Chapter 6 – Infection

Microorganisms: General Concepts

• Small living forms; include bacteria, fungi, protozoa, viruses.

• Many grow in artificial culture media.

• Non-pathogenic microbes

  • Normally do not cause disease unless host or environmental conditions change.

  • Often part of normal flora; can be beneficial (e.g., vitamin synthesis, competition with pathogens).

• Pathogens = disease-causing microbes.

Bacteria - ABX can kill the bacteria

• Classified as prokaryotes (no nuclear membrane, no true nucleus).

• Metabolically active; reproduce by binary fission.

• Do not require living tissue; survive in varied environments.

• Vary widely in size/shape; major morphologies

  • Bacilli (rod-shaped)

  • Cocci (spherical) • diplococci • streptococci • staphylococci • tetrads • palisades

  • Spirochetes (spirals, Vibrio spp., spirilla)

  • Pleiomorphic (irregular forms)

  • if the bacteria is left to grow it can casue C diff

Reproduction

• Binary fission sequence

  1. Vegetative bacterium duplicates DNA.

  2. Cell divides → two identical daughter cells.

  3. Each daughter continues cycle, allowing exponential growth.

Basic Structure (4 parts)

1. Rigid cell wall

   • Maintains shape & protects.

   • Chemically distinct types: Gram-positive vs. Gram-negative.

   • Gram reaction guides antimicrobial selection.

2. Cell (plasma) membrane

   • Inside wall; selectively permeable.

3. External features

   • Capsule/slime layer: extra protection, antiphagocytic.

   • Flagella: motility.

   • Pili/fimbriae: hair-like; tissue adhesion; DNA transfer (conjugation).

4. Internal contents

   • Cytoplasm with chromosome (single circular DNA), ribosomes, RNA.

   • Plasmids (extrachromosomal DNA) – exchanged in conjugation, mediate drug resistance.

Toxins & Enzymes

• Exotoxins: secreted by Gram-positive bacteria; often neurotoxins or enterotoxins.

• Endotoxins: in Gram-negative wall; released on lysis; vasoactive → fever, septic shock.

• Enzymes: damage tissues and promote spread (e.g., hemolysins, collagenase, streptokinase).

Spore Formation

• Some genera (e.g., Clostridium, Bacillus) form dormant, highly resistant spores.

• Spores survive extreme heat, dryness, disinfectants for prolonged periods.

Viruses - need a living cell (can only be supressed not killed)

• Very small obligate intracellular parasites; require host cell machinery.

• Consist of nucleic acid (DNA or RNA) + protein coat (capsid); some have lipid envelope with glycoprotein spikes.

• RNA viruses with reverse transcriptase convert RNA → DNA.

Shapes

• Helical, icosahedral, complex (e.g., bacteriophage), enveloped/ non-enveloped.

Active Viral Infection (lytic cycle)

1. Attachment to specific host-cell receptors.

2. Penetration & uncoating; viral genome enters cytoplasm/nucleus.

3. Viral genome commandeers host synthesis of viral proteins & nucleic acids.

4. Assembly in cytoplasm.

5. Release via cell lysis or budding through host membrane (acquires envelope).

Latent Viral Infection

• Virus enters cell, expresses limited proteins inserted in host membrane.

• Host immune attack may destroy the cell.

• Virus reactivates during immunosuppression (e.g., HSV, VZV).

Chlamydia, Rickettsiae, Mycoplasmas

• Obligate intracellular bacteria; cannot grow on artificial media.

• Share features of viruses (intracellular) & bacteria (binary fission, prokaryotic).

• Chlamydia trachomatis

  • Common STI → pelvic inflammatory disease, infertility.

• Rickettsiae

  • Gram-negative; arthropod vectors (ticks, lice) transmit; cause Rocky Mountain spotted fever, typhus.

• Mycoplasmas

  • No cell wall → resistant to β-lactams.

  • Cause atypical (“walking”) pneumonia.

Fungi (Mycetes) - Grows where it can (oportunistic)

• Eukaryotic; nucleus present; reproduce by budding, spores.

• Found on animals, plants, humans, foods.

• Mostly opportunistic; infections begin on skin/mucosa, may disseminate when host immunosuppressed.

Examples

• Histoplasma capsulatum: inhaled spores → pulmonary or neurologic disease; transplacental.

• Tinea pedis (athlete’s foot): dermatophyte.

• Candida albicans: normal flora → thrush, vaginitis when conditions favor overgrowth.

• Pneumocystis jirovecii: opportunistic pneumonia (fungal & protozoal traits).

Protozoa - Antiprotozoles

• Single-celled eukaryotes; lack cell wall.

• Many free-living; pathogenic species are parasitic.

Major Diseases

• Trichomoniasis (Trichomonas vaginalis): STI.

• Malaria (Plasmodium spp.): invade RBCs → cyclical hemolysis.

• Amebic dysentery (Entamoeba histolytica): colonic ulcers, liver abscess.

• Naegleria fowleri: fatal primary amoebic meningoencephalitis.

Helminths (Worms)

• Multicellular parasites; flatworms (platyhelminths) & roundworms (nematodes).

• Life cycle: \text{ovum} \rightarrow \text{larva} \rightarrow \text{adult}

• Entry via skin penetration or ingestion; common in children; severe in immunosuppressed.

Selected Infections

• Pinworms (Enterobius): inhale/ingest ova from dust, perianal pruritus.

• Hookworms (Necator/Ancylostoma): larvae penetrate skin from soil.

• Tapeworms (Taenia): ingest cysticerci in undercooked pork/beef.

• Ascaris lumbricoides: ingest eggs on fecally contaminated produce.

Prions - Antiprions

• Misfolded protein agents; induce abnormal folding of host CNS proteins.

• Transmission: contaminated meat, surgical instruments, blood, donor organs.

• Lead to rapidly progressive, fatal neurodegeneration.

Human Diseases

• Creutzfeldt-Jakob (sporadic, variant), Gerstmann–Sträussler–Scheinker, Fatal familial insomnia, Kuru.

Animal Diseases

• Bovine spongiform encephalopathy, Chronic wasting disease, Scrapie, etc. (mad cow disease)

Resident (Normal) Flora (good bacteria

• Mixed microbes colonizing: skin, nasal cavity, mouth, gut, vagina, urethra.

• Provide competition; can become opportunistic if displaced or host defenses lowered.

Principles & Patterns of Infection

• Infection: microbe reproduces in/on host tissues.

• Occurrence terms

  • Sporadic: single individual.

  • Endemic: continuous transmission inside a population. -like one neighborhood

  • Epidemic: higher-than-normal incidence / new area. -the whole city

  • Pandemic: global (≥ several continents). -the entire state

Temporal Course

1. Incubation: entry → appearance of symptoms.

2. Prodromal: nonspecific malaise, headache. - when youre the most infective

3. Acute: signs/symptoms at peak; pathogen proliferates. - active sickness

4. Recovery/Convalescence: pathogen numbers decline, tissue repair.- when youre getting better

5. Chronic/Latent: some organisms persist, low-grade symptoms or latent state.

Infection Types

• Local vs. focal vs. systemic (septicemia, bacteremia, viremia, toxemia). - like a cut that gets infected (Local) Whole body is effected (systemic)

• Mixed (several pathogens), primary vs. secondary, subclinical.

Transmission: Links in Chain

1. Agent (microbe)

2. Reservoir: environment, humans, animals (symptomatic or carriers).

3. Portal of exit: path for agent to leave reservoir.

4. Mode of transmission

   • Direct contact (sex, blood).

   • Indirect contact (fomite, contaminated food/hands).

   • Droplet (large respiratory/salivary droplets).

   • Aerosol (small particles suspend & travel further).

   • Vector-borne (insects, animals).

5. Portal of entry (skin break, mucosa, inhalation, ingestion).

6. Susceptible host (age, immunity, nutrition, health status).

Factors Reducing Host Resistance

• Extremes of age, pregnancy, genetic deficits, immunodeficiency, chronic disease, malnutrition, severe stress, inflammation/trauma, impaired inflammatory response.

Virulence Determinants

• Invasiveness, toxin production, adhesion mechanisms (pili, fimbriae, receptors), evasion of immunity.

Emerging & Superinfections

• New strains (e.g., novel influenza) expand geographic reach.

• Multidrug-resistant TB, MRSA, VRE etc.

Nosocomial (Health-Care–Associated) Infections

• Occur in hospitals, nursing homes, clinics.

• Incidence: 10\%–15\% of inpatients.

• Contributing factors: high microbe load, undiagnosed carriers, shared environment/equipment, invasive procedures, immunocompromised patients, multiple reservoirs (staff, fomites).

Breaking the Chain / Control Measures

• Standard precautions: hand hygiene, PPE with any body fluid.

• Specific (isolation) precautions for known pathogens.

• Target points: isolate reservoir, sanitize food/water, block exit/entry portals, interrupt transmission (sterilize, disinfect, hand-wash), bolster host resistance (vaccines, nutrition).

• Environmental measures: adequate cleaning of surfaces/clothing; safe waste disposal.

Sterilization & Disinfection

• Sterilization: heat (autoclave), chemicals; equipment must be pre-cleaned.

• Disinfectants: inanimate objects.

• Antiseptics: skin/living tissue.

Diagnosis of Infection

• Culture & staining of specimens; determine drug sensitivity.

• Blood counts

  • Leukocytosis → bacterial.

  • Leukopenia → viral.

• Differential WBC count, C-reactive protein, ESR.

• Disk diffusion (Kirby–Bauer) & minimal inhibitory concentration (MIC) assess antimicrobial efficacy.

• Immunologic tests: identify antigens, measure antibody titers.

Clinical Manifestations

• Local: pain, redness, warmth, swelling; purulent exudate (bacterial) vs. serous (viral).

• Systemic: fever, fatigue, weakness, headache, nausea.

Antimicrobial Therapy Principles

• Complete prescribed course; do not share meds; consult provider if no improvement.

• Resistance concerns → may require combination therapy.

Classification

• Antibiotics: originally natural; many now synthetic.

• Antimicrobials subdivided into antibacterial, antiviral, antifungal, antiprotozoal.

• Bactericidal vs. bacteriostatic.

• Spectrum

  • Broad: active vs. Gram + and Gram –.

  • Narrow: limited to one class.

• Generations: 1st (original) vs. later improved versions.

Modes of Action (Antibacterials)

1. Inhibit cell-wall synthesis (e.g., penicillin).

2. Increase membrane permeability (e.g., polymyxin).

3. Inhibit protein synthesis (e.g., tetracycline).

4. Block essential metabolite synthesis (e.g., sulfonamides inhibit folate pathway).

5. Inhibit nucleic-acid synthesis (e.g., ciprofloxacin blocks DNA gyrase).

Antivirals

• Block viral entry, inhibit gene expression/replication, prevent viral assembly/release.

Antifungals

• Interfere with fungal mitosis or ergosterol synthesis → increased membrane permeability.

• Due to eukaryotic similarity, systemic antifungals can be toxic; require monitoring.

Antiprotozoals

• Similar pharmacologic challenges as antifungals (eukaryotic target).

• Multi-stage life cycles often necessitate stage-specific drugs.