Examples of bacterial infections and their interaction with the host

1. Examples of bacterial infections and their interaction with the host We ask the lab for a diagnosis, expecting a yes or no, but often end up with just a maybe… Professor Mark Pallen

2. The Normal Flora “A New Year Greeting After an article by Mary J. Marples in Scientific American, January, 1969 On this day tradition allots to taking stock of our lives, my greetings to all of you, Yeasts, Bacteria, Viruses, Aerobics and Anaerobics: A Very Happy New Year to all for whom my ectoderm is as Middle-Earth to me. For creatures your size I offer a free choice of habitat, so settle yourselves in the zone that suits you best, in the pools of my pores or the tropical forests of arm-pit and crotch, in the deserts of my fore-arms, or the cool woods of my scalp. Build colonies: I will supply adequate warmth and moisture, the sebum and lipids you need, on condition you never do me annoy with your presence, but behave as good guests should, not rioting into acne or athlete's-foot or a boil..” W.H. Auden

3. The Normal Flora • Our bodies are like mobile warm-blooded coral reefs, rich in microbial biodiversity and home to vast numbers of bacterial cells • more bacterial cells (1014) associated with the human body than there are human ones (only 1013)! • What are they? • Bacteria, Protozoa, Fungi, Archaea • Metazoa? Viruses? • Where are they? • External surfaces (not internal!) • composition of normal flora varies from individual to individual • some bacterial species carried only transiently • most fairly permanent • difficult to alter composition of the normal flora of gut in a healthy individual

4. Relevance of normal flora • (1) Diagnostic microbiology • Which microorganism is a pathogen? • (2) Opportunistic Infections • Normal flora can cause disease • Even organisms not normally considered invasive or pathogenic occur in compromised hosts • E.g., immunocompromised, skin breaches, other infections • Can be medically induced (iatrogenic), e.g., urinary catheters, venous catheters

5. Microbial Loads on “External” Surfaces • Large intestine 1014 • Skin 1012 • Vagina 1010 • Mouth 1010 • Nose 1010 • Throat 1010

6. Site skin large intestine vagina Ratio of Anaerobes: Aerobes ~ 1:1 1000:1 10:1 Anaerobic Normal Flora

7. Changes in normal flora • with changes in hormal physiology and development • female genital tract and lactobacilli • when antibiotics select for a 'resistant flora’ • Candida overgrowth in mouth, vagina • Clostridium difficile (antibiotic-associated colitis) • new organisms may be acquired • neonate from maternal genital tract during birth • Gram-negative colonisation of gut and URT in hospitalised patients • Cross-infection with C. difficile, MRSA, VRE etc

8. Normal flora at various body sites Mims C et al. Medical Microbiology Textbook. 2004.

9. Why care about the normal flora?it may be good for you! • colonization resistance: • competition for space and nutrients with pathogens • release of bacteriocins and colicins (antibacterial substances) to prevent pathogen growth • vitamin K production in gut • continued antigenic stimulation from commensals • cross-reacting protective immunity against pathogens • commensal neisseriaceae and Neisseria meningitidis

10. Why care about the normal flora? • commensal bacteria may cause disease at their site of carriage or nearby, e.g. • Streptococcus mutans (mouth) • causes dental caries • Streptococcus pneumoniae (upper airways) • causes otitis media, sinusitis • Some members of the normal flora can become pathogenic if they acquire additional virulence factors (e.g. E. coli) or are introduced into normally sterile sites (e. g. Staphylococcus aureus)

11. Why care about the normal flora?Normal flora as contaminants • To allow interpretation of • Gram stains on clinical samples • Culture results • Skin flora in blood cultures • BUT coagulase-negative staphylococci can be pathogens in device-associated sepsis, so can be hard to interpret • Perineal flora in urine • Take an MSU! • Mixed culture=contamination • Throat flora in sputum • Need to assess whether • Heavy pure growth • Obtained repeatedly • Fits clinical picture

12. Normal gut flora Mims C et al. Medical Microbiology Textbook. 2004.

13. Harmful effects of gut bacteria • escape of normal flora to abnormal sites • perforated appendix leads to peritonitis with • Bacteroides spp. and facultative aerobes inc. E. coli • cholecystitis and cholangitis • often mixed infection, E. coli predominant, also including enterococci • urinary tract infection • most frequent organism in normal urinary tract is E. coli • vaginal candiosis

14. antibiotic use leads to sensitive gut flora killed leads to overgrowth with resistant flora inc. Clostridium difficile leads to C. difficile toxin production leads to Diarrhoea, pseudomembraneous colitis Treatment stop precipitating antibiotic give oral metronidazole or vancomycin recovery requires re-establishment of normal flora ? probiotics Harmful effects of alterations in normal gut flora

15. Bacterial infections & clinical syndromes • Syndromes caused by bacterial infection can be classified into two basic types: • those defined on basis of pathogen, where a given species of bacterium causes a clearly defined syndrome • those defined on the basis of anatomical site of infection • caused by many different sorts of bacteria, individually or even in combination. • There is overlap between these types of syndrome because some bacteria cause characteristic infections at several sites (e.g. Haemophilus influenzae meningitis and epiglotitis).

16. The top 7 killers Mims C et al. Medical Microbiology. 2004.

17. Some syndromes defined by pathogen • typhoid fever • legionnaires disease • tuberculosis • diphtheria

18. Some syndromes defined by site • urinary tract infection • pharyngitis • pneumonia • septicaemia • endocarditis • meningitis • osteomyelitis

19. Urinary tract infection • Definitions • infection of urinary tract • lower UTI (cystitis) of bladder alone • upper UTI (pyelonephritis) of kidney & bladder • Signs & Symptoms • Dysuria • Frequency • Tender bladder and/or kidneys • Samples • Mid-stream urine (MSU)

20. Meningitis • Definition • Infection of meninges & adjacent brain • Signs & Symptoms • Headache • Photophobia • Malaise • Neck stiffness • Coma • Samples • Cerebrospinal fluid, • Blood cultures

21. Septicaemia • Definition • Infection of the blood ("blood poisoning") • Bacteria multiply in the blood • Signs & Symptoms • Fever • Malaise • Hypotension ( "septic shock") • Tachycardia • Samples • Blood cultures

22. Endocarditis • Definition • Infection of the heart valves • Signs & Symptoms • Fever • Malaise • Weight loss • Heart failure • Samples • Blood cultures

23. Osteomyelitis • Definition • Infection of bone • Signs & Symptoms • Fever • Malaise • Local pain & tenderness • Samples • Blood culture • Bone chippings

24. Gastroenteritis • Definition • Infection of gut • Signs & Symptoms • Nausea • Vomiting • Diarrhoea • Samples • faeces

25. Pneumonia • Definition • Infection of lungs • Signs & Symptoms • Dyspnoea • Cough • Chest pain • Samples • sputum • Various clinical syndromes • Bronchopneumonia • Diffuse patchy consolidation • S. pneumoniae, H. influenzae • Lobar pneumonia • Typically S. pneumoniae • Interstitial pneumonia • Characteristically viral • Lung abscess • Atypical pneumonia

26. Pharyngitis • Definition • throat infection • Signs & Symptoms • sore throat • malaise • Samples • throat swab

27. Pyrexia of unknown origin • Definition • varies - a common definition is that of a fever of more than 2-3 weeks duration, with no cause that be ascertained from initial tests. • Signs & Symptoms • various • Samples • many & varied