Infection Flashcards
In what ways can you get an infection?
Directly from a source
Indirectly from a source via an intermediary (vector) or the environment (water, air, food, surfaces)
Directly from animals
From the patient themselves (microbiota= commensals)
What is infection?
The invasion of a hosts tissues by micro organisms causing disease
What are microbiotae/ commensals?
Microorganisms carried on skin and mucosal surfaces that are normally harmless or even beneficial, but can be harmful and cause disease if and when they are transferred to other sites
What are some methods of horizontal transmission?
Contact- direct, indirect and vectors
Inhalation- droplets (influenza) and aerosols (TB, chickenpox - spreads vastly)
What are some methods of vertical transmission?
Mother to child
Before or at birth
What 5 stages are involved in how microorganisms cause disease?
Exposure Adherence Invasion Multiplication Dissemination
What are some virulence factors of infection?
Exotoxins - cytolytic, AB toxins, super antigens, enzymes
Endotoxins
What are virulence factors?
Molecules expressed and secreted by pathogens that enable them to achieve Exposure, Adherence, Invasion, Multiplication and Dissemination and cause host cellular damage
What are the 4 P determinants of disease?
Pathogen (virulence factors, inoculum size (dose), antimicrobial resistance (antibiotics))
Patient (site of infection, comorbidities)
Practice
Place
What precedent would you follow to find out whether a patient has an infection?
History
Examination
Investigation
What history would you take of a patient you’re suspecting of having an infection?
Symptoms
- focal (specific), systemic (not specific)
- severity
- duration
Potential exposures
- e.g. Travel- where? what? who with? animals involved?
What main examination would you do on a patient you’re suspecting of having an infection?
Check for organ dysfunctions
What investigations would you do on a patient you’re suspecting of having an infection?
Specific
- looking at microorganisms directly
Supportive
- full blood count - neutrophils and lymphocytes
- C Reactive Protein
- blood chemistry- liver and kidney function tests
- imaging - x ray, ultrasound, magnetic resonance imaging (MRI)
- histopathology
—-> virology - antigen detection, antibody detection, detecting viral nucleic acid (DNA/RNA)
—-> bacteriology - specimen types (swabs, fluids, tissues), MC&S microscopy (bacterial and patient cells), culture, antibiotic susceptibility
What’s a pathogen?
Disease causing microorganism
Briefly describe viruses
10^-8 - 10^-7 m
Spikes- for attaching to specific surfaces
Envelopes
Protein coats (protects and organises)
Can be antigens - immune response promoted, facilitates viral entry into cell
What is the Baltimore classification of viruses?
I dsDNA II ssDNA III dsRNA IV (+)ssRNA , (-)ssRNA V (-)ssRNA VI ssRNA- RT DNA RNA dsDNA VII ds-DNA-RT
–> mRNA
Briefly describe bacteria
10^-6 - 10^-5m
Pilii, cell wall, capsule, cytoplasm, plasma membrane, plasmid, nucleoid, ribosomes, flagellum
Coccus- (circular) Stapphy (clusters) Strepty (chains)
Spirillus- (spiral)
Bacillus- rods
Gram positive
Gram negative
Aerobes (obligate)
Anaerobes (obligate)
*exception of obligate anaerobe - require O2 free environment for survival –> spores - survive at high temperature, pressure etc, don’t cause disease as spores
What is the pathogenesis of bacteria?
Virulence factors
- host entry (polysaccharide capsule)
- adherence to host cells (Pilii, fimbriae)
- invasiveness (collagenases)
- iron sequestration
Toxins- exo (diphtheria) endo (lipopolysaccharide)
Briefly describe fungi
Yeasts (single celled) - Candida albicans (thrush) - cryptococcosis neoformans (trees) - pneumocystis jiroveci Moulds (multicellular) - aspergillus species (bread) - dermatophytes (ringworm, athletes foot)
Briefly describe parasites
Protozoa (single celled) - gardia lamblia (diarrhoea) - cryptosporidium parvum (diarrhoea) - plasmodium falciparum (malaria) - trypansosoma cruzi Helminths (worms, multicellular) - roundworms (enterobius vermicularis) - tapeworms (taenia saginata) - flukes (schistosoma mansoni)
What does Coccus mean?
Round bacteria
What does stapphy- mean?
Clusters of cocci bacteria
What does strepto- mean?
Chains of cocci bacteria
What does spirillus mean?
Spiral bacteria
What does bacillus mean?
Rod shaped bacteria
What is an example of a single-stranded, non-enveloped DNA virus?
Parvovirus 19
What are some examples of double-stranded, non-enveloped DNA viruses?
Adenovirus
BK virus
Human papilloma virus
JC virus
What are some examples of double-stranded, enveloped DNA viruses?
Herpes virus
Hepatitis B
Molluscum contagiosum
What are some examples of single-stranded, positive, icosahedral, non-enveloped RNA viruses?
Coxsackievirus Echovirus Enterovirus Hepatitis A & E Norovirus
What are some examples of single-stranded, positive, icosahedral or helical, enveloped RNA viruses?
HIV Hepatitis C Rubella virus Encephalitis viruses Yellow fever virus West Nile virus
What are some examples of single-stranded, negative, helical, enveloped RNA viruses?
Ebola, Lassa, Marburg
Influenza, Parainfluenza
Respiratory syncytial virus (RSV)
What is an example of a double-stranded, icosahedral, non-enveloped RNA virus?
Rotavirus
Describe parvovirus
Single stranded Non enveloped DNA virus Child hood rash Slap cheek syndrome
Describe adenovirus
Double stranded Non enveloped DNA virus Respiratory Common cold Pneumonia
Describe BK virus
Double stranded Non enveloped DNA virus Polyomavirus Immunosuppressed Asymptomatic
Describe human papilloma virus
Double stranded Non enveloped DNA virus Keratinocytes, mucous membranes Benign papillomas/cancers, warts STDs
Describe JC Virus
Double stranded Non enveloped DNA virus Polyoma virus Immunosuppression
Describe herpes virus
Double stranded Enveloped DNA virus STD Hepstein Barr
Describe Hepatitis B
Double stranded Enveloped DNA virus Liver Flu like symptoms Unprotected sex Sharing needles
Describe molluscum contagiosum
Double stranded Enveloped DNA virus Small firm raised papules on skin Not painful but itchy Highly contagious- skin to skin
Describe coxsackievirus
Single stranded Positive Icosahedral Non enveloped Enterovirus Digestive tract Unwashed hands and contaminated surfacesFlu symptoms Red blisters Haemorrhagic conjunctivitis
Describe echovirus
Single stranded Positive Icosahedral Non enveloped GI tract Liver failure Myocarditis
Describe Enterovirus
Single stranded Positive Icosahedral Non enveloped Genus
Describe Hepatitis A & E
Single stranded Positive Icosahedral Non enveloped Virus found in stool Liver E in particular - pets/eating meat
Describe norovirus
Single stranded Positive Icosahedral Non enveloped High temp, stomach cramps, headache, aching limbs, dehydration, vomiting, diarrhoea Very contagious
Describe HIV
Single stranded Positive Icosahedral of helical Enveloped Lentivirus (AIDS) Affects helper T cells (CD4+)
Describe hepatitis C
Single stranded Positive Icosahedral of helical Enveloped Liver Conc in blood Blood to blood contact
Describe rubella virus
Single stranded Positive Icosahedral of helical Enveloped First week of pregnancy German/ 3 day measles
Describe encephalitis viruses
Single stranded
Positive
Icosahedral of helical
Enveloped
(Japanese, St. Louis, tick borne, Venezuelan, equine)
Inflammation of brain
Most commonly caused by herpes simplex virus
Describe Yellow fever virus
Single stranded Positive Icosahedral of helical Enveloped Fevers, chills, loss of appetitie nausea, muscle pain, headache Bite of female mosquito Vaccine exists Flavivirus genus
Describe West Nile fever
Single stranded Positive Icosahedral of helical Enveloped Flavivirus genus Mosquito Africa--> NY --> USA No vaccine
Describe Ebola, Lassa, Marburg
Single stranded Negative Helical Enveloped Vomiting Diarrhoea Rash Deceased liver and kidney function Fruit bats
Describe influenza, parainfluenza viruses
Single stranded Negative Helical Enveloped Flu symptoms
Describe respiratory syncytial virus (RSV)
Single stranded Negative Helical Enveloped Lower respiratory tract infections
Describe rotavirus
Double stranded Icosahedral Non enveloped Severe diarrhoea among infants Stools- virus passes out
What are some examples of gram positive cocci bacteria?
Staph aureus Coagulate -ve staph Alpha haemolytic streptococci Beta haemolytic streptococci (inc. strep pyogenes) Streptococcus pneumoniae Enterococcus faecalis
What are some examples of gram negative cocci bacteria?
Neisseria meningitidis
Neisseria gonorrhoea
Mortadella cattarhalis
Acinetobacter baumannii
What are some examples of gram positive bacilli bacteria?
Listeria monocytogenes
Bacillus anthracis
Bacillus cereus
What are some examples of gram negative bacilli bacteria?
Escherichia coli Klebsiella pneumoniae Proteus species Salmonella typhi Pseudomonas aeruginosa Haemophilus influenzae
What are the main constituents of the infection model?
Pathogen Patient Mechanism of infection Infection Management Outcome
Expand on Pathogens in the infection model
Virus
Bacterium (prokaryotic)
Fungus - yeast, mould (eukaryotic)
Parasites - protozoa, helminthology (worm) (eukaryotic)
Expand on the patient in the infection model
Person - age, gender, physiological state, pathological state, social factors
Time - calander time, relative time
Place - current, recent
Expand on the mechanism of infection in the infection model
Contiguous spread (direct) Inoculation Haematogenous Ingestion Inhalation Vector Vertical transmission
Expand on the infection in the infection model
Attachment –> toxin production –> host damage
Attachment –> interaction with host defences –> host damage
Attachment –> interaction with host defences –> inflammation –> host damage
Expand on management in the infection model
History
Examinations
Investigations
Treatment
- Supportive - symptom relief, physiological restoration
- Specific - antimicrobials, surgery- drainage, debridement, dead space removal
Infection prevention - hospital and community
- prevent infection transmission to - other patients, staff and contacts
Expand on the outcome of the infection model
Spectrum of Cured to Death with disability and chronic infection being intermediates
How are antimicrobials classified?
Antibacterial agents
Antifungal agents
Antiviral agents
Antiprotozoal agents
How are antibacterials classified?
Bactericidal/ bacteriostatic Spectrum- broad vs narrow Target site (mechanism of action) Chemical structure (antibacterial class)
What does bactericidal mean?
Antibiotic kills organism completely
What does bacteriostatic mean?
Antibiotic inhibits the organism but it can come back
What is the relevance of ‘classes of drugs’?
Groups together drugs with the same basic function and mechanism of action
What are the ideal features of antimicrobials?
Selectively toxic Few adverse effects Reach site of infection Oral/ IV formulation Long half life (infrequent dosing) No interference with other drugs
What are the 4 mechanisms of action of antibacterials?
Those that affect: Cell wall synthesis Cell membrane function Protein synthesis Nucleic acid synthesis
What antibacterials affect cell wall synthesis?
B-lactams (penicillin, cephalosporins)
Glycopeptides (vancomycin)
What antibacterials affect cell membrane function?
Polymixins (colistin)
What antibacterials affect protein synthesis?
Tetracyclines
Aminoglycosides (gentamicin)
Macrolides (erythromycins)
What antibacterials affect nucleic acid synthesis?
Quinolones (ciprofloxalin, trimethoprim, rifampcin)
How do B-lactams work to affect cell wall synthesis?
Cross linkage between peptidoglycan - gives cell wall rigidity
Achieved by penicillin binding protein
Penicillin gets in and blocks penicillin binding protein so protein can no longer bind to chains of amino acids- no cross linkage
How do Glycopeptides work to affect cell wall synthesis?
Sits on peptidoglycan chains and stops penicillin binding protein from binding (acts at an earlier stage than B- lactams)
What is the most common mechanism of action of antibacterials?
Interupting cell wall synthesis
What is the rarest mechanism of action of antibacterials?
Interrupting cell membrane function
In what three ways can organisms become resistant to antibacterials?
Drug inactivating enzymes- B-lactamases, aminoglycoside enzymes
Altered target- target enzyme has lowered affinity for antibacterials e.g. resistance to meticillin, macrolides and trimethoprim
Altered uptake- reduced ability of antibiotic to get close to bacteria; decreased permeability (e.g. B-lactams) or increased efflux (e.g. Tetracyclines)
What is the genetic basis of antibiotic resistance?
Chromosomal gene mutation- bacteria undergo spontaneous gene mutation conferring resistance; when exposed to antibiotics, bacterial cell with resistance survives and multiplies
Horizontal gene transfer- plasmid to plasmid or plasmid to chromosome; genetic material moves from one organism to another by conjugation, transduction and transformation
In what two ways can you measure antibiotic activity?
Disc testing- impregnate antibody into paper filter disc and observe bacterial growth- organism won’t grow where there is sufficient antibiotic to inhibit its growth
Minimum inhibitory concentration- more mathematical, lots of test tubes with a range of antibiotic concentrations and the same concentration of organism- organism growth is monitored
What are the 4 types of B-lactams?
Penicillins
Cephalosporins
Carbapenems
Monobactams
What is the mechanism of action of B-lactams?
Affect cell wall synthesis
Benzylpenicillin
B-lactam, penicillin
Affect cell wall synthesis
Mainly active against streptococci
Penicillin V
B-lactam, penicillin
Affect cell wall synthesis
Mainly active against streptococci
Amoxicillin
B-lactam, penicillin
Affect cell wall synthesis
Mainly active against streptococci
Also active against gram negatives
Flucoxacillin
B-lactam, penicillin
Affect cell wall synthesis
Active against staphylococci and streptococci
Coamoxiclav
B-lactam, penicillin
Affect cell wall synthesis
Active against staphylococci, streptococci, anaerobes and Gram negatives
Tazocin
B-lactam, penicillin
Affect cell wall synthesis
Active against staphylococci, streptococci, anaerobes, and High activity against gram negatives including pseudomonas
Describe cephalosporins
B-lactam,Cephalosporin
(Generations with high gram negative and low gram positive activity; broad spectrum but no anaerobe activity: concern over association with C. difficile)
Cefalexin
1st generation cephalosporin, B-lactam
Cefuroxime
2nd generation cephalosporin, B-lactam
Cefotaxime
3rd generation cephalosporin, B-lactam
Ceftriaxone
3rd generation cephalosporin, B-lactam
Blindness/ meningitis
Good activity in CSF
Ceftazidime
3rd generation cephalosporin, B-lactam
Meropenem/ imipenem
Carbapenem, B-lactam
Very broad spectrum (including anaerobes)
Active against most(not all) gram negatives
Generally safe in penicillin allergy, other than anaphylaxis
Aztreonam
Monobactam, B-lactam
What is the main mechanism of action of Glycopeptides?
Affect Cell wall synthesis
Vancomycin
Glycopeptides
Affects cell wall synthesis
Active against most Gram positive (not gram negative)
Some enterococci resistant (VRE)
Resistance in staphs is rare
Not absorbed (oral for C.difficile only)
Therapeutic drug monitoring (TDM) required as there is a narrow therapeutic window - give enough, not too much, toxicity
Teiccplanin
Similar activity to vancomycin, but much easier to administer
Glycopeptides
Affects cell wall synthesis
Active against most Gram positive (not gram negative)
Some enterococci resistant (VRE)
Resistance in staphs is rare
Not absorbed (oral for C.difficile only)
Therapeutic drug monitoring (TDM) required as there is a narrow therapeutic window - give enough, not too much, toxicity
What is the main mechanism of action of tetracyclines?
Affecting protein synthesis
Tetracycline and doxycycline
Similar, broad spectrum
Both oral only
Specific use in penicillin allergy usually from gram positive
Active in atypical pathogens in pneumonia
Active against chlamidya and some Protozoa
Shouldn’t be given to children younger than 12 years
What is the main mechanism of action of aminoglycosides?
Affecting protein synthesis
Gentamicin
Aminoglycosides
Most common agent
Profound activity against gram negative
Good activity in blood and urine
Potentially nephrotoxic/ototoxic
Therapeutic drug monitoring (TDM) required- toxicity to kidney
Generally reserved for sever gram negative sepsis
What is the main mechanism of action of macrolides?
Affecting protein synthesis
Erythromycin and clanthromycin
Macrolides
Affects protein synthesis
Well distributed including intracellular penetration
Alternative to penicillin for mild gram positive infections
Also active against atypical respiratory pathogens
What is the main mechanism of action of Quinolones?
Affects nucleic acid synthesis
Ciprofloxacin
Quinolone Affects nucleic acid synthesis Commonest example Inhibits DNA gyrase (coiling of nucleic acid) Very active against gram negatives Also active against atypical pathogens Increasing resistance and risk of CDI
Trimethoprim and sulphonamides
Inhibitors of frolic acid synthesis
Trimethoprim used alone in UK for UTIs
When combined with sulphamethoxazole- cotrimoxazole, used to treat PCP (pneumocystitis pneumonia) , has activity against MRSA
What are two types of antifungals?
Azoles
Polyenes
How do Azoles work?
Antifungal
Active against yeasts, and or moulds
Inhibit cell membrane synthesis
Fluconazole
Antifungal Inhibits cell membrane synthesis Used to treat candida Hra, vori, posaconazol Also active against aspergillus
How do polyenes work?
Antifungals
Inhibit cell membrane function
Nystatin and amphotericin
Antifungals
Inhibit cell membrane function
Nystatin for topical treatment of candida
Amphotericin for IV treatment of systemic fungal infections (e.g. Aspergillus)
What are two common antivirals?
Aciclovir
Oseltamivir (tamiflu)
Aciclovir
Antiviral
When phosphorylates inhibits viral DNA polymerase
Herpes simplex - genital herpes, encephalitis
Varicella zoster - chicken pox and shingles
Oseltamivir (Tamiflu)
Antifungal
Inhibits viral neuraminidase
Influenza A & B
Metronidazole
Antibacterial and antiprotozoal agent Active against anaerobic bacteria Also active against Protozoa - amoebae (dysentery and systemic) - giardia (diarrhoea) - trichomonas (vaginitis)
Look at infection model for acute sepsis in the emergency model
Neisseria Meningitidis
Define the immune system
Cells and organs that contribute to immune defences against infections and non infectious conditions (harmless substances)
Define infectious disease
When the pathogen succeeds in evading and / or overwhelming the hosts immune defences
What are the four broad stages of an immune response?
Pathogen recognition - cell surface and soluble receptors
Containing / eliminating the infection - killing and clearance mechanisms
Regulating itself - minimum damage to host (resolution)
Remembering pathogens - preventing disease from recurring
What are the two types of immunity?
Innate
Adaptive
What are the 4 first lines of defence in innate immunity?
Physical barriers
Physiological barriers
Chemical barriers
Biological barrier
What are the physical barriers of the first line of defence of innate immunity?
Skin (SA 1-2m^2)
Mucous membrane (mouth, resp tract, GI tract, urinary tract)
Bronchial cilia
What are the physiological barriers of the first line of defence of innate immunity?
Diarrhoea- food poisoning, allergies
Vomiting- food poisoning, hepatitis, meningitis
Coughing- pneumonia
Sneezing- sinusitis
What are the chemical barriers of the first line of defence of innate immunity?
Low pH - skin(5.5) stomach(1-3) vagina(4.4)
Antimicrobial molecules
-IgA (tears, saliva)- binds specifically to microorganisms and prevents it from attaching to mucous membrane
-Lysozyme (sebum, perspiration, urine)
-Mucous (mucous membrane)
-Beta defensins (epithelium)
-Gastric acid and Pepsin
What are the biological barriers of the first line of defence of innate immunity?
Normal flora
- non pathological microbes
- strategic locations- nasopharynx, mouth/throat, skin, GI tracts, vagina, (lactobacillus spp)
- absent in internal organs
Benefits - compete with pathogens for attachement sites and resources, produce antimicrobials chemicals, synthesise vitamins (K, B12 and others)
What are some normal flora found on skin?
Staphylococcus aureus Staphylococcus epidermidis Streptococcus pyogenes Candida albicans Clostridium perfringens
What are some normal flora found in the nasopharynx?
Streptococcus pneumoniae
Neisseria meningitidis
Haemophilius species
What are some clinical problems associated with normal flora?
–>Normal flora can be displaced from its normal location to a sterile location
-breaching skin integrity (skin loss, burns; surgery; injection drug users; IV lines)
-fecal oral route (food borne infection)
-fecal perineal urethral route (UTI)
-poor dental hygiene/ dental work (dental extraction, gingivitis, flossing) (common cause of harmless bacteraemia)
Serious infection in high risk patients
-asplenic/hyposplenic
-damaged prosthetic valves
-previous infective endocarditis
-antibiotic prophylaxis
- -> Normal flora overgrows and becomes pathogenic when host becomes immunosuppressed
- diabetes, AIDS, malignant diseases, chemotherapy (neutrophils)
- -> When normal flora is depleted by antibiotics
- intestine –> severe colitis (clostridium difficile)
- vagina –> thrush (Candida albicans)
What are the second lines of defence of innate immunity?
Phagocytes
Chemicals
How are phagocytes involved in the second line of defence in innate immunity?
Phagocyte-microbe interaction
- RECOGNITION
- -microbial structures: Pathogen Associated Molecular Patterns (PAMPs) - carbohydrates, lipids, proteins, nucleic acid
- -phagocytes: Pathogen Recognition Receptors - Toll like receptors
- -opsonisation of microbes: coating proteins called opsonins that bind to the microbial surfaces leading to enhanced attachment of phagocytes and clearance of microbes
- ENGULFMENT
- DEGRADATION OF INFECTIOUS MICROBES
- -phagocyte intracellular killing mechanisms
- –O2 dependent - ROS via NADPH oxidase
- –O2 independent - lysozyme, lactoferrin/transferrin, cationic proteins, proteolytic and hydrolytic enzymes
PAMP- lipopolysaccharide (LPS) G-
PRR?
PRR- TLR4
PAMP- lipoproteins and lipopeptides G-
PRR?
PRR- TLR2
PAMP- peptidoglycan G+
PRR?
PRR- TLR2
PAMP- lipoteichoic acid G+
PRR?
PRR- TLR4
PAMP- lipoarabinomannan and mannose rich glycans (Mycobacterium)
PRR?
PRR- TLR2
PAMP- flagellin (bacterial flagella)
PRR?
PRR- TLR5
Describe opsonins and when they are required
Complement proteins- C3b C4b
Antibodies- IgM, IgG
Acute phase proteins - CRP, mannose binding pectin (MBL)
Essential in clearing encapsulated bacteria
- neisseria meningitidis
- streptococcus pneumoniae
- haemophiliis influenzae b
How are chemicals involved in the second line of defence in innate immunity?
Complement system- 20 serum proteins, most important C1-C9
- 2 activating pathways (actually 3)
- alternative pathway - initiated by cell surface microbial constituents
- MBL pathway - initiated when MBL binds to mannose containing residues of proteins found on Salmonella spp Candida albicans
Cytokines
- phagocytosis - chemo attraction, phagocyte activation, inflammation
- antimicrobials actions of macrophage derived TNF alpha, IL-1, IL-6
- liver (opsonins) CRP, MBL (complement activation)
- bone marrow - neutrophil mobilisation
- inflammatory actions - vasodilation, vascular permeability, adhesion molecules, attraction of neutrophils
- -hypothalamus- increased body temp
What are some examples of major complement proteins and their action?
C3a and C5a - recruitment of phagocytes
C3b and C4b - opsonisation of pathogens and inflammation
C5 - C9 - killing of pathogens in the Membrane Attack Complex
What are some clinical problems associated with the second line of defence in innate immunity?
Infection –> microbial toxins (LPS) –> overreaction of TLR4 receptor –> overreaction of complement (neutrophils, endothelium and monocytes) –> excessive systemic inflammatory response –cytokines shower, coagulopathy, vasodilation, capillary leak (tissue organ perfusion)–> sepsis and multi organ failure
Clinical problems start when phagocytosis is reduced
- deceased spleen function (asplenic, hyposplenic)
- decreased neutrophil number (cancer chemo, certain drugs, leukaemia and lymphoma)
- decreased neutrophil function (chronic granulomatous disease, no resp burst)
- chediak higashi syndrome (no phagolysosomes formed)
What is a hospital acquired infection?
Infections arising as a consequence of providing healthcare
So in hospital patients- infection is not present nor incubating at the time of admission -e.g. Onset is at least 48 hours after admission
Can also include infections in hospital visitors and health workers
What are some common viruses which cause a hospital acquired infection?
Blood borne: Hepatitis B, C, HIV
Norovirus
Chicken pox
Influenza
What are some common bacteria which cause a hospital acquired infection?
Staphylococcus aureus (inc. MRSA) Clostridium Difficile Escherichia Coli, Klebsiella Pseudomonas pneumoniae, aeruginosa Mycobacterium TB
What are some common fungi which cause a hospital acquired infection?
Candida albicans
Aspergillus species
What is a common parasite which causes a hospital acquired infection?
Malaria plasmodium falciparum
What are some patient factors which increase the risk of getting a hospital acquired infection?
Extremes of age Obesity/ malnourished Diabetes Cancer Immunosuppression Smoker Surgical patient Emergency admission
What are some general patient interventions, used to manage a HAIs?
Optimise patients condition- smoking, nutrition, diabetes
Antibiotic microbial prophylaxis
Skin preparation
Hand hygiene
What are some specific patient interventions, used to manage a HAIs?
MRSA screens
Mupirocin nasal ointment
Disinfectant body wash
How can you avoid patient to patient transmission of a HAI?
Physical barriers- isolation of infected patients, protection of susceptible patients
What are some health worker interventions, used to manage a HAIs?
Healthy- disease free and vaccinated
Good practice- good clinical techniques, hand hygiene, PPE, antimicrobial prescribing
What are some environmental interventions, used to manage a HAIs?
Built environment- space, layout, toilets, wash hand basins
Appropriate furniture and furnishings
Cleaning- disinfectants/ steam cleaning/ H2O2 vapour
Medical devices- single use equipment, sterilisation, decontamination
Appropriate kitchen and ward facilities, good food hygiene practice
Theatres- positive/ negative pressure rooms
Immune suppressed patients
What are the 4 Ps for infection prevention and control?
Patient - general and specific patient risk factors; interactions with other patients, healthcare workers and visitors
Pathogen - virulence factors; ecological interactions- other bacteria and antibiotics/ disinfectants
Practice - general and specific activities of healthcare workers, policies and their implementation, organisational structure and engagement, regional and national political initiatives, leadership at all levels from government to the world
Place - healthcare environment- fixed and variable features
What type of organism is clostridium difficile?
Gram positive anaerobic, bacillus, spore forming bacteria
Example of a hospital acquired infection
How does the carriage frequency of clostridium difficile change with length of hospital stay?
Carriage frequency increases with duration of hospital stay
Describe the mechanism of infection of clostridium difficile
When gut micro flora are disturbed by antibiotics (cephalosporins and amoxicillin) overgrowth can occur
Enterotoxin A and B and binary toxin production causes tissue damage and fluid diarrhoea
Some strains which are fluoroquinolone resistance and have evidence of enhanced toxin production are associated with more ever disease and extensive hospital outbreaks
What are some clinical features and symptoms of a patient infected with clostridium difficile?
History of previous antibiotic exposure
3/4 loose/ unformed stools per day
Possible development of abdominal pain
Pseudomembranes seen on sigmoidoscopy on mucosal surface of rectum and sigmoid colon
Possible complications of toxic mega colon, bowel perforation and systemic toxicity —> high mortality
What is the treatment pattern for clostridium difficile?
Stop the inciting agent (antibiotic)
Treat with metronidazole for 10 days
Oral vancomycin and IV metronidazole for severe cases and treatment failures
Rapid and strict isolation is essential
What investigations would you carry out for clostridium difficile detection?
Detection of toxin or glutamate dehydrogenase (GDH) by enzyme immunoassay (EIA)
Detection of toxin genes by nucleic acid amplification test (NAAT)
Typing- generally by ribotyping
Full blood count
U&Es
CRP
MC&S
How can you prevent clostridium difficile infection?
Enhanced ward cleaning and attention to hand hygiene is essential Suspect Isolate Gloves and apron Hand hygiene Toxin test
What are some other clostridium bacteria? And what diseases do they cause?
Botulinum- botulism
Perfringens- gas gangrene, food poisoning
Tetanii- tetanus
What are some common travel infections?
Malaria Typhoid Meningococcal septicaemia Dengue Yellow fever
What is the incubation period for malaria?
1-3 weeks or longer after bite
What are the four main species that cause malaria?
Plasmodium falciparum, vivax, ovale and malariae
What is the vector of malaria?
Female anopheles mosquito
What areas of the world is malaria common in?
Africa, Asia, Middle East and South and Central America
What is a typical history taken of someone with malaria?
Headache Cough Fatigue Malaise Asthsalgia Myalgia Fever chills and sweats which eventually cycle every 3rd/4th day
What signs of malaria are there (ie. From examinations)?
Other than fever, often few signs (+/- splenomegaly)
Cerebral features - coma
Respiratory distress (metabolic acidosis, pulmonary oedema)
What investigations should be carried out for malaria?
Should be managed by an ID physician
Blood smear to detect parasites
FBC, U&Es, LFTs, glucose
Head CT if CNS symptoms
What treatment is available for malaria?
Depends on species causing malaria
- plasmodium falciparum- (malignant) quinine, artemisinin
- p, vivax, ovale, malaria- (benign) chloroquine +/- primaquine for exo erythrocytic phase)
How can one prevent malaria?
Assess risk - knowledge of at risk areas
Bite prevention- repellant, adequate clothing, nets, chemo prophylaxis before travel (must include regular returning travellers)
Chemoprophylaxis - specific to region, start before and continue after return -doxycycline
What is the most common species that causes typhoid (enteric fever)?
Salmonella enterica serorar Typhi/ Paratyphi A, B or C
What type of bacteria is Salmonella enterica serorar Typhi/ Paratyphi A, B or C?
Enterobacteriaceae
Aerobic gram negative rods
What is the mechanism of infection of Salmonella enterica serorar Typhi/ Paratyphi A, B or C?
Gram negative endotoxin VI antigen
Invasion which allows IC growth
Fimbriae adhere to epithelium over ideal lymphoid tissue (Peyers patches)–> RE system
What are some symptoms and signs of typhoid and paratyphoid?
Fever, headache Incubation period- 7-14 days Abdominal discomfort, constipation, dry cough, hepatosplenomegaly, occasionally rash Relative bradycardia Intestinal haemorrhage and perforation Paratyphoid generally milder
What is usually found upon investigation in someone with typhoid?
Moderate anaemia
Relative lymphopenia
Raised LFTs (transaminase and bilirubin)
Culture- faeces, blood
Serology (antibody detection)- no longer used
What is the pattern of treatment of typhoid?
Usually treated with ceftriaxone or azithromycin 7-14 days
Resistance may be present against chloramphenicol, ampicillin. Cotrimoxazole, ciprofloxalin
How can typhoid be prevented?
Food and water hygiene precautions
Typhoid vaccine- high risk travel, lab personnel
Vicapsular polysaccharide antigen or live attenuated vaccine
Modest protective effect (50-75%)
What are some examples of non typhoid all salmonella infections?
Food poisoning salmonellas- salmonella typhimurium, S.enteritidis
Symptoms- diarrhoea, fever, vomiting, abdominal pain
Generally self limiting but bacteraemia and deep seated infections may occur- excreting organism in diarrhoea
What causes brucellosis?
Primary animal pathogen
- brucella abortus (cows)
- brucella melitensis (goats and sheep)
Gram negative cocobacillus - short rounded rods
Where is brucellosis most common?
South Europe, Africa, Asia, central and South America
What is the mechanism of transmission of brucellosis?
Transmission through skin breaks / GI tract (milk)
What are some symptoms/ clinical signs of brucellosis?
Non specific febrile illness (undulant fever)
Bone, joint involvement
Epididymitis - inflammation/ swollen testes
How is brucellosis generally diagnosed?
From blood cultures
How is brucellosis commonly treated?
With doxycycline and rifampicin
In adaptive immunity, what type of pathogens are considered intracellular microbes? And what MHC class do they correspond to?
Bacteria, viruses, Protozoa
Class I MHC (found on all nucleated cells)
HLA: A, B, C
In adaptive immunity, what type of pathogens are considered extracellular microbes? And what MHC class do they correspond to?
Bacteria, parasites, worms, fungi
Class II MHC (found on all dendritic cells. Macrophages, B cells)
HLA: DR, DQ, DP
In adaptive immunity relating to MHC class I what is the endogenous pathway?
Virus (protein) is taken up and presented on cell surfaces
In adaptive immunity relating to MHC class II what is the exogenous pathway?
Bacteria taken up and presents in endocytic vesicle which fuses with lysosomes and destroys bacteria
What does the endogenous pathway of adaptive immunity stimulate?
CD8+ T cells
- cytotoxic T lymphocytes - process and kill the virus
CD4+ T cells (stimulates CD8+ T cells and..)
- B cells- antibodies- opsonisation, neutralisaiton, complement activation
- macrophages- kill opsonised microbes
What does the exogenous pathway of adaptive immunity stimulate?
CD4+ T cells
- eosinophils- killing of parasites
- B cells- Antibody: IgG4 (opsonisation), IgA (mucosal protection), IgG&IgE (antibody dependent cell toxicity) and IgE (allergies)
- mast cells- local inflammation allergies (IgE)
- neutrophils- phagocytosis
What type of pathogen is streptococcus pneumonia?
Gram positive, diplococcus (seen in pairs) Alpha haemolytic (can be variable)
Describe how streptococcus pneumoniae causes infection
Streptococcus pneumoniae has a polysaccharide capsule that protects it’s from phagocytosis
There are over 90 highly antigenic capsule sero types and antibodies to specific types are protective
Pathogenicity-
- pro inflamm cell wall components (e.g. c-polysaccharide) F-antigen
- IgA2 protease
- pneumolysin, a cytotoxin that stimulates immune responses
- adhesins that bind to cell surface carbohydrates (e.g. Choline binding protein A, pneumococcal surface protein A)
- tissue damaging enzymes
Describe how non invasive pneumococcal infections present
- these occur outside the major organs or the blood and tend to be less serious
- bronchitis- infection of bronchi
- Otis media - ear infections
- sinusitis - infection of sinuses
Describe how invasive pneumococcal infections presents
These occur inside the major organs or the blood and tend to be more serious than non invasive ones
- Bacteraemia
- Septicaemia
- Osteomyelitis
- Septic arthritis
- Pneumonia
- Meningitis
What investigations should be carried out when suspecting streptococcus pneumoniae infection and what results are expected?
Distinctive crackles on chest Blood test Radiography- x ray fluid on lungs Ct scan, MRI scan Blood pressure (low) Lumbar puncture test - sample of CSF Urinary antigen test- urine sample, immunochromatographic assay
What treatment can be given to someone with a streptococcal pneumonia infection?
Non invasive infection
- treating bronchitis, middle ear infection, sinusitis
Invasive infection
- confusion, resp rate >30, low BP, 65 years old ***
How can you prevent streptococcal pneumonia infections?
Conjugate vaccine incorporating 13 capsular stereotypes
Highly immunogenicity in small children
What are 11 different causes of (travellers) diarrhoea?
Enterotoxigenic escherichia coli Enteroinvasive escherichia coli Campylobacter Salmonella typhi Shigella Vibrio cholera Giardia lamblia Entamoeba histolytica Cryptosporidium parvum Rotavirus Norovirus
What type of diarrhoea do you get with Enterotoxigenic escherichia coli?
Profuse and watery
What type of diarrhoea do you get with Enteroinvasive escherichia coli?
Mild with abdominal cramp
What type of diarrhoea do you get with campylobacter?
Bloody
What type of diarrhoea do you get with salmonella typhi?
Bloody
What type of diarrhoea do you get with shigella?
Bloody
What type of diarrhoea do you get with vibrio cholera?
Profuse and secretory
What type of diarrhoea do you get with giardia lamblia?
Explosive
What type of diarrhoea do you get with entamoeba histolytica?
Bloody
What type of diarrhoea do you get with cryptosporidium parvum?
Watery
What type of diarrhoea do you get with rotavirus?
Watery mild-severe
What type of diarrhoea do you get with Norovirus?
Watery
Describe the structure of influenza virus and how this affects it function
Enveloped orthomyoxovirus (100nm) Contains a negative single stranded RNA genome divided into 8 segments Structure allows genetic reassortment- so that virus can change its surface antigens
What fluenza strains can influenza virus take up genetic material from?
Avian and pig
How many proteins does influenza virus express? Describe their arrangement.
7 proteins - 3 of which are responsible for RNA transcription
Nucleoprotein has 3 antigenic types that designate 3 main virus groups- A , B and c
Matrix protein forms a shell under the lipid envelope with haemagglutin and neuraminidase proteins - expressed as 10 nm spikes on the envelope which interact with host cells - virus immunity directed against H and N
What are some clinical features of influenza virus?
Incubation period- 1 to 4 days
Patients infectious for 3 days - starting from one day before symptoms emerge
Headache, myalgia, fever, cough lasts for 3 - 4 days
Complications which are more common in elderly people and patients with cardiopulmonary disease, include primary viral and secondary bacterial pneumonia
How is influenza diagnosed?
Immunofluorescence inf A, B and C
Nucleic acid amplification test (NAAT)
- more sensitive and can identify specific stereotype which can indicate whether a patient is infected with a pandemic strain
Describe the treatment of influenza
Amantadine
Neuraminidase inhibitors- zanamivir, oseltamivir (tamiflu), vaccination
Where is legionella pneumophilia often found?
Found in rivers, lakes, warm springs, domestic water supplies, fountains, air conditioning systems, swimming pools and jacuzzis
Between what temperatures does multiplication of legionella pneumophilia occur?
Multiplication occurs at temps between 20 and 40 degree Celsius inside acanthamoeba
How is legionella pneumophilia transmitted from person to person?
Transmission via aerosols generated from showers, and air conditioning systems
What are some risk factors for legionella pneumophilia infections?
Infection associated with previous lung disease, smoking, high alcohol intake, but previously healthy patients can be infected.
Immunocompromised patients in hospitals are vulnerable to infection if the hospital air conditioning is not adequately maintained
What is the pathogenesis of legionella pneumophilia?
Major outer membrane protein that inhibits acidification of phagolysosomes
Macrophage infectivity is required for optimal internalisation
Legionella pneumophilia expresses a potent exoprotease
What are some clinical features of legionella pneumophilia?
Mild influenza like illness (pontiac)
Severe pneumonia (legionnaires disease) which can lead to respiratory failure and high mortality
Patients may complain of nausea, vomiting, malaise before lung symptoms become prominent
Cough which is unproductive and dyspnoea which is progressive
Confusion is common
Inappropriate natiuretic hormone production associated with low serum sodium
How is legionella pneumophilia infection diagnosed in the lab?
Culture of sputum, bronchoalveolar, lavage fluid
Rapid diagnosis by antigen detection in urine
Direct Immunofluorescence or nucleic acid amplification test (NAAT) of respiratory specimens
Serum antibodies can provide retrospective diagnosis for epidemiological purposes
How is infection by legionella pneumophilia treated and prevented?
Effective regimens usually consist of a macrolide antibiotic together with rifampicin
Legionellosis- prevented by adequate maintenance of air con systems and by ensuring that hot water supplies are above 45 degrees Celsius to prevent multiplication
What type of bacteria is neisseria meningitidis?
Gram negative diplococcus bacteria
Describe the structure of neisseria meningitidis and relate this to the function of the structure
Number of sero groups (ABC, W-135) based on polysaccharide capsular antigen (acts as endotoxin) - promotes adherence, prevents phagocytosis, and triggers inflammation by cytokines
Evades immune system by preventing phagocytosis
Outer membrane acts as an endotoxin
How does neisseria meningitidis cause disease?
Endotoxin binds to macrophages
Local- Cytokines (tissue necrosis factors and interleukins TNF alpha and IL1) stimulate inflammatory response to promote wound repair and recruit RE system
Systemic- Cytokines released into circulation stimulate oath factor macrophages and platelets, goal is for homeostasis to be restored
SIRS- homeostasis not restored
Also - cytokines promote coagulation and inhibit fibrinolysis causing microvascular thrombosis and organ ischaemia and failure
What is SIRS?
Systemic inflammatory response syndrome
Response to non specific insult (trauma, Ischaemia and infection)
What is bacteraemia?
Presence of bacteria in blood with or without clinical features
What is septicaemia?
Generalised clinical term related to generalised sepsis
What is sepsis?
Systemic response to infection- SIRS + documented/ presumed infection
What is severe sepsis?
SIRS + organ dysfunction / hypoperfusion –> hypotension/ decreased urine output
What is septic shock?
Severe sepsis + persistently low BP despite administration of IV fluids
How can SIRS be diagnosed?
2 or more of : Temp- 38 degrees Celsius H/R > 90/min R/R >20/ min WBC 12x10^9/L.
What are some common symptoms of an infection caused by neisseria meningitidis?
Abdominal pain, fever, nausea, weakness, muscle aches, eye pain on exposure to light, pale, cool extremities, widespread purpuric rash
What investigations are required for diagnosis of neisseria meningitidis?
FBC U&Es EDTA bottle for PCR Blood sugar Liver function test C Reactive Protein Clotting studies Blood gases
What 3 investigations would confirm the diagnosis with neisseria meningitidis?
Blood culture
PCR of blood
Lumbar puncture- culture of CSF (only after checking contraindications- glucose and protein elimination in biochem M&C) PCR of CSF (appearance- turbidity and colour, microscopy - WBCs and RBCs, gram stain- PCR referral)
How would you treat neisseria meningitidis?
Sepsis 6 within 1 hour
1) give high flow O2
2) take blood cultures and other cultures
3) administer empirical antibiotics (IV)
4) measure serum lactate
5) start IV fluid resuscitation
6) commence accurate urine output measurement
Antibiotics : ceftriaxone
How would you prevent infection by neisseria meningitidis?
Vaccination- meningococcal vaccines conjugate, achy vaccine- immunocompromised patients and travel protection, serogroup B vaccine,
Antibiotic prophylaxis- close contact to infected individuals
What are some life threatening complications cause by infection with neisseria meningitidis?
Irreversible hypotension Respiratory failure Acute kidney injury (renal failure) Raised IC pressure Ischaemic necrosis of digits, hands and feet
What type of bacteria is escherichia coli?
Gram negative, anaerobic, rod shaped bacterium
Commonly found in lower intestine of warm blooded organisms (commensal)
Strains vary in fimbriae - giving the consequential disease and mechanism of infection differences
Describe the 5 main strains of E. coli.
Enterotoxigenic E. coli - produce LT and ST toxins that act on the enteric yet to stimulate fluid secretion- diarrhoea
Enteroaggregative E. coli - secrete plasma encoded toxin, a serine protease that binds alpha ford in and causes disruption of actin cytoskeleton - strains express ST toxins and haemolysin like toxins - chronic diarrhoea
Enteropathogenic E. coli- colonise epithelial cell lining of small intestin and inject effector proteins that causes efface net of microvilli and intimate adherence
Enterohaemorrhagic E. coli- strains produce a veto toxin (in vitro) - Haemorrhagic diarrhoea, complicated by haemolysis and acute renal failure (commensal in cattle - transmitted via hygiene failure)
E. coli in ureter- express mannose binding fimbriae - associated with lower UTIs and cystitis
How is E. coli transmitted?
Eatubg/ drinking food contaminated with faeces
Meat (infected during processing) - if not heated above 71 degrees celsius
Milk and dairy products and raw fruit and veg (which could have come in contact with faeces)
What are some symptoms of E. coli infections?
Bloody diarrhoea, stomach cramps, nausea and vomiting, dehydration, some are Asymptomatic, blood, kidney problems
Fever, weakness, bruising, passing only small amounts of urine
What investigations are used to diagnose a E. coli infection?
Stool sample, M,C&S, microbiological investigation (blood, and or mucus in stool or immunocompromised patient)
FBC
Renal function
Urea and electrolytes
How is E. coli treated?
Most cases- home care and plenty of fluids
IV fluids if hospitalised
Antibiotics
How is E. coli prevented?
Washing hands
Washing fruit and veg properly
Avoiding cross contamination
Using a meat thermometer and cooking meat at proper temp
What type of virus is Norovirus?
Single stranded, positive, icosahedral, non enveloped, RNACalcivirus- can cause outbreaks of acute diarrhoea and vomiting in hospitals, care homes, cruise ships and other confined communities
Divided into 5 genogroups
How is Norovirus transmitted?
Faecal oral route
Aerosols
How long is the incubation period for Norovirus?
Symptoms develop after a short incubation period of 24-48 hours
Where does Norovirus replication occur? What is the consequence of this?
Virus replication occurs in the mucosal epithelium of the small intestine which results in broadening and flattening of villi and hyperplasia of crypt cells
What are the main symptoms of Norovirus infections?
Self limiting acute diarrhoeal illness
Can be present with sudden onset projective vomiting and explosive diarrhoea
How can Norovirus be diagnosed?
NAAT
Sequencing is required for epidemiological purposes and to monitor design of future NAAT detection assays
How is Norovirus transmission prevented?
Isolation
Ward closure
Good hand washing techniques
What type of bacteria is staphylococcus aureus?
Gram positive clusters of cocci
Where is staphylococcus aureus found commensally?
A symptomatic carriage found on 40% of healthy people
In nose, skin, axilla or perineum- important in. Healthcare workers especially if they carry an invasive or resistant strain (MRSA)
What are the 5 main potential pathogenicity determinants of staphylococcus aureus?
Coagulase Adhesion molecules Lytic enzymes Protein toxins Biofilm formation
What is the activity and effect of coagulase in the pathogenicity of staphylococcus aureus?
Coagulase converts fibrinogen to fibrin and may be involved in forming a protective Barrier
What is the activity and effect of adhesion molecules in the pathogenicity of staphylococcus aureus?
Adhesion molecules bing fibronectin and assist with adherence
What is the activity and effect of lytic enzymes in the pathogenicity of staphylococcus aureus?
Lytic enzymes such as lipase breakdown the host tissue
What is the activity and effect of protein toxins in the pathogenicity of staphylococcus aureus?
Protein toxins such as panton valentine leucocidin (pvl), the toxic shock syndrome toxin (tsst), enterotoxins cause shock and toxicity
What is the activity and effect of biofilm formation in the pathogenicity of staphylococcus aureus?
Biofilm formation causes slower growth in extracellular matrix and is difficult to treat with antibiotics- adheres to plastics
What is the clinical importance of staphylococcus aureus infection?
Primary skin infections- impetigo- person to person
Secondary skin infections- associated with eczema, surgical wounds, intravenous devices, burns
Pneumonia- rare but may follow influenza and progress rapidly with cavity formation
Endocarditis- rapid and destructive, associated with intravenous drug misuse or colonisation of IV devices
Osteomyelitis
Septic arthritis
Describe the antibiotic resistance of staphylococcus aureus
It was initially susceptible to penicillin but strains that produce B lactamases soon predominated so methicillin and related (flucoxacillin) agents were introduced and replaced penicillin
Methicillin resistant S.Aureas (MRSA) emerged- resistance caused by presence of mecA gene - codes for a penicillin binding protein that binds the drug less well. Glycopeptides such as vancomycin or teicoplanin started to be required for these strains
Intermediate or hetero resistance to Glycopeptides emerged as an increasing issue and fully Glycopeptide resistant strains (GRSA) have now emerged, resistance being mediated from vanA and vanB genes acquired from enterococci
How is staphylococcus aureus treated?
Penicillin if susceptible
Flucoxacillin if penicillin resistant
Vancomycin or teicoplanin if MR
Contril measures are needed in hospitals
How is staphylococcus aureus infection prevented and controlled?
Isolation of MRSA and GRSA
Topical mupirocin and chlorhexidune to eradicate carriage
How is staph Aureas spread from individual to individual?
Spreads by airborne transmission and hands of healthcare workers
How is staph aureus infection investigated and diagnosed?
Blood, U&Es
Grows readily on most lab media- selective medium contents high salt to which staph aureus is relatively tolerant
Phenotypic identification depends on demonstrating coagulase, catalase enzymes and typical cluster of grapes morphology on gram stain
Typing by molecular means can support interventions to control outbreaks
What genus is HIV from?
Lentivirus
Describe the structural composition of HIV
Spherical Enveloped Diploid ss +RNA virus 80-100nm in diameter Non segmented Linear
How does HIV cause disease?
Retrovirus- uses reverse transcriptase to produce a DNA copy from viral RNA that is incorporated into the host nucleus to become the template for further viral RNA
3 genes are required for viral replication- gag, pol and env
2 types of HIV that are pathogenic to humans- HIV1 (most common around world) and HIV2 (largely confined to W Africa, appears less virulent)
How is HIV transmitted from person to person?
Sexually
By blood and body fluids
From mother to child
What is the pathogenesis of HIV?
Viral RNA is transcribed to ssDNA and integrates into host genome
Antigenic variation is rapid
Virus principally infects cells with a CD4+ receptors- (T Cells and macrophages)
Viral replication results in progressive T cell depletion and diminished cell mediated immunity
Lacking T cells means that B cell function is also reduced
Damage to neural cells stimulates cytokines release - neurological damage
Clinical signs mostly caused by secondary infections which occur because CD4+ is decreased and cell mediated immunity is non functional
What are the clinical features of HIV?
50-70% of patients have an acute syndrome occurring 2-6weeks after acquisition of HIV –> rash, fever and lymphadenopathy
Only about 25% of these patients have symptoms severe enough to have to seek medical attention
CD4+ count declines and if untreated reaches a point ( AIDS
Non specific symptoms- fever, malaise, arthralgias, headache, sore throat, with lymphadenopathy
Early invasion of nervous system - meningitis, encephalitis, peripheral neuropathy, myclopathy
In HIV infection, what secondary infections commonly occur?
Bacteria- MTB, mycobacterium intracellulare, Salmonella, streptococcus pneumoniae
Protozoa- toxoplasma Gondi, cryptosporidium parvum
Fungi- candida sp, cryptococcus neoformans
Virus- varicella zoster
What’s the lab diagnosis for HIV?
Virus can be cultured from circulating mononuclear cells
Genome detected by PCR and p24 antigen detected prior to seroconversion (where body makes and antibody to a virus)
ELISA is used for antibody screening tests
Confirmation either by western blot or line immunoassay
What is the treatment for HIV infection?
Several classes of antiretrovirals
HAART- night a ruche anti retroviral therapy
-Nucleoside reverse transcriptase inhibitors (NRTI’s)
-Non NRTI’s
-Protease inhibitors
-Fusion inhibitors
-Integrase inhibitors
-Co receptor/ entry inhibitors
-Zinc finger inhibitors
(Prevent transmission, maintain virus at less than 50 copies, prevent emergence of resistance, restore immunological function)
How is HIV infection prevented?
Avoidance of partners who have a high risk factor and unprotected intercourse
Screening of blood products
Health education and free needle exchange programme for IV drug users
Antigenic diversity has frustrated vaccine development
Antiretroviral prophylaxis for infected needle stick injury
Mother to child- c section
Describe hepatitis b
Hepednavirus
Enveloped
Contains partially double stranded DNA encoding surface antigen (HBcAg) pre core protein (HBeAg) a large active polymerase protein and a transactivator protein
How does hepatitis b virus replicate? Using what enzyme?
Replicates through reverse transcriptase
How is hepatitis b transmitted?
Parenteral, congenital/ vertical and sexual routes
What is the incubation period for hep b?
2-6months
What are some clinical features of hep b?
Congenital infection carries high risk of
10% patients develop chronic hepatitis complicated by cirrhosis or hcc
Fulminant diseases carries a 1-2% mortality
Acute hepatitis of variable severity developes insidiously
Fever malaise jaundice
Liver failure, liver cirrhosis, hcc
How is hepatitis b diagnosed?
Immunoassay so for HBsAg HBeAg and HBcAg (and associated antibodies) enable diagnosis of acute infection and previous exposure
Viral load measured by NAAT and sequencing for resistance mutations allows monitoring for therapy and directs drug choice
What treatment is available for hep b infections?
Pegylated alpha interferon
Lamitudine, adefovir, entecavir, tenofovir, telbinudine and clerudine - antiviral efficacy
Emtricitabine and valtorcitabine are nearing clinical introduction
Therapy should be considered in chronic infection as responders have reduced risk of liver damage and liver cancer in the long term
HBeAg seroconversion often seen as a success of treatment
How can hepatitis b be prevented?
Those at high risk should be immunised with recombinant HBV vaccine- HBsAg based, 3 doses at 0,1,6 months or 0,12,12 months, 95% effective
Vaccine and specific immunoglobulin should be administered to neonates of infected mother to reduce transmission
Post exposure prophylaxis- (HBsAg) positive source, newborns from HBsAg positive mothers, needle stick injury for HCW’s without protection
Blood donations must be effectively screened
Needle exchange programmes for drug misusers and sexual health education schemes can help to reduce transmission
What two surfaces are commensal bacteria found on?
Skin- epithelia, hair, nails
Mucosal surfaces- conjunctival, gastrointestinal, respiratory, genitourinary
What viruses are normally found on the skin?
Papilloma
Herpes simplex
What bacteria are normally found on the skin?
G+ve staphylococcus aureus, coagulative negative staphylococci, corynebacterium
G -ve enterobacteriaceae
What fungi are normally found on the skin?
Yeasts
Dermatophytes
What parasites are normally found on the skin?
Mites
What pathogens are normally found in the vagina?
Lactobacilli
Yeasts
What pathogens are normally found in the urethra?
Enterobacteriaceae
Lactobacilli
Streptococci
Enterococci
What pathogens are normally found in the intestine?
Eubacterium
Lactobacillus
Coliform
Clostridium
What pathogens are normally found in the stomach?
Helicobacter
Streptococci
Staphylococci
What pathogens are normally found in the mouth?
Viridans streptococci
What pathogens are normally found in the nasopharynx?
Neisseria meningitidis
Streptococci pneumoniae
Haemophilius influenzae
What pathogens are normally found in the nares?
Staphylococcus aureus
What pathogens are normally found in the eye?
Coagulase negative staphylococci
Saprophytic neisseria
Viridans group streptococci
How do people get infections?
Microbiota- commensals; microorganisms carried on skin and mucosal surfaces; normally harmless or even beneficial, transfer to other sites can be harmful
Invasion- e.g. Streptococcus pyogenes pharyngitis
Migration- e.g. E. coli urinary tract
Innoculation- e.g. Coagulase negative staphylococcus prosthetic joint infection
Haematogenous- e.g. Viridans streptococcus endocarditis
What are some external natural surface infections?
Cellulitis Pharyngitis Conjunctivitis Gastroenteritis UTI Pneumonia
What are some internal natural surface infections?
Endovascular- endocarditis, vasculitis
Septic arthritis
Osteomyelitis
Empyema
What can prosthetic surface infections develop on?
Intravascular lines Peritoneal dialysis catheters Prosthetic joints Cardiac valves Pacing wires Endovascular grafts Ventriculooeritoneal shunts
What bacteria can cause prosthetic valve endocarditis less than a year after operation?
Coagulase negative staphylococci
What bacteriae (5) can cause prosthetic valve endocarditis more than a year after operation?
Viridans streptococci Enterococcus faecalis Staphylococcus aureus HACEK group Candida
What are the two main organisms that cause prosthetic joint infection and cardiac pacing wire endocarditis?
Coagulase negative staphylococci
Staphylococcus aureus
What are the four broad stages in pathogenesis of an infection at a surface?
Adherence to host cell or prosthetic surfaces (pili, fimbriae)
Biofilm formation
Invasion and multiplication
Host response- pyogenic (neutrophils –> pus) or granulomatous (fibroblasts, lymphocytes, macrophages –> nodular inflammatory lesions)
How does a biofilm form in infections at surfaces?
Starvation can induce bacteria to shrink and adopt a spore like state known as ultra-micro bacteria which wait in water soil rock or tissue until conditions are suitable for active growth
Active bacteria can attach to almost any surface – changes in gene expression transform swimmers to stickers within minutes
Attached bacteria multiply and encase colonies with a slimy matrix
Nutrients defuse into the matrix
Close proximity of cells in the matrix facilitates exchange of molecular signals that regulate behaviour
Although antimicrobials damage outer cell layers – biofilm community is
Propelled by shear forces aggregated cells can become detached or roll or ripple along the surface in sheets and remain in their protected biofilm state
What is quorum sensing?
Controls- sporulation, biofilm formation, virulence factor secretion
3 principles- signalling molecules (auto inducers), cell surface cytoplasmic receptors, gene expression–> cooperative behaviour and more AI production
How are surface infections managed?
Diagnosis- aim is to identify infecting organism and it’s antimicrobial susceptibilities (sterilise tissue and reduce bio burden); challenges- adherent organisms and low metabolic state/small colony variants; blood cultures; tissue/prosthetic material senication and culture; antibacterials; remove prosthetic material; surgery (resect infected material)
Challenges- low metabolic activity of biofilm microorganisms; poor antibacterial penetration into biofilm
How do you prevent infection on natural surfaces?
Maintain surface integrity
Prevent bacterial surface contamination
Remove colonising bacteria
How do you prevent infection on prosthetic surfaces?
Prevent contamination
Inhibit surface colonisation
Remove colonising bacteria
What does hypersensitivity mean?
Antigen specific immune responses that are either inappropriate or excessive and result in harm to host
Describe the sensitisation and effector phase of a hypersensitive reaction
Sensitisation phase - first encounter with the antigen
Effector phase - clinical pathology upon reexposure to the same antigen
What are the 4 types of hypersensitivity reactions?
Type I - immediate, allergy, (<30min); environmental non infectious allergens (antigens)
Type II - antibody mediated (5-12 hours)- antibodies directed against an antigen on the surface of pathogen
Type III - immune complex mediated (3-8 hours)- antibodies directed against soluble antigens on immune complex
Type IV - cell mediated (24-48 hours)- T cells and B cells - environmental infectious agents and self antigens
What is an anaphylaxis?
Most forms of hypersensitivity are non-life threatening. Anaphylaxis however is a severe form of Type I hypersensitivity reaction, triggered by the exposure of a pre-sensitised individual to an allergen, causing systemic mast cell degranulation. This leads to:
o Vasodilation
o Tissue oedema
o Airways obstruction
o Fall in blood pressure
o Shock
Acute anaphylaxis should be treated with intramuscular adrenaline, which promptly reverses the symptoms and signs with an increase in blood pressure and reversal of airways obstruction.
What is the allergen hypothesis?
Explains why people have allergies
List some common allergens
House dust mite, cockroaches
Animals especially domestic pets- cats and dogs
Tree and grass pollens
Insect venom such as that contained in wasp and bee stings
Medicines - e.g. Penicillin
Chemicals such as latex
Foods- peanuts, milk, nuts etc.
What are the main cells involved in hypersensitivity reactions?
Mast cells
What are the 5 broad mast cell mediators?
Enzymes- Toxic mediators- Cytokines Chemokines Lipid mediator
How do enzymes mediate mast cell action?
tryptase, chymase- remodel connective tissue matrix
How do toxic mediators mediate mast cell action?
histamine, heparin- toxic to parasites, increase vascular permeability cause smooth muscle contraction
How do cytokines mediate mast cell action?
IL4, IL13 - stimulate and amplify TH2 cell response
IL3-IL5 - promote eosinophil production and activation
TNF-alpha - promotes inflammation, stimulation of cytokines production by many cell types activates endothelium
How do chemokines mediate mast cell action?
CCL3 (MIP-1alpha) - attracts monocytes, macrophage and neutrophils
How do lipid mediators mediate mast cell action?
Leukotrienes- C4, D4, E4
Cause smooth muscle contraction increase vascular permeability, stimulate mucus secretion
Platelet activating factors- attracts leukocytes, amplifies production of lipid mediators , activates neutrophils, eosinophils and platelets
Describe the immune mechanism of a type I hypersensitivity (allergic) reaction
Cross-Linking of Antigen-Specific IgE molecules on surface of mast cells or basophils.
The cross-linking leads to the degranulation of the cells and the release of vasoactive substances. Reactions typically occur in minutes and form the basis of most common types of allergies, and represent a component of childhood asthma (HDM etc.).
Describe the immune mechanism of a type II hypersensitivity reaction
Type II – Antibody Mediated Hypersensitivity
IgG antibodies reacting with antigen present on tissues or on the surface of cells.
Once the antibodies have bound with the antigen, they interact with complement or the Fc receptor on phagocytic cells, activating these innate mechanisms leading to the induction of a localised inflammatory response and tissue damage.
These reactions may occur very quickly, but may also lead to prolonged activation.
Examples include:
o Goodpasture’s syndrome
• Autoantibodies to basement membrane in the lung and kidney
o Haemolytic anaemias / Rhesus disease
o Stimulating Ab’s
• TSH in Grave’s disease
o Blocking Ab’s
• Ach R in Myasthenia Gravis
• Insulin receptor in diabetes
Describe the immune mechanism of a type III hypersensitivity reaction
Type III – Immune Complex Mediated Hypersensitivity
Deposition of immune complexes, usually IgG antibodies.
The immune complexes are deposited in various tissues, where they set up inflammatory reactions similar to Type II reactions (Complement activation, phagocyte Fc receptor).
The commonest sites of Type III reactions are the skin, joints and kidney, and so present with rash, arthritis and/or nephritis.
Examples include:
o Systemic Lupus Erythematosus
o Farmer’s lung
Describe the immune mechanism of a type IV hypersensitivity reaction
Type IV – Delayed Hypersensitivity
T helper cells activate macrophages or cytotoxic T cells.
Activated macrophages/cytotoxic T cells cause tissue damage. Typically delayed hypersensitivity reactions occur two to three days after exposure to the antigen. Examples include: o External antigens • Tuberculoid Leprosy • Contact dermatitis o Autoimmune • Coeliac disease • Multiple sclerosis
What are three effects of the degranulation?
Increased vascular permeability
Vasodilatation
Bronchial constriction
How can an allergy be diagnosed?
Blood, serum levels of mast cell products
What is the skin prick test for allergies?
Inner arm usually
Mast cells in epidermis activated
Due to increased vascular permeability and vasodilation - wheal and flare reaction- urticaria
Needs a trained personell, risk of anaphylaxis in highly sensitive subjects
What changes occur in the face during an allergic reaction?
Mast cells in deep dermis are activated
Angio oedema- lips, eyes, tongue, upper respiratory airways (fatal)
What are some systemic changes in the body as a result of an allergic reaction?
Bloodstream-
Anaphylaxis
Systemic activation of mast cells
Hypoventilation, cardiovascular collapse, generalised urticaria, angio oedema - face and resp tract, wheezing
What treatment is available for anaphylactic shock?
Epinephrine/ adrenaline (IM)-acts on alpha1, beta 1 and beta 2 receptors
Reverses peripheral vasodilation and reduces oedema
Reverses airway obstruction/ bronchospasm
Increases force of myocardial contraction
Inhibits mast cell activation
Do not delay treatment- 30 minute window
Monitor pulse, BP, EG and oximetry
How would you diagnose the allergy?
Clinical history- atopy, allergens, seasonality and route of exposure
Blood test- serum allergen specific IgE
Serum mast cell tryptase, histamine (systemic degranulation)
Skin prick tests- range of allergens - wheal and flare reaction (>3mm), no antihistamines
Challenge tests: food and drug allergies - slight risk of anaphylaxis in highly sensitive patients
How would you manage an allergy?
Allergen avoidance / elimination
Education- parents recognise symptoms, EPIPEN use and call emergency services
Medic alert identification tags
Drugs- antihistamines (alternate sedating/ non sedating), corticosteroids (topic/systemic), anti IgE igG (omalizulab), anaphylaxis- give injectable adrenaline 0.5mg
Allergen desensitisation - involves administration of increasing doses of allergen extracts over a period of years given to patient by injection/ drops/ tablet under tongue (sublingual) ; 90% effective in patients with bee and wasp venom anaphylaxis; given to patients with increased risk of systemic attacks; specialist hospital based unit with resuscitation equipment
What is endocarditis?
Heart valves may become infected during transient bacteraemia
Congenitally abnormal or damaged valves are at greater risk
Bacteria may originate from mouth, urinary tract, intravenous drug misuse or colonised intravascular lines
What are some causes of native valve and late prosthetic valve endocarditis?
Viridans group streptococci Enterococci Other streptococci Staphylococcus aureus Coagulase negative staphylococci Fastidious gram negatives
What are some causes of early prosthetic valve endocarditis?
Coagulase negative staphylococci Staphylococcus aureus Viridans group streptococci Enterococci and other streptococci Fungi
What are some causes of culture negative endocarditis?
NB. Serological diagnosis Previous antibiotic therapy Chlamydophila pneumoniae/chlamydia psittaci Coxiella brunetti- Q fever Mycoplasma
What are some causes of right sided endocarditis?
Nutritionally deficient strains
Staphylococcus aureus
Mixed infections
Fungi
What’s the pathogenesis of endocarditis?
Damage and roughening of endothelium –> fibrin and platelet deposition –> colonisation of deposit –> bacterial multiplication, further fibrin and platelet deposition, immune activation –> systemic signs of infection! development of vegetation, toxic, embolic and immune complex phenomena
What are some clinical features of endocarditis?
Malaise, fever, variable heart murmurs, arthralgia
Classical stigmata - splinter haemorrhages, oilers nodes, microhaematuria, retinal infarcts, finger clubbing, janeway lesions (only in long standing infection)
Later stages- septic emboli may cause a stroke
With aggressive organisms staphylococcus aureu, disease progresses rapidly and valves may rupture
How would you diagnose endocarditis?
Diagnosis is made if there are two major Dulce criteria present, or 1 major and 3 minor
Major- blood culture with characteristic organisms; persistently positive blood cultures with any organism; evidence of endocardial involvement demonstrated by echocardiogram; new valvular regurgitation
Minor- predisposition, fever (>8C), immunological signs
What are some complications of endocarditis?
Local progression may lead to aortic root abscess
Valve destruction may lead to cardiac decompensation
Cerebral / limb infarction ya follow septic embolus
Nephritis secondary to immune complex deposition can progress rapidly if sepsis is uncontrolled or if antibiotics with renal toxicity are given without care
What investigations are involved in the diagnosis of endocarditis?
Echocardiography
Transthoracic or grand oesophageal demonstrate vegetations in valves
Plain chest x ray - evidence of cardiac failure
At least 3 sets of blood cultures an hour apart while fever is present
Antibiotic therapy should await blood culture - serum tested for antibodies to Coxiella, bartonella, and chlamidya psittaci
How would you manage a patient with endocarditis?
Antibiotics - on,y when causative organism is known
Based on MIC and MBC of antibiotics
If gentamicin is used, concentrations must be monitored closely
2-6 weeks
Surgical management
Describe the communicable nature of infection
Many (all) infections are transmissible:
- From a non human source to a human ( food- E. coli, water- cholera, environment- legionella, animals- rabies)
- From person to person directly (influenza, reovirus, neisserria gonorrhoea) or indirectly (mosquitoes- dengue, malaria, cats- cat scratch/ toxoplasmosis, ticks- Lyme disease, spotted fever)
What are the four global consequences of transmission of an infection?
Endemic disease
Outbreak
Epidemic
Pandemic
What is an endemic?
The usual background rate
What is an outbreak?
Two or more places linked in time and place
What is an epidemic?
A rate of infection greater than the usual background rate
What is a pandemic?
Very high rate of infections spreading across many regions, countries and continents
What is the basic reproduction number and how does it relate to infection?
R0 the average number of cases one case generates over the course of its infectious period in an otherwise uninfected, non immune population
If R0 > 1 => increase in cases
If R0 = 1 => stable number of cases
If R0 < 1 => decrease in cases
What are the important concepts of antimicrobial stewardship?
Appropriate use of antimicrobials
Optimal clinical outcomes
Minimise toxicity and other adverse events
Reduce the cost of healthcare for infections
Limit the selection for antimicrobial resistant strains
What are the main elements of an antimicrobial stewardship programme?
Multidisciplinary team and relationships to other quality/ safety teams
Surveillance- process measures (measuring what you do) and outcome measures (measuring results you get as a result of what you do)
Interventions- persuasive, restrictive, structural
What is the infectious dose?
Number of microorganisms required to cause infection
Determines transmissibility
How does infectious dose vary?
By organism
By presentation of microorganism
By immunity of potential host
What interventions can help eradicate a pathogen?
Antibacterials including disinfectants
Decontamination
Sterilisation
What interventions can help eradicate a vector?
Eliminate vector breeding sites
What interventions help to improve the health of the patient?
Nutrition
Medical treatment
What interventions help the immunity of the patient?
Passive- e.g. Maternal antibody, intravenous immunoglobulin
Active- i.e. Vaccination - herd immunity
Define herd immunity
Herd immunity is a form of immunity that occurs when the vaccination of a significant portion of a population (or herd) provides a measure of protection for individuals who have not developed immunity or been vaccinated
What interventions help to avoid the pathogen or vector in practice?
Geographic- don’t go there
Protective clothing/ equipment- long sleeves, trousers against mosquito bites; personal protective equipment in hospitals (PPE) (gowns, gloves, masks)
Behavioural- safe sex, safe disposal of sharps, food and drink prep
What interventions or environmental engineering help with prevention of infection transmission in a place?
Safe water
Safe air
Good quality housing
Well designed healthcare facilities
What are some good consequences of control of infection?
• Decreased incidence or elimination of disease/organism
– Smallpox
– Polio
– Dracunculiasis
What are some bad consequences of control of infection?
• Decreased exposure to pathogen –> decreased immune stimulus –> decreased antibody –> increased susceptibles –> outbreak
• Later average age of exposure –> increased severity
– e.g. polio, hepatitis A, chicken pox, congenital rubella syndrome
How do chronic diseases affect a patient?
Chronic diseases cause a change in the structure or function of affected tissues/ organs which may have the potential for changing the interaction between the patient and microorganisms
This may be subsequently and further affected by changes caused by the altered presence of microorganisms and the consequences of treatment e.g. with antibiotics and steroids
Describe the basic pathogenesis of Cystic fibrosis
AR, defect in CF transmembrane conductance regulator gene in exocrine glands
Range of different mutations
Most frequent
What are some clinical consequences of cystic fibrosis?
Defect in CFTR- defect in Cl- transmembrane transport
Mucus becomes dehydrated and thick causing blockage in small ducts / characteristic salty sweat
Long colonisation and infection with a procession of different organisms
Lung damage, antibacterial and steroid treatment
What are some pathogens which are likely to cause infection in CF patients?
H. Influenzae
Staph Aureus
Pseudomonas Aeruginosa, Burkholderia Cepacia
Atypical Mycobacteria, Candida albicans, Aspergillus fumigatus
Why is CF so common?
Heterozygosity provides resistance to cholera, typhoid, TB
In vitro interactions between CFTR protein and cholerol toxin, salmonella typhi, IC entry but no in vivo demonstration of benefit
In COPD what cells primarily cause the chronic inflammatory response to inhaled irritants?
Neutrophils and macrophages
What bacterial microorganisms can cause infection in a COPD patient?
S.Pneumoniae H.influenzae Moraxella catarrhalis Ps. Aeruginosa E.Coli
What viral microorganisms can cause infection in a COPD patient?
Respiratory syncytial virus Rhinovirus Parainfluenza virus Human metapneumovirus Coronavirus Adenovirus Influenza A virus
How does having diabetes affect your immunity and consequently cause infections?
Hyperglycaemia and acidaemia impair- humoral immunity, polymorphonucleanuclear leukocytes and lymphocyte functions
Diabetic microvascular and macrovascular disease result in poor tissue perfusion and increased risk of infection
Diabetic neuropathy- diminished sensation resulting in areas of skin which become unnoticed
What ENT infections are common in diabetic patients?
Malignant or necrotising otitis externa
- pseudomonas aeruginosa
- infection starts in external auditory canal and spreads to adjacent soft tissue, cartilage and bone
- patients typically present with severe ear pain and otorrhoea
Rhino cerebral mucormycosis
- in patients with poorly controlled diabetes - especially diabetic ketoacidosis
- mould fungi
- organisms colonise nose and paranasal sinuses, spreading to adjacent tissues by invading blood vessels and causing soft tissue necrosis and bony erosion
What UTIs are common in diabetic patients?
Neurogenic bladder due to diabetic neuropathy leads to defects in bladder emptying
Increased risk of a symptomatic bacteriuria and pyuria, cystitis and upper UTIs
Enterobacteriaceae (e.g. E.Coli), Ps Aeuroginosa
What neurological disorders affecting bladder control are common in diabetics?
CNS diseases- Alzheimers, MS, Parkinson’s, Encephalitis, Stroke
PNS diseases- nerve damage, due to long term heavy alcohol abuse, long term diabetes, neuropathy, syphilis, herniated disk, spinal canal stenosis, pelvic surgery; vitamin B12 deficiency
Sensory neuropathy, atherosclerotic valvular disease and hyperglycaemia all predispose patients to an increased risk of infection of what? By what causative microorganisms?
Skin and soft tissue
S.Aureus (folliculitis, cellulitis)
Group A B haemolytic streptococcus (cellulitis)
Poly microbial- including 2 of above- enterobacteriaceae, various anaerobes - diabetic foot ulcers and necrotising fascitis
What infections are common in patients with Down’s syndrome?
Respiratory tract infections (viral and bacterial)
More common in young people with DS
Due to true immunodeficiency or to other factors- altered mucus secretion/ structure of mouth and airways
Otherwise healthy person with DS will probably not suffer more serious infections than siblings and will respond to vaccinations
How is humoral immunity affected in a patient with Down’s syndrome?
Decreased neutrophil and monocyte function (chemotaxis, phagocytosis, oxidative burst)
Normal number of neutrophils and monocytes
Lower (children) or raised (adults) Ig levels despite normal B cell number
Normal or high levels of serum IgA and secretory IgA
Lowered specific antibody responses upon immunisation
Normal/ raised levels of C3/C4/C5
How is cellular immunity affected in a patient with Down’s syndrome?
Altered distribution of T cell populations (e.g. Low CD4+:CD8+) but normal T cell number
Decreased T cell function including response to specific antigens and some mitogens
Altered T cell intracellular signalling
Abnormal cytokines production
Lowering of some/ not all NK functions - increased number of NK cells
What can pseudomonas aeruginosa infection generally cause?
Endocarditis Pneumonia Bacteraemia Meningitis ENT- external otitis Eye infections UTIs GI tract infection Skin and soft tissue infection
What is an immunocompromised host?
State in which the immune system is unable to respond appropriately and effectively to infectious microorganisms
Qualitative and quantitative defect of one or more components of the immune system
How is SPUR used to diagnose immunodeficiencies?
Infections suggesting underlying immune deficiency are defined as SPUR and so will be: Severe Persistent Unusual Recurrent
What are immunodeficiencies associated with?
An increase in frequency and severity of infections
Autoimmune deficiencies and malignancy
What is a primary immunodeficiency?
Single gene disorder (or polygenic) which affects the immune system directly
HLA polymorphisms
What is a secondary immunodeficiency?
Underlying disease or condition affecting immune components
Causing decreased components produced and increased loss and catabolism of immune components
What are 4 examples of B cell deficiencies?
CVID- inability of B cells to mature into plasma cells
IgA deficiency- B cell unable to switch to IgA
Bruton’s disease- impaired B cell development
Hyper IgM syndrome- CD40 ligand on activated T cells
How would someone with a B cell deficiency present?
Reduced production of IgA –> recurrent upper and lower respiratory tract infections (bronchiectasis); GI complications including infections (Giardia)
Arthropathies (including mycoplasma and urea plasma)
Increased incidence of AI disease and lymphoma & gastric carcinoma
Low IgM and IgG because vaccines don’t amount in antibody production
How would you manage someone with a B cell deficiency?
Prophylactic antibiotics
Immunoglobulin replacement therapy ( serum IgG > 8)
Management of other infections and respiratory function
Avoid unnecessary exposure to radiation
What are 4 examples of T cell deficiencies?
Di George syndrome- defect in embryogenesis and incomplete development of thymus gland
STEM CELL DEFECT- Severe combined immunodeficiency (SCID - decreased B and T cells)- defect in gamma chain used by many receptors- IL2,4,7,9
DEATH OF DEVELOPING THYMOCYTES - Severe combined immunodeficiency (SCID) - defect in adenosine deaminase (ADA) purine nucleoside phosphorylase (PNP)
DEFECTIVE T CELL DEVELOPMENT- Severe combined immunodeficiency (SCID) and Omenns syndrome- defect in genes critical for TCR rearrangement and maturation
How would someone with DiGeorges syndrome present?
Cardiac abnormalities Abnormal facies Thymic hypoplasia Cleft palate Hypocalcaemia 22- chromosomal abnormality
How would you manage someone with Di George’s syndrome?
Neonatal cardiac surgery
Supplement to correct hypocalcaemia
Immune defect variable (low T cell number)
- if lower than 0.4x10^9/L- PCP prophylaxis with antibiotics
- bone marrow transplantation (severe forms)
Use only X irradiated and CMV (-) blood
No live vaccines (BCG, MMR, oral polio)
How would someone with SCID present?
Failure to thrive Long term Antibiotic therapy Deep skin and abscesses of organs Low lymphocyte count (<4-10 cells /ul) Hugh susceptibility to fungal and viral infections - PCP, VZV, CMV, EBV
How would you manage someone with SCID?
Short term- no live vaccines, only irradiated, CMV- blood products; aggressive treatment of infections, prevention of new infections
Long term- bone marrow/ stem cell transplant, gene therapy
What are 4 examples of phagocyte deficiencies?
Periodicity- Cyclic neutropenia
Leukocyte adhesion deficiency (LAD)- adhesion to endothelium affected, lack of CD18 protein on phagocytes
Chronic granulomatous disease- intracellular killing affected, lack of respiratory burst- NADPH oxidase deficiency
Chediak Higashi syndrome- failure of phagolysosome formation
How would someone with phagocyte deficiencies present?
Prolonged and recurrent infections
- skin and mucous membranes
- osteomyelitis
- deep abscesses (staph A)
- commonly staphylococcal (cat +ve)
- invasive aspergillosis
- inflammatory problems- (GRANULOMA)
How would you manage a patient with phagocyte deficiencies?
Prophylactic antibiotics/ Antifungal agent/ immunisation Surgical management Interferon gamma - CGD Steroids- CHD Stem cell transplantation
What is an example of a complement deficiency?
Hereditary angio oedema
C1 inhibitor deficiency
C1 inhibitor usually inhibits C1 and bradykinin preventing the complement cascade
But in deficiency in HAO there is little/no control over the complement cascaded
So you get vasodilation and increased vascular permeability as well as increased phagocytosis etc.
How is hereditary angio oedema treated?
C1 inhibitor infusion
Fresh frozen plasma
What conditions cause secondary immune deficiencies by decreasing the production of immune components?
Malnutrition Infection (HIV) Liver diseases Lymphoproliferative diseases Drug induced neutropenia Splenectomy
What factors cause drug induced neutropenia?
Drugs- e,g, phenytoin, chloramphenicol, alcohol (abuse)
Autoimmune
Infections- hep B/C, HIV, CMV, Typhoid
Bone marrow infiltration with malignancy
Aplastic anaemia
Vitamin B12/ Folate/ Iron deficiency
Chemotherapy- cytotoxic and immunosuppressants
Exposure to chemical agents- benzene, organophosphate
Radiotherapy
How would you manage drug induced neutropenia?
Neutrophils (< 1 x 10 ^ 9)
Treat suspected neutropenic sepsis as an acute medical emergency and offer empiric antibiotic therapy immediately
Assess patients risk of septic complications
What may cause someone to have to have their spleen removed?
Infarction (sickle cell anaemia) Trauma Autoimmune haemolytic disease Infiltration (tumour) Coeliac disease Congenital
How would someone present post-splenectomy?
Increased susceptibility to encapsulated bacteria- haemophiliis influenzae, streptococcus pneumoniae, neisseria meningitidis
OPSI- (overwhelming post splenectomy infection) - sepsis and meningitis
How would you manage someone having had a splenectomy?
Penicillin prophylaxis (life long)
Immunisation against encapsulated bacteria (at least 2 weeks before splenectomy if possible)
Patient info- medic alert bracelet
What are the normal functions of the spleen?
Immune
- blood borne pathogens- encapsulated bacteria
- antibody production- acute response: IgM production; long term production: IgG production
- splenic macrophages - removal of opsonised microbes, removal of immune complexes
Which three bacteria are encapsulated and thus dealt with by the spleen?
haemophiliis influenzae, streptococcus pneumoniae, neisseria meningitidis
What conditions cause secondary immune deficiencies by increasing the loss/ catabolism of immune components?
Protein losing conditions
- nephropathy and enteropathy
Burns
Which infections are pyogenic? What immune cells deal with them?
Staph aureus and strep pyogenes
Neutrophils
