Lecture 7 - Entry, Exit, and Transmission PDF

Lecture 7 - Entry, Exit and Transmission Stages of pathogenesis Host-Pathogen interaction ➔ The host-pathogen interaction during infection is complex Pathogen Aim: To successfully infect host ➔ Depends on their ability to evade or overcome host defenses (primary aim) ➔ Need to be in sufficient...

Lecture 7 - Entry, Exit and Transmission Stages of pathogenesis Host-Pathogen interaction ➔ The host-pathogen interaction during infection is complex Pathogen Aim: To successfully infect host ➔ Depends on their ability to evade or overcome host defenses (primary aim) ➔ Need to be in sufficient numbers to cause infection ➔ Need to be transmissible to new host (needs to find a portal of exit to leave original host) Host Aim: To prevent infection ➔ Must have useful defence mechanisms ➔ Depends on susceptibility to infection Microbial mechanism of pathogenicity ➔ Parenteral route – through IV or injection ➔ Pathogens have mucous membranes that allow them to adhere ➔ Pathogen established itself and can damage the host ➔ Siderophores – iron chelated mechanisms ➔ Exit portals so that they can transmit to other hosts Portals of entry ➔ Sites through which pathogens can enter the body ➔ Major portals of entry: skin, mucous membranes or intestinal epithelium (surfaces that normally act as microbial barriers) ➔ Most of these act as barriers but can allow the pathogens to enter under certain circumstances Entry via the skin Dendritic cells are a part of our dermis PMN – Polly mononuclear cells – neutrophils, basophils MO – Macrophage Endothelial cells – protector cells Protective defensives via the skin ➔ Dry, relatively impermeable outer layer ➔ Fatty acids and sweat (skin: pH 5.5) ➔ Peptides formed by keratinocytes protect against invasion by group A streptococci ➔ Chemicals produced by normal flora (allow for the pH of 5.5 to be maintained) Common sites of infection ➔ Wounds, abrasions or burns ➔ Microbes may cause a localized skin infection or infection elsewhere Pathogens on the skin ➔ Streptococci, Leptospira and Hep B virus can enter skin with only small break ➔ Several types of fungi (the dermatophytes) infect non-living keratinous structures of the skin eg nails and hair ➔ Some parasites, (eg hookworms) or their larvae (Ancylostoma, Schistosoma) can penetrate unbroken skin ➔ Some bacteria enter hair follicles or sebaceous glands → styes and boils Microorganisms that infect via the skin ➔ Staph species most common Entry via breaches in the skin ➔ Cuts/wounds/abrasions ➔ Biting arthropods – mosquitoes, fleas, ticks o Can penetrate skin during feeding and introduce infectious agent or parasites into host o Essential part of lifecycle of microbe ➔ Animal bites – rabies ➔ Burns Entry via the conjunctiva Protective defences ➔ Kept clean by continuous flushing action of tears and wiping action of eyelids ➔ Lysozyme Pathogens require ➔ Efficient attachment mechanisms ➔ Decreased lacrimal gland secretion ➔ Damage to conjunctiva or eyelid Pathogens ➔ Chlamydia ➔ gonococci Entry via respiratory tract ➔ Hair in nostrils – tap dust particles or microbes we inhale ➔ Turbinate baffles – cleaned and humidified air before it reaches our lungs ➔ Mucociliary escalator – mucus and cilia in lungs that catch microbes and is brought up as phlegm ➔ Mucus-secreting cells ➔ Ciliated cells ➔ Mucus-secreting glands ➔ Alveolar macrophages Airway clearance in normal lung Microbial attachment in the respiratory tract Pathogens entering via respiratory tract Interfere with cleansing mechanism ➔ Firmly attach to surface of cells of the mucociliary sheet ➔ Inhibit ciliary activity, eg B. pertussis, H. influenza ➔ Anything that inhibits the mucociliary sheets causes pathogen to get in Avoid alveolar macrophages ➔ Avoid phagocytosis ➔ Avoid destruction after phagocytosis, eg M. tuberculosis survive in macrophages Entry via GI tract Entry via Gastrointestinal tract Protective defences: ➔ Acid ➔ Mucus o Mechanical barrier to infection o Contains chemicals that bind to microbial adhesins and block attachment to host cells o Microbe-specific secretory IgA antibodies ➔ Stomach enzymes ➔ Bile ➔ Peristalsis ➔ Intestinal transit time: 12-18hrs o Not enough time for significant number of microbes to grow o Intestinal transit time – meaning the time it takes to go through large and small intestines and pass out via faeces ➔ Cleansing mechanisms: o None except maybe diarrhea and vomiting Pathogens require ➔ Specific receptors on gut epithelial cells ➔ eg Vibrio cholera, rotavirus ➔ Tropism - where a pathogen would infect o Shigella (large bowl) o Salmonella (small intestine) ➔ Mechanical devices o Protozoa eg Giardia lamblia has molecules for adhesion to microvilli of epithelial cells as well as microvillar sucking disk o Hookworms have large mouth capsule containing hooked teeth that allow them to attach o Other worms such as Ascaris “brace” themselves against peristalsis while tapeworms adhere to mucus of intestinal wall Entry via urogenital tract ➔ Microbes can easily spread from one part of tract to another due to continuity between these sites Potential sites of entry ➔ Vagina ➔ Urethra ➔ Bladder Entry via the vagina Protective defences ➔ pH ~5 due to presence of lactobacilli → lactic acid ➔ Presence of commensals Pathogens require ➔ Specific attachment mechanisms for vaginal/cervical mucosa ➔ Injury to mucosa during intercourse ➔ Continued exposure to potential pathogens during intercourse ➔ Impaired defenses - estrogen imbalance, presence of tampons/menstrual cups Entry via urethra and bladder Protective defences Pathogens require ➔ Secretory antibodies ➔ Specialized attachment mechanism to ➔ Mucus avoid being washed out ➔ Spermine in prostatic secretions ➔ Gonococcus, Chlamydia → parasite ➔ Flushing action of urine directed endocytosis ➔ Males: STIs more common in uncircumcised males than circumcised ➔ Females: UTIs common due to short urethra and proximity to anus (constant source of intestinal bacteria) Entry via oropharynx Protective defenses ➔ Flushing action of saliva ➔ secretory IgA antibodies (sIgA) ➔ Lysozyme ➔ Competition from normal flora ➔ Leukocytes on mucosal surface and in saliva Mechanisms of invasion: ➔ Gum infections ➔ Attachment to mucosal or tooth surface ➔ Decreased salivary flow between meals ➔ Dehydrated patients → overgrowth of mouth flora Summary ➔ Microorganisms must attach to, or penetrate body surfaces of the human host in order to cause an infection ➔ Various defense mechanisms exist at these surfaces which invading pathogens must overcome ➔ Successful pathogens therefore possess efficient mechanisms for attaching to, or penetrating these body surfaces Exit and Transmission ➔ Various mechanisms present to ensure that pathogens exit host and can be transferred from one host to another → transmission Effective transmission is dependent on 4 main factors: (1) Number of microbes shed from host (2) Stability of the in environmental (3) Infectious dose – varies greatly between microbes and route of infection also important (4) Genetics of microbe – can mutate continuously (eg) COVID Modes of Disease Transmission Transmission from respiratory tract Effective shedding/transmission aided by: ➔ Crowded indoor spaces ➔ Increased nasal secretions, with coughing and sneezing ➔ Generation of aerosols o A sneeze can contain up to 20, 000 droplets ➔ Droplet side o Largest droplets fall to the ground o Droplets ~10 µm diameter can be trapped on nasal mucosa o Droplets 1-4 µm in diameter likely to make it through nose and reach respiratory tract ➔ Air conditioning ➔ Handkerchiefs, hands and surfaces (fomites) Transmission from the GI tract ➔ Transmission primarily by fecal-oral route o Contaminated groundwater o Contaminated food o Flies may carry fecal matter onto food o Eg Salmonella spp., Vibrio cholera, Giardia lamblia ➔ Spread facilitated by o Lack of public health system or poor hygiene o Shedding of large numbers of pathogens in feces o Proximity of susceptible individuals Transmission from the urogenital tract ➔ Often sexually transmitted ➔ UTIs common → MOST NOT SPREAD VIA URINE ➔ Table shows some infections spread via urine Sexually transmitted disease (STDs) ➔ Intimate contact ➔ Presence of discharge increases transmission o Some microbes induce production of a discharge o Eg chlamydia, gonococci ➔ Transmission from mucosal ulcers/sores ➔ Dependent on social and sexual activity ➔ Transmission by semen Transmission facilitated by: Transmission from the oropharynx ➔ High number of sexual partners ➔ Often spread via saliva ➔ Use of oral contraceptives ➔ Contamination of fingers and objects by ➔ Limited availability of treatment for saliva STDs (in some countries) ➔ Deep kissing ➔ Genito-oro-anal contact Transmission from the skin ➔ Spread by shedding or direct contact o Dermatophytes o HSV, VZV, HPV o Staphylococci o Leishmania tropica o Streptococcus pyogenes Transmission in milk Transmission from blood ➔ Microbes are rarely shed in human milk ➔ Microbes can be spread by blood- ➔ Exceptions: HIV, cytomegalovirus, sucking arthropods or through needles HTLV1 (transfused blood or contaminated ➔ Milk from cows, goats, sheep may carry needles) pathogens eg Brucella, Coxiella ➔ Intravenous drug misuse known to burnetiid facilitate spread ➔ Contamination after collection and ➔ Pathogens in blood eg HIV, hepatitis pasteurization also possible virus Vertical and horizontal transmission Transmission from animals Depends on: ➔ Type of environment ➔ Zoonoses o Urban vs. rural o Invertebrate vs. vertebrate vectors o Tropical vs. temperate o Close contact with pets/livestock o Level of sanitation Transmission from invertebrate vectors ➔ Passive carriage ➔ Shellfish & molluscs ➔ Biological transmission ➔ Snails ➔ Blood-suckers Transmission from vertebrates ➔ Spread by: ➔ Occupational risks o Direct contact ➔ Geographic location – dietary o Inhalation preferences o Bites ➔ Close contact with domestic pets o Scratches o Contaminated food/water Disease communicability ➔ Communicability: ability of an infectious disease to spread from an infected host to a susceptible host either via direct or indirect transmission ➔ In contrast, non-communicable diseases (NCDs) are not spread from person to person ➔ Communicable: cold. Flu, measles ➔ NCD: cancer, stroke, diabetes