Lecture 12 - Microbial Pathogenicity

Microbial Pathogenicity Eiman Mokaddas MD, FRCPath Associate Professor Microbiology Department Faculty of Medicine

Quiz A patient with known blood borne pathogen was operated in the operating theatre, which involved the use of a flexible endoscope What is usually done to the reusable items in the theatre? Clean and place in CSSD bin

Quiz Endoscopes are heat-sensitive equipments. How would you make it fit to be used for the next patient? Wear gloves, clean carefully and then rinse with detergent and water. Flush through and then soak with 2% gluteraldehyde for 3 hours. Rinse in sterile water before use

Quiz There was spillage of blood and body secretions on the theatre floor during operation. How would you take care of the spillage? Answer: • Wear disposable gloves and plastic apron. Pour 1% hypoclorite solution (10,000 ppm) on the spilage • Clean the floor with detergent and hot water

Quiz To what group of disinfectants does gluteraldehyde belong? Answer: Gluteraldehyde is a chemical disinfectant an alkylating agent like formaldehyde and ethylene oxide and it belongs to the group of aldehyde disinfactants

Quiz What is the advantage and disadvantage of gluteraldehyde? Answer: Advantage: • Good activity against spores as well as vegetative bacteria, viruses and fungi

Disadvantage: • Moderate activity against Mycobacterium tuberculosis. • Need exposure for 3 hours to kill all microbes 9 new concentration) • Affected by PH • Toxic and may cause sensitivity reaction to skin, eyes or lungs

Quiz What type of disinfectant is hypochlorite? Answer: • Halogen • Oxidizing agent like hydrogen peroxide and chlorine gas

Quiz What are the advantages and disadvantages of hypochlorite? Answer: Advantage: • Active against viruses • Very usefull against HIV and Hepatitis B virus

Disadvantage: • • • •

Easily inactivated by organic matter Surface must be cleaned thoroughly before application Corrosive to metals Activity deteriorate rapidly When diluted

Quiz What are its uses? Extra strong solution (10.000 ppm) • Blood spliage from HBs Ag positive patient

Strong solution (2.500ppm) • General blood spilage • Laboratory pipette jar • Antiseptic in infected pressure sores

0.1% solution (1000ppm) • General environmental disinfectant

Weak solution (125ppm) MILTON • Cleaning infant feeding utensils

Definitions Pathogenicity • Capability to cause disease

Infectivity: • Ability to breach the new host’s defenses

Virulence: • Capacity of the pathogen to harm the host

Types of Pathogens Primary Pathogens: capable of establishing disease in a previously healthy individual with intact immunological defenses • Conventional • Conditional

Opportunistic pathogens: rarely cause disease in individuals with intact immunological and anatomical defenses • Cause infection only when such defenses are impaired by disease or treatment e.g. Coagulase negative staphylococci, candida spp etc…

Virulent Determinants Both primary and opportunistic pathogens have virulence determinants or aggresins that facilitate pathogenesis. Usually bacteria posses many of those virulence determinants to be able to cause disease Not all strains of a particular bacterial species are equally pathogenic e.g. Haemophilus influenzae

Establishment of Infection Potential pathogens may enter the body by various routs: • • • • •

Respiratory Gastrointestinal Urinary Genital Skin: bites, inoculation, trauma

Opportunistic pathogens are carried in the body and can enter readily in the compromised host

Source of infection Individuals with clinical disease ( patient) Carrier: symptoms are either absent or mild due to the early stage of the disease or due to the establishment of partial immunity to the pathogen Environmental: food, water, fomites, equipments ( act as reservoir and source for environmental contamination)

Colonization The establishment of a stable population of bacteria or other microbes in the host Normally requires adhesion to the mucosal surface This allows the establishment of focus of infection that remains localized without causing much harm However it may subsequently spread anytime to other tissues

Adhesion Adhesion is very important to allow resisting host defense, flushing action of mucous and saliva) Involves surface interaction between specific receptors on the mammalian cell membrane ( usually carbohydrates) and the bacterial ligands ( usually proteins) on the bacterial surface Specific receptors on the mammalian cell are responsible for the tissue specificity of infection

Types of adhesins Fimbrial: on the surface of many Gram-positive and Gram-negative bacteria Fimbriae: Thin, rigid rod-like structures Mediate attachment to mammalian cells Can carry various antigenic determinants Association with infection may differ according to the type of fimbrial antigens Non-fimbrial adhesins: haemagglutinins, outer membrane proteins, polysaccharides

Invasion Once attached to mucosal surfaces, some pathogens exert their pathogenic effect without penetrating the host tissues ( through toxins) Other pathogens, adhesion is the first step of tissue invasion Examples: Mycobacteria, salmonella, Shigella, E.coli etc… Cell invasion confer ability to escape humeral host defense mechanisms

Avoidance of host defense mechanism Available host defenses: • • • • •

Humeral-mediated immune system Cell-mediated immune system Complement components Lysosyme Phagocytes

Avoidance of host defense mechanism 1. Capsules: The most common mechanism to avoid phagocytosis by bacteria All pathogens associated with meningitis and pneumonia have capsules e.g. Haemophilua influenzae, Streptococcus pneumoniae, E.coli, Neisseria meningitidis Non-capsulated variants are usually less pathogenic Capsules are polysaccharides that reduce efficiency of phagocytosis as they are less immunogenic and prevent opsonization of the bacterium by complements

Avoidance of host defense mechanism 2. M-protein of Streptococcus pyogenes 3. Resistance to killing by phagocytic cells: intracellar multiplication ( resistance of intracellular killing) 4. Antigenic variation: Variation of surface antigen composition during the course of infection provides a mechanism of avoidance of specific immune response directed at those antigens (bacteria, viruses)

Toxins In many bacterial infections the characteristic pathology of the disease is caused by toxins Types of toxins: Endotoxins: • • • •

Called lipopolysaccharides (LPS) Is a component of the outer membrane of Gram-negative bacteria Released from the bacterial surface upon lysis of the bacteria Responsible for endotoxic shock and septic shock

Exotoxins: • In contrast to endotoxins are diffusable proteins secreted into external medium by the pathogen • Toxoids: denatured toxins which lack toxic effect but still immunogenic • Examples: enterotoxins( GI)