Microbiology Flashcards
1
Q
Acid Fast
A
Thick waxy walls
Peptidoglycan base layer
Additional layers of arabinogalactan, mycolic acid, and lipid
Slow bacterial growth
2
Q
Adenovirus
A
dsDNA No envelope Icosahedral capsid Decrease MHC-I expression (bind in ER) Small RNA prevent PKR Cytokine interference
DISEASES: Pharyngoconjunctival fever Pneumonia Intestinal illness (mesenteric adenitis, intussusceptoins) Hepatitis Conjunctivitis - pink eye Haemorrhagic Cyctitis
TREATMENT:
Ribavirin
Cidofovir
3
Q
Coronavirus
A
ssRNA +
Envelope
Helical capsid
DISEASES: Common cold Gastroenteritis Severe acute respiratory syndrome (SARS) Severe LRTI Encephalitis (via olfactory bulb)
TREATMENT:
No treatment
4
Q
Hepatitis A
A
Picornavirus ssRNA + No envelope Icosahedral capsid Single serotype worldwide
DISEASES:
Incubation 15-30 days
Symptoms 2-3 weeks
Hepatitis (jaundice, pale faeces, dark urine)
TREATMENT:
Normal IgG response
Inactivated Vaccine
5
Q
Hepatitis B
A
dsDNA (circle, gapped)
Envelope
Icosahedral capsid
DISEASES: Incubation 60-90days Acute (adults) and chronic (children) hepatitis can be acquired by child at time of delivery (maternal blood) Cirrhosis Hepatocellular carcinoma Acute: HbsAg, anti-HBc IgM, Chronic: HbsAg, anti-HBc IgG
TREATMENT:
Interferon alpha for HBeAg +ve carriers
Nucleoside/Nucleotide analogues (Lamivudine or Adefovir)
Vaccination + Hep B Ig
6
Q
Hepatitis D
A
ssRNA
Envelope
Heterogeneous satellite capsid
Requires Hep B to provide envelope proteins
DISEASES:
Acute and chronic hepatitis
Cirrhosis
TREATMENT:
Treat hep B
7
Q
Hepatitis C
A
Flavivirus ssRNA + Envelope Icosahedral capsid High genomic deversity
DISEASES:
Incubation 6-7weeks
Acute and chronic hepatitis
Cirrhosis
TREATMENT:
OLD: Peg-INFalpha + Ribavirin
NEW: RNA polymerase inhibitors, Protease inhibitors (Simeprevir) = curative
8
Q
Hepatitis E
A
ssRNA + No Envelope Icosahedral capsid Spread by enteric-oral route Fatality 15%-25% pregnant women
DISEASES:
Sporadic acute hepatitis
Incubation 40 days
TREATMENT:
Supportive
9
Q
Bacillus anthracis
A
Gram-positive Rods Endospore-forming Aerobic Has protein capsule (polypeptide) Environmental (soil)
DIAGNOSIS:
PCR
Fluroescent antibody stain
DISEASES:
Anthrax
TREATMENT:
β-lactam antibiotics (penicillin)
Fluroquinolones (ciprofloxacin)
Tetracycline (doxycycline)
10
Q
Candida albicans
A
Diploid Fungus
Yeast
Opportunistic pathogen (immunosuppressed)
Part of normal skin, mouth, intestine flora
Typically invades mucosal surfaces (white discharge and growth)
DIAGNOSIS:
Culture on SDA
Germ tubes (pseudohyphae) visible on microscopy
DISEASES:
Candidiasis (mucocutaneous, chronic, systemic)
Thrush
TREATMENT:
Topical antifungals (nystatin, miconazole)
Fluconazole for disseminated disease
11
Q
Clostridium perfingens
A
Gram Positive Rods Strict anaerobe Spore forming Normally found in environment and GI tract
DIAGNOSIS:
Haemolytic on HBA
Naglers test positive
Degrades litmus milk
DISEASES:
Gas Gangrene
Food poisoning
TREATMENT:
Wound debridement and cleaning
Penicillin prophylaxis (or metronidazle, imipenem)
Hyperbaric oxygen
12
Q
Enterococcus faecium
A
Gram Positive Cocci (diplococci and chains) Facultative anaerobe Heat & Salt tolerant GIT commensals
DIAGNOSIS:
Alpha haemolytic
Optochin resistant
DISEASES:
Urinary Tract Infection
Endocarditis
Septacaemia (following surgery and immunocompromisation)
TREATMENT:
Resistant to cephalosporins
Vancomycin Resistant Enterococcus (VRE)
Linezolid or daptomycin for VRE
13
Q
Escherichia coli
A
Gram Negative Rods Facultative anaerobe Motile (some strains) Some capsulated Normal gut flora
DIAGNOSIS: Lactose fermenter Grows on bile-containing selective media DISEASES: Urinary Tract Infection Diarrhoea Neonatal meningitic Septacaemia
TREATMENT: Antibiotic sensitivities vary widely (often plasmid mediated) Use susceptibility testing Amoxicillin Cephalosporins Amioglycosides
14
Q
Gram Negative Cell Wall
A
PINK
Outer membrane stabalised by Lipopolysaccharide (PAMP / endotoxin)
Has periplasmic space with peptidoglycan wall
15
Q
Gram Positive Cell Wall
A
PURPLE
Large amount of peptidoglycan and teichoic acids
peptidoglycan made of n-acetyl-glucosamine and n-acetal-muramic acid joined by pentapeptide bridges
16
Q
Haemophilus influenzae
A
Gram Negative
Rods (coccobacilli) - very very tiny
Facultative anaerobe
May have capsule (polysaccharide)
DIAGNOSIS: Catalase positive Oxidase positive Latex agglutination X+V growth (grows on CHA not HBA)
DISEASES: Otitis media!! URTI & LRTI Adult Meningitis!! Epiglottitis (Type B) Osteomyelitis Chronic bronchitis Grey/creamy expectorate with wheeze and cough
TREATMENT: Penicillin resistant Ampicillin (if susceptible) Cephalosporins (cefotaxime, ceftriaxone) Rifampicin Fluroquinolones
17
Q
Klebsiella pneumonia
A
Gram negative Rods Non-motile Facultative Anaerobe Has capsule Normal flora of skin and GI. Opportunistic pathogen
DIAGNOSIS:
Lactose fermenter
Bile tolerant
Oxidase Negative
DISEASES:
Urinary tract infections
Respiratory tract infections
TREATMENT:
Surgical clearing
Ampicillin (and other antibiotics)
Multiple antibiotic resistances (usually plasmid mediated)
Susceptibility testing generally required
18
Q
Myocbacterium tuberculosis
A
Gram Positive - Acid Fast (thick waxy walls – mycolic acid) Rods Highly aerobic Slow growing Infect respiratory system
DIAGNOSIS:
Ziehl-Neelsen Stain
PCR
DISEASE:
Tuberculosis
(esp. AIDS & immunocompromised)
TREATMENT:
Combination of antimycobacterial drugs
19
Q
Neisseria (gonorrhoeae & meningitidis)
A
Gram Negative
Cocci (diplococci - often intracellular)
N. meningitis has capsule
Complement immunity (MAC) important
Gonnorrhoea typically asymptomatic (80% of females)
Gonnorrhoea likes to grow in columnar epithelium
DIAGNOSIS: Extremely fastidious (rich growth medium needed) Growth on CHA Cervical swab in charcoal GNC visible inside WBCs Thayer Martin Agar growth
DISEASES: meningitis septicaemia (rash) Gonorrhoea (2-7 day incubation) Pelvic inflammatory disease Chlamydia co-infection common Neonatal gonococcal opthalmia
TREATMENT:
Highly antibiotic resistant (freely shares genes)
Penicillin
Ceftriaxone (third generation cephalosporin)
+ azithromycin
20
Q
Pseudomonas aeruginosa
A
Gram Negative Rod Has capsule Aerobic (or facultative) Motile (flagella, pili) Environmental (soil, skin, gut flora) Produces endotoxin A (LPS) - block protein synthesis Oportunistic pathogen Produces biofilm after quorum-sensing (slows growth, loses O-antigen, less invasive, more adherent, non-motile, increased resistance due to slowed growth and biofilm)
DIAGNOSIS: Lactose non-fermenter Clear colonies on MAC Catalase & Oxidase positive Blue-green pigment Growth on Citrimide
DISEASES: Pneumonia Sepsis External otitis (swimmers ear) UTI Skin and burns (post) Cystic Fibrosis infections (deadly) (LPS usuall binds to CFTR) Urinary tract infections Endocarditis
TREATMENT: Heavy resistance (chromosomal β-lactamase & acquired from other bacteria) – need to test Beta-lactam + Aminoglycoside Ticarcillin & Tobramycin Prevention!! - hand hygiene
21
Q
Rotavirus
A
dsRNA (segmented)
No envelope
Icosahedral triple/double capsid
uses trypsin (in gut) to shed outer layers so virus has access to receptors
DISEASES
Diarrhoea
Gastroenteritis
Dehydration (death)
TREATMENT:
Supportive
Vaccination
22
Q
Salmonella (enterica & typhi)
A
Gram Negative
Rods
Motile
Facultative anaerobes
From food chain (poultry, eggs, milk, meat)
Invade sub-mucosa or systemic
Typhi survive within macrophages (migrate via lymph to liver/spleen/bone/intestine)
patients deficient in IFN-gamma are susceptible to infection (latent liver/bone infections)
DIAGNOSIS: Non-lactose fermenting Oxidase negative Growth on MAC (white/clear colonies) Growth on DCA O,H antigens Vi antigen (S. typhi & paratyphi)
DISEASES:
Diarrhoea
Septacaemia (S. typhi)
Anaemia w/ slight splenomegaly (S. typhi)
Intestinal haemorrhage (late stage S. typhi)
Typhoid fever (S. typhi)
S. typhi induces apoptosis of macrophages (can hide inside them)
TREATMENT:
Susceptibility tests (antibiotics)
Antibiotic resistance is increasing
Ciprofloxacin
23
Q
Shigella
A
Gram Negative Rods Facultative Anaerobe 4 species (dysenteriae, flexneri, boydii, sonnei) Closely related to salmonella. same species as E.Coli Humans only reservoirs
DIAGNOSIS:
Negative motility
Non-lactose fermenting,
Growth on Mac (white/clear colonies)
DISEASES: Causes dysentery (intestinal infection) Presence of blood in faeces Induces macrophage apoptosis S. dysenteriae has shiga toxin
TREATMENT:
Ampicillin, fluroquinolones (e.g. ciprofloxacin)
Some Shigella resistant to antibiotics so administer sparingly
24
Q
Staphylococcus aureus
A
Gram Positive Cocci (grapelike clusters) Facultative anaerobe Some capsulated Normal flora of skin, upper respiratory tract & pathogen (gastroenteritis, sinusitis, skin infections) TSStoxin - binds MHCII Primary defense is innate (via neutrophils) Adaptive immune response is weak
DIAGNOSIS:
“golden staph” – white or yellow colonies on HBA
b-Hemolysis when grown on HBA
Catalase positive (produces catalase enzyme – converts H2O2 to water and oxygen)
Coagulase positive (fibrin clot formation)
Ferments mannitol anaerobically
DISEASES: Skin infection Pneumonia Toxic Shock Syndrome Endocarditis Osteomyelitis Post-op wound infection Catheter associated infection Gastroenteritis (ingested heat stable toxin - food poisoning 2-6hr incubation) UTI (kidney abcess via blood)
TREATMENT:
Penicillin (may be resistant due to β-lactams)
Flucloxacillin (for penicillin resistant bacteria)
Combination with gentamicin (may cause kidney damage)
Aminoglycosides not effective
Possible methicillin and vancomycin reisistance
25
Staphylococcus epidermidis
Gram Positive
Cocci
Opportunistic (part of normal human skin flora and some mucosal)
Facultative anaerobe
Infection associated with device-related sepsis (forms biofilms well)
DIAGNOSIS:
Forms white colonies on HBA
Non-haemolytic
Catalase positive (produces catalase enzyme)
Coagulase negative
Lactose fermenter
Novobiocin sensitive (otherwise its S. saprophyticus)
```
DISEASES:
Wound infections (can produce biofilms) - IV catheters
```
TREATMENT:
Often resistant to penicillin, amoxicillin, and methicillin
Vancomycin with aminoglycoside (gentamicin) are drugs of choice
Treat for a long time due to biofilm
26
Streptococcus pneumoniae
Gram Positive
Cocci (diplococci)
Pyogenic
Polysaccharide capsule
Normal flora of mouth & respiratory tract, may cause HCAIs involving neutropaenia or humoral immune defects (encapsulated)
Naturally transformable (takes up DNA easily)
Modified penicillin-binding proteins are the basis for penicillin resistance (not penicillinase)
```
DIAGNOSIS:
Alpha-haemolytic (greening)
Capsule may present as 'halo' on gram stain
Facultative Anaerobe
Catalase negative
Optochin susceptible
```
```
DISEASES:
Pneumonia (typically lobar)
Septacaemia
Meningitis
Otitis media
```
TREATMENT:
Penicillin
Vancomycin (if resistant to penicillin, quinolones, tetracyclines, and cephalosporins)
Pneumococcal conjugate vaccine
27
Streptococcus pyogenes
Gram Positive
Cocci (chains)
Group A Strep (group A antigen on cell wall)
Normal flora of skin, mouth and pharynx (strep throat) & pathogen (gastroenteritis)
Pyogenic
Has capsule (hyalurinoc acid) - not antigenic
```
DIAGNOSIS:
Beta haemolytic
Catalase negative
Facultative anaerobe
Bacitracin sensitive
No growth on MAC
```
DISEASES:
URTI
Skin, throat, and soft tissue infection (pharyngitis, cellulitis, lymphadenitis)
Scarlet fever, necrotizing fasciitis ('flesh eating')
Rheumatic Fever (M-proteins)
Glomerulonephritis (Type III hypersensitivity)
Septacaemia
Osteomyelitis
Toxic Shock Syndrome
TREATMENT:
Penicillin (long term due to likelyhood of reinfection)
Tetracyclines, cehpalosporin (cefotaxime), or vancomycin/genatmicin
Hygiene
(NB: Strep agalactiae similar - causes neonatal meningitis but also grows on MAC and is bacitracin resistant)
28
Yersinia pestis
Gram Negative
Rods
Facultative anaerobe
DIAGNOSIS:
Lactose non-fermenting (MAC white colonies)
Immunofluorescence
Growth on CIN agar
DISEASES:
Bubonic plague
Induce macrophage apoptosis
Invasive pathogen (gastroenteritis and infects mesenteric lymph nodes - haemorrhagic and necrotic lesions)
Reiter’s syndrome - arthritisi/urethriris/conjunctivitis following GI infection
```
TREATMENT:
Streptomycin
Tetracycline
Fluroquinolones
Doxycycline
Gentamicin
```
29
Influenza Virus
ssRNA -
Envelope
Helical capsid
Antigenic Drift
PATHOGENESIS:
Haemagglutinin attaches to sialic-acid receptors (alpha2-6)
Endocytosis
H+ causes confirmational change (via M2)
Replication
Budding
Neuraminidase cleaves sialic-acid from glycoproteins
Tryptase clara activates HA (becomes infectious)
If uncleared can move down airways (lead to secondary bacterial infection)
```
DISEASES:
Influenza (1-5 day incubation, 5-6 infectious)
Fever
Malaise & loss of appetite
Sore Throat
Cough
Pneumonia
```
TREATMENT:
Zanamivir (neurominidase inhibitor)
Amantidine/Rimantadine (M2 ion channel block)
Vaccination
30
Papillomavirus
dsDNA
No envelope
Icosahedral capsid
DISEASES:
Warts (sexually transmitted)
Carcinoma (cervix)
TREATMENT:
Freezing
Lazer
Cidofovir
31
Measles
```
Paramyxovirus
ssRNA -
Envelope
Helical capsid
Interferes with surface proteins (prevent T cell activation)
```
PATHOGENESIS
Respiratory, infects local macrophages & lymphocytes (Koplick spots), drains to LN and amplifies (spleen/liver), returns to lung and mouth.
```
DISEASES:
Fever
Nasal discharge
Rash
Subacute Sclerosing PanEncephalitis (SSPE) - slow growth between neural cells over 30 years (no budding) - (via blood)
```
TREATMENT:
Vaccination
32
Mumps
Paramyxovirus
ssRNA -
Envelope
Helical capsid
DISEASES:
Parotitis (salivary gland inflammation)
Aseptic Meningitis (via blood)
Incubation: 12-25days
TREATMENT:
Vaccination
33
Respiratory Syncytial Virus (RSV)
```
Paramyxovirus
ssRNA -
Envelope
Helical capsid
Decrease MCH-I expression
```
```
DISEASES:
Common cold
Bronchiolitis
Pneumonia
Incubation: 2-8 days
```
TREATMENT:
Aerosolized ribavirin
34
Parvovirus
```
ssDNA
No envelope
Icosahedral capsid
Incubation period 4-21 days
shortens lifespan of RBC progenitors in bone marrow
```
DISEASES:
Erythmea
Slap-cheek rash
Fever
Arthopathy/arthralgia (joint inflammation)
Acute aplastic crisis (chronic haemolytic anaemia)
Fetal Death (febrile convulsions) - due to RBC destruction
Hydrops foetalis
TREATMENT:
Intravenous IgG
35
Enterovirus
```
Include Coxsackie, Echo, Polio
Fecal-oral transmission
Picornavirus
ssRNA +
No envelope
Icosahedral capsid
Replicate in pharynx and GIT
```
DISEASES:
Aseptic meningitis
Rashes
36
Poliovirus
```
Picornavirus
ssRNA +
No envelope - lyses cells
Icosahedral capsid (hardy - enterovirus)
Low Neuroinvasiveness
High Neurovirulence
```
```
PATHOGENESIS:
Gut lymphoid tissue invasion
Migration to regional lymph
Viremia
Crosses BBB (8-12 days)
Replicates in anterior horn cells (has receptor)
Excreted in faeces (5-45 days)
```
DISEASES:
Aseptic meningitis (via blood)
Paralytic poliomyelitis
TREATMENT:
Vaccination (Sabin, Salk)
37
HIV
```
ssRNA +
Retroviridae
Envelope
Icosahedral capsid
Antigenic Drift
Decrease MHC-I expression
```
```
PATHOGENESIS
Binds to CXCR4 and CCR5
dsDNA integrated to host DNA
replicated in nucleus
assembles and buds at plasma membrane
```
```
DISEASES:
Mononucleosis
Aseptic Meningitis (via blood/monocytes)
AIDS -> Encephalitis -> Dementia
Weight loss
```
TREATMENT
Zidovudine, tenofovir and nevirapine:
nucleoside nucleotide, and non-nucleoside reverse transcriptase inhibitors.
Control maternal disease & lower viral load
38
Rhabdovirus
```
ssRNA -
Envelope
Helical capsid
Obligatory nerve cell growth
Highly Neuroinvasive
HIghly Neurovirulent
```
```
PATHOGENESIS:
puncture wound
replicates in myocytes
retrograde travel via axonal fibres
replicates in spinal neurons
retrograde to brain & salivary glands (acinar)
```
```
DISEASES:
Rabies (incubation 12-70days)
Meningitis/Encephalitis (via axons)
Aggression
Thirst
Seisures
Paralysis
Coma
Death
```
TREATMENT
Human rabies specific
Vaccination during window of opportunity (cell mediated immunity takes approx 10 days)
39
Rubella
```
Togavirus
ssRNA +
Envelope
Icosahedral capsid
25-50% asymptomatic
spread in nasopharyngeal secretions
inbubation 14-21 days
```
```
DISEASES:
Mild rash (face, trunk, limbs)
low grade fever
lymphadenopathy (behind ears and neck)
rash
Congenital rubella syndrome (slows down rate of cell division causing microcephaly, patent ductus arteriosus, cataracts, deafness, neurological, IDDM, thrombocytopaenia, etc.)
```
TREATMENT:
Vaccination
40
Corynebacterium diphtheriae
Gram Positive
Rods
Facultative anaerobe
DIAGNOSIS:
Catalase positive
PCR
DISEASES:
Diphtheria (throat or skin)
TREATMENT:
Antitoxin
Penicillin
Immunization
41
Clostridium tetani
```
Gram Positive
Rods
Spore forming
Strict Anaerobe
Environmental (soil)
```
DIAGNOSIS:
Ground glass appearance on HBA
DISEASES:
Tetanus (lockjaw)
Muscle spasms / convulsions
```
TREATMENT:
Anti-toxin
Metronidazole
Anti spasmolytic drugs
Immunization with toxoid
```
42
Clostridium botulinum
Gram Positive
Rods
Spore forming
Strict anaerobic
DISEASES:
Botulism - inhibit ACh release.
Muscle paralysis and respiratory failure.
Typically due to ingestion of preformed toxin
TREATMENT:
Trivalent antitoxin
Penicillin and metronidazole for wounds
43
Legionella pneumophilia
Gram Negative
Rod
Aerobic
Lives in air-conditioning systems
DISEASES:
Legionnaires (atypical pneumonia)
TREATMENT:
Fluroquinolone
44
Pneumocystis JirovecIi (Carinii)
Fungus (originally classified as protazoa)
Lives extracellularly within alveoli
AIDS defining pathogen (pneumocystis pneumonia)
DISEASE:
Pneumonia-like (diffuse interstitial)
TREATMENT:
Co-trimoxazole
45
Coxsackie Virus
Picornavirus
ssRNA+
No envelope
Icosahedral capsid
```
DISEASES:
Aseptic Meningitis (via blood)
Encephalitis
Herpangina
Myopericarditis
Hand-foot-mouth disease
```
46
Rhinovirus
Picornavirus
ssRNA+
No envelope
Icosahedral capsid
DISEASES:
Common cold
Optimal growth at 33deg (URT)
47
Atypical pneumonia causative agents and clinical signs
Mycoplasma, coxiella, chlamydia pneumoniae, legionella
no cough, no mucus, no sputum, no abcesses, no consolidation
infection in INTERSTITUM (macrophages, lymphocytes, plasma cells)
Systemic symptoms predominate over respiratory
Walking patient CXR shows pneumonia
48
Acute pneumonia causative agents and clinical signs
Strep pneumoniae, H, influenzae, S. aureus, Klebsiella, Legionella
Inflammation in AIRWAYS
Acutely ill, high fever, evidence of consolidation, productive cough
49
Mycoplasma pneumoniae
No cell wall
DISEASES:
Atypical pneumonia
TREATMENT:
Doxycycline
Erythromycin
beta-lactams useless due to no cell wall
50
Protein Kinase R
Stimulated by IFN
requires viral RNA to help autophosphorylate
inactivates translational enzymes
51
Viral Immune Evasion
Antigenic Drift - Inflenza, HIV
Latency - HSV in neurones, EBV in B cells (inhibits proteosome)
Decrease MHC I - HIV, RSV, adenovirus (bind in ER)
(PKR) Small RNA - adenovirus, EBV
(PKR) RNA protection - reovirus, vaccinia
(PKR) eIF2a homologue - vaccinia
Cytokine production block - vaccinia, cowpox
Cytokine interference - adenovirus
TLR signal transduction - HSV
TAP block - HSV, CMV
TLR4 homologue - vaccinia
Surface Protein interference (TCell activation) - measles, CMV
MHC I homologue - CMV (inhibit death signal from NK)
52
Which sense RNA must bring its own RNA polymerase?
Negative
53
Diarrhoea Syndromes #1
1. Non-specific gastro
2. Dysentery
3. Foodborne
4. Travellers' diarrhoea
1. Viruses, bacteria protozoa
2. Shigella, EIEC, protazoa
3. S. Aureus, Salmonella, C. Perfringens, Bacillus, Vibrio, Listeria, viruses.
4. ETEC, other bacteria, viruses, protazoa
54
Diarrhoea Syndromes #2
1. Antibiotic associated colitis
2. Haemorrhagic colitis (blood no pus)
3. Cholera-like (severe watery)
4. Enteric fever (systemic infections)
1. C. Difficle
2. EHEC
3. Vibrio Cholerae, ETEC
4. Salmonella Thyphi, S. Paratyphi
55
ETEC
```
Enterotoxigenic
Colonisation factor antigen (adhesin in small bowel)
enterotoxins (LT/ST)
- heat stable
- heat labile (similar to cholera toxin)
Adhere to microvilli (CFA)
```
Symptoms:
Cholera-like: watery diarrhoea (Travellers)
Epidemiology:
infants in LDCs, travellers
56
EPEC
Enteropathogenic
intimin, Bfp
T3SS (intimin&TIR)
Destroy microvilli
Symptoms:
non-specific gastro
Epidemiology:
Children in LDCs
57
EHEC
Enterohaemorrhagic
intimin, Efa
Shiga toxins (interfere with protein synthesis)
Does not ferment sorbitol (unlike other E.coli)
Symptoms:
bloody diarrhoea
Shiga toxin cause HUS
```
Epidemiology:
any age (developed countries)
```
58
EIEC
Enteroinvasive
- Shigella-like but does not have shiga-toxin so does not cause haemolytic uraemic syndrome or haemorrhagic colitis
Symptoms:
dysentery (similar shigella dysenterae)
```
Epidemiology:
any age (mainly LDCs)
```
59
EAEC
Enteroaggregative
Symptoms:
watery diarrhoea
Epidemiology:
Children in LDCs
60
Parasite Definitions
- Definitive Host
- Intermediate Host
- Paratenic Host
- Reservoir Host
Definitive Host
- host in which the parasite REACHES SEXUAL MATURITY
Intermediate Host
- host in which DEVELOPMENT OCCURS but parasite does not reach sexual maturity
Paratenic Host
- host in which parasite enters the body and does not undergo development but REMAINS INFECTIVE
Reservoir Host
- ANIMAL HOST for parasite that also INFECTS HUMANS
61
Lice
| Pediculus humanis, P. capitis, Phthirus pubis
Obligate blood sucking parasite
P. humanis - body louse, clothing spread
P. capitis - head louse, contact spread
P. pubis - 'crabs', contact spread
SYMPTOMS: itch, macules, 2nd degree infection
DIAGNOSIS: detection of eggs
TREATMENT: topical insecticides
SIGNIFICANCE: vector of rickettsia and spirochetes
62
Mites (Sarcoptes scabei)
Live in tunnels in epidermis (fingerwebs etc.)
Lifecycle on single host
Contact spread
SYMPTOMS: itch, dermatitis, crusting (in immunosuppressed patients)
DIAGNOSIS: detection of mite in scrapings
TREATMENT: Ivermectin, topicals
CONTROL: sterilize clothes/bedding
63
Ticks (Ixodes holocyclus)
Major infectious vector (bacteria, virus, rickettsia)
Some cause paralysis ( Guillian-Barre like neurotoxin)
Spread lime disease outside of Australia
SYMPTOMS: rapid ascending paralysis
64
Entamoeba histolytica
Amoeba
Invades tissues in colon
Fecal-oral transmission
May cause liver / brain abscess (migration through colon wall)
Commensal or pathogen (ingests red cells)
DISEASES
Cause amoebic dysentery (large watery volume, very dehydrating)
DIAGNOSIS: faecal cysts, serology
```
TREATMENT: metronidazole + paromomycin
reinfection common (low immune response)
```
65
Giardia intestinalis/lamblia
```
Flagellate, primitave eukaryote
Faecal-oral transmission
Zoonotic (possums)
Asymtomatic
lives in duodenum as trophozoite
```
SYMPTOMS: diarrhoea (acute to chronic), bloating, flatulence
DIAGNOSIS: cysts in faeces
TREATMENT: tinidazole
reinfection common (low immune response)
66
Toxoplasma gondii
Obligate intracellular parasite (protozoan)
Primarily in cats & birds (infects all mammals)
Humans intermediate host (becomes cysts)
Infection persists for life
Can form cysts (organ transplant complications)
Congenital infection can be serious (rash, LN, hydrocephalus) - 70/80% asymptomatic at birth
SYMPTOMS: asymptomatic, CNS lesions, muscle cysts, occular disease in HIV
DIAGNOSIS: serology (screen pregnant)
TREATMENT: bactrim
CONTROL: cook food, avoid cats
67
Enterobius vermicularis
```
Pinworm (nematode)
Highly contagious
1cm long
female lays eggs outside of anus at night
(transferred to fingers / faeces)
```
SYMPTOMS: perianal itch
DIAGNOSIS: stickytape test
TREATMENT: antihelminthic
reinfection common (low immune response)
68
Ascaris lumbricoides
Large intestinal roundworm (30-40cm)
Female lays 200,000 eggs per day
Embryonisation occurs in soil
FO route w/ fertalized egg (double layered)
Migrate from intestines to lungs (mature) and down oesophegus
Approx 2-3months from ingestion to oviposition
Adult can live 1-2 years
```
SYMPTOMS: GI obstruction, cholecystis, pneumonitis (possibly asthma-like), anaemia (loss of iron & protein)
DIAGNOSIS: eggs in faeces, obstruction imaging
TREATMENT: antihelminthic (benzimidazoles)
reinfection common (low immune response)
```
* hookworms similar but less complications
* Ancylostoma duodenale, Necator americanus
* penetrate through skin (can cause local itching
69
Strongyloides stercoralis
```
Nematode
>100m infections worldwide (esp. Vietnam Vets)
Penetration of skin (usually feet)
Migrate via circulatory system
Bronchotracheal migration (causes pathology)
Live in small intestine epithelium
Female lays 50 ova/day
Embryonisation in colon
Produce eggs (hatch rapidly)
Autoinfection or larvae passed in stool
```
SYMPTOMS: migration may bring gram negative bacteria from gut (GN hyperinfection)
DIAGNOSIS: eggs in faeces, serology
TREATMENT: antihelminthic (ivermectin)
reinfection common (low immune response)
70
Schistosoma mansonii
Fluke causing bilharzia
Lives in intestinal veins
transmitted by fresh water snails (penetrates skin)
SYMPTOMS: swimmers itch, hepatomegaly, splenomegaly, portal hypertension, pulmonary fibrosis
DIAGNOSIS: eggs in faeces, serology
TREATMENTS: antihelmintic
IMMUNITY: persistent (re)infections and immune evasion
71
Echinococcus granulosus
Tapeworm
Zoonotic (sheeps, dogs)
Humans are accidental intermediate host (but don't produce viable eggs)
Larval cysts known as HYDATID cysts (liver, lungs)
DIAGNOSIS: imaging, serology
TREATMENTS: surgery, PAIR (puncture, aspirate, inject, reaspirate), antihelmintics
IMMUNITY: vaccination (livestock) induces protection against egg infection
72
Taenia saginta & solium
Tapeworm causing neurocystercercosis
Zoonotic (pork)
Humans can be both definitive and intermediate hosts
10m long, 300,000 eggs/day
T. solium forms cysts in subcutaneous and neural tissues
SYMPTOMS: cysts, epileptic foci
DIAGNOSIS: serology, imaging
TREATMENTS: antihelmintics (caution) - cyst breakdown can cause systemic immune response & seizure
73
Helicobacter pylori
GNR
Catalase, Oxidase, Urease positive
Breaks down urea in food products to amonia
74
Main GI Bacteria
Bacteroidetes (Bacteroides, Prevotella)
Firmicutes (Clostridia, Ruminococcus, Lactobaccillus)
Actinobacteria (Bifidobacterium)
Proteobacteria (E.Coli) relatively rare
75
GI Immune Cells & Responses
Innate Lymphoid Cells (ICL's)
resemble Th subsets (produce IFNg, IL-17, IL-22, IL-5, IL-13)
Include
- Lymphoid Tissue Inducer (LTI) cells - recruit DC/T/B cells to PP & ILF
- Intraepithelial Lymphocytes (IEL) - host protection, repair, promote tolerogenic DCs, IL-22, αβTCR (10%γδ)
- NK Cells (NK-22), produce IL-22
Also:
MAIT (mucosal associated invariant T cells) - rapid response to bacterial antigens
Invariant NKT cells - proinflamatory cytokines
Macrophages - low TLR expression and hyporesponsive
76
Clostridium difficile
Gram Positive
Rods
Spore forming
Strict Anaerobe (hard to culture - PCR/EIA faster)
Diseases:
GI - pseudo-membranous collitis (toxin causes necrosis of epithelial cells)
Treatment:
Metronidazole / vancomycin
rePOOPulate
77
Treponema pallidum (Syphillis)
Spirochete
oro-genital contact
```
DISEASES
First Degree
- painless chancre
Second Degree (6-8 weeks)
- maculopapular rash (palms/soles), alopecia, hepatosplenomegaly, lymphadenopathy
Third Degree (decades)
- chronic granulomas
- aortitis (vasa vasorum destruction)
- ataxia
- joint destruction
- neurosyphillis
Congenital syphilis
- stillbirth
- rash on feet / palms
- hepatosplenomegaly
- lymphadenopathy
```
```
DIAGNOSIS
serology treponemal (specific) and nontreponemal (nonspecific)
(EIA = positive for life, + RPR = current active infection)
```
TREATMENT
Penicillin G
78
Common Aetological Agents of UTI
E.Coli
Proteus (GNR)
Staph saprophyticus
Other: (common nosocomial)
Klebsiella, Enterobacter, Pseudomonas
79
Microbial Factors of UTIs
Adhesins (E.Coli: type 1 fimbrae, flagella, PAP - pyelonephritis associated pili)
Polysaccharide Capsule (E.Coli, Klebsiella)
Intracellular bacterial communities
Biofilm formation
Haemolysin (E.Coli) breaks down RBCs
Siderophores - greater affinity for iron than transferrin
Urease & Struvite stones (Proteus)
80
Diagnosis of UTI (Quantitative)
```
WBC > 10^5
RBC > 10^5
Squamous = 0
MSU Bacteria > 10^5 (esp if only one species)
Catheter Bacteria > 10^5
SPA Bacteria > 0
```
(transport under 1 hour, keep at 4deg for 18 hours)
81
UTI treatment (Cystitis & Pyelonephritis)
CYSTITIS:
Alkalinise
Cephalexin OR co-amoxyclav OR trimethoprim
(3-5 days women, 14 days for men)
PYELONEPHRITIS:
Cephalexin OR co-amoxyclav OR trimethoprim (10 days)
w/ sepsis use ampi/amoxycillin + gentamicin
82
What is the most common cause of meningitis?
Viruses, particularly enteroviruses
e.g. Coxsackie, echo
Also: mumps, VZV, influenza, HIV, HSV2
Viruses are typically self limiting and resolve on their own.
Bacteria should always be treated if meningitis is suspected (cefotaxime/ceftriaxone)
83
Which three bacteria are the commonest cause of meningitis in Adults?
H. influenza* (GNR)
N. meningitidis (GNC)
S. Pneumoniae (GPC)
Normal commensals of nasopharynx
Good at evading immune system (polysaccharide capsule -> able to evade complement fixation)
84
Which three bacteria are the commonest cause of meningitis in Neonates?
group B strep -s. agalactiae (GPC)
Listeria Monocytogenes (GPR)
E. coli / other GNRs
Common bacteria in birth canal
*type B in west, type A worldwide
Treat with IV 3rd generation cephalosporin (e.g. cefotaxime/ceftriaxone)
+ IV penicillin
+ IV gentamicin
85
Common presenting symptoms of meningitis (Adult vs Child)
```
ADULT
Fever
Vomiting/nausea
Headache
Stiff Neck
Altered Mental State
Photophobia
Seizures
```
```
CHILD
Fever
Irritable/unsettled
Refusing food/drink
Altered Mental State
Bulging fontanelle
```
86
CSF meningitis diagnosis (NORMAL, VIRAL, BACTERIAL, TB)
NORMAL
pressure: 150mmH20
appearance: clear
WBC: 60% Blood
VIRAL
WBC: 100*10^6/L
Protein: 0.4-1g/L
```
BACTERIAL
pressure: raised
appearance: cloudy
WBC: 1000*10^-6L
Gram Stain: positive
Protein: >1g/L
Glucose: <30% Blood
```
* NB: WBC count in sample rapidly decreases due to cell lysis
* Glucose decreased in mumps
87
CHA
Heated Horse Blood agar to lyse blood cells and release nutrients.
Good for fastidious organisms like H. influenzae and N. meningitidis
88
HBA
Good for isolation of fastidious bacteria
b-haemoloysis (clear) = S. pyogenes, C. perfringens, B. cerus, S. aureus
a-haemoloysis (green) = S. pneumoniae, Viridans strep
89
MAC
```
Pink = lactose fermentater
Yellow/Clear = non lactose fermenters
```
Contains Bile salts so good for intestinal bacteria
90
How does cholera toxin work?
Acts through second messenger
Causes cAMP to form in intestinal epithelium
- close Na+/Cl- chanels at tip of microvilli
- hypersecretion of ions from crypt
net water excretion
91
```
Definitions:
Neurotropic
Neuroinvasive
Neurovirulent
Primary Viral Encephalitits (acute)
Secondary Viral Encephalitis (post-infective)
```
Neurotropic: capable of replicating in nerve cells
Neuroinvasive: capable of entering or infecting the CNS
Neurovirulent: capable of causing disease within nervous system
Primary: direct viral infection
Secondary: results from complications of viral infection
92
What is the most common cause of viral encephalitis?
HSV1&2
Rabies
Arbovirus (insect borne)
Enteroviruses
93
How do the presenting features between viral meningitis and encephalitis differ?
Meningitis:
Headache, Fever, Neck Stiffness, Photophobia, Vomiting
Encephalitis
As above + personality & behavioural changes, partial paralysis, hallucinations, altered consciousness, coma, death.
94
Herpesviridae (HSV)
```
dsDNA - linear
Envelope
Icosahedral capsid
Obligatory nerve cell growth
Low Neuroinvasive
HIghly Neurovirulent
Antigentic Drift
TLR signal transduction
TAP block
```
```
PATHOGENESIS:
Infected saliva
Primary infection of mucosa (mouth/throat)
Replication locally and clearance (80%)
Primary disease (20%) of nerve endings
Migrate to ganglia (tigeminal/sacral)
Latency & reactivation
-> CNS temporal lobe
```
```
DISEASES:
cold sores
vesicular rash
temporal lobe encephalitis/meningitis (via axonal fibres & olfactory),
gential herpes
```
TREATMENT:
Antivirals (acyclovir)
Reduce stressors to prevent outbreaks (cold, UV, stress, immunosuppression, illness)
95
Herpesviridae (VSV)
```
dsDNA - linear
Envelope
Icosahedral capsid
Obligatory nerve cell growth
Low Neuroinvasive
HIghly Neurovirulent
```
```
PATHOGENESIS:
Infected conjunctiva/saliva (via resp/direct contact)
Replication in regional lymph
Primary viremia (4 days)
Replication in spleen/liver
Secondary viremia
Rash (10 days)
Axonal retrograde infection (latent in dorsal root ganglia)
Acute cerebellar ataxia (2-4 weeks)
```
DISEASES:
chickenpox (fever, lethargy, vesicular rash)
secondary bacterial infection (staph, s.pyogenes)
pneumonitis (tachypnea, cough, haemoptysis)
shingles
meningitis/encephalitis (acute cerebellar ataxia)
Reye's Syndrome - cerebral oedema (associated w/ asprin during fever)
congenital varicella
TREATMENT:
Antivirals (acyclovir)
Reduce stressors to prevent outbreaks
96
Herpesviridae (EBV, CMV)
```
dsDNA - linear
Spherical lipid envelope
Icosahedral capsid
EBV latent in B cells (inhibit proteosome)
EBV small RNA inhibit PKR
CMV TAP block
CMV MHC-I homologue (prevent NK)
CMV surface protein interference (prevent T cell activation)
```
```
PATHOGENESIS:
latent infection (WBCs)
reinfection with different strains
shed in all body secretions
survives in environment for up to 24 hours
```
DISEASES:
EBV - Mononucleosis (Glandular fever), hepatitis
CMV - Mononucleosis, hepatitis, pneumonitis
Guillain-Barre Syndrome
congenital CMV - damage to developing organs (hepatosplenomegaly, rash)
postpartum CMV - sepsislike syndrome (hepatitis, pneumonitits)
Immunocompromised CMV - multi organ failure, graft damage
TREATMENT:
Antivirals (acyclovir, ganciclovir)
Reduce stressors to prevent outbreaks
97
Anti-Streptolysin O Test (ASOT)
Test for Strep Gp A, C, G
Antibodies coat streptolysin (endotoxin) so it can't lise the cell
If lysis occurs there are no antibodies pressent in serum
if lysis is stopped there must be antibodies to streptolysin present
98
Anti-Nuclear Antibody (ANA) Test
Test for Antihuman dsDNA, or rNA
positive to autoimmune diseases like SLE and rheumatoid arthritis
Likely to see low complement levels in Type III autoimmunity given that they are used up faster than they can be replaced or host in naturally deficient
99
Frequently Encountered Opportunistic pathogens
```
E. coli
Staph aureus*
Klebsiella pneumoniae*
Enterococcus*
Pseudomonas Aeruginosa*
Enterobacter*
Serratia
Porteus*
Clostridium difficile
```
*may cause nosocomial epidemics
100
Host factors affecting colonisation
LOCAL:
- anatomical defects
- surgical / wounds
- burns (staph, pseudomonas)
- catheters
- foreign bodies
SYSTEMIC
- Age
- Leucopenia
- Malignancy
- Malnutrition
- Diabetes (candidiasis may be first sign)
- liver disease
- certain infections (measles very immunocompromising)
- antimicrobials (c. difficile)
- primary (congenital) immunodeficiency
101
Fungal Classifications
Unicellular (yeasts)
- facultative anaerobes
- reproduce asexually by budding
- produce colonies on agar (may be confused with bacteria but are usually 2x larger and can see budding)
Fliamentous (moulds)
- aerobes
- reproduce by conidia (asexual spores)
- produce mycelia on agar
Dimorphic
- most pathogenic
102
Fungal Virulence Factors
Most are saphrophytes (live on organic material)
Dimorphic fungi
- best adapted to grow in our tissues
- filamentous in environment
- yeast when invasive (facultative anaerobe)
Dermatophytes
- ringworm fungi (e.g. microsporum - cause tinea)
- very common
- grow on skin, eat keratin, don't usually invade
Subcutaneous mycoses
- low grade pathogens
- inoculated directly subcutaneously
Opportunists
Toxic fungi
- e.g. poisonous mushrooms
- aspergillus (aphlatoxin)
103
Common Fungi and their associated diseases
Microsporum (dermatophyte)
- causes tinea
- lives off keratin in skin/hair
Madurella (fungi) (or Nocardia - bacteria)
- cause myceroma (maduromycosis)
- sulphur granules with yellow discharge
Candida Albicans
- cause candidiasis (mucocutaneous, chronic, systemic)
- chronic vaginal thrush
- systemic in neonates or immunodeficient (AIDS)
- opportunistic
- germ tubes (pseudohyphae) visible on microscopy
Cryptococcus neoformans & gattii
- cause cryptococcosis
- primarymild pulmonary infection (route of entry)
- meningitis (AIDS defining illness)
- gattii more virulent than neoformans
- neoformans more common than gattii
- opportunistic
Aspergillus
- cause aspergillosis
- saphrophytic fungus ball (e.g. previous TB cavitation)
- allergic response (aphlatoxin)
- systemic (in immunocompromised patient)
104
Antifungal Treatments
Candida Albicans - fluconazole, amphotericin B
Cryptococcus - amphotericin B + 5-fluorocystosine
Aspergillus - voriconazole, amphotericin B
Dimorphic fungi - amphotericin B
Dermatophytes
- topical
* ternomafome
* clotrimazole (canesten)
* amorolfine
- oral
* terbinafine
* fluconazole
* only use for difficult to treat topical infections (nails) or widely disseminated
105
Classifications of Osteomyelitis
Hematogenous
- Asymptomatic bacteraemia
- Septicaemia
Non Heamatogenous - Direct inoculation
- Trauma
- Surgery
Non Haematogenous - Local Invasion
- Ulcer
- Peridontal
- Sinus
106
Common aetiological agents of bone and joint infection
```
GRAM POSITIVE
Staph aureus (Most common)
Step pyogenes (post chickenpox)
Group B strep (newborns - from mother)
Coagulase negative staph (post trauma/surgery)
```
GRAM NEGATIVE
Haemophilus influenzae type B (newborns until vaccination)
Kingella kingae
Other gram neative (newborns - from mother)
OTHER
TB, Fungi, Parasites
Treat w/ flucloxacillin for GPs and cefotaxime for GNs via IV for 3-5 days then oral for 3 weeks
107
Plasmodium falciparum, vivax, ovale, malariae,
Malaria
Falciparum - Africa
Vivax - Asia, PNG, South America
Ovale & Malariae - limited, mild disease
0 hours - Skin infection by female (anopheles) mosquito
1-2 hours - sporozites get to liver
7-10 days - incubation (vivax lays dorment)
Release of merozites that infect RBCS
replication in blood stream (host is symptomatic)
reinfection of RBCs or mosquito takes up parasite
DISEASES:
- 'flu-like' illness - fever, malaise
- severe anaemia
- cerebral complications (coma, convulsions)
- lung damage -> acidosis
- kidney failure / multiple system failure
- clotting problems (RBC shape and adhesins)
- splenomagaly
- falciparum more deadly (infects all stages of RBCs, multiple parasites per RBC)\
- potential hypoglycamia (parasite uses glucose)
```
DIAGNOSIS:
Thick film (screening) - no fixative, stain lyses RBCs
Thin film (speciation) - multiple ring forms / RBC = falciparum
```
TREATMENT:
Antimalarials
Artemisinin Combination Therapy (older - chloroquine)
Primaquine (for clearance of vivax from liver)
IV for 7-10 days if severe
Blood transfusion
108
Increase risks for travellers
- Exotic agents
- Poor sanitation
- Low immunisation (greater human reservoir)
- Overcrowding
- Cultural behaviours
- Agriculture and animal handling
- Risk taking behaviour ('in the moment')
- Length of stay
- Visiting friends / relatives (closer contact with locals in substandard accommodation)
109
Incidence of Illness during Travel to Developing Countries
```
20-60% Travelers Diarrhoea
5-20% Acute Respiratory Infection
2% Malaria
0.1% Dengue Fever
0.3% Animal bites with rabies risk
0.03-0.3% Hepatitis A
```
110
Chlamydia trachomatis
```
GNC/R
no cell wall (har dto see on gram stain)
oro-genital contact
most common STI (2-20%)
obligate intracellular parasite
(require cellular ATP to reproduce)
```
PATHOGENESIS:
lives in columnar epithelium
elimentary body infects columnar epithelial cells
formation of reticulate body and binary fusion
reorganisation into elementary bodies
lysis and release
DISEASES:
females: cervicitis (strawberry cervix, dysuria, irregular bleeding, pelvic inflammatory disease)
males: urethritis (dysuria, redness, clear discharge, prostatitis, testicular pain)
80% asymptomatic in females
neonatal chlamydia
- conjunctivitis (2-28 days) can be haemorrhagic
- pneumonia (2-8 weeks)
LGV serovar causes ulcerative lesions and inguinal lymphadenopathy
DIAGNOSIS:
Swabs
Urine
TREATMENT:
azithromycin or doxycycline
longer course of IV azithromycin for pelvic inflammatory disease
111
Trichomonas vaginalis (trichomoniasis)
```
protazoon
motile (flagellae)
sexually transmitted
frequently asymptomatic
frothy green-yellow vaginal discharge
cervical erythema
pH above 5.0 (usually lower)
itch, dysuria, abdominal pain
associated with increased risk of HIV acquisition
```
DIAGNOSIS:
vaginal swab 'wet prep' and culture
urine pcr
TREATMENT:
metronidazole or tinidazole
112
Mycoplasma genitalium
```
no cell wall
fastitious and difficult to culture
sexually transmitted
antibiotic resistant
prevalence 3-5%
```
```
DISEASES:
men - urethritis
women - cervicitis, PID, endometritis
preterm labour and delivery
incrased risk of HIV
```
DIAGNOSIS:
nucleic acid amplification
TREATMENT:
azithromycin (30% failure rate)
moxifloxacin
113
Effect of Group B Strep (strep agalactiae) on pregnancy
```
lives in vagina (25-30%)
premature rupture of membranes
ascending infection or colonised during delivery
premature labour
pneumonia, septacaemia, meningitis
treatment: penicillin + gentamicin,
```
114
Ro & Rt
| Core group & Non-core group
Ro - basic reproductive rate
Ro = BcD
B = probability of transmission
- condoms, type of sex, organism load, treatments
c = rate of partner change
- core/noncore groups, mixing patterns
D = duration of infection
- symptom recognition, asymptomatic, chronic
number of secondary cases of an affection that arise from a primary case at t=0
Ro of 2 = one case leads to two secondary cases
Rt - affective reproductive rate (at time t)
Rt = BcD(x)
B = probability of transmission
c = rate of partner change
D = duration of infection
x = proportion susceptible (100% at t=0)
Rt of 1 = people curing infection at same rate as being infected
core group non core group
core group = many partners, high rate of STIs
noncore group = few partners, low rate of STIs
assortitive mixing - core group with core group (Ro >> 1)
disassortitive mixing - core group with non-core (Ro < 1)
115
Important HIV Genes
ENV GENE
- surface glycoprotein gp120
- transmembrane anchor gp41
GAG GENE
- matrix layer (p17)
- capsid layer (p24)
- nucleocapsid (p7)
VIRAL ENZYMES (POL GENE)
- reverse transcriptase (p66/51)
- integrase (p32)
- protease (p11)
116
HIV replication
binds CD4
gp120 variable region opens
gp120 binds coreceptor (CCR5, CXCR4)
promotion of gp41 fusion with host plasma membrane
six-helix bundle forms to bring envelopes together
fusion of lipid bilayer of virus with cell
release capsid
ssRNA+
reverse transcription (high error rate)
cDNA
integrase enzyme translocates cDNA into nucleus of cell and cDNA becomes part of DNA = provirus (esp in latent memory T cells)
5'LRT (Long Terminal Repeats) act as HIV gene promotor
LRT has binding sites for proteins such as NFkb (causes upregulation during T cell activation)
transcription
translation
budding
cleavage of gag polyprotein into matrix and capsid (protease enzyme)
117
HIV Infection Phases
```
Acute HIV infection
- incubation 2-4 weeks
- clinical illness 1-4 weeks
- HIV antibodies (ELISA) detectible in 50%
massive loss of (body) CD4 cells
- >60% of mucosal T-cells killed
- massive loss of memory T cells in GALT
- GI epithelial apoptosis
Fever
Myalgia
Nausea/vomiting/diarrhoea
Weight loss
Malaise
Rash
Oral Thrush
Headache
```
latent HIV infection (Asymptomatic)
- equilibrium between viral replication and host defence
- viral RNA levels constant
- immune response & CD4 T cell loss
- chronic immune activation
- viral diversity
- GIT distruption & infection -> activation of immune response
late phase
- chronic immune activation
- depletion of CD4 T cells = deficient B cell activation and neutrophil/macrophage killing ability
- opportunistic infections & AIDS related illnesses
118
AIDS Related Illnesses
```
Pneumocystis jirovecii Pneumonia (PCP)
Candida albicans (oral thrush)
EBV (Hairy leukoplakia - tongue, and primary CNS lymphoma)
CMV (retina - blindness)
Cachexia/wasting
non-AIDS related illnesses in the era of HAART
- chronic inflammation
- T cell depletion
- lymphoid fibrosis
- cardiovascular
- hepatitis
- non-AIDS cancers
- liver disease
```
119
HIV median Survival rate after <200 CD4 count
3.7 years
120
HIV median survival rate after AIDS
1.3 years
121
HIV median CD4 at AIDS
65 cells/uL
122
HIV
- TAT
- TAR
- REV
- RRE
- Vpr
- Vpu
- Nef
- Vif
TAT
Transactivator of HIV Transcription
binds to TAR RNA
leads to phosphorylation of carboxy terminus of RNApolymerase II
increases rate of viral expression
promotes transcriptional elongation (longer RNA translated)
Inhibits promotor of MHC-I gene
TAR
transactivation response RNA element
very first RNA structure at 5' end of genome
has stem, bulge, and loop
Rev
Regulator of structural gene expression through binding of RRE
allows switch from early stage of expression (TAT, REV) to late stage of expression (GAG, ENV, POL)
RRE
Rev-responsible RNA element
Vpr
virion protein for nuclear import of cDNA
cell growth cycle arrest
weak transcription transactivator
Vpu
regulator of particle release and ENV processing
promotes MHC-I and CD4 degradation (directs MHC-I to the proteosome and lysosome for destruction)
Antagonises tetherin and allows virus to escape
Nef
multifuncitonal protein important for in vivo pathogenesis
Downmodulates cell MHC-I and CD4
Directs MHC-I to the lysosome for destruction
Vif
Promotes infectivity of cell free virus
block cell defences targeting single stranded cDNA
binds APOBEC3G and targets it for death through proteosome
123
HPV
```
Human Papilloma Virus
HPV1,2,4 = skin infections
HPV16,18 = anogenital carcinomas
dsDNA
- early genes (E6,E7 - block p53 and Rb)
- late genes (capsid genes)
infects sqamous epithelium (basal first)
- 0 to 6 weeks - first lesion
- weeks to months - immune response
- (80-90%) DNA -ve clinical remission
- (10-20%) DNA +ve integrated into host DNA - CIN2/3 risk
```
124
Streptococci Classifications
```
beta-haemolytic - complete haemolysis
Lancefield A - Strep pyogenes (M-types)
Lancefield B - Strep agalactiae
alpha-haemolytic - 'greening' - RBCs release bile
Strep pneumoniae (capsule types)
Strep viridans (oral)
non-haemolytic
```
125
Strep pyogenes virulence determinants
- hyaluronic acid capsule (antiphagocytic)
- M protein (acts as adhesin and antiphagocytic)
- lipoteichoid acid acts as adhesin
- streptokinase (fibrinolysis)
- hyaluronidase (helps spreading)
- C5a peptidase (acts on compliment)
- SpeB (protease)
- DNAses (break NETS - neutrophil traps)
- streptolysin (haemolysis)
- leukocidins (break down WBCs)
- SpeA (pyrogenic superantigen)
- toxins (superantigens)
126
Staph aureus virulence factors
- modified peptidoglycan (avoid phagocytosis)
- techoic acids (act as adhesin)
- polysaccharide capsule (antiphagocytic)
- protein A (interferes with opsonisation)
- staphylokinase (antiphagocytic)
- aureolysin (protease)
- hyaluronidase (helps spreading)
- DNAase (break NETS)
- toxins (superantigens)
- leukocidins (breakdown WBCs) [Panton-Valentine leukocidin] & haemolysins
- inhibit chemotaxis via CHIPS (block compliment)
- biofilm formation and abcess formation
- 90% resistant to penicillin
127
Sterilization
Process that provides acceptably low probability that any microorganism or spore will not survive the treatment
'sterility assurance' = probability that a microorganism survives sterilisation and a proportion of sterilised articles may be unsterile (i.e. 1 in 1000)
More costly and damaging than disinfection
- filtration for fluids
- steam heat for objects
- dry heat for glass
- ionizing radiation for prepackaged articles
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Disinfection
- process of removing or killing most, but not all, viable organisms.
- cannot usually kill bacterial spores
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D Value
- Decimal reduction time
| - time it takes for 90% reduction in organisms due to disinfection/sterilisation
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Common Agents of Skin and Soft Tissue Infections
- Bacteria
- Fungi
- Parasites
- Arthropods
- Viruses
BACTERIA:
S. aureus, S. pyogenes, clostridia
FUNGI:
Candida (yeast), and filamentous fungi
PARASITES:
Leishmania, schistosomes, hookworms
ARTHROPODS
Insects, ticks, mites
VIRUSES:
HSV, VZV, HPV, measles, rubella, enterovirus, Parvo B19, warts
* also systemic infections:
Enteric fever 'rose spots', petechiae in septicaemia, rash in syphilis, scarlet fever, toxic shock syndrome
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4 Pieces of information required to design appropriate sterilisation process
1. Sterility Assurance - Level of sterility required
2. D-value - how fast organism is killed
3. Bioburden - how many organisms we start with
4. Material - will the equipment survive the process
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HIV evasion of immunity
- Sequence variation (esp gp160)
- MHC I downregulation
- Loss of effector cells (clonal exhaustion)
- Latency
- Privileged sites (brain, testes)
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Ebola
Filovirus
From bats
- ssRNA
Enveloped
Helical Capsid
Transmission during clinical illness (body fluids) (doesn't persist on fomites)
Enters through broken skin / mucous membranes
SYMPTOMS (2-21 days after infection)
- fever
- headache
- muscle pains
- diarrhoea, vomiting
- abdominal pain
- maculopapular rash
- haemorrhagic (late)
DIAGNOSIS
- ELISA
- PCR
- Antibody (IgM/IgG)
TREATMENT
- Blood transfusion (antibodies)
- Zmapp (monoclonal antibodies)
- Supportive treatment
