Establishing Infection In order to cause disease pathogen must follow a series of steps: – Adherence – Colonization – Delivery of effector molecules 1

Establishing Infection Adherence – Adhesins attach to host cell receptor Often located at tips of pili (called fimbriae) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Receptor Host cell Bacterial cell Pili with adhesins 2

Establishing Infection Colonization – Growth in biofilms – Siderophores – Avoidance of secretory IgA – Compete with normal microbiota, tolerate toxins 3

Establishing Infection Delivering Effector Proteins to Host Cells Type III secretion system (injectisome) o Injected proteins = Effector proteins Effector Bacterial cytoplasm Bacterial periplasm Host cell Courtesy of Chihiro Sasakawa, University of Tokyo Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 4

5 Principles of Infectious Disease Infection Pathogen Infectious disease

6 Principles of Infectious Disease Infection – a condition in which pathogenic microbes penetrate host defenses, enter tissues, and multiply Pathogen – infectious agent Infectious disease – an infection that causes damage or disruption to tissues and organs

7 Infections That Go Unnoticed Asymptomatic (subclinical, inapparent) infections – although infected, the host doesn’t show any signs of disease

Principles of Infectious Disease A primary infection refers to the first time you are exposed to a pathogen. Additional infections resulting from primary infection (treatment) termed secondary infection True pathogens – capable of causing disease in healthy persons with normal immune defenses Influenza virus, plague bacillus, malarial protozoan Opportunistic pathogens – cause disease when the host’s defenses are compromised Pseudomonas sp & Candida albicans Severity of the disease depends on the virulence of the pathogen 8

Characteristics of infectious disease – Disease that spreads from host to host termed communicable or contagious – Ease of spread partly determined by infectious dose Infectious dose is number of organisms required to establish infection Diseases with small infectious dose more easily spread than those requiring large numbers. I.e. microbes with small IDs have greater virulence Principles of Infectious Disease 9

Characteristics of infectious disease – Disease that spreads from host to host termed communicable or contagious – Ease of spread partly determined by infectious dose Infectious dose is number of organisms required to establish infection Diseases with small infectious dose more easily spread than those requiring large numbers. I.e. microbes with small IDs have greater virulence Principles of Infectious Disease 10

11 Requirement for an Infectious Dose (ID)

Principles of Infectious Disease Course of infectious disease – Disease course follows several stages Incubation – Time between introduction of organism to onset of symptoms – Incubation period depends on numerous factors Illness – Follows incubation – Individual experiences signs and symptoms of disease Convalescence – Period or recuperation and recovery – Infectious agents may still be spread Duration of symptoms – Acute Symptoms have rapid onset and last only short time – Chronic Symptoms develop slowly and persist – Latent Infection never completely eliminated Infection becomes reactive 12

Principles of Infectious Disease Course of Infectious Disease – Incubation period: time between infection and onset Varies considerably: few days for common cold to even years for Hansen’s disease (leprosy) Depends on growth rate, host’s condition, infectious dose – Illness: signs and symptoms of disease May be preceded by prodromal phase (vague symptoms) – Convalescence: recuperation, recovery from disease – Carriers may harbor and spread infectious agent for long periods of time in absence of signs or symptoms Incubation periodConvalescenceIllness Acute. Illness is short term because the pathogen is eliminated by the host defenses; person is usually immune to reinfection. Incubation period Chronic. Illness persists over a long time period. Incubation period Latent. Illness may recur if immunity weakens. Illness Convalescence Latency Recurrence Illness (long lasting) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 13

Principles of Infectious Disease Duration of Symptoms – Acute infections: symptoms develop quickly, last a short time (e.g., strep throat) – Chronic infections: develop slowly, last for months or years (e.g., tuberculosis) – Latent infections: never completely eliminated; microbe exists in host tissues without causing symptoms 14

16.3. Principles of Infectious Disease Distribution of Pathogen – Localized infection: microbe limited to small area (e.g., boil caused by Staphylococcus aureus) – Systemic infection: agent disseminated throughout body (e.g., measles) – Suffix -emia means “in the blood” Bacteremia: bacteria circulating in blood – Not necessarily a disease state (e.g., can occur transiently following vigorous tooth brushing Toxemia: toxins circulating in bloodstream Viremia: viruses circulating in bloodstream Septicemia or sepsis: acute, life-threatening illness caused by infectious agents or products in bloodstream 15

16 The Process of Infection and Disease 4 distinct stages of clinical infections: – Incubation period – time from initial contact with the infectious agent to the appearance of first symptoms; agent is multiplying but damage is insufficient to cause symptoms; several hours to several years – Prodromal stage – vague feelings of discomfort; nonspecific complaints – Period of invasion – multiplies at high levels, becomes well-established; more specific signs and symptoms – Convalescent period – as person begins to respond to the infection, symptoms decline

17 Stages in the course of infection and disease

18 Distribution of the infection Patterns of infection: Localized infection – microbes enter the body and remain confined to a specific tissue Systemic infection – infection spreads throughout the body, usually in the bloodstream Focal infection – when infectious agent breaks loose from a local infection and is carried to other tissues

Koch’s Postulates 1.The same pathogen must be present in every case of the disease 2.The pathogen must be isolated from the diseases host and grown in pure culture 3.The pathogen from the pure culture must cause the disease when it is inoculated into a healthy, susceptible lab animal 4.Organism must be recovered from experimental host 19

Koch’s Postulates 20

Koch’s Postulates 21

Mechanisms of Pathogenesis Several general patterns – Produce toxins that are then ingested – Colonize mucous membranes, produce toxins – Invade host tissues, avoid defenses – Invade host tissues, produce toxins 22

Mechanisms of Pathogenesis Several general patterns – Produce toxins that are ingested Clostridium botulinum double vision, blurred vision, drooping eyelids, slurred speech, difficulty swallowing, dry mouth, muscle weakness 23

Mechanisms of Pathogenesis – Colonize mucous membranes, produce toxins E.g., Vibrio cholerae, E. coli O157:H7, Corynebacterium diphtheriae Symptoms include: watery diarrhea vomiting leg cramps 24

Mechanisms of Pathogenesis – Invade host tissues, avoid defenses – E.g., Mycobacterium tuberculosis, Yersinia pestis, Salmonella enterica 25

Mechanisms of Pathogenesis – Invade host tissues, produce toxins E.g., Shigella dysenteriae, Clostridium tetani Dysentery 26

Invasion 27