Examples of bacterial infections and their interaction with the host

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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

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Microbes and humans
Very few microbes are
always pathogenic
Many microbes are
potentially pathogenic
Most microbes are
never pathogenic
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Definitions

• Pathogen
• an organism that can cause infection in
  individuals with normal host defences, e.g.,
  Salmonella enteritidis, Vibrio cholerae
• Commensal
• an organism that is found normally on those parts
  of the body that are exposed to, or communicate
  with, the external environment, eg. Bacteroides
  fragilis, Staphylococcus epidermidis the 'normal
  flora'
• Opportunistic pathogen ('opportunist')
• an organism that can cause infection in
  individuals with abnormal host defences.
  Commensals may be opportunistic pathogens.

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Microbes and humans

• Disease can come about in several overlapping
  ways
• 1. Some bacteria are entirely adapted to the
  pathogenic way of life in humans. They are never
  part of the normal flora but may cause
  subclinical infection, e.g. M . tuberculosis
• 2. Some bacteria which are part of the normal
  flora acquire extra virulence factors making them
  pathogenic, e.g. E. coli
• 3. Some bacteria which are part of the normal
  flora can cause disease if they gain access to
  deep tissues by trauma, surgery, lines, e.g. S.
  epidermidis
• 4. In immunocompromised patients many free-living
  bacteria and components of the normal flora can
  cause disease, especially if introduced into deep
  tissues, e.g. Acinetobacter

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How do we know that a given pathogen causes a
specific disease?

• Koch's postulates
• the pathogen must be present in every case of the
  disease
• the pathogen must be isolated from the diseased
  host grown in pure culture
• the specific disease must be reproduced when a
  pure culture of the pathogen is inoculated into a
  healthy susceptible host
• the pathogen must be recoverable from the
  experimentally infected host

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The iceberg concept of infectious disease
poliomyelitis in a child
0.1-1 of infections are
clinically apparent
classical
clinical disease
less severe
disease
rubella
50 of infections are
clinically apparent
asymptomatic infection
Spectrum of virulence
rabies
100 of infections
are clinically apparent
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How do we know that a given pathogen causes a
specific disease?
Diagnosis and effective treatment of infection
depends not just on isolating an organism, but in
establishing a plausible link between the
laboratory findings, recognised syndromes and the
patient's clinical condition
Recognised syndromes
e.g.
septicaemia, endocarditis,
osteomyelitis meningitis,
UTI, pneumonia
pharyngitis
patient's clinical condition
potential pathogen isolated from or detected in
clinical samples
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Microbes and humans

• Evidence for a potential pathogen being clinical
  significant (particularly for bacteria)
• Isolated in abundance
• Isolated in pure culture
• Isolated on more than one occasion
• Isolated from deep tissues
• Evidence of local inflammation
• Evidence of immune response to pathogen
• Fits with clinical picture

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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
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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

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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

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Microbial Loads on External Surfaces

• Large intestine 1014
• Skin 1012
• Vagina 1010
• Mouth 1010
• Nose 1010
• Throat 1010

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Anaerobic Normal Flora

• Site
• skin
• large intestine
• vagina

• Ratio of Anaerobes Aerobes
• 11
• 10001
• 101

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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

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

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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)

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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 culturecontamination
• Throat flora in sputum
• Need to assess whether
• Heavy pure growth
• Obtained repeatedly
• Fits clinical picture

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

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Harmful effects of alterations in normal gut
flora

• 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

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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).

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The top 7 killers Mims C et al. Medical
Microbiology. 2004.
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Some syndromes defined by pathogen

• typhoid fever
• legionnaires disease
• tuberculosis
• diphtheria

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Some syndromes defined by site

• urinary tract infection
• pharyngitis
• pneumonia
• septicaemia
• endocarditis
• meningitis
• osteomyelitis

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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)

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Meningitis

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

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Septicaemia

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

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Endocarditis

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

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Osteomyelitis

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

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Gastroenteritis

• Definition
• Infection of gut
• Signs Symptoms
• Nausea
• Vomiting
• Diarrhoea
• Samples
• faeces

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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

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Pharyngitis

• Definition
• throat infection
• Signs Symptoms
• sore throat
• malaise
• Samples
• throat swab

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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