Medical Microbiology SBM 2044

1. Medical MicrobiologySBM 2044 Assoc Prof Dr Othman Abd Samah Tel : 09-5716744 Email : oas@iiu.edu.my Sr. Intan Azura Shahdan Tel : 09-5716400 ext 2816 Email : intan_azura@iiu.edu.my

2. SBM 2044 LECTURE 1 INTRODUCTION TO MODULE • Methods of assessment • Module Aims & Objectives • Course structure, Reading, etc. • Introduction – Recall some foundations from Principles of Microbiology SBM 2053 Value: 4 credit hours

3. SBM 2044: Aims To foster knowledge and understanding of certain microbial pathogens, selected to illustrate: • various kinds of host-pathogen interactions • experimental approaches used to study bacterial/viral pathogens • molecular mechanisms in bacterial pathogenicity • clinical diagnosis and treatment

4. Course Content • Microbes – Man interactions Week 1-3 • Medical Bacteriology Week 4-6 • Medical Virology & Biological Agents of Warfare Week 7-10 • Medical Mycology Week 11-12 • Emerging infectious diseases Week 13 • Introduction to the diagnosis and treatment of infection Week 14

5. Microbes – Man interactions Lecture 1: • Why is this subject important? • The normal human flora • Factors influencing bacterial-host interactions Lecture 2: • Introduction to bacterial pathogenesis Lecture 3: • Weapons delivery and deployment

6. Today • How do we recognise pathogens? Only a tiny proportion of all known microbes cause disease • How do we identify a particular microbe as the cause of a particular disease? • Which microbes cause disease? • How do they do it? • How do we stop them? • How do we identify a particular microbe as the cause of a patient’s illness?

7. Nutritional Injury Various Non- communicable INFECTIOUS DISEASE Perinatal Deaths in children (0 – 4 years) in 1998 Data from WHO 1999

8. Vineeth, 7 months old and identified as HIV-positive, cries at the Community Health Education Society orphanage in Madras, India. The WHO estimates 800,000 children were infected with HIV in 2001 alone, almost all through mother-to-child transmission.

10. Premature deaths (0 – 44 years) in 1998 Nutritional Maternal Perinatal 2% 3% 10% INFECTIOUS DISEASE 18% 48% 19% Various non- communicable Injuries Data from WHO 1999

11. Human priorities ? Spending 1995 (in billions $) Deaths 1945 – 1993 (in millions) AIDS + Malaria + TB War 15 23 150 864 AIDS + Malaria + TB Military

12. Malaysian Facts • Population: 24,821,286 (July 2007 est.) • Death rate: 5.05 deaths/1,000 population (2007 est.) • HIV/AIDS (2003 est.) – • adult prevalence rate: 0.4% • people living with HIV/AIDS: 52,000 • HIV/AIDS - deaths: 2,000 • REFERENCE: www.cia.gov/library

13. How do we identify a particular microbe as the cause of a particular disease? • The Koch Henle postulates • Isolate the organism from every case • Propagate in pure culture in vitro • Reproduce disease by injecting the organism into a suitable recipient • Re-isolate the organism • OK for major acute diseases like plaque, smallpox, typhoid..

14. Pathogens vs. non-pathogens: the Normal Flora • Only a minute fraction of the organisms in the environment cause disease. • Isolation of an organism from a patient does not imply disease. • many different forms of association between microbes and humans • many yet unknown, non-culturable eg. In soil, water, extreme environments • Others colonise other living organisms, virtually all multicellular organisms have their own normal flora, organisms with which they coexist.

15. Factors controlling growth 1. Nutrient availability • Essential elements: • Major: C, O, H, N, S, P, K, Mg, Ca, Fe, Na, Cl • Minor: Zn, Mn, Co, Cu • All present in vivo, but all not readily available • to infecting bacteria – e.g. Fe • Concentration in plasma ca. 20µM • Freely available: 10-18M • Pathogens • All heterotrophic (need organic C source) • Many fastidious

16. Factors controlling growth Facultative or Obligate 2. Physical environment • Water activity (aw) - not limiting in vivo • Osmotic pressure (π) - moderate/high • Too high for some bacteria • Oxygen – availability depends on location in vivo • Anaerobic • Aerobic • Microaerophilic

17. Factors controlling growth pathogens mesophiles 2. Physical environment – contd. • Temperature: 37ºC – little variation • pH: Mostly ca. pH 7.0 in vivo, but can vary • Skin: pH 5.5 • Stomach: pH 2.0 – 5.0

18. Factors controlling growth 3. Competition – from normal flora • Cells occupying your space Approx. number % Total 10% 1013 Human 90% 1014 Bacteria

19. NORMAL HUMAN FLORA • Internal organs/tissues normally sterile • External surfaces & accessible ‘internal’ niches colonised by certain bacterial species – include: • Skin • Conjunctiva (eye surface) • Oral cavity • Upper respiratory tract • Nares (nostrils) & nasopharynx • Gastroinsteinal tract • Urogenital tract

20. NORMAL HUMAN FLORA Site numbers of bacteria • Numbers & composition varies depending on location Mouth 1010 Skin 1012 Intestines 1014 • May also vary at different sites on same tissue e.g. skin - approx 2 square meters - moist areas more densely populated • Complex flora : > 200 species

21. NORMAL HUMAN FLORA • Skin – dominated by: • Staphylococcus epidermidis • Micrococcus sp. • Coryneforms (e.g. Propionibacterium acnes) • 20 – 30% individuals: Staphylococcus aureus • Conjunctiva • Numbers usually low • Mostly S. epidermidis & certain coryneforms • Occasionally S. aureus, some streptococci, • Neisseria sp., Haemophilus sp

22. NORMAL HUMAN FLORA • Oral cavity – multiple sp., including: • Oral streptococci (α – haemolytic) • S. salivarius, S. mutans, S. sanguis • Lactobacillus sp, Staphylococcus sp. • Corynebacterium sp. • Many anaerobes – esp. Bacteroides sp. • Upper respiratory tract • Nares: S. epidermidis, Corynebacteria, • S. aureus (20 – 30% individuals) • Nasopharynx: Mostly α-haemolytic streptococci • other Streps., Neisseria sp.,

23. NORMAL HUMAN FLORA • GI Tract – multiple sp., including for example: • Escherichia coli & other Enterobactericeae • Clostridium perfringens • Enterococcus faecalis • Bacteroides sp. • Urogenital tract: • Antherior urethra: S. epidermidis, enteric bacteria • Vagina: various sp., including: • Lactobacillus acidophilus

24. Different types of symbiotic associations Mutualism Commensalism reciprocal benefit Harmless Parasitism unilateral benefit

25. Factors controlling growth B H 4. Host defences – Innate and specific • Dynamic, interactions with bacteria – outcome depends on the balance Host defences Bacterial virulence Multiple factors Multiple factors • Pathogenicity usually a multifactorial process • Normal flora - balance in a particular host niche, but not necessarily at other sites

26. Virulence B H H B • Quantitative – extent of ability to cause disease Completely avirulent Extremely virulent Overwhelm defenses rapidly kills host No capacity to survive in/on host

27. Opportunistic pathogens Completely avirulent Extremely virulent B H H B Normal defences No disease Compromised defences Disease

28. Other sites are normally sterile, and the presence of bacteria suggests an infection: • Blood (septicaemia)s • Cerebrospinal fluid (meningitis) • Deep tissues (abscesses) • The digestive tract contains large numbers of organisms – up to 1/3 of faeces can be bacteria: some anaerobes are actually oxygen-sensitive

29. The vast majority of normal flora organism do not cause disease, but coexist with the host - commensals • Much of the normal flora is actually beneficial to the host – they can exclude pathogen, by producing antibiotics, or other bactericidal substances (bacteriocins) • Removal of the normal flora by e.g. antibiotics can make the host much more susceptible to pathogenic organisms which would otherwise not cause disease because the normal flora will prevent them from colonising the host.

30. Homework • Read about the Roles of Normal Flora • Brooks chapter 11 OR • Schaechter chapter 2