Lecture 25

1. Lecture 25 Disease

2. Health “ a state of complete physical, mental and social well being” …..World Health Organisation (WHO)

3. Disease • Infectious or communicable diseases – diseases caused by other living organisms, they can be transmitted from one person to another. • Non infectious diseases – social, deficiency, genetic or congenital (present at birth), ageing and degenerative, mental illness. These are not transmitted by contact.

4. Infection “The successful invasion, establishment and growth of microorganisms in the tissues of the host”.

5. Association Between Microbe and Man • Parasitic – one benefits at the expense of the other. • Symbiotic – mutual benefit. • Commensalism – one organism derives benefit by living near on on its surface without causing any damage.

6. Terminology • Disease = state of being not in good health (not at ease, "dis-ease"). • Every disease is a race between pathogen trying to gain a foothold and host defences trying to prevent pathogen. Many factors involved: virulence and numbers of pathogen, health and age of host, etc. • Wrong to equate "one pathogen" = disease. Much more complex. • Parasite often used to refer to protozoans or worms; the term "Pathogen" is typically used when referring to bacteria, virus, or fungus that causes disease. All are parasitic.

7. Terminology • Pathogen = organism with potential to cause disease • Infection = pathogen is growing in or on host • Virulence = degree or intensity of pathogenicity • Invasiveness = ability of pathogen to spread to other tissues in body • Infectivity = ability of pathogen to establish infection • Toxigenicity = ability of pathogen to secrete toxins • Septicemia = infection in which pathogen grows massively in the body, being found in blood and throughout organs. Usually leads to death

8. Koch's Postulates Developed in late 1800's , provide basic logical proof that disease is caused by a microbe • Microbe must be present in every case of disease, but absent from healthy individuals. • Suspected microbe must be isolated from diseased host and grown in culture. • Same disease must result when isolated microbe is introduced into healthy host. • Same microbe must be isolated again from second diseased host

9. Epidemiology • Tracking the incidence and patterns of disease. • Depends critically on data. Accuracy much better in developed countries than in most developing countries. • Global: World Health Organization (WHO) in Geneva maintains records on health statistics, infection rates, epidemics in most of World. View The World Health Report 2001

10. Epidemiology • U. S.: Centers for Disease Control and Prevention (CDC) maintains records on health statistics, infection rates, epidemics in U. S. • Every licensed clinic, physician, hospital must submit weekly reports of every instance of reportable diseases (about 50 on current list) to state public health office, which forwards this information to CDC. • CDC publishes weekly reports (now available on Web and via e-mail): Morbidity & Mortality Weekly Reports. • View Morbidity & Mortality Weekly Report summary from CDC (Centers for Disease Control) • U.S. and other countries in developed world have cut many diseases by sanitation, public health (vaccines, etc.)

11. Spread of Infection • Multiply within host • Spread from one host to another – two types of transfer horizontal and vertical. • Horizontal spread – polio, influenza, thyphoid. Spread by infected air, water, food or by insect vectors. • Vertical spread – parent to offspring congenital rubella, leukemia viruses. • Zoonoses – spread of infection from one species to another.

12. Intracellular vs Extracellular Pathogens • Most pathogens have evolved to live either inside or outside of host cells, rarely if ever in both habitats. • Inside the cell – intracellular • Outside the cell - extracellular

13. Intracellular Life • Poses special problems for host. • Can't easily attack pathogen without harming its own tissues. Many pathogens are adapted for intracellular life, including all viruses, certain bacteria (e.g. TB, plague), • Since white blood cells (macrophages, lymphocytes) are major components of defence system, many successful pathogens target these cells specifically for intracellular growth. • Problem: to be successful, pathogen at some point must leave cells, exit host. Best chance to prevent infection is sometime during exit -- transmission -- entry to new host, before it has a chance to hide in new cells. • Some intracellular parasites are so highly evolved that they can't survive at all outside their host's cells. Ex: Chlamydia, Rickettsia. To be successful, these must rely on mechanisms such as sexual contact or animal bites to transmit them to new hosts.

14. Extracellular Life • Pathogen must deal with host's defensive strategies: white blood cells, immune system, etc. • But does provide greater opportunities for grown, reproduction, and spreading than living inside cells. • Can rapidly colonize a habitat; Ex. when cholera invades intestine, can quickly multiply, spread to cover large surface area • Typical bacterial pathogens that act extracellularly: E. coli, Pseudomonas sp., Vibrio cholera

15. Virulence Factors • Virulence Factors are specific adaptations that allow pathogen to: • Attach selectively to host tissues. • Gain access to nutrients by invading or destroying host tissues. 3. Avoid host defences. 4. Toxins – exotoxins and endotoxins. 5. Siderophores.

16. 1. Specific attachment & entry factors • Pathogen must be able to bind to some receptor molecule on cell surfaces. These typically have necessary functions for cell. • Most diseases are tissue specific, because only certain tissues have receptor molecule needed. Ex: HIV binds to cells that have CD4 receptor (only certain lymphocytes). • Fimbriae or pili are used by some bacteria to attach selectively to certain tissues. Ex: Neisseria gonorrhaea binds to genital epithelium by fimbriae. In mutant cells w/o fimbriae, infectivity and pathogenicity are lost.

17. 2. Invasive enzymes • Many bacteria have specific enzymes that allow cells to penetrate host tissues • Example 1: collagenase produced by Clostridium perfringens. Enzyme degrades collagen, the primary structural fibre of connective tissue (25% of body's protein), allows penetration deeper into tissues ---> fulminating gangrene. Strictly anaerobic process, only occurs when tissue is damaged so blood can't supply oxygen (e.g. serious wounds, frostbite). • Example 2: hemolysin enzymes produced by Streptococcus pyogenes dissolves cell membranes of tissues, produces typical symptoms of "strep throat".

18. 3. Tricks to avoid host defenses • Capsules - Many pathogens have thick extracellular polysaccharide capsules. Capsules inhibit phagocytosis, prevent quick disposal of bacterium by WBCs. Loss of capsule typically causes loss of infectivity. • "Nasty Enzymes" Leukocidins - some pathogens secrete chemicals that specifically kill WBCs. Eg: Staphylococcus aureus. Accumulation of pus at infected site is caused by dead WBCs. Coagulase - Staph. aureus produces enzyme that coagulates blood. Result: WBCs, other body defences can't reach site of infection. Staph typically remains localized, "walled off" from defenses, produces many nasty types of localized infections such as boils, abcesses, etc.

19. 4. Exotoxins • Most exotoxins are proteins, secreted from cell, often damaging tissues at some distance. Very potent, small amounts are very toxic. • Often coded by plasmid DNA (ex. E. coli) or lysogenic phage DNA (ex. botulism, diphtheria) • Almost always inactivated by heat. Most are good antigens when inactive, can make toxoids (antigens without poison activity) = strong immune response. • Visit cholera (Vibrio cholerae) web page from Bacteriology 330, by Kenneth Todar, University of Wisconsin Department of Bacteriology

20. 1. Diphtheria toxin. Corynebacterium diphtheriae. Enters cell, inactivates elongation factor needed for protein synthesis. Cell gradually loses ability to make proteins (same toxin molecule keeps inactivating more and more factors), shuts down. 2. Botulin toxin, a neurotoxin (attacks nervous system). Clostridium botulinum, anerobic soil bacterium. Most potent toxin known- 1 gram could kill 10 million people. Toxin interferes with synaptic transmission at nerve-muscle junctions ---> flaccid paralysis. Occurs most typically in improperly canned 4. Exotoxins

21. 3. Tetanus toxin, another neurotoxin. Clostridium tetanus, anerobic soil bacterium. Blocks synaptic transmission to inhibitory neurons, leads to rigid paralysis. Common from deep wounds, pulled teeth. Treatment: antitoxin. Prevention: toxoid immunization (lasts 5-10 yrs). 4. Cholera toxin = an enterotoxin (attacks enteric tract). Vibrio cholerae. is free-living in fresh water. Binds to receptors on intestinal cells, chemically alters molecule involved in c-AMP production, leaves cAMP stuck in the "on" position. Causes massive outflow of water (chasing outflow of Na+/Cl-). Similar mode of action for other enterotoxin. Can be spread by drinking water, food (shellfish common). Untreated, mortality is ~50%. With fluid replacement, <1%. Prevention: clean drinking water. 4. Exotoxins

22. 4. Endotoxins • Endotoxins are integral parts of Gram-negative outer membrane (= LPS, lipolysaccharide). • Unlike Exotoxins, they are typically heat resistant, active only in sizable amounts, and remain bound to cells. • Mechanism of action is very diverse. "When we sense LPS, we are likely to turn on every defence at our disposal" (Lewis Thomas), including fever, decrease in iron, inflammation, blood clotting, reduced sugar in blood, etc. Most important clinical problems are fever and shock. • Typical scenario: Gram-negative bacteria (e.g. E. coli, Pseudomonas) enter body via clinical procedure (improperly sterilized kidney dialysis tubing, catheter, etc.), cause sudden decrease in blood pressure (hypotension) = "septic shock". Can be lethal.

23. 5. Siderophores • Iron plays special role in control of infection. • Most bacteria require iron to synthesize cytochromes. • Iron in human body is tightly bound, either in hemoglobin (blood cells), on transferrin proteins (serum and lymph), or lactoferrin (milk, tears, saliva, mucus, etc.). • Some bacteria (Streptococci) do not require iron -- metabolism is strictly fermentative, no respiratory system. But most bacteria have to find way to get iron or cannot grow. • Siderophores = iron-binding factors that allow some bacteria to compete with the host for iron. Ex: Enterochelin produced by enteric bacteria (E. coli, Salmonella). Mutants that cannot synthesize enterochelin lose virulence. These mutants can regain virulence if pure enterochelin is injected along with mutant bacteria.

25. Common Infections

26. Diseases of Developing Countries

27. Controlling Infectious Diseases • Treatment – prophylaxis such as antibiotics, antiviral drugs. • Prevention – hygiene, disinfectants, sterilization, antiseptics and vaccination.

28. Antiseptics and Disinfectants • Chemical substances that destroy microorganisms. • Antiseptic can be applied safely to the body. e.g on skin, ethanol and isopropanol. • Disinfectants cannot be used on the body directly but are used to clear work surfaces, crockery, cutlery, instruments etc. e.g hypochlorites in commercial disinfectants, phenol, aldehydes, chlorxylenol (dettol) and iodine in more dilute form can be used as antiseptics.

29. Sterilisation • Removal of any living organisms from a non-living object or material. E.g water, operating theatre gowns. • Heat – pasteurising milk , tinned food. • Steam - autoclave where steam under pressure is fed into a sealed chamber. • Radiation – Longer wave lengths have no effect shorter wavelength such as UV light results in death.

30. Vaccination • Giving antigens from a disease causing organism, either by injection or orally. • In order for the immune system to learn to make antibodies against the organism. • So that the body will be able to respond fast enough to prevent the organism from causing an infection. • Artificial active immunity

31. Different Types of Vaccines • Toxoid – detoxified yet antigenic property remains and when used as a vaccine will elicit production of antibodies in the host e.g tetanus toxoid • Killed organisms – heat inactivated e.g flu vaccine • Live organisms – attenuated e.g measles vaccine • New vaccines – genetic engineering has enabled antigens to be made in bacteria and isolated, purified and used in a vaccine.

32. Infectious Diseases • The spread of an infectious disease is critically influenced by social, economic, and behavioral factors in the human population. • In infected populations, viruses and their hosts co-evolve, with each influencing the other's destiny. • Often the most successful pathogens evolve to avoid killing their hosts. • Infectious diseases will never be eradicated as a group, but individual diseases can be controlled through public health measures, vaccination, and specific therapy.

33. Assignment 8Common Infections What organisms cause the following infections? Give details of symptoms and how are the infections are treated. • Measles • Chicken Pox • Hepatitis (Jaundice) • Malaria • Diarrhoeal diseases • Mumps • Throat Infections