Human Microbe Interactions

1. Human Microbe Interactions In this lecture we will look at microbial pathogenesis and epidemiology.

2. Pathology: the scientific study of disease. • Concerned with etiology as well as structural and functional changes brought about by the disease. • Etiology: what caused the disease? • Infection: invasion and colonization of body by pathogenic microorganisms. • Infection may exist in spite of an absence of detectable disease. • Disease: occurs when an infection results in any change from a state of health • An abnormal state in which part or all of body is incapable of performing normal functions.

3. Normal Microbiota • # of body cells in an average individual = 1 x 1013 • # of bacterial cells that inhabit an individual’s body normally = 1 x 1014 • The microbes that normally inhabit a healthy individual’s body is called normal microbiota or normal flora. • Microbial antagonism: normal microbiota can benefit host by preventing overgrowth of harmful microorganisms. In other words, the good bacteria help defend against the bad bacteria.

4. The good bacteria defend against the bad bacteria by: • Competing for attachment sites. • Competing for nutrients. • Making antibiotics against invading microbes. • Disease occurs when this balance between the normal flora and the host is upset. • For example the use of antibiotics kills not just invading bacteria but the normal flora as well, leaving attachments sites available, more nutrients available, etc. This in turn leads to increased risk for another infection. • An infection that results from a prior infection is called a secondary infection.

5. Events in Infection • Becoming Established: There are 3 main factors that aid a microbe in becoming established. • 1. It enters the body through the correct portal of entry. • 2. The number of cells that enter the body is enough to escape the body’s defenses. • 3. Other predisposing factors that may make the host more susceptible to disease.

6. Portal of Entry: ways to enter the host • Microbes can’t cause disease unless they enter the body through the right opening. • For example, if you eat a cold virus, you won’t get a cold. • The body has 3 main ways that microbes enter. • 1. Mucous membranes: respiratory tract (RT), gastro-intestinal tract (GIT), urogenital tract (UT), Conjunctiva (membranes that line the eyes). • RT-inhale droplets of moisture or dust • GIT-food and water, fingers, pencils • UT-sexual intercourse • Conjunctiva-rubbing eyes with dirty hands.

7. 2. Skin: unbroken, impenetrable to most people • Can gain access through hair follicles, sweat ducts, abraisons • 3. Parenteral Route: deposited directly into tissues beneath skin • Punctures, injections, cuts, wounds, surgery, cracking • 2. Size of Innoculum: number of cells that enter through the portal of entry • ID (Infectious Dose): minimum number of cells required to cause infection • Some organisms require 100’s of cells to cause infection while others require as few as 10.

8. 3. Predisposing Factors: one that makes the body more susceptible to a disease and may alter the course of the disease • Gender • For example, urinary tract infections occur more often in females simply because their anatomy is such that fecal material can easily enter the urinary tract leading to infection by E.coli. • Climate and weather • For example, winter weather brings on more dry air. The dry air dries out mucous membranes causing them to be more susceptible to invasion. • Winter weather also results in more people crowding together indoors creating more opportunities for infection to spread. • Others include nutrition, age, fatigue, etc.

9. Attachment • After the microbe has entered the body, the next step is to attach and colonize the body surfaces. • Adhesion: fimbriae, surface proteins, and capsules are used by microorganisms to adhere to and colonize body surfaces. • Mechanical means such as suckers, hooks, and barbs are used by parasites, such as tape worms, to adhere and colonize body surfaces.

10. Surviving Host Defenses • Once the organism has made it into the body and attached it still has to avoid or defend itself from the bodies internal defenses, the immune system. • Avoiding Phagocytosis: some white blood cells gobble up cells that don’t belong in the body, break them down and discard the garbage. That process is called phagocytosis. • Capsules or other disguises are used by microorganisms to avoid these vacuum cleaners of the cells. • Some microorganisms make chemicals that are toxice to white blood cells called Leukocidins

11. Process of Disease • Stages of Disease (See Pg. 396 tan box) • Incubation period: time interval between the initial infection and the first appearance of any signs or symptoms. (in other words, no signs or symptoms but the organism has entered the body). • Prodromal period: short period that follows the period of incubation in some diseases • Early, mild symptoms • You’re just starting to feel that a cold may be coming on, a scratchy or mildly sore throat.

12. Period of Illness: most acute stage of the illness. The person exhibits full signs and symptoms of the disease. • Number of white cells increases or decreases. • If the patient were going to die, death would occur during this period. • Period of Decline: signs and symptoms subside. • Patient is susceptible to secondary infections. The immune system has just fought off an infection and the body is weak. It is the perfect time for a new infection to begin. • Period of Convalescence: person regains strength and the body returns to its pre-diseased state. • The period during which the disease is spread is dependent upon the infecting organism. For example, some organisms are contagious before signs and symptoms are manifest. Others are contagious during the worst portion of the manifest signs and symptoms.

13. How disease is caused: • Virulence factors: any characteristic or structure of the microbe that helps it to establish itself in the host or cause damage in the host. • Exoenzymes: enzymes that break down and damage tissues or dissolve host defense barriers • Ie. Mucinase: digest protective coating on mucous memb. • Keratinase: digest principal components of skin and hair

14. Collagenase: digest principal fiber of connective tissue • Hyaluronidase: digests hyaluronic acid, substance that cements animal cells together • Toxins: chemical products that are poisonous to other organisms. • Toxemia: toxin spread by the blood from the site of infection to other parts of the body. • Intoxication: ingestion of toxin. • Toxins named according to mode of action • For example, neurotoxins affect the nervous system. An example of a neurotoxin is tetanospasim. Tetanospasim is the toxin made by Clostridium tetanii. This organism causes the disease known as Tetanus. Tetanospasim binds to nerve cells and blocks relaxation pathways, or in other words it causes uncontrollable muscle spasms. • Death occurs when the toxin affects the function of the heart or lungs.

15. 2 Types of Toxins • 1. Exotoxins: made inside a living microbe, released into surrounding environment. • This type of toxin is usually carried on plasmids or phages. • They work by destroying host cells or blocking metabolic fuctions • 1. Cytotoxins: kill host cells (damage cell memb) • 2. Neurotoxins: interfere with nerve impulse transmission • 3. Enterotoxins: affect cells lining GIT

16. The body produces antibodies to exotoxins called antitoxins. The antitoxins help the body fight off the effects of toxins made by bacteria. • Pharmaceutical companies inactivate toxins with heat and use them as vaccinations for some diseases, such as the tetanus shot. • Altered exotoxins are called toxoids. • Ex. Clostridium tetani , tetanus toxin

17. Endotoxins: are part of the LPS in the outer membrane of the G- cell wall. • When the G- bacteria die, the cells are lysed which liberates the toxin. • Responses by host are fever, chills, weakness, aches, and in some cases leads to shock and death. • Endotoxins can also induce miscarriage and activate blood clotting proteins which can in turn lead to heart attack or stroke.

18. Septic shock: is the life threatening loss of blood pressure. • Phagocytosis of G- bacteria causes the phagocyte to release tumer necrosis factor (TNF). • TNF damages capillaries causing them to become more permeable. As a result, they loose large amounts of fluid and more bacteria can cross the barrier. • Shock is when large amounts of fluid are lost the blood becomes thick and it is difficult for the heart to continue pumping the blood through the body. The organs eventually fail and the patient dies. • Endotoxin without live bacterial cells can still cause disease. Remember that it is the lysis of G- bacterial cells that releases the toxin which then results in shock and death.

19. Classifying Disease • Symptoms: changes in body function • ex. Malaise, lethargy • Signs: measurable or observable changes • Red throat • fever • Syndrome: a specific group of symptoms and signs that always accompany a disease • Ear infection: tugging pulling at ear, disinterest in eating or sucking, crying at night, ear hurts, inflammation in ear canal, perhaps a slight fever, etc.

20. Communicable Disease: spreads from host to host either directly or indirectly • Ex. Herpes: type 1 causes cold sores. Spread by direct contact with open sore. • Contagious Disease: disease that is easily spread from person to person • chickenpox • Noncommunicable Disease: not spread from host to host • Tetanus, acquired by coming into contact with organism in the environment.

21. Pathologic Effects of Disease • Local infection: invading microorganisms are limited to small area of body (boils) • Systemic: microorganisms or their products spread throughout body (tetanus). • Focal infection: local infection spreads to other areas of body where they are confined • Ex. Infection in tooth causes sinus infection

22. Bacteremia: presence of bacteria in blood • Septicemia: bacteria multiply in blood • Viremia: presence of viruses in blood • Toxemia: presence of toxin in blood • Primary infection: acute infection that causes initial infection. • Secondary infection: caused by opportunistic pathogen after primary infection weakened the body’s defenses. • Subclinical infection: one that does not cause any noticeable illness.

23. Severity or Duration of Disease • Acute: develops rapidly, but lasts a short time. (several days). • cold • Chronic: develops more slowly, disease is continual, or recurrent for long periods (can last for months or years). • Mono • Subacute: a disease that is in between • Latent: causative agent remains inactive for a time but becomes active with certain triggers • Cold sores brought on by stress

24. Rate at which disease spreads and the number of people involved are determined partly by the immunity of the population. • The immunity of the population is determined by the number of people who are current on their vaccines and the number of people who have had previous exposure to a particular organism. • Herd immunity: means that many people in community are immune to a particular organism. They help provide immunity to a small number of individuals in the community who are not immune.

25. Portals of Exit • Org. have definite routes of exit for spread. • Most common portals of Exit are the respiratory and GI tracts. • Exit in discharge from mouth and nose. • Some exit through feces. • Urogenital tract and reproductive tracts are also portals of exit. • Drainage from wounds and infected blood can also be portals of exit. • Keep in mind that an organism doesn’t cause disease because it hates you and wants you to die, it causes disease as a result of it’s efforts to stay alive and grow.

26. Epidemiology • Epidemiology studies when and where diseases occur and how they are transmitted. • Epidemiologists look for factors and patterns concerning the people who are affected by the disease. • Then he/she assembles and analyzes the data collected such as age, sex, occupation, history of immunization, presence of other diseases and common history of affected individuals.

27. Epidemiologists are also concerned with methods of controlling disease in the future with ways such as water treatment, pasteurization, and food inspection.

28. Occurrence of Disease • Incidence: # of people in a pop. who develop a disease within a particular time period. • For example Flu season is October through March. The incidence of Flu would be the number of people reported to have been diagnosed with Flu during those months. • Prevalence: # of people in a pop. who develop a disease at a specified time, regardless of when it first appeared. • The prevalence of Flu in the population would be how many people who had Flu on December 25. • Sporadic Disease: disease only occurs occasionally. Not predictable. • Stomach flu, doesn’t coincide with any months of the year.

29. Endemic Disease: disease constantly present in a population • Ex. Cold or stomach flu • Epidemic Disease: many people in a given area acquire a certain disease • Usually a smaller area, such as a city, state, continent. Ex. E.coli outbreak. • Pandemic Disease: epidemic disease that occurs worldwide • AIDS is now considered a pandemic.

30. Reservoirs of Infection • Reservoir of Infection: a continual source of the organism that causes a particular disease. • The source can be either living or inanimate. It simply need to provide the pathogen with adequate conditions for survival and multiplication and an opportunity for transmission. • Human: people who harbor a disease without signs or symptoms (carrier) can be reservoirs of infection. • HIV • Herpes

31. Animals can be reservoirs of infection. • Diseases that primarily occur in wild and domestic animals but can be transmitted to humans are called zooneses. • Ex. Rabies • Transmission: direct contact with infected animals, direct contact with infected waste, contamination of food and water, air from contaminated hides, fur, or feathers, consuming infected animal products, or insect vectors (fleas biting rats and then biting humans).

32. Nonliving reservoirs: soil and water are two major examples • Ex. A deer infected with Giardia goes to a beautiful mountain stream to take a drink and defecates next to the water while there. • An unsuspecting hiker sees the beautiful mountain stream and takes a drink. (One case of Giardia coming up….)

33. Transmission of Disease • 3 principle routes: • 1. Contact: direct contact, indirect contact, droplet transmission • Person to person: touching, kissing, sexual intercourse • AIDS, Mono, colds • Transmission through fomites. Fomites are inanimate objects that can carry the disease. • Kleenexs, bedding, diapers, drinking cups, eating utensils, money, thermometers, syringes, etc) • AIDS, Hepatitis B • Droplet: Coughing, sneezing, laughing, talking • Influenza

34. 2. Vehicle: transmission by a medium such as water, food, or air • Food poisoning • Giardia • Fungal spores in air • 3. Vectors: • Mechanical transmission: passive transport of org. on insects body or feet • Flies can transport typhoid fever, shigellosis. • Biological transmission: insect bites infected person, transfers org. to an uninfected person upon biting the new victim. • Malaria, West Nile Encephilitis, etc.

35. Nosocomial Infections • A nosocomial infection is an infection that is acquired as a result of a hospital stay. (You are admitted for one thing and acquire an infection while there.) • CDC estimates that 5%-15% of all hospital patients acquire some type of nosocomial infection. • It happens because the hospital is a major reservoir for a variety of pathogens;

36. Hospitalized persons are in a weakened state and more susceptible to infection; • Resistance to infection is impaired by disease, therapy, or burns • Two principle conditions compromise host: • Broken skin or mucous membranes • Immunocompromised • Risk of infection is also related invasive procedures such as catheters, tracheotomy, injections, intravenous catheters, • There are more antibiotic resistant strains in hospitals.

37. Transmission of Nosocomial Infections • Direct transmission from hospital staff to patient and from patient to patient. • Indirect contact transmission through fomites and the hospital’s ventilation system. • Certain areas of hospital reserved for specialized care such as burn, intensive care, oncology to prevent nosocmial infections.

38. Control of Nosocomial Infections • Hand washing is the most important means of preventing the spread of infection. • Disinfection of tubs used to bathe patients, humidifiers and respirators, and materials used for bandages and intubation. • Physicians should prescribe antibiotics and immunosuppressive drugs only when necessary.

39. How Scientists Discover the Etiology of Infectious Disease • Koch’s Postulates: • 1. Same pathogen must be present in every case of the disease • 2. Pathogen must be isolated from the diseased host and grown in pure culture • 3. Pathogen from pure culture must cause the disease when inoculated into a healthy, susceptible lab animal • 4. Pathogen must be isolated from the inoculated animal and must be shown to be the original organism.

40. Exceptions to Koch’s Postulates • Org. such as Mycobacterium leprae, the organism that causes leprosy, has never been grown on artificial media because its growth requirements are difficult to reproduce. • Many other pathogens cannot be cultivated on artificial media because they are obligate intracellular parasites. That means they can only grow within particular host cells. • Some pathogens cause several diseases • S. pyogenes can causesore throat, scarlet fever, skin infections, inflammation of bone, as well as others.

41. Many org. that cause same kind of disease such as pneumonia. • For some diseases, the only host is humans. For obvious reasons we can’t experiment on humans. • For the most part, the principles and steps that Koch used almost 200 years ago to identify Anthrax in sheep, are still applicable today in identifying disease causing organisms. • No HW today.