Bacterial Pathogenesis: Definitions and Mechanisms

• At the end of this chapter, the student should be able to: define common terms involved in the production of disease by bacteria; explain the components of Koch's postulates; discuss thoroughly the various factors that play a role in the chain of infection; compare the various mechanisms by which bacteria produce disease, citing examples for each mechanism; describe the various ways by which infectious diseases are classified; and compare the events involved in the various stages of an infectious disease.

Definition of Terms

• Bacteremia stands for the presence of bacteria in the blood.
• Commensalism is a form of symbiosis where one organism benefits without harming the other.
• Contamination is the presence of unwanted materials that may not necessarily lead to harm.
• Disease results from an undesirable host-pathogen relationship, interrupting normal body functions.
• Infection is the invasion of the body by pathogenic microorganisms, not synonymous with disease.
• Mutualism is a symbiotic relationship where both organisms benefit.
• Parasitism occurs when one organism benefits at the expense of another, causing harm.
• Pathogenicity is the ability of an organism to cause disease, especially in humans.
• Pollution is the presence of contaminants causing adverse biological effects.
• Pyemia indicates pus-producing bacteria in the bloodstream.
• Septicemia indicates actively multiplying bacteria in the bloodstream, often from an infection source, also known as sepsis.
• Symbiosis is a prolonged interaction between different species.
• Toxemia indicates the presence of toxins in the blood.
• Viremia indicates the presence of viruses in the blood.
• Virulence describes the degree of pathogenicity, or how much an organism can produce disease.

Koch's Postulates

• Robert Koch, a German physician, proved microorganisms cause specific diseases.
• Koch's postulates were published in 1884.
• Postulate 1: The suspected organism must be present in diseased individuals but absent in healthy ones.
• Postulate 2: Isolate the suspected organism from the infected host and grow it in pure culture.
• Postulate 3: Organisms from the pure culture should cause the same disease when inoculated into a susceptible animal.
• Postulate 4: Re-isolate the same organism from the experimentally infected host.
• Limitations include growing pathogens in artificial media, as viruses need living cells.
• Not all infected individuals develop overt disease.
• Human reactions to pathogens vary.
• Cultured organisms need to be species-specific.
• Some pathogens change when grown artificially, affecting pathogenicity.

Factors Influencing Infection: The Chain of Infection

• Development of infectious disease involves the etiologic agent, the host, and the environment.
• Transmission starts when pathogens leave a host or reservoir through a portal of exit.
• A susceptible organism acquires infection through transmission and enters via a portal of entry, leading to multiplication and disease.

Reservoir

• Reservoirs continuously source of disease-causing microorganisms.
• Reservoirs are sites where infectious agents reside, multiply, and survive.
• Reservoirs include animals, humans, and the environment.

Animal Reservoirs

• Zoonotic infections are transmitted from animals to humans; humans are incidental hosts.
• Examples include anthrax, plague, and rabies.

Human Reservoirs

• Pathogenic organisms reside humans.
• These organisms transmit directly.
• Respiratory pathogens and STIs are examples.
• Infected humans may be subclinical or carriers.
• Asymptomatic carriers do not show symptoms.
• Incubatory carriers transmit during the incubation period.
• Chronic carriers harbor organisms long-term.
• Convalescent carriers transmit after recovery.
• Carriers transmit unknowingly, posing public health risks.

Environmental Reservoirs

• Water, soil, and plants harbor infectious organisms.
• Water is a reservoir for Entamoby-histolynca causing amoebiasis.
• Watercress harbors Fasciola hepatica larvae damaging the liver.

Portal of Exit

• The portal of exit: the route by which agents exit.
• The portal of exit is usually where the agent is localized.
• Schistosoma haematobium exits via urine.
• Respiratory infections exit via droplets.
• STIs exit via vaginal/urethral secretions.
• Malaria exits via blood-sucking arthropods.

Mode of Transmission

• Direct contact involves contact with sources harboring infectious agents.
• Schistosoma spp. transmits when wading in water with snails.
• Person-to-person contact involves skin-to-skin contact, kissing, or sexual transmission.
• Warts and mononucleosis are spread through contact.
• Droplet spread transmits respiratory infections through coughing/sneezing.
• Droplets are larger than 5 microns.
• Close proximity is needed for droplet transmission.
• Airborne transmission involves aerosols smaller than 5 microns.
• Aerosols remain suspended longer and travel farther.
• Cryptococcus neoformans transmits through dust in dried pigeon droppings

Vehicle Transmission

• Vehicle transmission involves food, water, milk, and fomites.
• Gastrointestinal infections transmit through contaminated water.
• Cholera and typhoid are examples.
• Food-borne transmission comes from raw or poorly cooked, refrigerated food from fecal-oral transmission.
• Food poisoning and gastroenteritis are examples.

Vector Transmission

• Vector transmission involves insects spreading infectious agents.
• Mechanical transmission is passive, via insects' body parts.
• Biological transmission is active, with organisms entering insect vectors.
• Malaria transmits via Anopheles mosquitoes.
• Dengue, chikungunya, and Zika transmit via mosquito vectors.
• Versinia pestis, the plague agent, transmits via rat fleas.

Portal of Entry

• The portal of entry is how agents enter a susceptible host.
• It provides access for multiplication.
• It is commonly the same as the portal of exit.
• Organisms entering the respiratory tract do so via inhalation.
• Food/waterborne organisms enter through the mouth and exit through feces.
• Schistosoma haematobium penetrates skin.
• Hepatitis B and HIV enter through blood.

Host

• The host is the infection chain's last link.
• Susceptibility is affected by genetics and immune status.
• Sickle cell trait protects against malaria.
• Effective immune response prevents disease.
• Poor nutrition and alcohol intake weaken immunity.

How Organisms Produce Disease

• Mechanical: Invasiveness, that is directly damaging tissues.
• Colonization is an aspect of this and involves entering the host and establishing in the portal of entry.
• Adhesins, like pili in Gram-negative bacteria, promote adhesion.

Immune Response

• The immune system responds to invading pathogens.
• Capsules evade phagocytosis.
• Staphylococus aureus uses coagulase to hide from surveillance cells.
• Mycobacterium tuberculosis survives inside macrophages.
• Neisseria gonorrhoeae multiplies within host cells and spreads
• Collagenase from Clostridium perfringens breaks down collagen, causing gas gangrene.

Chemical: Toxin Production

• Toxins are poisonous substances that cause disease.
• Exotoxins are secreted by bacteria and have three types- cytotoxins, enterotoxins, and neurotoxins.
• Endotoxins are integral components of Gram-negative bacteria and are released when the cell dies.

Immunologic

• The hosts immune response leads to some diseases
• Hepatitis is due to Cytotoxic T cells destorying Hepatocytes

Childhood Diseases

• Measles is die to the immune system attacking the infection

Classification of Infectious Diseases

• Communicable diseases spread from host to host, either directly or indirectly. Examples include measles, tuberculosis, and typhoid fever.
• Contagious diseases transmit easily and rapidly. Chickenpox is one such example
• Fulminant infections quickly result in death. Meningococcemia is such an example
• Non-communicable diseases originate from within or outside the body due to organisms. Clostridium tetani and other examples are the agent that causes tetanus.
• Exogenous infections come from outside the body. Cholera is an example
• Endogenous infections come from within. Escherichia coli is an example

Disease By Occurrence

• Sporadic diseases happen occasionally.
• Endemic diseases are constantly present. eg malaria,
• Epidemics infect many quickly. Influenza and other pathogens are such diseases
• Pandemics are worldwide. Examples include influenza viruses

Disease Duration

• Acute diseases develop and resolve quickly, e.g., the common cold.
• Chronic diseases occur over a long time, like tuberculosis.
• Hepatitis B can be acute or chronic.
• Latent diseases are inactive and then reactivate, as with herpesviridae causing shingles.

Extent of Host Involvement

• Localized infections affect a small area.
• Systemic infections spread throughout the body.
• Focal infections spread to specific areas from a localized area.
• Primary infections cause the initial illness.
• Secondary infections occur when the immune system is weak.
• Subclinical infections do not cause noticeable illness.

Infectious Disease Development

• Incubation period: The time between the entry of the offending agent and the appearance of the initial signs and symptoms of the disease
• Prodromal period: A relatively short period, is characterized by early, mild symptoms of disease which are generally nonspecific
• Period of illness: Corresponds to the period of maximal invasion. The signs and syptoms of the diesease are clear at this point
• Period of decline: corresponds to what is known as the period of defervescence. Signs and symptoms start dissapating
• Period of convalescence: the recovery of the patient and return to "normal"