Infections of Upper GIT

Infections of Upper GIT

• Microorganisms are swallowed daily, but rarely cause infection due to the body's defense mechanisms
• These mechanisms prevent microorganisms from reaching the intestine in sufficient numbers to cause infection.

Defense Mechanisms Against GIT Infections

• The mouth contains a flow of liquids (saliva), lysozyme, and normal bacteria flora
• The esophagus has a flow of liquids (also swallowing) and peristalsis
• The stomach contains acid (pH)
• The small intestine contains flow of gut contents, peristalsis, mucus, bile, secretory IgA, lymphoid tissue (Peyer's patches) and shedding/replacement of epithelium.
• The large intestine has normal flora, peristalsis, shedding/replication of epithelium, and mucus.

Normal Flora

• Approximately 1,200 species of bacteria, yeasts, and other organisms are present in the human gastrointestinal tract.
• The oral cavity has around 10³ cells/ml of Firmicutes, Streptococcus, Candida, Helicobacter pylori, and Peptostreptococcus.
• The stomach has around 10³cells/ml of Lactobacillus and Candida.
• The Duodenum, Proximal ileum and Distal ileum all have around 10⁶ cells/ml Lactobacillus, Bacteroides, Clostidium, Actinomycinae, Corynebacteria, etc
• The colon has approximately 10¹² cells/ml of Clostridium groups IV & XJV, Bifidobacterium, and Enterobacteriaceae.

Types of Gastrointestinal Infections

• Infections of the upper GIT (Stomatitis, Esophagitis, Gastritis)
• Microbial causes of Diarrhea (Bacterial, Viral, Parasitic)
• Food poisoning
• Parasites of the gastrointestinal tract
• Microbial causes of Hepatitis

Infections of Oral Cavity

• Fungal causes: Oral candidiasis (Oral thrush) - Whitish patches on the tongue and oral cavity mucosa
• Viral causes: Herpes simplex virus infections (Herpetic stomatitis) - Vesicular eruptions & ulcerations in the oral cavity; Coxsackievirus A infections (Herpangina, hand, foot, and mouth disease) - Fever, blisters, ulceration in the soft palate/throat, hand, feet, mouth sores

Infections of Esophagus

• Fungal causes: Esophageal candidiasis
• Viral causes: Herpesviruses (cytomegalovirus, herpes simplex virus) - Most cases occur in immunocompromised patients.

Infections of Stomach

• Bacterial causes: Helicobacter pylori (A spiral/curved bacilli bacterium that colonizes the gastric mucosa.
• Most common chronic bacterial infection worldwide, infecting over 50% of the global population. This bacterium is an etiology for various gastroduodenal diseases.

Helicobacter pylori

• Morphology: Gram-negative, spiral, or curved bacilli; motile with multiple unipolar flagella (lophotrichous); non-capsulated, non-spore forming.
• Cultural characteristics: Microaerophilic (requires 5% O₂, 5-10% CO₂, and high humidity); grows best at 37°C for 3-6 days; uses fresh blood or serum agar media; Skirrow's medium is a selective medium; colonies are translucent, pinpoint.
• Biochemical reactions: Does not ferment sugars; oxidase positive (possesses cytochrome oxidase); catalase positive; urease positive (produces large quantities of urease)

Urease Test

• The urease test involves culturing the organism in a medium containing urea and the indicator phenol red.
• Urease-producing strains break down urea through hydrolysis to produce ammonia and carbon dioxide
• Ammonia release makes the medium alkaline, causing a change in the indicator to pink-red.

Virulence Factors and Pathogenesis

• Pathogenesis depends on colonizing the stomach mucosa.
• Several virulence factors enable the bacterium to survive in the extreme acidic environment, reach the more neutral environment of the mucous layer, and resist the human immune response, leading to persistence.
• Urease: Neutralizes acid, facilitates colonization, localized tissue damage.
• Multiple unipolar flagellae: Corkscrew motility enables penetration into viscous environments (mucus)
• Mucinase: Degrades gastric mucus, contributing to localized tissue damage
• Adhesins & LPS: Adherence to epithelial cells
• VacA: Forms pores and intracellular vacuoles, induces apoptosis, and breaks down tight junctions between cells.
• CagA: Stimulates inflammatory responses (gastritis)

Transmission of H. pylori

• Direct human-to-human transmission (oral-oral or fecal-oral routes)
• Transmission through shared objects is possible.
• Clustering of H. pylori infection is higher within families.
• Transmission in childhood through close contact with the mother

Clinical Outcomes of H. pylori Infections

• MALT Lymphoma (<1%)
• Gastric Ulcer (10%)
• Acute/Chronic Gastritis (100%)
• Gastric Atrophy (5%)
• Duodenal Ulcer
• Gastric Cancer (1%)

Clinical Pictures

• Mostly asymptomatic
• Manifestations of gastritis/peptic ulcer: Epigastric dull/burning pain (heartburn), nausea, indigestion (dyspepsia), frequent burping (eructation), bloating, loss of appetite, weight loss, and dark/tarry stools or bloody vomit.

Laboratory Diagnosis

• Non-Endoscopic Tests:
  • Serology (qualitative or quantitative IgG)
  • Urea breath test
  • Stool antigen test
• Endoscopic Tests:
  • Histology
  • Rapid Urease Test (RUT)
  • Culture
  • PCR assay

Urea Breath Test (Non-Endoscopic)

• ¹³C or ¹⁴C labeled urea is ingested.
• Urease of H. pylori hydrolyzes the urea into labeled CO₂, which is exhaled with breath.
• The CO₂ is detected by radioisotopes.

Stool Antigen Detection (Non-Endoscopic)

• ELISA
• Immunochromatography

Serology (Non-Endoscopic)

• Detects H. pylori antibodies in serum.

Endoscopic Tests (Specimen Collection, Rapid Urea Test (RUT), Cultivation, Histological Assessment, PCR)

• Biopsies are taken during endoscopy.
• The gastric biopsy sample is placed on a medium containing urea and PH indicator.
• Red color indicates a positive result for RUT
• Cultivation: Skirrow's medium; 37°C for 3-6 days
• Histology: H. pylori can be visualized with H&E stained slide.
• PCR: for identifying the bacteria

Treatment

• Triple drug regimen (14 days): PPI + Clarithromycin + either Amoxicillin or Metronidazole
• Quadruple drug regimen (14 days): PPI + Bismuth salt + Tetracycline + Metronidazole

Diagnosis Summary

• High-Risk Patient: Invasive endoscopy with gastric biopsy and culture/histology/RUT.
• Low-Risk Patient: Non-invasive methods (Urea breath test or stool antigen).
• Serology: Not first choice as antibodies can persist after infection.