comma-shaped, gram-negative bacilli. It is halophilic, acid labile, and commonly isolated on thiosulfate-citrate-bile-sucrose (TCBS) agar. There are 3 clinically relevant species: Vibrio cholerae (V. cholerae), Vibrio vulnificus (V. vulnificus), and Vibrio parahaemolyticus (V. parahaemolyticus). Vibrio infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease

The following table briefly summarizes the milder form of gastroenteritis caused by non-cholera Vibrio Vibrio Vibrio is a genus of comma-shaped, gram-negative bacilli. It is halophilic, acid labile, and commonly isolated on thiosulfate-citrate-bile-sucrose (TCBS) agar. There are 3 clinically relevant species: Vibrio cholerae (V. cholerae), Vibrio vulnificus (V. vulnificus), and Vibrio parahaemolyticus (V. parahaemolyticus). Vibrio species:

Yersinia

Pathogen

• Yersinia enterocolitica Yersinia enterocolitica A species of the genus yersinia, isolated from both man and animal. It is a frequent cause of bacterial gastroenteritis in children. Yersinia spp./Yersiniosis are gram-negative, oxidase-negative coccobacilli.
• Facultative anaerobes Facultative anaerobes Yersinia spp./Yersiniosis
• Pleomorphic Pleomorphic Bacteroides bacterium that belongs to Enterobacteriaceae Enterobacteriaceae A family of gram-negative, facultatively anaerobic, rod-shaped bacteria that do not form endospores. Its organisms are distributed worldwide with some being saprophytes and others being plant and animal parasites. Many species are of considerable economic importance due to their pathogenic effects on agriculture and livestock. Cephalosporins
• Obligate pathogen
• Distinguishing features:
  • Motile at 25.0°C (77°F), nonmotile at 37.0°C (98.6°F)
  • Cold growth

Transmission

• Foodborne (raw or undercooked pork, unpasteurized milk)
• Blood products
• Contaminated water
• Direct or indirect contact with an infected animal (livestock, rabbits, rodents)

Pathogenesis

• Adheres to epithelial cells in the ileum Ileum The distal and narrowest portion of the small intestine, between the jejunum and the ileocecal valve of the large intestine. Small Intestine: Anatomy → invades the intestinal wall, likely through M cells M cells Salmonella → colonizes lymphoid tissue (Peyer’s patches Patches Vitiligo)
• Can invade mesenteric lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy and disseminate
• Enterotoxin Enterotoxin Substances that are toxic to the intestinal tract causing vomiting, diarrhea, etc. ; most common enterotoxins are produced by bacteria. Diarrhea production similar to ETEC
• Leads to mucosal ulceration Ulceration Corneal Abrasions, Erosion, and Ulcers in the terminal ileum Ileum The distal and narrowest portion of the small intestine, between the jejunum and the ileocecal valve of the large intestine. Small Intestine: Anatomy
• Iron overload Iron overload An excessive accumulation of iron in the body due to a greater than normal absorption of iron from the gastrointestinal tract or from parenteral injection. This may arise from idiopathic hemochromatosis, excessive iron intake, chronic alcoholism, certain types of refractory anemia, or transfusional hemosiderosis. Hereditary Hemochromatosis states increase the pathogenicity.

Clinical presentation

• Incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus period is around 4–6 days; the duration is 1–2 weeks.
• Inflammatory bloody diarrhea Bloody diarrhea Diarrhea
• Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
• Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
• Abdominal pain Abdominal Pain Acute Abdomen
• Pharyngitis Pharyngitis Pharyngitis is an inflammation of the back of the throat (pharynx). Pharyngitis is usually caused by an upper respiratory tract infection, which is viral in most cases. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, and hoarseness. Pharyngitis (approximately 20%)

Management

• Generally only requires supportive care
• Antibiotics may be used based on severity, but there is questionable clinical benefit:
  • Fluoroquinolones Fluoroquinolones Fluoroquinolones are a group of broad-spectrum, bactericidal antibiotics inhibiting bacterial DNA replication. Fluoroquinolones cover gram-negative, anaerobic, and atypical organisms, as well as some gram-positive and multidrug-resistant (MDR) organisms. Fluoroquinolones 
  • TMP-SMX
  • 3rd-generation cephalosporins Cephalosporins Cephalosporins are a group of bactericidal beta-lactam antibiotics (similar to penicillins) that exert their effects by preventing bacteria from producing their cell walls, ultimately leading to cell death. Cephalosporins are categorized by generation and all drug names begin with “cef-” or “ceph-.” Cephalosporins

Complications

• Reactive arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis
• Erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion nodosum
• Systemic infection
• Abdominal (rare): 
  • Mesenteric lymphadenitis Mesenteric Lymphadenitis Inflammation of lymph nodes in the mesentery. Pediatric Gastrointestinal Abnormalities (“ pseudoappendicitis Pseudoappendicitis Inflammation of lymph nodes in the mesentery. Yersinia spp./Yersiniosis” with right lower quadrant Right lower quadrant Anterior Abdominal Wall: Anatomy pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways)
  • Mesenteric vein thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus (can lead to bowel necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage)
  • Bowel perforation Bowel perforation Perforated viscus or GI perforation represents a condition in which the integrity of the GI wall is lost with subsequent leakage of enteric contents into the peritoneal cavity, resulting in peritonitis. The causes of perforated viscus include trauma, bowel ischemia, infections, or ulcerative conditions, all of which ultimately lead to a full-thickness disruption of the intestinal wall. Perforated Viscus
  • Toxic megacolon Toxic megacolon An acute form of megacolon, severe pathological dilatation of the colon. It is associated with clinical conditions such as ulcerative colitis; Crohn disease; amebic dysentery; or Clostridium enterocolitis. Megacolon
  • Cholangitis
  • Peritonitis Peritonitis Inflammation of the peritoneum lining the abdominal cavity as the result of infectious, autoimmune, or chemical processes. Primary peritonitis is due to infection of the peritoneal cavity via hematogenous or lymphatic spread and without intra-abdominal source. Secondary peritonitis arises from the abdominal cavity itself through rupture or abscess of intra-abdominal organs. Penetrating Abdominal Injury

Clostridium

Clostridium perfringens Clostridium perfringens The most common etiologic agent of gas gangrene. It is differentiable into several distinct types based on the distribution of twelve different toxins. Gas Gangrene enterocolitis Enterocolitis Inflammation of the mucosa of both the small intestine and the large intestine. Etiology includes ischemia, infections, allergic, and immune responses. Yersinia spp./Yersiniosis will be discussed here.

Pathogen

• Clostridium perfringens Clostridium perfringens The most common etiologic agent of gas gangrene. It is differentiable into several distinct types based on the distribution of twelve different toxins. Gas Gangrene type A are gram-positive Gram-Positive Penicillins, anaerobic, spore-forming rods.
• Distinguishing features:
  • Non-motile
  • Anaerobic: “stormy fermentation” in milk media
  • Double zone of hemolysis on blood agar Blood agar Nocardia/Nocardiosis

Transmission

• Foodborne (undercooked or poorly refrigerated meat, reheated meat dishes, legumes)
• Spores Spores The reproductive elements of lower organisms, such as bacteria; fungi; and cryptogamic plants. Anthrax can survive cooking temperatures.
• Proliferates on foods that are improperly stored

Pathogenesis

• Spores Spores The reproductive elements of lower organisms, such as bacteria; fungi; and cryptogamic plants. Anthrax germinate under anaerobic conditions.
• Enterotoxin Enterotoxin Substances that are toxic to the intestinal tract causing vomiting, diarrhea, etc. ; most common enterotoxins are produced by bacteria. Diarrhea is produced in the intestines → disrupts ion transport → watery diarrhea Watery diarrhea Rotavirus, cramps Cramps Ion Channel Myopathy

Clinical presentation

• Incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus period of 6–24 hours, resolves within 24–48 hours (usually < 24 hours)
• Severe abdominal cramping Abdominal cramping Norovirus
• Non-inflammatory, watery diarrhea Watery diarrhea Rotavirus
• Vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia and fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever are uncommon.

Management

• Supportive care 
• Usually a self-limited disease

Other pathologic manifestations

• Gas gangrene Gangrene Death and putrefaction of tissue usually due to a loss of blood supply. Small Bowel Obstruction
• Cellulitis Cellulitis Cellulitis is a common infection caused by bacteria that affects the dermis and subcutaneous tissue of the skin. It is frequently caused by Staphylococcus aureus and Streptococcus pyogenes. The skin infection presents as an erythematous and edematous area with warmth and tenderness. Cellulitis and fasciitis
• Necrotizing enterocolitis Enterocolitis Inflammation of the mucosa of both the small intestine and the large intestine. Etiology includes ischemia, infections, allergic, and immune responses. Yersinia spp./Yersiniosis (from type C strains):
  • Beta-toxin produces segmental necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage of the intestine.
  • Presents with bloody diarrhea Bloody diarrhea Diarrhea, abdominal pain Abdominal Pain Acute Abdomen, and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
  • Treatment:
    • Antibiotics ( penicillin Penicillin Rheumatic Fever G, metronidazole Metronidazole A nitroimidazole used to treat amebiasis; vaginitis; trichomonas infections; giardiasis; anaerobic bacteria; and treponemal infections. Pyogenic Liver Abscess)
    • Possible surgery for failure to respond, perforation Perforation A pathological hole in an organ, blood vessel or other soft part of the body, occurring in the absence of external force. Esophagitis, or obstruction

Rotavirus

Pathogen

• Rotavirus Rotavirus A genus of Reoviridae, causing acute gastroenteritis in birds and mammals, including humans. Transmission is horizontal and by environmental contamination. Seven species (rotaviruses A through G) are recognized. Rotavirus is a non-enveloped, segmented, double-stranded RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure reovirus.
• The most common cause of severe diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea among infants and children worldwide

Transmission

• Fecal-oral route Fecal-oral route Echovirus
• Only a small inoculum is required for transmission.
• Common during the winter Winter Pityriasis Rosea months

Pathophysiology

• Penetrates cells of the small intestinal villi → cholera Cholera An acute diarrheal disease endemic in india and southeast Asia whose causative agent is Vibrio cholerae. This condition can lead to severe dehydration in a matter of hours unless quickly treated. Vibrio toxin–like protein production → destruction and blunting of the microvilli → disrupts electrolyte and water absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption
• ↓ disaccharidase Disaccharidase Enzymes belonging to the class of glycoside hydrolases which break down disaccharides into simpler sugars, monosaccharides. Rotavirus activity → malabsorption Malabsorption General term for a group of malnutrition syndromes caused by failure of normal intestinal absorption of nutrients. Malabsorption and Maldigestion of lactose and D-xylose → osmotic influx Osmotic influx Rotavirus into the intestine 
• Watery stools develop due to active water secretion Secretion Coagulation Studies and impaired absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption.

Clinical presentation

• Incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus period is < 48 hours, and the duration is 4–5 days.
• Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
• Malaise Malaise Tick-borne Encephalitis Virus
• Abdominal pain Abdominal Pain Acute Abdomen
• Vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
• Non-inflammatory, non-bloody, watery diarrhea Watery diarrhea Rotavirus: can be severe and lead to serious dehydration Dehydration The condition that results from excessive loss of water from a living organism. Volume Depletion and Dehydration

Management and prevention

• Disease is self-limited.
• Oral rehydration Rehydration Dengue Virus
• IV fluids IV fluids Intravenous fluids are one of the most common interventions administered in medicine to approximate physiologic bodily fluids. Intravenous fluids are divided into 2 categories: crystalloid and colloid solutions. Intravenous fluids have a wide variety of indications, including intravascular volume expansion, electrolyte manipulation, and maintenance fluids. Intravenous Fluids in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with severe dehydration Severe Dehydration Fluid Replacement Therapy in Children
• Live attenuated vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination: 
  • Given to all children before 8 months of age 
  • Contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation:
    • Severe combined immunodeficiency Immunodeficiency Chédiak-Higashi Syndrome disease ( SCID SCID Severe combined immunodeficiency (SCID), also called “bubble boy disease,” is a rare genetic disorder in which the development of functional B and T cells is disturbed due to several genetic mutations that result in reduced or absent immune function. Severe Combined Immunodeficiency (SCID))
    • History of intussusception Intussusception Intussusception occurs when a part of the intestine (intussusceptum) telescopes into another part (intussuscipiens) of the intestine. The condition can cause obstruction and, if untreated, progress to bowel ischemia. Intussusception is most common in the pediatric population, but is occasionally encountered in adults. Intussusception

Complications

• Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures
• Encephalopathy Encephalopathy Hyper-IgM Syndrome
• Encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis

Norovirus

Pathogen and epidemiology

• Norovirus Norovirus Norovirus is a nonenveloped, single-stranded, positive-sense RNA virus belonging to the Caliciviridae family. Norovirus infections are transmitted via the fecal-oral route or by aerosols from vomiting. The virus is one of the most common causes of nonbacterial gastroenteritis epidemic worldwide. Symptoms include watery and nonbloody diarrhea, nausea, vomiting, and low-grade fever. Norovirus (also known as Norwalk virus Norwalk virus Norovirus is a nonenveloped, single-stranded, positive-sense RNA virus belonging to the caliciviridae family. Norovirus infections are transmitted via the fecal-oral route or by aerosols from vomiting. The virus is one of the most common causes of nonbacterial gastroenteritis epidemic worldwide. Symptoms include watery and nonbloody diarrhea, nausea, vomiting, and low-grade fever. Norovirus) is a non‑enveloped RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure calicivirus.
• Community outbreaks Outbreaks Sudden increase in the incidence of a disease. The concept includes epidemics and pandemics. Influenza Viruses/Influenza (nursing homes, hospitals, cruise ships, etc ETC The electron transport chain (ETC) sends electrons through a series of proteins, which generate an electrochemical proton gradient that produces energy in the form of adenosine triphosphate (ATP). Electron Transport Chain (ETC).) are common. 
• Causes the most common type of adult gastroenteritis

Transmission

• The virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology is highly virulent.
• Fecal-oral route Fecal-oral route Echovirus through contaminated food, water, or contaminated surfaces
• Person‑to‑person contact
• Aerosolized

Pathogenesis

• Mechanism is not entirely understood.
• Delayed gastric emptying Gastric emptying The evacuation of food from the stomach into the duodenum. Gastrointestinal Motility leads to nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia.
• Jejunal biopsy Jejunal biopsy Norovirus shows blunting of microvilli, but the mucosa is otherwise intact.
• Cytoplasmic vacuolization Cytoplasmic vacuolization Norovirus is seen along with mononuclear infiltrates of tissue.
• The virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology appears to decrease brush border enzymes Brush border enzymes Digestion and Absorption, causing malabsorption Malabsorption General term for a group of malnutrition syndromes caused by failure of normal intestinal absorption of nutrients. Malabsorption and Maldigestion.

Clinical presentation

• Incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus period is 24–60 hours.
• Abrupt onset of nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
• Watery, non-bloody diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
• Abdominal cramps Cramps Ion Channel Myopathy
• Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess
• Myalgias Myalgias Painful sensation in the muscles. Tick-borne Encephalitis Virus
• Malaise Malaise Tick-borne Encephalitis Virus

Diagnosis and management

• Diagnosis is usually based on clinical suspicion.
• Management includes rehydration Rehydration Dengue Virus with oral or IV fluids IV fluids Intravenous fluids are one of the most common interventions administered in medicine to approximate physiologic bodily fluids. Intravenous fluids are divided into 2 categories: crystalloid and colloid solutions. Intravenous fluids have a wide variety of indications, including intravascular volume expansion, electrolyte manipulation, and maintenance fluids. Intravenous Fluids.