Helicobacter pylori Microbiology

• Gastrointestinal System: Theoretical Revision of Microbiology

Gastritis

• Helicobacter pylori stands out as the most significant pathogen

Helicobacter pylori

• Heliobacters are motile, curved, Gram-negative bacilli

Virulence Factors of Helicobacter pylori

• Urease enables to generate ammonia from urea, neutralizing stomach acid for its survival
• Cytotoxin-associated antigen (CagA) is linked to a higher incidence of peptic ulcers and gastric malignancy
• Vacuolating toxin (VacA) creates pores in host cell membranes

Diagnosis: Helicobacter pylori

• Clinical manifestation is key in diagnosis
• Patients with gastritis often experience dyspepsia (epigastric pain, burning), nausea, and vomiting; some may be asymptomatic
• Patients with peptic ulcers typically have epigastric pain, which may be relieved by food intake
  • A complication is gastrointestinal bleeding

Laboratory Diagnosis of Helicobacter pylori

• The urea breath test involves ingesting radiolabeled urea
  • If Helicobacter pylori is present, urease will cleave the ingested urea, leading to the evolution of radiolabeled CO2, which is then identified in the breath

Additional Diagnostic Tests

• The stool antigen test is deployed for initial diagnosis and to monitor the success of treatment
• The urease test is employed on biopsy specimens for diagnosis

Invasive Tests for Helicobacter pylori

• Upper endoscopy with gastric biopsy stands out as the definitive diagnostic strategy

Acute Diarrhea

• Mechanism involves disruption of the normal absorption and secretory processes in the small intestines by either preformed exotoxins in food eg. Staphylococcus aureus, Bacillus cereus or the actions of infectious agents in the intestinal tract either mucosal invasion or production of toxins

Watery Diarrhea vs Bloody Diarrhea

• Watery Diarrhea:*
• No red or white blood cells in stool, indicating no inflammation
• Typically afebrile, with a large volume diarrhea
• Infection often targets the small intestine
• Bloody Diarrhea:*
• Presence of both red and white blood cells in stool, signifying an inflammatory response
• Frequently febrile, involves small volume diarrhea
• Infection usually occurs in the colon

Organisms Causing Diarrhea

• Watery (Non-inflammatory) Diarrhea:*
• Enterotoxigenic Escherichia coli
• Vibrio cholerae
• Staphylococcus aureus
• Bacillus cereus
• Clostridium perfringenes
• Bloody (Inflammatory) Diarrhea:*
• Shiga toxin-producing E. coli (STEC) (O157:H7 serotype)
• Shigella species
• Salmonella
• Campylobacter jejuni
• Clostridium difficile
• Yersinia enterocolitica

Campylobacter jejuni

• Campylobacter jejuni: Curved, Gram-negative bacilli (comma- or S-shaped), microaerophilic (5% oxygen), oxidase-positive, motile with a single polar flagellum; it grows well at 42°C
• It is a frequent cause of enterocolitis, especially in children

Campylobacter jejuni: Reservoirs and Transmission

• Reservoirs include domestic animals like cattle, chickens, and dogs
• Mode of transmission is typically fecal-oral
  • Occurs through ingestion of contaminated food and water containing animal feces
  • Foods commonly implicated include undercooked poultry, meat, and unpasteurized milk
  • Human-to-human transmission is less frequent
• Pathogenesis involves inflammation of the intestinal mucosa, often accompanied by blood in stools (bloody diarrhea)

Campylobacter jejuni: Clinical Manifestations

• Manifestations starts with watery, foul-smelling diarrhea followed by bloody stools
• Other symptoms are fever and severe abdominal pain
• Associated with Guillain-Barré syndrome, an autoimmune condition resulting from antibodies against Campylobacter jejuni that cross-react with antigens on neurons
• Also associated with Reactive arthritis and Reiter's syndrome

Escherichia coli: Diarrhea Causing Groups

• II- Escherichia coli (Inflammatory and non-inflammatory Diarrhea)
• Enteric bacteria with groups causing diarrhea
• Enterotoxigenic E. coli (ETEC)
• Enterohemorrhagic E. coli (EHEC)
• Enteroinvasive E. coli (EIEC)
• Enteropathogenic E. coli (EPEC)
• Enteroaggregative E. coli (EAEC)

E. coli Pathogenesis

• ETEC : Enterotoxin LT/ST
• EHEC: Shiga toxin
• EIEC: Invasion of epithelium of the large intestine
• EPEC: Adherence & eliminate surrounding microvilli
• EAEC: Adherence & enterotoxin

Target Sites of E. coli

• ETEC and EPEC target Small intestine
• EHEC and EIEC target Large intestine
• EAEC tarhets Small intestine

Manifestations of E. coli

• ETEC : Watery diarrhea
• EHEC: Bloody diarrhea, abdominal cramping, and Fever
• EIEC: Bloody diarrhea
• EPEC: :Watery diarrhea
• EAEC: :Watery diarrhea

ETEC Pathogenesis

• The heat-labile toxin (LT) stimulates adenylate cyclase, leading to an increase in intracellular cAMP
  • This increase or increase in cGMP causes loss of fluid and ions (potassium, chloride) from the enterocytes into the lumen of the gut causing watery diarrhea
• The heat-stable toxin (ST) stimulates guanylate cyclase, leading to increase of intracellular (cGMP)

Enterohemorrhagic E. coli (EHEC)

• The main reservoir for Enterohemorrhagic E. coli (EHEC) is cattle, and humans acquire the organism by consuming undercooked beef
• Shiga toxin-producing E. coli (STEC) that produces Shiga toxin, acts by inhibiting protein synthesis

Treatment for Enterohemorrhagic E. coli (EHEC)

• Treatment of diarrhea caused by O157:H7 strains with antibiotics e.g., ciprofloxacin, increases the risk of HUS, especially in children
• Antibiotics shouldn't be used to treat diarrhea caused by EHEC

Food Poisoning

• Different organisms have different key characteristics for food poisoning

Staphylococcus aureus Food Poisoning

• Ingestion of preformed enterotoxin in foods, especially dairy and carbohydrate-rich ones
• Short incubation period of 1-8 hours
• The enterotoxin acts as a superantigen, stimulating the vomiting center in the brain, leading to vomiting being more prominent than diarrhea

Staphylococcus aureus: Diagnosis

• Diagnosis involves recognition of the clinical signs, vomiting and epigastric pain, and diarrhea
• Detection of the toxin is done in food and stool samples
• Treatment is primarily supportive

Clostridium perfringenes Food Poisoning

• Spores are widespread in soil and can contaminate food
  • These heat-resistant spores survive cooking and germinate
• Organisms grow to large numbers in reheated meat dishes
• The enterotoxin cause diarrhea

Clostridium botulinum (Botulism)

• Ingestion of canned food (e.g., alkaline vegetables and smoked fish) containing the preformed Botulinum toxin
• Affects the nervous system
• The toxin is a neurotoxin - blocks the release of acetylcholine at nerve synapses
• Botulism is a severe form of food poisoning characterized by neurotoxic effects

Diagnosis of Clostridium botulinum

• Clinical manifestations include symptoms beginning 18–24 hours after ingestion of the toxic food, presenting as descending weakness and paralysis (diplopia, dysphagia, and respiratory muscle failure)
• Laboratory diagnosis is confirmed through Botulinum toxin demonstrable in uneaten food and the patient's serum via mouse protection tests or enzyme-linked immunoassay (EIA) tests

Treament of Clostridium botulinum

-The heptavalent antitoxin is preferred to the trivalent antitoxin containing types A, B, and E

• Proper sterilization of all canned and vacuum-packed foods is crucial
• Foods must be adequately cooked to inactivate the toxin, and swollen cans should be discarded

Clostridium difficile

• Clostridium difficile is spore forming Gram-positive bacilli
• C. difficile is the most common cause of hospital-acquired diarrhea
• Virulence factors like Exotoxins A and B, which are cytotoxins that cause death of the enterocytes
• The organism is carried in the gastrointestinal tract
• Approximately 3% of the general population and up to 30% of hospitalized patients carry the organism

Diagnosis and Treatment of Clostridium difficile

• In clinical manifestations, diarrhea is usually not bloody
  • Neutrophils are found in the stool
  • Fever and abdominal pain are common
  • The pseudomembranes are visualized by sigmoidoscopy
• Laboratory diagnosis involves detecting the presence of exotoxins in the filtrate of a patient's stool specimen using ELISA or PCR
• Treatment involves the use of causative antibiotics such as Metronidazole or vancomycin
  • Monoclonal antibody against exotoxin B is effective for preventing relapses
• In in life-threatening, requires surgical removal of colon

Shigella

• Characterized by the virulence factor Shiga Toxin, which inhibits the protein synthesis
  • Causes hemolytic uremic syndrome (HUS)

Bacillary Dysentery Pathogenesis

• Involves inflammation of the intestine, abdominal pain, and diarrhea with stools that often contain blood and mucus
• The reservoir is human, and the mode of transmission is fecal-oral route

Viral Infections of GIT

• Salivary glands infection is associated with Mumps virus
• Small intestinal infection is linked to Reoviruses and Caliciviruses
• Liver infection suggests a Hepatitis virus

Infection of Salivary Glands With Symptoms

• Paramyxoviridae family
• -(MuV) is a member of Paramyxoviridae family
• VE sense SS RNA virus enveloped, with two spikes hemagglutinin HA and neuraminidase NA
• Mumps has symptoms that are often in childhood and Neutralizing antibody is directed against HA

Mumps: Mode of Transmission

• Respiratory droplets.
• IP: 18-21 days

Mumps Pathogenesis

• Enters the upper respiratory tract blood salivary glands especially
  • (Parotid gland, Testes, Ovaries, Pancreas and Meninges).
• Clinical picture is Prodromal stage
  • Fever, malaise, anorexia
  • Tender swelling of the salivary glands (unilateral or bilateral)
• resolves spontaneously within 1 week

Complications from Mumps

• Orchitis , if bilateral, can result in sterility and Meningitis, which is usually benign, self-limited

Mumps Diagnosis and Treatment

• The diagnosis is usually clinically but also by Specimens or PCR . But test the specimen by doing four fold test
• Since there is no antiviral therapy, prevention is key

Prevention

• Infection is once in life and gives lifelong immunity
• Active immunization : MMR vaccine and 2 doses one at 15 months
• A booster dose at 4 to 6 years will allow for long term effects

Viral Gastroenteritis

• Viral GASTROENTERITIS (GE) is an acute watery diarrhea of short duration where viruses respond
• Clinical picture is similar with symptoms without blood or pus in stool (fever, vomiting, diarrhea, abdominal pain)
• Causes:*
  • Rota virus
  • Caliciviruses
  • Adenovirus
  • Astroviruses

Rotavirus Strucutre

• Reoviridae family and segmented with a double layer
• outer protein elicits response
• transmission is fecal-oral route

Roatavirus Clinical Findings and Diagnosis

• Nausea, vomiting, and watery diarrhea, and dehydration often affect young children
• Lab diagnosis : Rotavirus found through stool or microscopy and through PCR

Roatavirus Treatment and Prevention

• oral rehyrdation or intravenous fluids to treat dehydration
• live attenuated vaccines, intussusception will occur

Clinical Findings and Treatment For Caliciviruses

• Clinical findings includes but not limited to Vomiting, watery diarrhea,low grade fever
• Many asymptomatic infections from clinical diagnosis
• Treatment requires a vaccine

Hepatitis A

• A virus from the route to test for recovery

• Most infections are the most asymptomatic

HEP

• structure lacks it so it has to hijack the infection, often by sexual transmission