Detailed Notes on Infectious Diseases and Their Pathogens

Mycobacterium Tuberculosis

  • General

    • Odds of infection:
    • 10-20% chance of no infection, either through innate immune response or rapid activation of the immune system.
    • 80-90% chance of infection:
      • 90-95% of those clear the infection.
      • 5-10% develop disease.

  • Ecology

    • Humans are the only reservoir for Mycobacterium tuberculosis.

  • Transmission

    • Spread through aerosols (droplet nuclei):
    • Very small and light droplets containing about 3 bacilli.
    • An infected person releases about 3,000 droplet nuclei per minute when talking.
    • These droplets can suspend in the air for several months and reach deep into the lungs.
    • Infectious dose (ID50) = 10.

  • Predisposing Factors

    • Smoking
    • Alcoholism
    • Poor nutrition and healthcare access
    • Crowding
    • Immunocompromised status
    • Genetics (innate susceptibility or resistance)
    • Presence of HIV

  • Disease Processes

    • Primary Tuberculosis

    • Infection begins with inhalation that targets alveolar macrophages.

    • The critical factor is how long the macrophage remains uninactivated.

      • Pathogen can replicate inside macrophages for 7-21 days.
      • Typically, quicker immune responses can prevent disease onset.

    • Immunological responses:

      • T helper 1 (Th1) cells increase inflammation, TNF production, and activation of cytotoxic T cells.
      • Pathogen manipulates immune response by promoting Th2 cell response (not cytotoxic).

    • Early Controlled Response

      • Immune cells surround the infection and create a focal area (tubercule) that contains the spread.
      • Tubercules:
      • Too small to detect on X-ray, require microscopy for diagnosis.
      • Granulomas indicate control measures.

    • Late Controlled Response

      • Granuloma Composition:
      • Interior: Caseous necrosis (pus-filled area) and giant cells (fused macrophages).
      • Exterior: Layers of T cells, macrophages, polys (neutrophils), and fibroblasts.
      • Bacterial Virulence Factors:
      • Mycolic acid: protects against various immune responses.
      • Cord factor: toxic to mammalian cells, inhibits neutrophil migration.

  • Asymptomatic effects:

    • Ghon complex (calcified lesion) can harbor viable bacilli.
    • Ranke complex indicates complete calcification, with bacteria dead.
    • Both complexes can appear the same on chest X-rays, complicating diagnosis.

  • Secondary (Reactivated) Tuberculosis:

    • Change in immune status leads to necrotic lesions liquifying, rupturing, and spreading the infection.
    • Symptoms:
      • Prolonged cough, bloody sputum, chest pain, and increased transmission due to coughing.
      • Late-stage symptoms include fever, chills, night sweats, appetite loss, pallor, and fatigue.
      • If replication continues unchecked in the lungs, it poses a 60% fatality risk without treatment.

  • Extrapulmonary Tuberculosis:

    • Infection spreads beyond lungs to organs such as kidneys, genitals, bones, and meninges.
    • Can cause necrosis, structural collapse, and severe complications.
    • Untreated cases lead to high fatality rates (up to 50%).

  • Diagnosis and Treatment

    • Tuberculin Testing:

    • Detects cytotoxic T cell activation through skin injection.

    • Induration (red wheel) shows exposure but false negatives/positives can occur.

    • Chest X-Rays:

    • Look for granulomas; Ghon complexes indicate past infections.

    • Staining:

    • Microscopy required for sputum analysis for acid-fast bacilli.

    • Treatment

    • Nonresistant Forms:

      • 2-month regimen of isoniazid, rifampin, pyrazinamide, ethambutol.
      • Followed by 4-month regimen of isoniazid and rifampin.

    • Resistant Forms:

      • MDR Strain: Resistant to first-line drugs.
      • XDR Strain: Resistant to first and second-line drugs; treated with more toxic but less effective third-line drugs.

    • Calmet-Guerin Vaccine:

      • Provides effective prevention against acute infections but is not given in endemic countries due to false positives in tests.

Neisseria Gonorrhoeae

  • Epidemiology

    • Humans are the reservoir; does not spread between species.
    • Most common in ages 18-24, with an infectious dose of 100-1000 cfu’s.

  • Transmission

    • Occurs primarily through sexual intercourse; risk increases with the number of partners.
    • 20% risk for men on a single encounter, 50% chance for women.
    • Other transmission includes mother to child during childbirth.

  • Pathogenesis

    • Virulence Factors:
    • Pili: Attachment to host and evasion of phagocytosis.
    • Protease: Cleaves IgA, disrupting mucosal defenses.
    • LOS: Uncontrolled inflammation and tissue damage.
    • Capable of living and multiplying inside PMNs (polymorphonuclear leukocytes).

  • Infection in Males:

    • Can present as urethritis (painful urination, purulence, incubation 2-5 days), prostatitis, or epididymitis leading to infertility.

  • Infection in Females:

    • Urethritis (similar to males), cervicitis, and pelvic inflammatory disease (PID) can result in heavy discharge and abdominal pain.

  • Treatment

    • Increasing drug resistance necessitates complex treatments, with cephalosporin being common but also facing growing resistance.
    • No vaccine currently available, prevention keys include abstinence, monogamy, and education on safe practices.

Neisseria Meningitidis

  • Epidemiology

    • Reservoir: Human only, approximately 40% carriage rate.

  • Transmission

    • Spread via respiratory droplets, primarily in nasopharynx region.

  • Disease

    • Second most common cause of bacterial meningitis; can quickly progress and potentially cause permanent damage.
    • Symptoms: fever, headache, sore throat, and stiff neck.
    • Quick onset; bleeding and petechiae may occur due to endotoxin effects.

  • Treatment

    • Often regarded as a medical emergency; treated with antibiotics (Rocephin) and anti-inflammatories for active infections.
    • Prophylactic care (rifampin or ciprofloxacin) for close contacts.

  • Vaccines: Menactra and Menomune for prevention.

Bordetella Pertussis

  • General

    • Causative agent of whooping cough; highly fastidious bacteria requiring specific growth conditions.

  • Epidemiology

    • Exclusively human, primarily transmitted through droplets.

  • Virulence Factors

    • Pertussis Toxin: Blocks cell signaling, increasing mucus production and nutrient release.
    • Tracheal Cytotoxin: Damages ciliated cells, increasing inflammation.
    • Filamentous Hemagglutinin (FHA): Adherence factor that aids in evading phagocytosis.

  • Stages of Disease:

    • Catarrhal Stage: Initial cold-like symptoms.
    • Paroxysmal Stage: Characterized by violent coughing spells and gasping, leading to cyanosis risk.
    • Convalescent Stage: Symptoms begin to subside but can result in secondary infections.

  • Treatment

    • Very effective vaccines available, with DTaP being preferred due to reduced side effects.

Viral Structures and Classifications

  • Common Viral Structures:

    • Central Core: Contains nucleic acid (either DNA or RNA), often with overlapping genes.
    • Capsid Structure: Either helical or icosahedral with capsomeres made of self-assembling proteins.

  • Classification:

    • Viruses classified into families based on genome type (DNA vs RNA), capsid structure (enveloped or naked), and replication sites (nucleus vs cytoplasm).

Viral Replication

  • Steps in Viral Replication:
    1. Adsorption: Virus attaches to host cell receptors.
    2. Penetration: Virus enters the cell, only nucleic acid, not whole virus.
    3. Replication: Viral nucleic acids replicate; DNA viruses typically replicate in the nucleus, RNA viruses in the cytoplasm.
    4. Maturation/Assembly: Production of capsids and assembly of further viral components.
    5. Release: New viral particles released by lysis or budding.

HIV (Human Immunodeficiency Virus)

  • Overview:

    • Contains a segmented ssRNA genome with specific glycoproteins necessary for entry and replication.

  • Transmission:

    • Blood, sexual contact, breastfeeding being major routes.

  • Disease Process:

    • Initial replication occurs with mild symptoms following viral inoculation.
    • Over time, CD4 T helper cells decrease, leading to opportunistic infections, known as AIDS when T cell count falls below 200 cells/ul.

  • Diagnosis:

    • Initial serological tests followed by more specific testing (Western blot).

  • Treatment:

    • No cure but antiretroviral therapy can maintain virus levels and improve patient quality of life.