Microbiologie - Bacteriologie

Samenvatting

  • taxonomy
    • X. sp.
      • unidentified species in genus X
      • plural: spp.
  • Gram-positive bacteria (GPB)
    • Staphylococcus aureus
    • Staphylococcus epidermidis
    • Streptococcus pneumoniae
    • Streptococcus pyogenes
    • Clostridium tetani
    • Clostridium difficile
    • Bacillus anthracis
    • Bacillus cereus
    • Listeria monocytogenes
    • Enterococcus faecalis
    • Mycobacterium tuberculosis
    • Corynebacterium diphtheriae
  • Gram-negative bacteria (GNB)
    • Escherichia coli
    • Salmonella spp.
    • Pseudomonas aeruginosa
    • Neisseria gonorrhoeae
    • Haemophilus influenzae
    • Klebsiella pneumoniae
    • Vibrio cholerae
    • Campylobacter sp.
    • Legionella pneumophila
    • Proteus mirabilis
    • Yersinia pestis
    • Helicobacter pylori
    • Shigella spp.

1 Intro

  • bacterial structure
    • cell wall
    • capsule
    • pili
    • flagella
  • labs
    • general
      • techniques
        • microscope
        • cultures
        • PCR
        • serology (blood)
        • drugs (AB, ...)
    • reference labs
      • surveillance
      • origin of epidemics
      • environment samples
      • techniques
        • whole genome sequencing (WGS)
        • seroloprevalentie?
  • drug resistance
    • biofilms
  • infection source
    • insects
      • lice
      • ticks
        • Lyme
      • fleas
        • plague
      • mosquitoes
    • environment
      • water
      • air
      • soil
      • food
    • animals (zoonosis)
    • humans
      • airborne
      • blood
      • STDs
      • direct contact
  • epidemiology
    • populations
      • susceptibles (S)
      • infectives (I)
      • removed (R)
        • recovered
        • died
    • types
      • outbreak
      • epidemic
      • pandemic
      • endemic
    • One Health
  • risk factors
    • risk = exposure x low access to prevention/care
    • risk = exposure x susceptibility
      • genetic
      • non-genetic
  • pathogenesis
    • phases
      • colonisation
      • adhesion
      • invasion
    • toxins
      • endotoxines
        • gram negatief
        • deel van celwand
          • o.a. lipopolysacchariden (LPS)
      • exotoxines
        • productie door bacteria
    • immune evasion
      • intracellular persistance in phagocytes
      • antigenic variation
      • immunomodulating molecules
      • IgA proteases
  • voorbeelden
    • Brucellosis
      • in unpasteurized milk
    • Bacillus anthracis
      • anthrax = miltvuur
      • transmission: direct contact
      • skin infection
    • Mycobacterium bovis
      • bovine TBC
    • Coxiella burnetii
      • Q fever
      • cf. influenza
    • Vibrio cholerae
      • cholera

2 Bacteriology

  • prokaryotic cell
    • capsule
      • difficult for AB to penetrate
      • can be used as vaccine components
        • polysaccharides
    • cell wall
      • gram positive
        • big layer of peptidoglycan
          • contains (lipo-)teichoic acid
          • synthesis
            • flippase
            • PBP = penicillin binding protein
              • PBP5: intrinsic resistance to beta-lactam
              • PBP2a: acquired resistance (e.g. MRSA)
            • PBPs: transglycosylation (link sugars)
            • PBPs: transpeptidation (crosslink peptides)
              • inhibited by
                • beta-lactam AB (via PBP)
                • glycopeptide AB (via peptides)
      • gram negative
        • small inner layer of peptidoglycan
        • extra outer membrane (lipid bilayer)
          • lipopolysacchariden (LPS)
            • endotoxins
      • special cases
        • Mycobacteria
          • e.g. Mycobacterium tuberculosis
          • complex cell wall (incl. capsule)
            • regular AB won't work
            • use Isoniazid (pro-drug) to treat TBC
              • katG
              • inhA
        • Chlamydia
          • wall-less
    • cytoplasm
    • genetic material
      • horizontal gene transfer
        • transduction
          • via bacteriophages (virusses)
        • conjugation
          • sex pilus
          • transfer plasmid
        • transformation
          • absorp DNA fragments of dead bacteria
      • antibiotics
        • Fluoroquinolones
          • inhibit DNA replication
        • Rifampicin
          • inhibits RNA polymerase
          • resistance: rpoB point mutation
    • ribosomes
      • large subunit
        • AB > Macrolides
      • small subunit
        • AB > Aminoglycosides
    • plasmid
    • pili
    • flagella
    • no mitochondria!
  • spores
  • examples
    • Clostridium difficile
      • toxins
    • Clostridium tetani
      • tetanus
    • Clostridium perfringens
      • food intoxication
      • Gaz gangrene
    • Heliobacter pylori
      • urease: urea -> CO2 + NH3 -> increase pH
      • breath test with marked urea
  • efflux pumps
    • pump out AB
  • respiration
    • aerobic
    • anaerobic
      • glycolysis
      • fermentation
        • lactate
        • ethanol + CO2

3 Diagnosis en identification

  • optical density of sample (urine, CSF, ...)
    • clear
    • cloudy
    • turbid
  • techniques
    • microscopy
      • shapes
        • coccus
          • diplococcus
          • streptococcus: in chains
          • staphylococcus: in clusters ("grape-like")
        • bacillus
        • vibrio: banana
        • spirillum
        • spirochete
      • gram staining
        • crystal violet: purple (positive)
        • safranin: pink (negative)
      • examples
        • E. coli
          • gram negative
          • rod
        • Staphylococcus aureus
          • gram positive
          • coccus
        • Streptococcus pneumoniae
          • gram positive
          • diplococcus
    • biochemical tests
      • old techniques
      • take at least 1 day
    • antigen-based rapid tests
      • cf. pregnancy test
      • Clostridoides difficile
      • Legionella pneumophila
        • gram negative
    • MALDI-TOF mass spectrometry
      • MALDI = Matrix-Assisted Laser Desorption/Ionization
      • TOF = Time of Flight
        • heavier = slower
      • most used
      • fast
      • laser
      • electrostatic field
        • to accelerate ionized charges
      • flight tube
      • sample
      • matrix
        • absorps UV light
        • helps ionize the sample
      • result: MS profile
        • x-axis: m/z
        • y-axis: intensity
        • match with library of known species
    • 16S RNA sequencing
      • fallback technique
      • 23S: large subunit
      • 16S: small subunit
        • contains conserved and variable regions
          • V4
      • lookup in "Genbank"
    • next generation sequencing: applications
      • since 10 years
      • metagenomics
      • whole genome sequencing (WGS)
        • strains
        • mutations
          • track outbreaks
        • AB effectiveness
    • standard panel for GI infections
      • parasites
        • Gardia
        • Antamoeba
        • Cryptosporidium
      • bacteria
        • Clostridium difficile (incl. toxins)
        • Campylobacter
        • Salmonella
        • Yersinia enterocolitica
      • viruses
        • rota
        • noro
    • TBC diagnosis
      • Mycobactericum tuberculosis
      • grows too slow
      • microscopy: special staining
      • PCR
      • AB
        • Isoniazid (specific for mycobacteria)
        • Ethambutol
        • Rifampicin (mRNA synthesis)
          • resistance: rpoB point mutation
        • Pyrazinamide (unclear mechanism)
  • bacterial meningitis
    • causes
      • Neisseria meningitidus
      • Streptococcus pneumoniae
      • E. coli
      • Haemophilus influenzae
      • Listeria monocytogenes
    • symptoms
      • CSF
        • low glucose
        • high protein
        • cells: polymorphonuclear leukocytes (PMNs)
  • bacterial vaginosis
    • clue cell

4 DST, PK-PD en TDM

Drug susceptibility testing (DST)

  • MIC = minimal inhibitory concentration
    • susceptible (S)
    • susceptible, increated exposure (I)
    • resistant (R)
  • natural susceptibility
  • acquired resistance
    • isoniazid
      • pro-drug
      • for mycobacteria
      • activated by katG?
        • INH / inhA (?)
        • katG S315T mutation -> resistance
  • phenotypic methods
    • disk diffusion methods (Kirby-Bauer)
      • measure zone of inihibition (mm)
    • E test
      • strip with increasing concentrations
    • Broth microdilution method
      • gold standard
      • rarely used
      • only in reference labs
      • grid with increasing concentrations
    • breakpoint concentrations
      • only low+high concentrations instead of all in between
        • 0/0 -> R
        • 0/1 -> I
        • 1/1 -> S
  • alternative methods
    • enzymatic
      • fast, does not require overnight incubation
    • PCR
    • sequence-based detection
      • Rifampicin resistance determining region (RRDR)
    • whole genome sequencing (WGS)

Pharmacokinetics (PK)

  • AB concentration
    • oral intake
    • 0 -> peak
      • stable duration
    • peak -> 0
      • variable (depends on half life)
        • example: longer in urine than in blood
    • window above MIC

Pharmacodynamics (PD)

  • AB dependent PK activity
    • concentration dependent
      • Amikacin (aminoglycoside - small subunit ribosome)
      • measure: Cmax
      • higer = more side effects
    • time and concentration dependent
      • Vancomycin (non lactam > glycopeptide)
      • measure: AUC above MIC
    • time dependent
      • Cephalosporins (beta-lactam)
      • measure: time above MIC
  • treatment regimen
    • new intake when below MIC
    • infusion: bolus vs continuous

Therapeutic drug monitoring (TDM)

  • therapeutic window
    • between %cured and %side effects
  • Amikacin
    • concentration dependent
    • next dosis when C < 1 mg/ml (otherwise toxic)
  • drug interactions
    • influence of cytochrome P450 enzymes (CYP)
      • CYP inhibitor -> less AB degradation/elimination
  • how to measure AB concentration in blood
    • liquid chromatography
      • graph: intensity vs m/z
    • ELISA
      • antigens

5 Antibiotics and Antimicrobial Resistance (AMR)

  • 1928: discovery Penicillin (Fleming)
    • Actinomycetes
  • 1940: production Penicillin
  • 1943: Streptomycin
  • 1950-60: golden age
  • AB mechanisms
    • cell wall
      • non lactam
        • glycopeptide (via peptides)
          • Vancomycin
            • works well against Gram positives
            • too big to cross outer membrane of Gram negatives
            • VRE = Vancomycin resistant enterococcus
              • VanA / VanB genes
      • beta-lactam (via PBP)
        • affects transpeptidation via PBPs
        • allergies
          • more severe second time
        • examples
          • Penicillins
            • Penicillin G
            • Amoxicillin
          • Cephalosporins
            • 1st gen
            • 2nd
            • 3rd
              • Ceftriaxone
            • 4th
            • (5th)
          • Carbapenems
          • Monobactams
            • 1 ring
        • resistance
          • PBP5: intrinsic resistance
          • PBP2a: acquired resistance (e.g. MRSA)
            • mecA gene
            • solution: use Vancomycin
          • Mycobacteria (e.g. TBC)
            • complex cell wall
              • use Isoniazid (pro-drug)
                • katG
                • inhA
          • Chlamydia
            • wall-less
            • use TODO -> doxycycline (S30)?
          • penicillinase / beta-lactamase
            • sensitive
              • Penicillin
              • Amoxicillin
            • resistant
              • methiciliin
              • flucloxacillin
    • DNA
      • Metronidazole (pro-drug)
        • only anaerobic bacteria and protozoa
          • activated in anaerobic environments
          • C. difficule
          • Trichomonas
          • Entamoeba
          • Giardia
    • DNA replication
      • Fluoroquinolones
    • RNA polymerase
      • Rifampicin / Rifampin
        • resistance: rpoB point mutation
    • ribosomes
      • large subunit (S60)
        • Macrolides
          • (Azithromycin)
          • (Clarithromycin)
        • Lincosamides
          • (Clindamycin)
      • small subunit (S30)
        • Aminoglycosides
          • Amikacin
            • concentration-dependent
          • (Gentamicin)
        • Tetracyclines
          • Doxycycline
    • folic acid synthesis
      • Sulfonamides
      • Trimethoprim
    • (bacterio)phage therapy
      • experimental
  • AMR
    • overuse
    • incorrect use
    • WHO prio
      • 1 critical
        • mainly hospital acquired
      • 2 high
      • 3 medium
        • mainly community acquired
    • mechanisms
      • decreased intracellular concentration
        • efflux pumps
        • ...
      • target modification
        • absence
        • mutation
        • alternative pathway
        • increased expression
      • enzymatic degradation
        • beta-lactamases
          • cut AB molecules

6 Vaccines

Live attenuated vaccines

  • old technique: heating
  • Vibrio cholerae
  • Mycobacterium tuberculosis
    • BCG vaccine
      • based on M. bovis
        • low virulence in humans
        • cross-immunity with M. tuberculosis
        • culture on bile salts (stress) -> loss of virulence
  • Salmonella enterica subsp. enterica serovar Typhi
    • types of salmonella
      • S. Typhi (vaccine)
        • typhoid fever
          • adhesion to M cells and Peyer patches in gut
          • diffusion via lymph
          • to liver and spleen, bone marrow
      • Non-typhoidal salmonella (NTS) (no vaccine)
        • gastero-enteric disease
        • invasive disease
  • Bacillus anthracis

Toxoid vaccines

  • harm caused by toxins instead of bacteria
  • formaldehyde treatment
  • DTaP vaccine
    • Diphtheria
      • Corynebacterium diphtheriae
      • causes necrosis in pharynx
    • Tetanus = kaakklem
      • Clostridium tetani
      • spores are everywhere (in soil, ...)
    • Pertussis = kinkhoest
      • Bordetella pertussis
      • droplet transmission
      • whole cell vaccine (DTP)
        • more effective
        • side effects
      • acellular vaccine (DTaP)
        • less effective
      • typically diagnosed only after infectious phase
      • vaccinate
        • during pregnancy (3rd trimster)
        • 8 weeks
        • 4, 6, 18 months
        • 4 years
        • ~13 years
        • repeat every 10 years

Polysaccharide and conjugated vaccines

  • polysaccharide
    • antigens on cell wall hidden by polysaccharides in capsule
    • Capsular Polysaccharide (CPS)
      • different versions are called serotypes
    • CPSs can be used as vaccine components
  • meningitis
    • bacterial or viral
      • bacterial: neutrophiles in CSF
      • viral: lymphocytes in CSF
        • less severe
    • symptoms
      • red rash
        • doesn't fade when you press a glass against it
      • fever
      • vomiting
      • headache
      • neck stiffness
      • light sensitivity
      • lethargy
    • in subarachnoid space
      • contains CSF
        • lumbar punction
          • low glucose
          • high protein
          • cells: polymorphonuclear leukocytes (PMNs)
          • makes CSF look turbid instead of clear
    • caused by many pathogens
      • treatment
        • Penicillin / Amoxicillin
        • Ceftriaxone
        • Vancomycin
      • E. coli
        • mostly in newborns
      • Listeria monocytogenes (LM)
        • mostly in newborns and adults
      • S. agalactiae (group B = GBS)
        • mostly in newborns
      • S. pneumoniae (SP)
        • not in newborns
        • non-invasive pneumococcal diseases
        • invastive pneumococcal diseases (IPD)
          • causes
            • meningitis
            • sepsis
            • complicated pneumonia
          • 100+ serotypes
          • incidence increases with age
          • seasonal
          • vaccine (pneumococcus)
            • details: see infectieziekten
            • for adults: without carrier protein
              • B cell + plasma cell response
            • for children: with carrier protein
              • B + T cell response
      • Haemophilus influenzae
        • uncapsulated types (no vaccine)
        • encapsulated types
          • type b (Hib vaccine)
            • very low incidence since vaccine
            • causes
              • meningitis
              • epiglottitis (exam!)
                • risk of suffocation in children
              • sepsis
              • pneumonia
      • Neisseria meningitidis (NM)
        • mostly in children
        • droplet transmission
        • often: colonization (in nasopharynx) without symptoms
        • bad luck: gets in bloodstream
          • sepsis
          • meningitis
        • "meningitis belt" in Africa around equator
        • ACWY vaccine
          • protects against four major serotypes (with different CPS)
          • not included: B, X
          • not used in Belgium
            • alternative vaccine using other targets

Vaccine program in Belgium

  • ignoring viruses
  • diphteria, kinkhoest, tetanus (DKT)
  • Haemophilus influenza b
  • Meningokokken C
  • pneumokokken

7 Skin and soft tissues

  • TODO
  • exam: focus on most frequent pathogens and diseases
  • Staphylococcus aureus
  • Streptococcus pyogenes (GAS)

8 Airways

  • TODO

9 UTIs and STDs

Urinary tract infections (UTIs)

  • symptoms
    • frequent urge
    • pain during urination
    • cloudy urine
  • more common in women
  • extra risk: katheter
  • upper UTI
    • kidneys: pyelonephritis
      • risk of urosepsis
    • ureters: ureteritis
  • lower UTI
    • bladder: cystitis
      • symptomatic
      • asymptomatic
        • still requires treatment in pregnant women
    • prostate: prostatitis
      • enlarged
        • compresses urethra
          • makes cystitis even worse
    • urethra: urethritis
  • urine sample
    • process
      • wash hands
      • use sterile cup
      • wipe genitals
      • midstream
        • first part will contain skin pathogens
      • send to lab quickly
    • result
      • in healthy people mostly sterile liquid
      • pyuria: white blood cells in urine
      • bacteriuria
    • tests
      • microscope
      • dip sticks
        • test for E. coli (gram negative)
          • won't test for enterococcus
      • semi-quantitative
        • grow culture from standardized volume
        • verify that it is a single bacteria
        • count colony forming units (CFUs)
  • uropathogens
    • enterobacteria
      • E. coli (majority)
        • gram negative
        • toxins
      • Klebsiella
      • Proteus
      • Enterobacter
      • ...
    • Enterococcus sp
    • S. saprophyticus
  • treatment
    • UTI
      • special oral AB
        • duration: few days
        • nitrofurantoine
        • fosfomycine
    • acute prostatitis
      • oral AB
        • duration: few weeks
        • levofloxacine
        • ciprofloxaxine
    • acute pyelonephritis
      • idem (shorter for women)
Special cases
  • catheter-associated UTI (CAUTI)
    • extra risk: some urine remains in bladder (stasis)
    • different set of pathogens
      • E. coli
      • Enterococcus spp
      • S. aureus
      • Candida spp
      • Pseudomonas aeruginosa
      • Klebsiella pneumonia
  • UTI during pregnancy
    • urine test during every checkup
    • foetus presses on bladder
      • more stasis
  • UTI during childhood
    • taught to keep urine up
    • recurrent
      • vesico-uretric reflux
        • risks kidney damage
        • requires treatment
  • UTIs and DM2
    • complicated UTI
      • more frequent
      • more severe course
      • unusual bacteria (not E. coli) more common
    • factors
      • glucosuria
        • more growth
      • vascular complications
        • lower immune reaction

Chorioamnionitis and neonatal meningitis

  • neonatal meningitis
    • aquired in utero or during childbirth
    • caused by beta-hemolytic streptococci
      • Lancefield classification
        • group A streptococcus (GAS) = Streptococcus pyogenes
        • group B streptococcus (GBS) = Streptococcus agalactiae
          • early onset disease (EOD)
            • week 1
          • late onset disease (LOD)
          • both can cause
            • sepsis
            • pneumonia
            • meningitis
  • chorioamnionitis
    • caused by vaginal flora
    • causes inflammation in mother and foetus
    • can cause preterm birth
    • difficult to diagnose
    • test: amniotic fluid sample

Sexually transmissed diseases (STDs)

  • STDs in Belgium
    • male > female
    • mostly in heteros or MSM
Gonorrhoea
  • Neisseria gonorrhoeae
    • not to be confused with N. meningitidis causing meningitis
  • symptoms
    • fever
    • pain
    • in newborns
      • sepsis
      • arthritis
      • meningitis (only in newborns!)
      • prevention: routine screening for STDs during pregnancy
Chlamydia
  • C. pneumoniae
    • atypical "walking" pneumonia
  • C. psittaci
    • zoonosis (birds)
  • C. trachomatis
    • serovars
      • A-B
        • transmission: direct contact (not STD)
        • main cause of blindness in developing countries
      • D-K (most common)
        • urethtritis
        • PID (see below)
        • neonatal pneumonia
        • neonatal conjunctivitis
      • L1-L3
        • in subtropical areas
        • more virulent
    • infects
      • penis
      • cervix
      • eye
    • lifecycle
      • outside of cell
      • inside of cell
        • replication
    • treatment
      • beta-lactam won't work due to special cell wall
Syphilis
  • first stage: ulcer (painless)
  • secondary stage: rash
    • typical symptom: spots on hands
  • tertiary stage: internal organs?
  • diagnosis
    • cultures don't work well
    • PCR does not work well
    • serology
      • complex diagnosis (examen!)
      • treponemal antibodies
        • test remains positive even after treatment
      • non-treponemal antibodies after treatment
        • test turns negative
  • treatment: AB (penicillin, beta-lactam)
  • congenital syphilis
    • test mother during pregnancy

Pelvic inflammatory disease (PID)

  • Mycoplasma genitalium
    • limited clinical symptoms
    • distorted falopian tubes
      • decreased infertility
    • treatment
      • no cell wall
      • beta-lactams don't work
      • macrolides

Screening

  • pregnant women
    • N. gonorrhoeae
    • syphilis
    • ..?
  • asymptomatic with higher risk
    • PCR
      • C. trachomatis
      • N. gonorrhoeae
  • symptomatic
    • PCR
      • C. trachomatis
      • N. gonorrhoeae
      • Mycoplasma genitalium
      • Trichomonas vaginalis

10 Gastro-intestinal infections

  • diarrheal diseases
    • (clean) water, sanitation, hygiene (WASH)

Food intoxication

  • bacteria die when cooking food
  • their toxins can remain stable
  • Staphylococcal food poisoning (SFP)
    • Gram positive
  • Clostridium botulinum
    • Gram positive
    • spores
    • anaerobic in food jars
    • neurological symptoms

Gastric and duodenal ulcers

  • Helicobacter pylori
    • transmission
      • feco-oral
      • airborne
    • uses urease to produce NH3 + CO2 from urea
      • NH3 protects against low pH
    • symptoms
      • stomach ulcer
      • stomach bleeding
    • diagnosis
      • biopsy
        • difficult to culture
      • breath test
        • drink marked urea
        • processed by bacteria using urease
        • detect marked CO2 in breath
    • treatment
      • AB
      • proton inhibitor
    • long term: can cause cancer

Gastro-intestinal infections

  • Campylobacter sp.
    • from chickens
    • mild gastro-enteritis
    • diarrhea
  • E. coli
    • pathotypes
      • Enterotoxigenic E. coli (ETEC) = traveler's diarrhea
        • enterotoxin
        • gut releases water and electrolytes
      • Enterophatogenic E. coli (EPEC)
        • no toxin
        • disturb villi
        • disturb tight junctions
      • Enterohemorragic E. coli (EHEC)
        • toxin
        • affects endothelial cells in blood vessels
        • thrombus
        • often infected during industrial food processing
      • Enteroinvasive E. coli (EIEC)
        • destroys colon epithelium
        • synonym: Shigella?
  • Clostridoides difficile
    • Gram positive
    • spores
    • anaerobic
    • existing gut flora inhibit these spores
      • die when taking AB -> dysbiosis
    • toxins
      • toxin A
      • toxin B
      • colon inflammation
    • outbreaks in hospitals
      • spores survive typical cleaning products
    • treatment
      • AB: vancomycin
        • big glycopeptide
        • typically given via IV because of poor absorption
        • here given orally
          • high dose in gut
          • low dose in blood
  • Vibrio cholerae
    • aquatic environment
    • heavy diarrhea

Foodborne infections causing systemic diseases

  • Salmonella
    • S. Typhi
      • gastero-enteric symptoms
      • typhoid fever (systemic)
      • physiopathology
        • M cell / Peyer patch invasion
        • spreads via blood to liver, spleen, bone
          • re-expose Peyer patches via bile
      • "wasting disease": patients waste away
      • transmission
        • feco-oral
    • Non-typhoidal (NTS)
      • gastero-enteric symptoms
      • systemic: less frequent
  • Yersinia sp.
    • Gram negative
    • Yersinia pestis -> plague
    • type 3 secretion system
      • "syringe" on outer membrane bacteria
      • injects toxins
    • Yersinia enterocolita
      • pseudo-appendicitis
      • infects lymph node next to appendix
      • diarrhea
      • weeks later: red patches on skin
        • caused by immuno system

Listeria monocytogenes

  • transmission
    • contaminated food
      • unpasteurized milk, cheese
  • affects
    • gut
    • liver
    • spleen
    • brain (in weak an elderly)
      • meningitis
    • placenta
      • change diet when pregnant

11 Bones and joints

Osteomyelitis

  • ends of long bones
  • hematogenous: spread by blood
  • bone is "eaten"
  • take long to develop
  • pus searches way out
    • fistula
  • pathogenesis
    • high virulence / rapid onset
      • S. aureus
      • beta-hemolytic streptococcus
      • gram negatives (Salmonella)
    • low virulence / late onset
      • CNS
      • Streptococcus viridans
      • Cutibacterium acnes
      • Mycobacterium tuberculosis
        • vertebra -> spinal tuberculosis (Pott's disease)
  • often due to infected prothesis
    • biofilm

Diabetic foot

  • nerve problems
    • can't feel pain
    • patients get more lesions
  • vascular problems
    • poor wound healing
  • ulcers
  • abscess
  • gangrene
  • amputation
  • diagnosis
    • extract pus
    • antibiogram
  • treatment
    • oral AB
    • surgery

Septic arthritis

  • in joints
  • types
    • mono- (90%) vs oligoarthritis (10%)
    • iatrogenic septic arthritis
      • cortisone injections
      • often S. aureus
    • S. penumoniae
      • upper+lower airway infections
      • meningitis
      • arthritis
    • N. meningitidis
      • sepsis
      • meningitis
      • bacteriemia
      • arthritis
    • SOA-associated
      • N. gonorrhoeae
  • other, atypical arthritis
    • Lyme arthritis
      • incl. neurological signs
      • diagnosis: serology (cf. Syphilis)
    • reactive (post-infection) arthritis
      • gastro-enteritis
      • STD

In young children

  • osteomyelitis + arthritis
  • different vascularization in immature bone
  • additional bacteria
    • S. aureus
    • S. pyogenes
    • S. pneumoniae
    • S. agalactiae: < 2m
    • Kingella kingae: 6m - 2y
      • gram negative

12 Invasive, zoonotic and vector-borne

Meningitis

  • see above

Endocarditis

  • bacteria colonize a heart valve
    • fibrotic tissue
    • biofilm
  • group can break off and travel through the body
    • septic emboli
  • fever comes and goes
  • unpredictable symptoms
  • higher risk patients
    • artificial valves
    • IV drug users
  • HACEK organisms
    • properties
      • Gram negative
      • slow growth
        • incubate for 21 days instead of 2-4
      • live in oropharynx
      • cause 1.4% of endocarditis
    • Haemophilus parainfluenzae
    • Aggregatibacter actinomycetemcomitans
    • Cardiobacterium hominis
    • Eikenella corrodens
    • Kingella kingae
      • cf. septic arthritis in young children

Septic thrombophlebitis

  • definitions
    • thrombus = blood clot
    • embolus = piece of clot
  • of cavernous sinusses
    • swollen eyes, bilateral
  • associated with IV drug use

Post-partum complications

  • chorioamnionitis
    • remaining piece of placenta

Leptospirosis

  • urine of rodents
  • increasing due to climate change

Mycologie

  • eukaryoten
    • celwand
      • chitine
      • glucaan
  • Onychomycosen
    • nagels
  • Candida
  • Aspergillus
  • medicatie: imidazolen
    • o.a. itraconazol

Parasitologie

  • eukaryoten
    • geen celwand
  • symbiose
    • commensalisme
      • afhankelijkheid in 1 richting
      • geen schade
    • mutualisme
      • win-win
      • voorbeeld: darmflora
    • parasitisme
      • win-lose
  • soorten
    • obligate: kan enkel als parasiet overleven
    • facultatieve
  • complexe levenscyclus
    • gastheer
      • tussengastheer
        • larven/aseksuele fase
      • eindgastheer
        • volwassen fase
        • betere kans op overleving
    • vector
      • transmissiekanaal
      • kan tussen- en eindgastheer zijn
    • reservoir
      • drager, vaak zonder ziek te worden
  • taxonomie
    • endoparasiet: binnenkant
      • protozoa: eencellig
        • sporozoa: niet-motiele eencelligen
        • amoeben
        • flagellaten
      • metazoa: meercellig
        • wormen
          • nematoden = rondwormen
          • platwormen
            • Cestoden = lintwormen
            • Trematoden = zuigwormen of botten
    • ectoparasiet: buitenkant (op huid)
      • out of scope
      • metazoa
        • luizen
        • mijten = scabies
  • ?
    • trofozoieten: actief, voedend
    • sporozoieten: infectieus (cf. sporen)
    • (oo)cysten: cyste vorm van zygote
  • behandeling: antiparasitaire middelen - kleiner aantal - toxischer voor mens (mede-eukaryoot) - resistentie: beperkt probleem
  • diagnose
    • microscopie
      • expertise nodig
    • serologie
      • enkel bij invasieve parasieten
        • wormen: geen antistof resposne
      • enkel bij eerste infectie
        • zinloos in ontwikkelingslanden
    • moleculaire detectie
      • moeilijk
      • stijgend aantal PCR testen
    • antigen detectie (sneltesten)
    • eosinofilie (richtinggevend)
      • WBC: hoog aantal eosinofielen
  • indeling per compartiment
    • bloedparasieten
    • GI parasieten
      • meest voorkomend
    • weefselparasieten
      • invasief -> serologie test
    • ander
      • genitaal
      • urinair
      • respiratoir

Protozoa (eencelligen)

Sporozoa
Malaria
  • etymologie
    • mal-aria = slechte lucht
  • Plasmodium
    • P. falciparum
      • belangrijkste
      • zit overal
    • P. vivax
      • Azie
      • Oost-Afrika
      • Zuid-Amerika
    • P. ovale
    • P. malariae
  • bloedparasiet
  • vooral in Sub-Sahara Afrika
  • risico rond luchthavens
  • levenscyclus
    • vector: mug
    • tussengastheer: mens
      • mug injecteert sporozoioten in bloed
      • asymptomatische fase in lever
        • sporozoioten -> schizonten -> merozoieten
        • P. vivax en P. ovale: ook sluimerende hypnozoieten
          • risico op relapse jaren nadien
      • symptomatisch fase in RBC
        • merozoieten -> trofozoieten
        • voeden met Hb en glucose
        • kleverige RBC wand
          • microtromboses
        • RBC hemolyse
        • toxische metabolieten
        • merozoieten -> gametocyten (M/V)
      • mug zuigt gametocyten opnieuw op
    • eindgastheer: mug
      • gametocyten -> sporozoioten
  • kliniek
    • P. falciparum
      • incubatie: 8-25d
      • koorts, braken, diarree, hoofdpijn, spierpijn, ...
      • nooit chronisch
      • ernstige vorm
        • microtromboses
          • neurale impact
          • nierfalen
            • zwart water koorts (afbraak Hb)
        • anemie
        • hypoglycemie
        • leverfalen
    • andere P. soorten
      • koorts in patronen
      • soms chronisch
      • langere incubatie
      • minder ernstig
        • vivax > ovale > malariae
  • immuniteit
    • slachtoffers: vooral kinderen en zwangere vrouwen
    • na meerdere infecties: eerder griep-achtig
      • transient, verdwijnt na paar jaar
  • hematologische afwijkingen: overlevingsvoordeel
    • Sikkelcel anemie
    • Thalassemie
    • G6PD deficientie
    • Duffy neg bloedgroep (?)
  • diagnose
    • microscopie van dikdruppel bloed
      • P. falciparum
        • "koptelefoon" in RBC
        • banaanvormige gametocyten
      • P. malariae
        • bandvormige patronen in RBC
    • sneltest (antigen)
      • hoge sensitiviteit
      • enkel voor P. falciparum
    • serologie (antistoffen)
      • beperkt gebruikt - enkel referentielabo's
  • preventie
    • bed nets = klamboe
    • profylaxe
      • medicatie
        • Atovaquone/proguanil
    • vaccin
      • enkel voor locals, niet voor reizigers
      • RTS,S vaccin
        • lage effectiviteit
        • boosters nodig
      • R21/matrix M vaccin
        • al beter
        • boosters nodig
  • behandeling
    • Chloroquine
      • resistentie bij P. falciparum
    • Artemisine-combinatie therapie (ACT)
    • primaquine tegen hypnozoieten bij P. vivax/ovale
Toxoplasmose
  • weefselparasiet
  • wereldwijd
  • milde ziekte
    • gevaar bij zwangerschap: moeder -> foetus
      • vroeger = ernstiger
      • klassieke triade (zeldzaam)
        • chorioretinitis
        • hydrocephalus
        • intracraniele calcificaties
  • lifecycle
    • tussengastheer: varia
      • oocyste -> tachyzoiet -> bradyzoiet
    • eindgastheer: kat
      • oocysten in faeces
  • transmissie
    • ingestie
      • onvoldoende doorbakken vlees
      • oocysten uit omgeving (moestuin, ...)
    • orgaantransplantatie
  • kliniek
    • vaak asymptomatisch
    • heropflakkering bij verzwakt immuunsysteem (HIV)
  • diagnose
    • serologie (IgG, IgM)
      • IgG aviditeit (affiniteit voor antigen)
        • laag -> recente infectie
        • hoog -> langer geleden (> 4m)
    • PCR
      • bloed
      • vruchtwater
      • CSF
      • voorkamervocht oog
Cryptosporidium
  • GI parasiet
  • C. parvum
  • C. hominis
  • enteritis
    • diarree
  • transmissie
    • feca-oraal
      • water met oocysten
  • lifecycle
    • oocysten
    • sporozoieten
    • trofozoieten
    • merozoieten
    • gametocyten
    • oocysten
  • diagnose
    • microscopie met speciale kleuring
    • PCR
    • antigen
  • behandeling
    • bij gezonde mensen: geen
    • HIV: HAART tegen HIV zelf
Amoeben - Entamoeba histolytica
  • GI- en weefselparasiet
  • transmissie: feco-oraal
  • invasieve enteritis
  • leverabces
    • meestal eerder microbieel
      • Klebsiella pneumoniae
      • polymicrobieel
    • of andere parasieten
  • behandeling: AB > metronidazole (7-10d)
    • standaard bij elk leverabces
  • diagnostiek
    • serologie
    • faeces
      • microsocopie
      • PCR
    • leveraspiraat
      • PCR
Flagellaten
Giardia lamblia
  • GI parasiet
  • vooral bij slechte hygiene
  • transmissie: feco-oraal
  • milde symptomen
  • diagnostiek
    • microscopie
    • antigen op faeces
    • PCR
  • behandeling
    • AB > metronidazole
Trichomonas vaginalis
  • genitaal
  • SOA
    • geen cystevorm
  • incubatie: 5-28 dagen
  • symptomen
    • vooral bij vrouwen
    • witverlies, geur, jeuk
    • urethritis
    • prostatitis
  • diagnose
    • micro
    • PCR
    • antigen
  • behandeling
    • AB > metronidazole
Trypanosoma brucei
  • slaapziekte
    • vooral in SS Afrika
  • bloedparasiet
  • lifecycle
    • vector: tseetsee vlieg (Glossina sp.)
    • reservoir: vee
    • tussengastheer: mens
    • eindgastheer: tseetsee vlieg
  • types
    • gambiense (97%)
      • C-/W-Afrika
      • vector: Glossina palpalis
      • chronisch
    • rhodesiense (3%)
      • O-/Z-Afrika
      • vector: Glossina morsitans
  • symptomen
    • eerste fase
      • "vervelend"
    • tweede fase
      • gambiense veel trager dan rhodesiense
      • zware neurologische symptomen
        • andere persoonlijkheid
      • mortaliteit (zonder medicatie): 100%
  • diagnose
    • microscoop
    • serologie
      • screeningsprogramma's
        • doel: eradicatie
  • behandeling
    • afhankelijk per fase en per type
    • zeer toxisch

Metazoa (meercelligen)

Platwormen
Trematoden (zuigwormen of botten)
  • GI parasiet
  • Schistosomiase
    • zwemmen in zoet water in tropisch gebied
      • Lake Malawi
      • recent ook al in Corsica
    • lifecycle
      • tussengastheer: zoetwaterslak
      • eindgastheer: mens?
    • huid -> bloed -> veneuze plexus (lever/blaas) -> stoelgang/urine
    • milde symptomen
      • swimmer's itch
      • vooral ontsteking rond verdwaalde eitjes
    • diagnostiek
      • serologie: eosinofielen
Cestoden (lintwormen)
  • GI parasiet
  • Taenia infecties – cysticercosis
    • 4-10m
    • transmissie: weefselcystes in voeding
      • risico bij rauw vlees
    • lifecycle
      • tussengastheer: koe/varken/mens
        • larven -> weefsel -> cyste
          • spieren
          • ogen
          • neuro (!)
            • hersenen
              • epilepsie
            • ruggenmerg
      • eindgastheer: mens
    • types
      • Taenia saginata = runderlintworm
      • Taenia solium = varkenslintworm
        • uitgeroeid in Belgie
        • enkel hier mens als tussengastheer
    • symptomen
      • mild
      • bij tussengastheer
        • cysticercus / cysticerose
      • bij eindgastheer
        • vermagering
    • diagnose
      • microscopie faeces
        • eieren
        • stukjes worm (proglottides)
Nematoden (rondwormen)
  • GI parasiet
Enterobius vermicularis (aarsworm)
  • ook in Belgie
  • transmissie: feco-oraal
  • geen tussengastheer nodig
  • symptomen
    • jeuk door eitjes aan anusrand
      • onder vingernagels -> mond -> auto-infectie
  • diagnose: tape test
    • plakband rond anus
    • plakband in petri schaal
    • bekijk onder microscoop
  • behandeling
    • Mebendazole
Ascaris lumbricoides (spoelworm)
  • minder belangrijk
  • 1B besmettingen
  • transmissie: feco-oraal
  • lifecycle
    • tussengastheer: mens
    • eindgastheer: ook mens
    • larven naar long
    • hoesten: long -> dunne darm
  • milde symptomen
  • eitjes moeten rijpen in omgeving
    • geen auto-infectie
Strongyloides stercoralis
  • minder belangrijk
  • iets ernstiger
  • auto-infectie
  • blote voeten -> huid -> bloed -> longen -> GI
  • diagnose
    • micro
    • serologie
    • PCR