:) Pathogens Flashcards
1
Q
Caries: Streptococcus mutans
A
- Infection often inherited from mother – primarily caused by S.mutans – grow on dietary sugars in plaque on teeth.
- Bacteria produce lactic acid which decalcifies teeth & causes decay.
- Don’t treat with antibiotics – fill tooth or extract tooth
2
Q
Dental Abceses
A
- Dental abscess occurs when infection from the tooth spreads to the underlying nerve and bone, can result from tooth decay left untreated.
- Treated with an oral antibiotic, e.g., penicillin, but really needs dental treatment.
3
Q
Periodontal Disease (Gum disease):
Bacteroides, Actinomyces
A
- Periodontal disease affects tissues supporting teeth & gums.
May cause of tooth loss in adults
Bacteria colonise the crevice where the teeth meet the gums.
gums becomes inflamed, bleeds, and later recedes
Eventually, it affects structures supporting teeth; teeth become loose and fall out.
GUM disease is not usually treated with antibiotics:
treatment aims to control any infection and slow disease progression - Use good dental hygiene such as flossing trips to the dentist, etc
Sometimes, pateints use mouth washes, but there is limited evidence that this is effective without other hygiene methods as well
4
Q
Oral thrush: Candida albicans
A
Can also get opportunistic superinfections in mouth.
This is again can be caused by Candida.
Get imbalance/ in natural microflora (mouth - ecosystem of > 300 spp) and overgrowth by one type of microorg
CA is type of yeast occurring naturally in mouth and overgrowth of this org can cause Oral thrush
Forms white spots on surface of tongue and roof of mouth.
seen in immunocompromised patients such as those with HIV.
Can also occur following treatment with a course of oral bs antibiotics:
Bacteria killed off. Enables overgrowth by organisms that naturally resistant to the antibiotic
yeasts are eukaryotic – naturally resistant to antibiotics targeting prokaryotic bacteria.
Organism causing superinfection doesn’t have to be multi-drug resistant super-bug; just naturally resistant to the antibiotic used to treat another infection
5
Q
GI infections
A
infections of gut.
Usually initiated & confined to gut. stmes initiated in gut, then spreads to other parts of body- causes a systemic infection.
Diarrhoea is most common symptom of GI tract infection.
maj. cause of mortality, esp in young children in dev world.
Also v. common complaint in developed world but usually self limiting, (except in v. young, elderly of people with weakened immune system.)
Wide range of bacterial pathogens capable of infecting
Acquired from food, fluids and fingers contaminated with faecal matter
swallow large numbers of micro-org but don’t cause disease because cant survive body’s defence mechanisms:
For an infection to occur, pathogen must be ingested in sufficient numbers,
must survive harsh conditions in stomach and small intestine & compete with commensal organisms to attach to GI tract .
Once localised to GI tract than has to cause disease
6
Q
E.Coli
A
E.Coli normally lives in the intestines of people (and animals).
Gram-ve rods.
Most harmless / required for digestion .
Infects GI or causes UTI
Several Strains that cause disease
Grouped according to diff ways cause illness – epidemiology (6 groups)
Common: - Enterohaemorrhagic strains; and Enterotoxigenic strains
Treatment - fluid replacement rehydration (& antibiotics if required)
7
Q
E.Coli: EHEC ETEC
A
- EHEC causes severe bloody diarrhoea.
- Bacteria attach to epithelial cells of the large intestine & produce toxins (verotoxin) acting on epithelial cells - cause excretion of lots of fluid, thus causing diarrhoea.
- Can cause HC - severe bloody diarrhoea with painful abdominal cramps
- Can lead onto HUS – haemolytic anaemia (caused by destruction of rbc) acute kidney failure & low platelet (particularly young children & the elderly) - a life-threatening disease
- ETEC produce powerful plasmid-associated enterotoxins
- Bacteria attach to epithelial cells lining small intestine – produce toxins which cause excessive fluid secretion & self limiting diarrhoea.
- Most Imp bacterial cause of diarrhoea in dev countries.
- Leading cause of travellers diarrhoea - risk of ‘Traveller’s diarrhoea’ may be reduced by drinking only bottled water, eating fruit which has been peeled and avoiding foods such as salads.
Should get better on its own
8
Q
Salmonella Self Limiting Diarrhoea
A
- Self limiting diarrhoea confined to epithelium is most common.
- Mostly caused by 2 main:
S. enteritidis & S. typhimurium - Large animal reservoir of infection.
- Usually transmitted via contaminated food esp raw eat poultry eggs & dairy products.
- People can be infected with S. Typhimurium in a number of ways such as not cooking their meat properly, not washing hands thoroughly after handling raw meat, or through cross-contamination with other food, surfaces, and utensils in the kitchen.
- Infection can be transmitted from person to person so secondary spread amongst people living together can occur.
- Most common symptom of infection is acute self limiting diarrhoea.
- Infection usually limited to intestines. 9. Sometimes enters blood & lymph. Causes septicaemia
9
Q
Salmonella: Typhoid fever
A
- 2 strains of Salmonella enterica can also cause systemic disease: typhoid fever.
S. enterica serovar typhi & S. enterica paratyphi. - Transmitted in contaminated water
- Acute gastroenteritis – Non specific flu like symptoms after up to 3 weeks incubation – fever, malaise, aches.
Fever increases without antibiotic treatment, person becomes acutely ill.
In absence of antibiotics Typically lasts 4-6 weeks : 12-16% people die. - Antibiotic treatment as soon as disease diagnosed.
- Treat with antibiotic which inhibits NA synthesis (ciprofloxacin, trimethoprim).
- Prevent spread by good hygiene, clean water supply, vaccination.
10
Q
Campylobacter
A
- Most common cause of diarrhoea in humans in UK
- Don’t grow on media & conditions used to isolate E.coli & salmonellae, so importance initially missed – microaerophilic & thermophilic, growing well at 42 degrees
- G-ve bacterium
- Large animal reservoir & dairy products & water.
- Transmission from person to person rare.
- Clinically like self-limiting diarrhoea seen with salmonellae but longer incubation & longer duration.
- Treatment rehydration & antibiotics (erythromycin) if required
11
Q
Food poisoning
A
- Can also get diseases through Food poisoning : contamination of food containing bacterial toxins – toxin is pathogen – rapid onset
- Food poisoning results from bacterial toxins present in food. It does NOT result from a bacterial infection.
- Bacteria destroyed when food properly cooked but toxins may be stable to heat & acid (in stomach) & cause the symptoms of food poisoning when they reach the small intestine.
- Diarrhoea (& stmes vomiting) caused by food poisoning occurs rapidly after ingestion (within hours or sometimes minutes) of contaminated food
98% of food poisoning caused by toxins from 2 different sp of bacteria:
Campylobacter Jejuni Most common cause of food poisoning in humans
Clostridium Boutlinium toxin one of most powerful toxins known. V. rare. acts on peripheral nerve synapses, blocks neural transmission, causes paralysis
Bacillus Cereus: Occurs in poorly cooked/re-heated rice and pulses. toxin induces severe nausea, vomiting and diarrhea after 1-5h (stms 15 min)
S.aureus – severe vomiting after 3-6 hr. no diarrhoea. Recovery within 24hr
NOTE: Some bacterial infections in the gut e.g. E.coli cause diarrhoea through the production of toxins. However, for this to occur, the bacteria must establish an infection (i.e. attach to the epithelium, multiply & evade host defences) then produce the toxins that cause diarrhoea. This typically requires a 1-3 day incubation period
12
Q
Anti-biotic associated diahorrea
A
- Diarrhoea can also arise from disruption of the normal gut flora as a result of using broad spectrum antibiotics.
- Called Antibiotic associated diarrhoae – opportunistic infection.
- BS abx disrupt normal flora. Gut becomes colonised with bacteria or yeasts that are resistant to the Abx.
- Can get overgrowth with Candida – example of a yeast
- Another example is overgrowth of C. difficile.
13
Q
Clostridioides difficile
A
- Most commonly diagnosed bacterial cause of HAI diarrhoea in HIC.
Infections require annual mandatory reporting to gov - Anaerobic spore producing bacteria resistant to many BS antibiotics.
- Produces toxins which cause severe diarrhoea & abdominal cramps . Over time, colonic surfaces become covered in fibrinous pseudomembrane (Pseudomembranous colitis)
Becomes progressively worse – diarrhoea can become bloody. - Stmes causes colon to expand, dilate & distend. Then colon unable to remove gas or faeces from body. If these build up, large intestine can eventually rupture – life threatening - bacteria in gut released into abdomen – leads to serious infection & even death.
- Resistant to most antibiotics; multiplies & produces 2 toxins that damage the cells lining the intestine (not infection itself but toxins that cause symptoms of disease).
- Usually spread by ineffective hygiene of healthcare workers.
- Its spores can contaminate floors, bedpans & door handles where they can survive for days.
- Severe form – pseudomembranous colitis – acute inflammation of the bowel – severe diarrhoea, abdominal cramps, fever.
Epithelial surface is inflamed & covered with yellow-green exudate - results for bacterial infection
Toxic megacolon –dilation of colon – can cause perforation of colon & intestinal haemorrage
Reasions in increases:
New strains
Over prescribing of antibiotics,
Poor cleaning & hosptial hygiene
Hospital overcrowding,
More elderly popluation
Treatment: Stop taking antibiotic causing condition
Treat with Metronidazole (1st line) , Oral vancomycin (2nd line), linezolid may be considered. Rehydration if required.
14
Q
Infections of CNS: Bacterial meningitis
A
- Meningitis – inflammation of meninges – membranes enveloping brain.
- Acute life threatening infection needing urgent specific treatment.
- Infections of CNS are usually from blood (sometimes via peripheral nerves).
- Caused by viruses & bacteria – important to know the cause.
- Viral meningitis more common but less severe.
- Usually self limiting (2-3 weeks). May need to be admitted to hospital.
- Bacterial meningitis is Rare. Mortality is 100% if not treated but 10% when treated
Common bacterial causative agents of meningitis are:
1. Neisseria meningitidis – G-ve coccus – (also called meningococcal meningitis)
2. Streptococcus pneumoniae – (pneumococcal meningitis)
3. Haemophilus influenzae B (Hib) – rarer due to vaccine
All these bacteria live in the back of the nose and throat in 1/10 people. They don’t usually cause disease.
Occasionally, bacteria penetrate body’s defences (especially if immune system is weakened in some way), Pass into blood stream where Bacteria can then go on to cause disease
Symptoms:
Severe headache, fever, aching muscles
& joints, drowsiness, neck stiffness, rash.
The skin rash associated with septacaemia.
Rash of tiny red/purple pin prick spots, which may spread to look like fresh bruising. Important feature is that if press on rash, it doesn’t go away (glass test), wont go away as it is a bruise under the skin.
Treatment: antibiotic therapy – usually penicillin
Prevention – vaccination
H. influenzae Type B: HIB vaccine
N. meningitidis Type C: Men C vaccine
S. pneumoniae: 2 vaccines:
(I) Polysaccharide vaccine (pneumovax).
Not in kids (weak immune response).
(ii) Pneumococcal Conjugate Vaccine (PCV)
If had meningitis , you have protection against that strain but not others
15
Q
Infections of the Skin
A
- Skin infections usually result from opportunists within the skin microflora.
- Wound abrasion allows bacteria to pentrate epidermis
- Most Common cause of bacterial infection is S. aureus
- Methicillin Resistant Staph aureus (MRSA) resistant to most commonly used antibiotics. (Some strains only treatable with vancomycin)
- MRSA one of the main hospital ‘superbugs.’ Patients now screened for MRSA prior to hospital admission – nasal swaps & swabs from groin.
- MRSA Prevention: also includes special wipes & sprays, screening of patients coming into hospitals (nose swab).
- Same pathogen can cause infections in different layers of skin:
- Infections in and around hair follicles can produce boils & folliculitis
- Can cause: epidermis impetigo, dermis erysipelas, cellulitis & gangrene
Some infections can invade bood steam & cause serious systemic infections
16
Q
Infections of the Epidermis
A
- Boils & folliculitis result from infection in & around hair follicles
- Boils infection around 1 or 2 hair follicles;
follicultitis infection of several hair follicles - Usually Caused by S.aureus
- Treated at home with hear or draining pus, can prescribe antibiotic if severe
- impetigo –
example of spreading infection of epidermis.
Typically caused by staph & strep sp. bacteria.
Characterised by blisters esp round mouth that can itch.
Blisters become crusty & weep.
Treatment: bacterial ointment containing antibiotic such as fusidic acid.
In severe cases add flucloxacillin – narrow spectrum penicillin taken orally
which is stable to enzymes (b-lactamases) sometimes produced by these types of bacteria.
17
Q
Infections of the dermis and underlying connective tissue
A
Erysipelas:
1. Erysipelas is a spreading infection of dermis.
2. Typically caused by S.pyogenes.
3. More common in elderly, infants & children.
4. Characterised by a red skin lesion which is warm & hardened & spreads rapidly. Patient has temp & feels unwell.)
Cellulitis
1. Infection occurs in dermis & underlying connective tissue.
2. Typically caused by (SA or Sp) 3. Staphylococcus aureus, Streptococcus pyogenes
4. Usually originates following skin damage e.g. from superficial skin lesions
5. Infection develops within a few hours or days of trauma & quickly produces a red swollen lesion
6. Spreads into deeper layers of skin & into connective tissue.
Area red, hot & painful. Patient has fever & feels unwell.
7. Complications Once below skin, bacteria can spread rapidly, entering the lymph nodes & the bloodstream, spreading throughout the body, systemic infection.
Treatment: antibiotics. – oral or i.v. if severe
Risk factors:
1. The elderly
2. Weakened immune systems
3. Diabetics due to impairment of blood circulation in their legs
4. Obesity.
18
Q
Infections of soft tissues: Gangrene
A
Infections of soft tissues: Gangrene
1. Infection of soft tissues below skin
2. Gangrene is necrosis (death) & subsequent decay of body tissues.
3. Occurs as result of lack of blood flow. 4. Normally affects extremities
5. Normally caused by S.aureus, S. pyogenes
Dry gangrene:
1. Occurs If the blood flow is interrupted for some reason e.g. diabetes, thrombosis).
2. No bacterial infection
3. Symptoms: dull ache & coldness in the area, pallor of the flesh.
4. If caught early, the process can sometimes be reversed by vascular surgery.
However, if necrosis sets in, affected tissue must be removed by amputation
Wet gangrene:
Results from impaired blood flow but there is also a bacterial infection.
Gas gangrene:
1. Gangrene usually caused by Clostridium perfringens bacteria.
2. Bacteria multiply in soft tissue causing anaerobic form of cellulitis.
3. Produces gas - opens & separates the internal tissues, leads to rapid progression of infection.
4. Enzymes (e.g. lethinase) & toxins cause massive haemolysis.
Treatment – surgery to remove affected tissue.
Antibiotics - penicillin & metronidazole –
Gas gangrene need to kill the anaerobic bacteria
Another example of a soft tissue infection
1. Necrotisng Fasciitis (or flesh eating disease)
2. Resembles gangrene but is a much more acute & highly toxic infection.
3. Streptococcus pyogenes is the most common cause.
4. Causes widespread necrosis – destruction of underlying tissues
5. Get large boil like blisters under skin.
6. Patients deteriorate rapidly & frequently die
Treatment – excision of dead tissue antibiotic therapy
19
Q
Infections of the dermis and underlying connective tissue - Lyme disease
A
- Lyme disease – tick borne disease that affects human & animals
- Caused by infection with – Borrelia burgdorferi
- Bacteria transmitted to human while tick carrying bacteria obtains blood from its host
- Only a small number of ticks are infected with the bacteria that cause Lyme disease.
- A tick bite can only cause Lyme disease in humans if the tick has already bitten an infected animal.
- It’s important to be aware of ticks and to safely remove them as soon as possible.
- Early symptoms a circular red skin rash around the tick bite.
- The rash can appear up to 3 months after being bitten & usually lasts for several weeks. Most rashes appear within the first 4 weeks. – increases in size. Sometimes has central clearing. Not itchy or painful.
- Systemic infection develops leading to acute flu-like symptoms
– headache, back-ache, chills, fatigue - Then readily treated with antibiotics
- If untreated can progress to chronic stage weeks to months after initial bite. Causes arthritis in 50% of those infected.
- Also other symptoms – weakness in limbs & heart damage
- Bacteria can become dormant causing additional chronic symptoms e.g. probs with vision and facial muscle movements or seizures.
20
Q
Infections of bone and joints: Osteoporosis & Septic arthritis
A
Infection of the bone called Osteoperosis:
1. Can occur as a result of local infections elsewhere in the body –
which spread to blood stream. i.e. secondary infections
E.g. cellulitis.
2. Can aresult from surgery e.g. prostheses following joint replacement
3. Most common species causing bone infections is S.aureus.
4. Typically involves growing end of long bone so tends to be disease of children & adolescents.
5. Causes pain & fever.
6. Get pus in blood vessels of bone. Leads to impaired blood flow & areas of dead cells with in bone.
7. Infection establishes itself as a biofilm, becoming difficult to treat –
& cells can detach & re-establish infection in other areas of the body.
- Septic arthritis is infection of joints.
- Bacteria enter through skin lesions, gets into blood stream & penetrates the joints
- Usually caused by S.aureus.
- Get pain redness swelling & fever.
- Can occur due to surgery, e.g. join replacement, or following local infections
6.Treatment: longterm antibiotic therapy (4-6 weeks).
- flucloxacillin or clindamycin (vancomycin for MRSA) for 4 – 6 weeks
Removal of damaged tissue (bone) or drainage (joints).
Chronic infections (associated with prostheses)
21
Q
Infections of heart: Endocarditis
A
Infections of heart: Endocarditis
1. Can result from secondary infection or transient bacteraemia.
(Presence of organisms in blood).
e.g. from minor dental procedures -such as a tooth extraction,
2. Inflammation of inner layers of heart especially heart valves.
3. Infective endocarditis –rare but Fatal if untreated.
- Normally blood flows smoothly through valves & they are well protected against infection.
BUT more common in people with :
A) A prosthetic heart valve
B) Congenital heart disease
C) Damaged heart valves - Biofilm may occurs on heart valves especially if already damaged in some way (e.g. as result of rheumatic fever).
- Easier for bacteria to attach. E.g. Streptococci, Staphylococci, Enterococci
- Body defence mechanisms cannot enter heart valves so if bacteria do become established, it is difficult for the body to get rid of them.
- Almost any organism can cause infective endocarditis
- Often oral streptococci resulting from dental procedures
S.mutans - low virulence, mild to mod illness
Many caused by staph e.g. SA- severe illnness - rapid progression
Enterococcal – e.g. E. faecalis - due to catheterised UTI infection
Symptoms:
10. few visible symptoms- mild muscle & joint pain
11. but patients almost always have fever, & heart murmur which can be diagnosed by electrocardiography
12. Blood culture negative as often caused by transient bacteraemia.
13. Also, if patient on AbX may not be signs of bacteria in blood
22
Q
Sepsis
A
- Serious life-threatening infection which gets worse v. quickly
a systemic disease. - Can be acquired in hospital or Community – more often in community.
- Occurs when an infection initiated elsewhere in the body e.g. in lungs, abdomen, skin bones, joints, CNS causes a severe bacterial infection of the blood.
- Most frequently identified pathogens that cause infections which can develop into sepsis: S. aureus, E. coli. Some strains of S. pyogenes.
- Sepsis is the body’s immune response to infection, resulting from severe bacterial or viral infection in blood, followed by an immune response to the infection.
- Symptoms: Fever, chills, slurred speech , confusion, rapid breathing, rapid heart rate, late stage Erythematous rash
(Bacteria release toxins into the blood which break down blood vessel walls. Blood then leaks out into skin).
Can progress to septic shock. - Systemic Inflammation & coagulation cause: reduced body temp, reduced blood pressure, & multiple organ failure
- Treatment – long term antibiotic therapy
e.g. Aminoglycoside + broad spectrum penicillin or cephalosporin
add metronidazole if anaerobe expected.
Add flucloxacillin or vancomycin if Gram-positive suspected (vascular catheter related)
23
Q
HAI (Hospital Acquired Infections)
A
C. difficile
1. Causes severe diarrhoea. Lives in your gut
2. Forms spores-Highly persistent can remain dormant on the hospital ward.
3. Outbreaks can cause closure of wards
MRSA- Antibiotic resistant Staphylococcus aureus
1. Commensal bacteria which lives on your skin-
2. Can cause skin infections-
3. In hospital causing wound infections.
4. MRSA now prevalent (superbug)
Pseudomonas aeruginosa
1. Gram negative opportunistic pathogen – common in soil & water
2. Causes respiratory & blood stream infections in those who are already sick or immune compromised.
3. Multidrug resistant strains.
E. coli:
1. The most common cause of UTIs in hospitals.
2. Huge problem particularly amongst catheterised patients
Klebsiella pneumonia:
1. Causes a variety of HAI-pneumonia, bloodstream infections, wound or surgical site infections, & meningitis.
2. Doesn’t usually affect healthy people.
3. Problem for those catheterised, on a ventilator, on long term antibiotics
CRE (Carbopenem Resistant Enterobacteriaceae)
Antibiotic resistant forms
E.coli and Klebsiella are members of the family Enterobacteriaceae (Gut living)
CRE-forms of both are a Huge problem in hospital
catheter, ventilator, on long term antibiotics
24
Q
Properties of a Virus
A
- Obligate intracellular parasites of bacteria, protozoa, fungi, algae, plants, & animals.
- Contain either DNA or RNA, not both
- Ultramicroscopic size, ranging from 20-450 nm (diameter).
- Not cellular in nature; structure is very compact & economical.
- Do not independently fulfil the characteristics of life.
- Inactive macromolecules outside the host cell and active only inside host cells.
- Most so small electron microscope needed to detect them or examine their fine structure.
- Lack the ability to synthesize proteins
- All viruses have a protein capsid that surrounds the nucleic acid in the central core. Together, the capsid and nucleic acid are referred to as the nucleocapsid.
- Majority of animal viruses also have an additional covering called the envelope. The envelope is likely from the host structure.
- Naked = nucleocapsid- Enveloped = nucleocapsid + envelope
25
Viral Capsid & Envelopes
1. Capsid protects the nucleic acid from the effects of various enzymes & chemicals when the virus is outside the host cell.
2. e.g. the capsids of enteric (intestinal) viruses such as polio & hepatitis A are resistant to acid- & protein-digesting enzymes of the GIT.
3. Capsids & envelopes are also responsible for helping to introduce the viral DNA or RNA into a suitable host cell, first by binding to the cell surface & then by assisting in penetration of the viral nucleic acid.
26
Viral Classification
1. All DNA viruses are double stranded except for parvoviruses, which have ssDNA.
2. All RNA viruses are single stranded except for dsRNA reoviruses.
3. Most DNA viruses are budded off the nucleus.
4. Most RNA viruses multiply in & are released from the cytoplasm
27
General Features of Replication
1. Adsorption – virus attaches to host cell by specific binding of its spikes to cell receptors.
2. Penetration – Virus is engulfed into a vesicle by endocytosis.
3. Uncoating. The envelope around virus is removed, & RNA is freed into the cytoplasm.
4. Synthesis: The viral genes controls the cell & synthesizes basic components of new viruses: e.g. RNA molecules, capsomers, spikes
5. Assembly – Viral spike proteins inserted into the membrane for the viral envelope, forming a nucleocapsid from RNA & capsomers.
6. Release – Enveloped virus bud out of membrane, able to infect another cell.
Viruses enter by endocytosis or fusion.
Fusion causes a virus to fuse with the cell membrane, leaving non-self within the body, leading to other possible diseases.
28
Outcomes of Viral Infection
Acute Infection:
A) Recovery with no residue effects
B) Recovery with residue effects e.g. acute viral encephalitis leading to neurological sequelae.
C) Death
D) Proceed to chronic infection
Chronic Infection:
A) Silent subclinical infection for life e.g. CMV, EBV
B) A long silent period before disease e.g. HIV, SSPE, PML
C) Reactivation to cause acute disease e.g. herpes and shingles.
D) Chronic disease with relapses and exacerbations e.g. HBV, HCV.
E) Cancers e.g. EBV, HTLV-1, HPV, HBV, HCV, HHV-8
29
Viral Pathogenesis
Viral pathogenesis: the process by which a viral infection leads to disease.
1. Viral pathogenesis is abnormal situation of no value to the virus.
2. Majority of viral infections are subclinical. It's not in the interest of the virus to severely harm or kill the host.
3. The consequences of viral infections depend on the interplay between a number of viral & host factors.
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Factors determining viral Pathogenesis
1. Effects of viral infection on cells (Cellular Pathogenesis)
2. Entry into the Host
3. Course of Infection (Primary Replication, Systemic Spread, Secondary Replication)
4. Cell/Tissue Tropism
5. Cell/Tissue Damage
6. Host Immune Response
7. Virus Clearance or Persistence
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Transmission of Viruses
1. Respiratory transmission e.g. Influenza A virus
2. Faecal-oral transmission e.g. Enterovirus
3. Blood-borne transmission e.g. Hepatitis B virus
4. Sexual Transmission e.g. HIV
5. Animal or insect vectors e.g. Rabies virus
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Sites of Viral Entry
A) 1. Skin: Most viruses which infect via the skin require a breach in the physical integrity of this effective barrier, e.g. cuts or abrasions.
2. Many viruses employ vectors, e.g. ticks, mosquitos or vampire bats to breach the barrier.
B) 1. Respiratory tract: Respiratory tract & all other mucosal surfaces possess sophisticated immune defence mechanisms, as well as non-specific inhibitory mechanisms (ciliated epithelium, mucus secretion, lower temperature) which viruses must overcome.
C) GIT - a hostile environment; gastric acid, bile salts, etc. Viruses that spread by the GI tract must be adapted to this hostile environment.
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Course of Viral Infection
1. Primary Replication: The place of primary replication is where the virus replicates after gaining initial entry into the host.
2. Frequently determines whether the infection will be localized at the site of entry or spread to become a systemic infection.
3. Systemic Spread: Apart from direct cell-to-cell contact, the virus may spread via the blood stream & the CNS.
4. Secondary Replication: Secondary replication takes place at susceptible organs/tissues following systemic spread.
5. Primary is less effective as virus will not be in optimal position for replication, which can greatly alter chances of pathogenesis. Less adapted to site of infection, less likely pathogenesis is to occur.
6. Secondary infection means a virus reaches a more optimal cell type for replication, which is likely more damaging.
34
Cell Tropism
Viral affinity for specific body tissues (tropism) is determined by:
1. Cell receptors for virus.
2. Cell transcription factors that recognize viral promoters & enhancer sequences.
3. Ability of the cell to support virus replication.
4. Physical barriers.
5. Local temperature, pH, & oxygen tension enzymes & non-specific factors in body secretions.
6. Digestive enzymes & bile in the GIT that may inactivate some viruses.
35
Immune response to viral infection
1. The immune response to the virus probably has the greatest impact on the outcome of infection.
2. In the most cases, the virus is cleared completely from the body & results in complete recovery.
3. In other infections, the immune response is unable to clear the virus completely & the virus persists.
4. In a number of infections, the immune response plays a major pathological role in the disease.
5. In general, cellular immunity plays the major role in clearing virus infection whereas humoral immunity protects against reinfection.
36
Interferons and Natural Killer Cells
Induction of Type I Interferons:
1. The double-stranded RNA (dsRNA) of the virus induces the expression of the interferons by the infected cell, as the body recognises the non-self.
2. The interferons start a general inflammatory response, & can help activate killer cells.
Interferons & Natural Killer Cells
3. In addition, IFN-α & IFN-β binding induces a specific protein kinase called RNA-dependent protein kinase (PKR)
4. The binding of IFN-α & IFN-β to NK cells induces lytic activity
5. Effective in killing virally infected cells
6. Enhanced by IL-12
37
Viral Neutralisation by Humoral Antibody
1. Antibodies produces to viral receptor can block infection by preventing viral binding to host cells.
2. Random & non-specific, not targeting a specific virus.
3. Viral Neutralization by antibody sometimes occurs after viral attachment.
4. Some may block viral penetration by binding to epitopes necessary to mediate fusion of the viral envelope with the plasma membrane.
5. Some cause the lysis of the enveloped virions
6. Some agglutinate viral particles & function as an opsonizing agent
38
Cell-mediated antiviral mechanisms
1. Antibodies, although crucial in containing the spread of the virus, are not able to eliminate the virus once infection has occurred.
2. Once infection occurs, cell-mediated immune mechanisms become the most important:
2 main components of cell-mediated antiviral defence
1. CD8+ Tc cells
2. CD4+ Th1 cells (CD4+ Tc cells)
Changes defence from innate to adaptive.
39
Viral response to host-immune response
1. Viruses encode proteins that interfere at various levels with specific or nonspecific host defences.
2. Some develop strategies to evade the action of IFN-α & IFN-β
3. Some inhibit the antigen presentation by infected hosts by preventing antigen delivery to class I MHCs, blocking adaptive immunity.
4. Some reduce levels of class II MHCs on cell surface
5. Others evade complement-mediated destruction
6. Some cause generalized immunosuppression-direct viral infection of lymphocytes or macrophages
7. Some constantly change their antigens e.g. Influenza
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The life cycle of a pathogen
1. Reservoir - Maintain reservoir
2. Transmission - Transport to and entry in host
3. Colonisation - Adhere & invade cells or tissues
4. Proliferation - Multiply in host in a nutrient-rich area
5. Evade host defence
6. Return to reservoir
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Bacterial pathogenicity Stages I & II
Bacterial pathogenicity I
1. Pathogenicity & Virulence
2. Transmission
3. Adhesion
4. Invasion
Bacterial pathogenicity II
5. Bacterial growth & colonisation
6. Evading host defence
7. Damage by toxins
8. Expression of virulence factors
42
Define: Pathogenicity & Virulence
How do pathogenic & virulence relate?
Pathogenicity: ability of organism to cause disease
Virulence: degree of harm caused by microorganism
Thus, an organism can be pathogenic & depending on conditions, may exhibit different levels of virulence.
Virulence depends on infectivity, invasiveness, & degree of damage.
This in turn means virulence, number of pathogen & host resistance will affect pathogenicity.
43
Virulence Factor
Components that contribute to pathogenicity & virulence, including factors involved in:
1. adhesion
2. invasion
3. evasion of host defence
4. obtaining nutrients from the host
5. toxicity
44
How is Virulence measured?
Using the Infectious & Lethal Dose:
Infectious Dose: ID50: dose to infect 50% of hosts
Lethal Dose: LD50: dose to kill 50% of hosts
45
What are the two methods of Transmission?
1. Direct host-to-host transmission
2. Indirect host-to-host transmission - facilitated by living or inanimate objects
46
What are the two Portals of Entry?
What must bacteria conquer?
Skin: Not common if skin is healthy; can be through e.g. hair follicles, punctures, cuts
Mucosal surfaces: More favourable for infection (warm, moist, more nutrients); e.g. respiratory tract, GI tract
Bacteria must compete with commensals, evade host defences & obtain nutrients
47
What are the 5 Direct transmission routes?
1. Respiratory system e.g. Mycobacterium tuberculosis
2. Body contact e.g. STDs, skin infections, ringworm, warts, through damaged skin e.g. Staphylococcus aureus
3. Faecal-oral route e.g. through contact (or indirect through e.g. food), GIT pathogens, e.g. Salmonella enterica
4. Body fluids: Hepatitis, HIV
5. Vertical transmission: Prenatal/perinatal/postnatal, Germline (through viral DNA; e.g. certain types of leukaemia)
48
What are the 5 Indirect transmission: vehicles?
1. Soil
2. Contaminated water e.g. Vibrio cholerae
3. Contaminated food
4. Fomites (inanimate objects: beds, toys, surgical instruments) e.g. Clostridium difficile
5. animals
49
Describe bacterial Adhesion
1. Bacteria must adhere to host cells or tissues to colonise.
2. Bacteria must also survive in host environment & compete with normal microbiota.
3. Adherence to surfaces depends on adhesins.
50
What are the four Bacterial adhesins?
Proteins
1. Fimbrial
2. Other surface proteins
Polysaccharides
1. Components of capsules
2. Teichoic/lipoteichoic acid - only in G+ve
51
Describe the Host factors for adhesion
Adhesins interact with receptors on the cell surface of the host
1. protein-protein interactions
2. protein-carbohydrate interactions
3. Receptors in host cells: membrane proteins, glycolipids, extracellular matrix proteins (collagen, fibronectin etc)
52
How does the Fimbriae of Escherichia coli cause UTIs?
1. Escherichia coli frequently causes UTIs
2. P-pili or type I pili bind to sugar moieties (mannose) of glycolipids on epithelial cells lining urinary tract.
53
Describe both Extracellular & Intracellular Invasion
After adherence, pathogens may invade further into tissues or cells
Extracellular invasion: Barriers of tissues broken down
Intracellular invasion: Microbes penetrate cells & survive intracellularly
54
Describe: Extracellular invasion
1. Allows access to niches in tissue that aid in proliferation & spreading.
2. Achieved through production of enzymes that:
A) attack extracellular matrix
B) degrade carbohydrate-protein complexes between cells
C) disrupt cell surface.
55
Describe: Intracellular invasion
1. Some pathogens penetrate cells & survive intracellularly
2. A few are obligate intracellular. Others use it as a means of proliferation or spreading.
3. Phagocytic cells invaded through phagocytosis
4. Non-phagocytic cells invaded using systems that induce a phagocytosis-like process.
56
Process of Phagocytosis
1. The phagocytic white blood cell encounters a bacterium the binds to the cell membrane
2. The phagocyte uses its cytoskeleton to push its cell membrane around the bacterium, creating a large vesicle, the phagosome
3. The phagosome containing the bacterium separates from the cell membrane & moves into the cytoplasm
4. The phagosome fuses with lysosomes containing digestive enzymes
5. The bacterium is killed & digested within the vesicle
57
How can pathogens survive Phagocytosis?
1. Reside in the phagolysosome (Coxiella burnetti)
2. Reside in unfused phagosome (Mycobacterium spp., Salmonella spp.)
3. Destroy or escape from phagosome and live in cytosol (Lysteria monocytogenes, Rickettsia rickettsii)
58
How do Gve- bacteria use proteins to Invade non-phagocytic cells?
1. Bacterial proteins recruit host proteins to induce phagocytosis
E.g. secretion system used by some Gve- bacteria (Salmonella, Pseudomonas)
2. Invasion proteins injected
3. Activate host signalling & recruit actin
59
How is host invaded by an Adhered bacterial pathogen?
Adhered bacterial pathogen:
Host invasion via phagocytosis or induced uptake through host cell membrane
Intracellular residence in:
- phagolysosome
- unfused phagosome
- host-cell cytosol
Adhered bacterial pathogen:
Proteases
Glycanases
Extracellular invasion of host tissues
60
Describe: Growth & colonisation
1. Pathogens must find niche that is optimal for growth & colonisation
2. Can be in blood, tissues, or intracellularly
3. Often involves formation of biofilms on biotic or abiotic surfaces
61
Describe: Biofilms
1. Bacteria attach to surface, grow, & become enveloped in matrix
2. A biofilm protects from phagocytosis, antibiotics, disinfectants by making them much more resistant
3. High bacterial density: production of virulence factors through quorum sensing
62
Describe why Iron is an issue for Microbial nutrition?
1. Iron is the main limiting nutrient in the host, as most iron is complex to proteins, making it hard to access.
2. In aerobic conditions, iron is oxidised in ferric form (FeIII); has very low solubility
In the body, most iron is complexed to proteins
- transferrin (serum)
- lactoferrin (other extracellular fluids)
- ferritin, haemoglobin (intracellular)
63
How do microbes get Iron?
Uptake of free iron or iron complexes:
1. direct contact using cell surface proteins:
e.g. transferrin binding protein (TBP) & haemoglobin binding protein (HBP)
2. by secreting small compounds (siderophores) with very high affinity for iron that capture iron from host proteins or insoluble ferric salts
64
Describe Siderphores
1. Produced when [iron] is low
2. Low mol weight, high affinity for iron
3. Compete for free or bound iron
4. Transport iron into cell
5 Use Catechol group or Hydroxymate group to bind to iron
65
Explain how the Siderophore-dependent iron transport works
1. Siderophore has higher affinity than the iron source for iron
2. Siderophore binds to iron, then releases it as the receptor/transport system has a greater affinity for iron
3. Reduces the iron to release it for use.
66
List the four methods to Evading host defence
1. Evade complement
2. Resist phagocytosis
3. Intracellular survival
4. Evade host antibody response
67
Describe Evading Complement
Capsules: Thick polysaccharide layer around cell, preventing complement activation.
LPS O-antigen: Elongated O chains prevent complement activation by keeping the antigens at a distance from detection.
68
How do microbes resist phagocytosis?
1. Prevent effective contact with phagocyte
- e.g. biofilms, capsules or specific proteins
2. Affect phagocyte migration
- S. pyogenes peptidase cleaves complement factor C5a
3. Destroy phagocytes
- Using toxins such as leukocidins
69
Survival inside cells
1. Intracellular life protects from e.g. phagocytes, complement, antibodies, some antibiotics
2. Some pathogens are phagocytosed but survive
- survive phagolysosome
- prevent formation of phagolysosome
- destroy or escape from phagosome & live in cytosol
3. Some pathogens invade non-phagocytic cells
70
How do pathogens evade host-antibody response?
1. Bind host proteins, e.g. fibronectin, albumin
e.g. M protein Streptococcus pyogenes not detected as “foreign”
2. Produce surface protein which bind antibodies “backwards”
e.g. protein A - Staphylococcus aureus or protein G - Streptococcus pyogenes
3. prevents opsination (coating in antibodies which stimulates phagocytosis)
71
Avoiding opsinisation
use of an anti-opsination with protein A from S. aureus
72
Damage by toxins
1. Products of microbes
- cause immediate host damage
- induce inflammation
Types of Toxins
2. Exotoxin: actively secreted during growth
3. Endotoxin: structural part of microbe, only released during lysis
4. Toxoid - inactive or very low activity; used for vaccination
73
Transmission of Exotoxins
1. Ingestion of pre-formed exotoxin - food poisoning
(N.B. in this type of "infection" there is no adherence/colonisation/growth of the pathogen in the host)
2. Colonisation followed by exotoxin production
3. Infection of tissue followed by toxin production
4. Damage can be local or toxin can spread though e.g. blood
74
Exotoxins
1. Usually proteins, thus heat-labile
2. Host-site specific exotoxins - Affect specific cells: neurotoxins, enterotoxins, cytotoxins
3. Membrane disrupting toxins - Leukocidins, haemolysins, phospholipases
4. Superantigen type: Stimulate T cells to release cytokines
75
Membrane disrupting toxins
1. Pore forming toxin
2. Exotoxin forms pore in membrance
3. Cell lysis – uncontrolled entry of water causes cell to swell & burst
4. Bilayer disruption
5. Phospholipase exotoxin causes disruption of bilayer
6. Cell lysis
76
Superantigens
1. Produced by e.g. staphylococci, e.g. toxic shock syndrome toxin (TSST) & several other enterotoxins.
2. Much higher proportion of T cells respond as compared to normal antigens (10% vs <0.01%)
3. Corrupts immune system, leading to massive non-specific inflammatory response.
4. Leads to tissue damage, circulatory shock, multi-organ failure – which can release nutrients for the pathogen
77
Endotoxin: lipid A component of LPS
1. Heat stable
2. In outer membrane of Gram-ve bacteria
3. Released only when bacteria are ruptured or destroyed (lysis)
4. Induces fever (pyrogenic), initiates complement & clotting cascades; toxic shock
5. Antibiotic treatment may lead to release of LPS
78
Expression of virulence factors
1. Bacteria may have to cope with very different conditions (nutrients, oxygen, temp etc.)
2. Pathogens can sense environment to regulate expression of virulence genes
3. e.g. early steps: produce adhesins; late steps: produce exotoxins, down-regulate adhesins (which may be target for host defence)
79
Regulation by numbers: quorum sensing
1. Many (pathogenic) bacteria only produce virulence factors until a quorum (minimal number) of cells is present.
Cell-cell communication, with 2 components:
2. Autoinducer (AI): small diffusable molecule
3. R protein: Activates transcription of genes when R protein binds AI; binding only occurs at high [AI]. High [AI] only at high cell density
The more AI there is, the more binds to the R protein, allowing the R protein to switch on or off the expression of genes.
80
Define Pathogen
pathogen –any organism that produces a disease
- includes bacteria which produces an agent (includes toxin)
E.g. Food poisoning – may be cause by a toxin rather than the bacteria itself -
81
Define Pathogenicity
Pathogenicity – the ability of a pathogen to cause disease
82
Define Virulence
Virulence – is the intensity of the disease- Different bacteria have different ‘strengths’ of diseases-
83
Define Acute, Chronic & Latent infections
Acute infection: Sudden/rapid, usually short-lived. Can be severe
Chronic infection: Develops slowly. Long lasting &/ or recurrent
Latent infection: Appears a long time after initial infection
84
Define Healthcare associated infection (HCAI) or (HAI) &
Opportunistic infections
Healthcare associated infection (HCAI) or (HAI): Results from direct treatment in a health-care setting
Opportunistic: Caused by organisms that DON’T normally infect healthy hosts.
85
Define Localised & Systemic infections & Bacteraemia
Localised infection: Infection that remains at one body site or organ.
Systemic infection: Infection that has spread to multiple organs/ the blood
Bacteraemia: Bacteria present in the blood
86
Define Primary & Secondary Infections
Primary infection: Initial infection within a patient
Secondary infection: Infections that follow a primary infection
87
Define Septicaemia, Sepsis & Septic Shock
Septicaemia: Life-threatening condition arising from pathogens in the blood
Sepsis: Host response to high level of infection in the blood-
Septic Shock: Sepsis accompanied by low blood pressure- High risk of death
88
Upper respiratory tract infections – Nose & throat
Upper respiratory tract infections – Nose & throat
Common infections = Pharyngitis and tonsillitis
Majority of infections here are viral, but a common bacterial infection here is S.pyogenes, as “Strep throat”
89
GAS (Group A Streptococcus)
Group A Streptococcus Also Known As GAS
E.g. Streptococcus pyogenes
Throat & skin infections.
invasive GAS= IGAS
Toxic shock syndrome & necrotizing fasciitis
90
GBS (Group B Streptococcus)
Group B Streptococcus AKA GBS
EG Streptococcus agalactiae
Present in Gut / urinary tract / Vagina–>(serious new-born infections including meningitis)
UTI, skin, bloodstream, pneumonia, soft-tissue bone & joint infections
Pregnant woman are offered a GBS swab to check for presence in the vagina
91
Group C, F & G Streptococci
Group C, F & G streptococci
Less common ( animals) – still potential to cause serious infection
92
Upper respiratory tract infections (URT): Pharyngitis & tonsillitis
Main symptoms:
Inflamed tonsils, Difficulty swallowing,
Fever, headache
Opportunistic Pathogen/ Spread by Respiratory droplets
Complications:
Tonsillar abscesses (quinsy), otitis media, sinusitis, bacteraemia.
Less common symptoms
Scarlet fever- Strep throat symptoms + a body rash which spreads. (bright red/ raised pin head rash)
Often occurs in spring - school children.
Can trigger Autoimmune effect- Rheumatic fever, glomerulonephritis (Kidney)
Invasive infection (iGAS) –
Occasionally GAS infection will breach barriers to infection & become a life threatening- Systemic infection
(necrotising fasciitis & Streptococcal toxic shock syndrome)
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Upper respiratory tract infections (URT): Acute otitis media (Ear)
Viral - Most common
Bacteria:
- Streptococcus pneumoniae
- Haemophilus influenzae
Symptoms: (ACUTE):
- Rapid onset, pain in ear, hearing loss,
- Dizziness (balance),
- fever, vomiting, diarrhoea
Ear infections are more common in children.
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Upper respiratory tract infections (URT): Chronic otitis media (Ear)
Viral most common
Bacteria:
- Streptococcus pneumoniae
- Haemophilus influenzae
Chronic infection can cause:
Tissues surrounding the Eustachian tube swell up.
Blocks Eustachian tube.
The air in the middle ear is absorbed into the surrounding tissues.
A vacuum forms in the middle ear.
Fluid accumulates.
Leads to Glue ear/ recurrent infections
Children get grommets fitted to help equalise the pressure
95
Upper Respiratory Tract (URT): Infections Conjunctivitis
Conjunctiva: loose connective tissue that covers the surface of eyeball
Causes:
Viral - most common
Bacterial
Allergic
Reactive
STI associated
Symptoms:
Redness in the white of the eye / inner eyelid
Increased amount of tears
Thick yellow discharge that crusts over the eyelashes especially after sleep
Green or white discharge from the eye
Burning, itchy eyes
Blurred vision
Increased sensitivity to light
Bacterial e.g.
- Staphylococcus sp.
- Streptococcus sp.
- Haemophilus sp.
Treatment: topical chloramphenicol
96
Upper Respiratory Tract (URT): STD associated conjunctivitis
Neisseria gonorrhoeae:
Severe conjunctivitis - new-born.
Perforation of cornea. (vision loss)
Chlamydia trachomatis:
Inclusion conjunctivitis in adults
Specifically associated with chlamydia
Repeated infection causes Trachoma: Roughening of inner surface of the eye lid
- Damages the eye
- Spread by contact (towels, touch, flies)
- Leading cause of blindness in low income countries – if left untreated
97
LRT infections: Acute bronchitis
95% viral
Bacterial - Mycoplasma pneumoniae
Atypical pneumonia
Symptoms:
Non-productive cough (no sputum),
shortness of breath,
fever, chest pains
(lasts 10-11 days)
Self limiting
Primary infection (viral or bacterial)
can lead to complications:
2ry bacterial infection
Streptococcus pneumoniae
Haemophilus influenzae
=SEVERE ACUTE bronchitis
(Productive cough)
98
LRT infections: Chronic bronchitis
Inflammation of trachea & bronchi- but is long term
Usually due to smoking/irritants *(not infection)
Exacerbated by bacterial infection:
Streptococcus pneumoniae
Haemophilus influenzae
Symptoms
persistent cough (> 3 months),
excessive mucous secretion
Associated with COPD
(Chronic Obstructive Pulmonary Disease)
99
LRT infections: Lungs - Pneumonia
Infection of lungs; inflammation of alveoli
Can be viral but in adults it is usually bacterial
Streptococcus pneumoniae
Haemophilus influenzae
Staphylococcus aureus
Klebsiella pneumoniae
Symptoms:
fever, cough (productive)
shortness of breath
difficulty / pain on breathing
Patient will be ILL if they have pneumonia
Major cause of death in the elderly
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LRT infections: Lungs -Tuberculosis
Lung infection which can develop into a latent infection.
Mycobacterium tuberculosis
Symptoms
Persistent productive cough (> 3 weeks)
Blood in sputum
Chest pain, shortness of breath,
Loss of appetite / weight loss
Fever (night), fatigue
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Urinary Tract Infections (UTI)
Ascending UTI
– Bacterium enter urethra & travels upwards
Bacteria attach strongly to urinary epithelium & overcome flushing effect of urine. E.g. Pilli on some strains of E.coli
Commonly caused by Gram negative bacteria (part of normal gut flora)
E. coli (85%)
Descending UTI
(UT becomes infected from the blood)
Much rarer.
Infection from blood e.g. Staphylococci
Factors predisposing to ascending UTI Infection:
Length of urethra-
more common in women
More common in children under 10
Catheterisation (HAI)
(50% will get UTI)
Disruption of normal urine flow-
e.g. pregnancy, enlarged prostate/ kidney stone
Older age (incomplete bladder emptying)
Diabetes (more severe infections)
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Urinary Tract Infections (UTI): Ascending UTI
Lower urinary tract e.g. cystitis - E. coli *
Symptoms
Difficulty in passing urine/ pain on urination (dysuria)
Increased urge to urinate.
Urine may be cloudy/ smelly.
Dull pain in pubic region
Back pain/ generally unwell
Asymptomatic in elderly or catheterised patients (difficult to diagnose)
Upper urinary tract e.g. pyelonephritis - E. coli
Symptoms:
Fewer UTI symptoms
Pain in your side / lower back
fever / loss of appetite/ feeling sick
haematuria (blood in the urine)
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Sexually Transmitted Infections (STIs)
Bacterial most common
Viral e.g. Human papilloma virus, Herpes type 2, HIV, HepB
Fungal e.g. Candida albicans
Protozoa (not usually in the UK)
Bacterial
Chlamydia trachomatis
Neisseria gonorrhoeae (a lot of AMR- an increasing problem)
Treponema pallidum (Causes syphilis)
104
Chlamydia trachomatis: Atypical bacteria
Symptoms
Women: discharge, pelvic pain → Pelvic Inflammatory Disease (PID), infertility, pain on urination
Men: discharge → inflammation of epididymis, pain on urination prostate, urethra. Infertility
75% of Women and 50% of men have NO symptoms
Complications
Adult: sterility, kidney disease, trachoma
Baby: premature birth, ectopic pregnancy,
neonatal conjunctivitis (trachoma), pneumonia
Diagnosis: from urine or swab. Kits available from the pharmacy
Vaccine:
in early trials
Treatment : antibiotics
105
Neisseria gonorrhoeae
Symptoms
Women: discharge, pelvic pain → PID, infertility
Men: discharge → inflammation of epididymis,
prostate, urethra. Infertility
(No symptoms in 50% women, 30% men)
Complications
Adults (women) : sterility, systemic infection
Baby: neonatal conjunctivitis →blindness
Diagnosis Kits available-
swab from cervix or urethra
detect bacteria-specific antibodies
Treatment
Used to be 100% curable by penicillin
Now high levels of beta lactam resistance
Current PHE guidance:
- Ceftriaxone 1g IM or
- Ciprofloxacin 50mmg stat (if sensitivity known)
MUST ALERT SEXUAL PARTNERS
106
Transmission: Direct, Indirect
Direct host-to-host transmission
Indirect host-to-host transmission - facilitated by living or inanimate objects
107
Avoiding opsination
Bacteria binds to Fc portion of antibodies (IgG), preventing effective binding to phagocyte receptors. Reduces opsonization & immune activation. E.g. in S. aureus
108
Superficial infections
Superficial infections are limited to the outer most layers of the skin, nails, hair & mucous membranes. Dermatophytes & candidiasis are the principle groups that cause such infections.
109
Fungi overview - 6
2 types:
1. yeasts unicellular & reproduce by budding or fission
2. moulds are multicellular & have spores.
3. Hyphae are long, branching tubular structures
4. Fungi are encased in rigid cell wall composed of chitin
5. Fungi cells are similar mammalian cells, making drugs only selecting fungal cells more difficult
6. Heterotrophic: fungi need preformed organic compounds to survive
110
Define: Geophilic, Zoophilic, Anthropophilic
Geophilic: grow in soil
Zoophilic: grow in animal
Anthropophilic: grow in people
111
Dermatophytes - 5
1. Moulds
2. Keratinophilic: Associated with infections of skin, nails & hair.
3. Spread through direct contact & spores
4. Symptoms – itching, burning, pain, irritation – relapse can occur
5. Risk factors – environmental, clothing, hyperhidrosis, immunocompromised
112
Ringworm - 5
1. E.g. Tinea corporis (ringworm of skin)
2. Presentation - Itchy pink or red scaly patch, well-defined inflamed boarder.
3. Lesions may overlap to produce a single large lesion & appear polycyclic.
4. Scalp ringworm presentation: Circular patches of alopecia, marked scaling
5. Treatment: antifungal creams (e.g. clotrimazole) &/or shampoos
113
Advice for all Tinea infections - 6
1. Clothing
2. Hygiene
3. Drying after washing
4. Avoid scratching
5. Wash clothes & bed linen
6. No need to avoid school or nursery
114
Ringworm treatment - 5
1. Tinea Corporis & Cruris – mild non-extensive disease
2. Imidazole – e.g. Clotrimazole. Multiple topical corticosteroids if needed
3. Terbinafine (> 12’s only)
4. Oral therapy if topical fails/immunocompromised/widespread infection: Terbinafine
5. If not tolerated or contraindicated: Itraconazole, Griseofulvin
115
Why is prompt & accurate diagnosis important for ringworm diagnosis?
Prompt & accurate diagnosis important, mistaken for eczema & treated with topical corticosteroids appearance becomes atypical & looses characteristic scaling & won’t heal.
116
Tina Capitis (scalp ringworm): Treatment - 3
1. Tinea Capitis (scalp ringworm) – generally PO treatment required:
2. Ketoconazole shampoo twice weekly for 2-4 weeks
3. >5yrs old use imidazole creams daily for 7 days to prevent risk of transmission
117
Terbinafine vs Griseofulvin (ringworm)
1. Sensitivity testing recommended (treat empirically initially – Terbinafine urban areas, Griseofulvin rural areas)
2. Griseofulvin for Microsporum spp. 1g OD, 4-8 weeks, continue for 2 weeks if symptoms improve but continue
3. Terbinafine for Trichophyton tonsurans. 250mg OD, 4 weeks
4. Review 4-8 weeks for signs of hair growth or treatment failure
118
Self-help measures for Tinea capitis - 4
Advise on self-care management strategies:
1. Soften surface cuts (e.g. moisturise) then tease away
2. Discard/disinfect object which transmit spores (e.g. hats)
3. Don’t share towels, washed frequently.
4. Inspect scalp regularly
119
Griseofulvin - 5
1. First antifungal drug. Resistance is rare
2. Narrow therapeutic range: Only effective for dermatophyte infections
3. Long courses: Short half-life, doesn’t persist in keratinous tissue after the end of therapy
4. Contraindicated in patients with severe liver disease & Lupus
5. Avoid if breastfeeding or pregnant, don’t father for 6 months
120
Griseofulvin metabolism, side effects - 5
1. Metabolised hence elimination is in the liver ergo contraindicate in patients with liver disease – inactive metabolites excreted in the urine.
2. Lupus: drug induced skin disorder, butterfly shaped rash on face, Griseofulvin worsens
3. S/Es: GI, headache, skin sensitivity, dizziness, confusion
4. Monitoring not normally required unless: anorexia, nausea, vomiting, fatigue or ab pain occurs & urine becomes very dark
5. Absorbed via GI tract – fatty meals will help absorption
121
Athlete's foot patterns - 5
Tinea pedis (Athlete’s feet) has various patterns:
1. Chronic hyperkeratotic tinea: patchy fine dry scaling on sole
2. "Moccasin" tinea: entire sole, heel & sides of the foot is dry but not inflamed.
3. Athlete's foot: moist peeling irritable skin between the toes
4. Clusters of blisters or pustules on the sides of the feet or insteps
5. Round dry patches on top of foot (ringworm) like tinea corporis
122
Tinea Pedis (Athlete's foot) - 4
1. Diagnostic tests not normally required – base diagnosis on appearance
2. Skin becomes scaled, macerated & fissuring
3. Geophilic or anthrophilic
4. Causative species: T. rubrum, T. mentagrophytes
123
Self-help measures: Athlete’s foot - 5
Advise on self-care management strategies:
1. Wear footwear which keeps feet cool & dry
2. Maintain good foot hygiene
3. Avoid scratching affected skin
4. Dry feet thoroughly after washing
5. Don’t share towels
124
Treatment: Tinea Pedis - 7
1st line:
1. Imidazole cream: 2-4 weeks
2. Terbinafine cream: 1 week (over 12)
3. Combine with hydrocortisone if required
4. Topical fails or severe infection – oral treatment: Terbinafine – 250mg OD, 2-6 weeks
5. If not tolerated or terbinafine contraindicated:
6. Itraconazole – 100mg OD, 30 days or 200mg BD, 7 days
7. Griseofulvin – 500-1000mg OD, 4-8 weeks (& two weeks after resolved)
125
Terbinafine - 4
1. Metabolized in the liver
2. Half life of 17hrs
3. Concentrated in keratinous tissue
4. Avoid in pregnancy, history of autoimmune disease, liver disease & severe renal impairment
126
Terbinafine S/Es - 4
Terbinafine S/Es:
1. GI disturbances – mild, headache
2. Hepatotoxicity (monitor every 4-6 weeks)
3. Serious skin reactions (e.g. Lupus) – stop therapy
4. Reported psychiatric disturbances
127
Onychomycosis (nails) - 4
1. Treatment: Terbinafine or itraconazole - Because both absorbed into nail matrix & remain active for months.
2. Common species: T. rubrum, T. mentagrophytes, Candida
3. Possible pain & discomfort
4. Treatment is difficult – nail clippings/scrapings needed
128
Onychomycosis (nails) advice - 6
1. Keep nails trimmed short.
2. Avoid sharing toenail clippers
3. Wear cotton, absorbent socks
4. Maintain good foot hygiene, including prompt treatment of any associated tinea pedis
5. Avoid prolonged or frequent exposure to warm, damp conditions if possible
6. Avoid trauma to the nails if possible
129
Onychomycosis (nails) treatment - 4
If topical treatment inappropriate or unsuccessful
1. Terbinafine 250mg OD, 6 weeks for fingernails (12-24 weeks for toenails)
2. Itraconazole (pulse therapy) 200mg BD 7 days, subsequent courses at 21-day intervals, 2 pulses for fingernails, 3 pulses for toenails
3. If cause is Candida infection: Oral itraconazole
4. Monitor after start of treatment for treatment success
130
Pityriasis versicolor - 5
1. Multiple macules & discoloured patches surrounded by lesions
2. Lesion severity worse in tropical climates
3. Member of the normal skin flora, lives only on skin because has growth requirement for medium chain fatty acids present in the sebum.
4. Lighter skin - pigment darkens. Darker skin - pigment is lighter.
5. Diagnosis: Wood lamp causes yellow-green fluorescence
131
Pityriasis versicolor Treatment - 4
1. Topical – shampoo if large areas affected e.g. Ketoconazole shampoo
2. Topical – imidazole if only small areas affected e.g. Clotrimazole
3. Systemic – only if topical fails: Itraconazole 200mg OD, 7 days
4. Do not prescribe topical or oral corticosteroids
132
Superficial Candida infections - 3
1. Commonly affected: mouth, vaginal, groin, under breasts & nappy area in babies (moist or chafe)
2. ‘Yeast like fungus’, normal flora of GI tract & mucous membranes
3. Species: Candida albicans, C. glabrata
133
Superficial Candida infections Treatments - 4
1. Systemic absorption: consider DDI with miconazole – e.g. warfarin – available OTC
2. Topical to avoid adverse effects.
3. >2 – topical miconazole. Oral not recommended in <18s, limited safety evidence. – for>18s fluconazole oral first line
4. Oral fluconazole (& HIV) – eradicates infection from all sites
134
Genital candidiasis – vaginal - 7
1. Candida albicans normal vaginal flora, problematic if level perturbed.
2. Vaginal candidiasis – common in pregnancy & diabetes mellitus
3. Symptomatic following broad spectrum antibiotic treatment
4. Recurrent episodes need investigating (>4 cases per year)
Presentation:
5. Intense vulval + vaginal pruritus
6. Thick white adherent plaques &/or discharge – odourless
7. Pain on intercourse & on urination
135
Genital candidiasis Treatment - 5
1. Oral therapy – fluconazole (150mg stat) first line
2. Topical treatment (clotrimazole) 500mg as a stat dose if oral treatment contraindicated
3. If vulval symptoms present: 1-2% clotrimazole cream 2-3 times daily, a week
4. Pregnant: clotrimazole 10% vaginal cream
5. If treatment failure/reoccurrence is a problem, check for balanitis in a male partner
136
Cutaneous candidiasis - 3
1. Folds of skin- esp. nappy area, groin, under breasts & between folds of fat
2. Risk factors: Systemic antibiotics, HIV, skin conditions, skin maceration, occupational
3. Presentation: pruritus and irritation, burning & pai
137
Cutaneous candidiasis Management - 5
1. Skin care advice
2. Topical imidazole +/- hydrocortisone
3. Oral treatment only when severe or when treatment has failed – fluconazole 50mg OD 2 weeks
4. For children – treat topically
5. Seek specialist advice if considering oral agent & <16
