CH_10_Infection1 (1)

Chapter 10: Infection

Adapted from McCance, K. L., Huether, S. E. & Rogers, J. (2023). Pathophysiology: The biologic basis for disease in adults and children (9th ed.). (V. L., Brashers, Ed.). Elsevier.

Learning Outcomes

• Describe the factors that influence infection by a pathogen

• Characterize mechanisms pathogens use to circumvent host defenses

• Examine the problem of HIV/AIDS, process of infection, disease course, and prevention/treatment

• Consider factors that contribute to the pathogenesis and virulence of bacteria, viruses, and fungi

Emerging Infections

• Infectious diseases lead to significant mortality and morbidity due to:

  • Reemergence and spread of old infections

  • Emergence of unknown infections

  • Development of antibiotic-resistant infections

• Most deaths related to infections occur in individuals with compromised immunity:

  • Elderly

  • Young children

  • Individuals with chronic diseases

Microorganism and Humans

• Mutual symbiotic relationship:

  • Benefits for both microorganisms and humans

  • Normal microbiome:

    • Resident microorganisms found in various body parts

    • Produce enzymes aiding digestion

    • Generate antimicrobial substances

    • Synthesize metabolites like vitamins K and B

Factors for Infection

Process of Infection

• Phases:

  • Transmission: Infectious microorganisms are transmitted (direct/indirect, droplet/airborne, vertical/horizontal)

  • Colonization: Pathogens survive/multiply within the human environment; adhere to tissues via specific receptors

  • Invasion: Pathogen invades surrounding tissues, evades host defenses

  • Dissemination: Spread of infection via direct extension, blood, or lymphatic vessels

  • Cell/Tissue Damage:

    • Occurs by lysis or toxin production, or indirectly via immune response

    • Tissue damage enhances organism's pathogenicity

Stages of Infection

• Stages:

  • Incubation: Time from exposure to initial symptoms

  • Prodromal: Initial mild symptoms, discomfort

  • Invasion: Further tissue invasion

  • Convalescence: Recovery with symptom decline, or fatality or latency periods

• True pathogens: Bypass normal defenses to cause infection; infectious likelihood increases with higher microorganism numbers rather than host defense compromise

Infectious Disease Classification

• Infectious disease: Spread from person to person

  • Endemic: Constant levels in a population

  • Epidemic: Sudden increase in infections in a population

  • Pandemic: Widespread epidemic, extended over a large area

Pathogenic Defense Mechanisms

• Pathogens successfully cause disease by:

  • Competing with normal flora

  • Producing toxins

  • Producing enzymes to avoid phagocytosis and destroy connective tissues

  • Avoiding lysis by halting the complement cascade

  • Paralyzing ciliary activity

  • Forming biofilms for protection against immune cells and antibiotics

Bacterial Infection: Virulence Factors

• Factors aiding bacterial infection include:

  • Iron acquisition (siderophores)

  • Polysaccharide capsules

  • Suppression of complement activation

• Bacteremia vs. Septicemia:

  • Bacteremia: Presence of bacteria in blood

  • Septicemia: Growth of bacteria in blood leading to systemic effects like hypotension and cardiovascular shock

Bacterial Infections Overview

• Staphylococcus aureus:

  • Major cause of nosocomial infections, commonly found on skin and nasal passages

  • Produces endotoxins and exhibits antibiotic resistance

Gram Staining Characteristics

• Gram-negative bacteria:

  • Do not retain crystal violet dye

  • Thin peptidoglycan layer with LPS (endotoxin)

• Gram-positive bacteria:

  • Retain crystal violet dye

  • Thick peptidoglycan layer with teichoic acids

Lipopolysaccharide Effects

• Low Quantity:

  • Monocyte/macrophage activation

  • TNF, IL-1, IL-6/IL-8 release

• Moderate Quantity:

  • Fever and low cardiac output

• High Quantity:

  • Causes systemic inflammatory responses, local inflammation, and potential septic shock

Clinical Manifestations of Infectious Disease

• Symptoms vary based on pathogen; can be caused directly or through products.

• Common manifestations include fatigue, malaise, weakness, fever, and appetite loss.

Countermeasures Against Bacterial Pathogens

• Antibiotic resistance: Significant public health concern due to misuse of antibiotics

  • Mechanisms include horizontal gene transfer and enzymatic inactivation of antibiotics

MRSA (Methicillin-resistant Staphylococcus aureus)

• A major international healthcare crisis due to overuse of antibiotics.

  • Treatment challenges include antibiotic resistance and the need to consider alternative therapies like bacteriophages.

Fungal Infections Overview

• Types of fungi:

  • Molds: Filamentous fungi

  • Yeasts: Ovoid/spherical, reproduce by budding

• Fungal diseases (mycosis) spread through inhalation or wound contamination.

Systemic Fungal Infections

• Usually result from immunosuppression.

  • Example: Pneumocystis carinii (now P. jiroveci) adapts to host conditions to evade immune response

Parasitic and Protozoan Infections

• Most common parasitic infections include Toxoplasma gondii and Trichomonas vaginalis

• Transmission often through vectors and contaminated resources (water/food)

Viral Infections Overview

• Most prevalent human afflictions; often self-limiting.

• Viruses are intracellular parasites reliant on host cell machinery for replication.

• Transmission modes: aerosol, sexual contact, vectors, or infected bodily fluids.

Harmful Effects of Viruses

• Viruses can disrupt normal cellular functions through various mechanisms, including apoptosis and transformation into cancer cells.

Stages of Viral Infection

• Attachment, penetration, genetic material release into host cytoplasm, and virus assembly are stages followed in viral replication.

HIV and AIDS Overview

• AIDS results from infection with HIV, impacting T helper cells, leading to immune deficiency and vulnerability to infections and cancers.

• Global prevalence data indicates high incidence rates, particularly in Africa.

HIV Types and Transmission

• HIV-1: Predominant type in various regions

• HIV-2: Less common, primarily in specific areas

• Transmission routes: blood, sexual contact, maternal-child transmission.

HIV Mechanism of Injury

• HIV is a retrovirus that integrates its genetic material into host cells, potentially activating or remaining dormant.

Clinical Manifestations and Diagnosis of HIV

• Symptoms may be absent for years; diagnosis involves assessing T-cell levels and detecting antibodies.

HIV Life Cycle

• Infection involves attachment, reverse transcription, integration into host DNA, and subsequent viral protein synthesis.

Phases of HIV Disease

• Distinct phases: acute, chronic (clinical latency), and late HIV/AIDS.

HIV Treatment and Prevention

• Antiretroviral therapy (ART): Combination of drugs to manage HIV, though no cure exists.

HIV/AIDS Prevention and Research

• Ongoing efforts focus on vaccine development and reducing risk behaviors among populations at high risk.

Pediatric HIV/AIDS

• More aggressive in children, transmitted during pregnancy, delivery, or breastfeeding. Immediate intervention is critical to improve outcomes.

Vaccines

• Designed to induce an immune response without causing disease; examples include mRNA vaccines and toxoids.

SARS-CoV-2 and COVID-19

• The pandemic highlights the importance of understanding viral transmission and control measures.

Countermeasures

• Infection control strategies include environmental management, antibiotic stewardship, and vaccine development to reduce disease spread.