10.4 Pathology of Infectious Diseases: Transmission, Tissue Reaction Patterns & Diagnostic Morphology

Why this area matters

The TOS lists:

• transmission and dissemination of microbes;
• inflammatory responses to infections;
• viral infections (acute viral, herpesviruses, hepatitis B, Epstein-Barr virus);
• bacterial infections (gram-positive and gram-negative, mycobacteria, spirochetes, anaerobes, chlamydia, rickettsia);
• fungal infections;
• parasitic infections (protozoa and metazoa).

Infections remain a leading cause of illness in the Philippines. The pathologist's task is to recognize the tissue reaction and identify the organism.

Transmission, spread and injury

Routes of entry:

• skin, through breaks, insect bites or needles;
• the respiratory tract, by droplets and aerosols;
• the gastrointestinal tract, by the fecal-oral route;
• the urogenital tract, sexually;
• vertically, through the placenta, at birth or in breast milk.

Spread within the body: local invasion (helped by hyaluronidase and collagenase), lymphatics, blood (bacteremia, viremia, fungemia), and nerves (rabies, herpes simplex, varicella-zoster).

Mechanisms of injury:

• direct cell killing by viruses;
• toxins, either endotoxin (lipopolysaccharide, which causes septic shock) or exotoxins such as cholera, tetanus, botulinum and diphtheria toxins;
• enzymes;
• injury from the host immune response, as in hepatitis B hepatocyte killing, post-streptococcal glomerulonephritis and tuberculous caseation.

The five patterns of tissue reaction

Viral infections

Bacterial infections

• Gram-positive:
  • S. aureus forms abscesses, furuncles, carbuncles and osteomyelitis; its toxins cause toxic shock syndrome and scalded skin.
  • Streptococcus pyogenes causes spreading cellulitis and necrotizing fasciitis, and later rheumatic fever and glomerulonephritis.
  • Clostridium perfringens causes gas gangrene: myonecrosis with gas bubbles and few neutrophils.
  • Corynebacterium diphtheriae forms a gray pseudomembrane, and its exotoxin causes myocarditis and neuritis.
• Gram-negative:
  • Typhoid (Salmonella Typhi) causes hyperplasia and ulceration of Peyer patches (oval ulcers along the bowel axis) with mononuclear cells, and perforation in the third week.
  • Shigella causes superficial colonic ulcers.
  • Neisseria meningitidis causes purulent meningitis and adrenal hemorrhage.
  • Pseudomonas causes vasculitis (ecthyma gangrenosum).
• Mycobacteria:
  • Tuberculosis forms caseating granulomas with Langhans giant cells. Primary infection forms the Ghon complex (a subpleural focus near the interlobar fissure plus the draining hilar node). Secondary (reactivation) disease forms apical cavities. Miliary seeding produces tiny nodules throughout the organs. In AIDS, granulomas may be poorly formed.
  • Leprosy (M. leprae, still reported in the Philippines):
    • Tuberculoid: strong Th1 response, well-formed granulomas, few bacilli, asymmetric anesthetic patches and thickened nerves.
    • Lepromatous: weak cell-mediated immunity, sheets of foamy lepra cells full of bacilli (globi), nodular lesions, leonine facies, symmetric neuropathy.
• Spirochetes:
  • Syphilis shows endarteritis obliterans with plasma cells at every stage. Stages are chancre, secondary mucocutaneous lesions and condylomata lata, then tertiary gummas, aortitis (ascending aneurysm) and neurosyphilis. Congenital syphilis causes Hutchinson teeth, saddle nose and saber shins.
  • Leptospirosis causes vasculitis with hepatic and renal injury (Weil disease) and pulmonary hemorrhage.
• Anaerobes: lung abscess after aspiration, actinomycosis (sulfur granules, draining sinuses), mixed intra-abdominal abscesses.
• Chlamydia: urethritis, cervicitis, pelvic inflammatory disease, lymphogranuloma venereum (stellate abscesses in nodes), neonatal conjunctivitis and pneumonia, trachoma.
• Rickettsia (scrub typhus is endemic in parts of the Philippines): infect endothelium, causing vasculitis, rash and multi-organ microinfarcts; an eschar at the chigger bite.

Fungal infections

Parasitic infections

Protozoa:

• Entamoeba histolytica causes flask-shaped colonic ulcers with trophozoites that contain ingested red cells, and liver abscesses with "anchovy paste" contents.
• Plasmodium falciparum malaria causes sequestration of parasitized red cells in brain capillaries (cerebral malaria with ring hemorrhages), malarial pigment (hemozoin), splenomegaly and hemolysis.
• Toxoplasma, Leishmania and Giardia are other key protozoa.

Metazoa (helminths):

• Schistosoma japonicum (endemic in parts of the Visayas and Mindanao) lays eggs in mesenteric venules. Eggs trapped in the liver provoke granulomas with eosinophils, then pipe-stem (Symmers) periportal fibrosis, presinusoidal portal hypertension, splenomegaly and varices.
• Taenia solium cysticercosis forms cysts in the brain (seizures) and muscle.
• Filariasis (Wuchereria, Brugia) blocks lymphatics, causing lymphedema and elephantiasis.
• Ascaris can obstruct the bowel and biliary tree.
• Strongyloides hyperinfection occurs with corticosteroid use.
• Capillaria philippinensis causes protein-losing diarrhea.

Special stains for organisms