Infectious disease Flashcards
Chlamydia causes
(Chlamydia trachomatis)
Gonorrhoea cause
(Neisseria gonorrhoea)
Trichomoniasis cause
(Trichomonas vaginalis)
Syphilis causes
(Treponema pallidum)
Chlamydia physiology
Transmission of chlamydia is through minute abrasions in mucosa which then establish an infection. However, it can also infect a newborn during birth
Generally speaking, the clinical symptoms are caused by cell destruction and the hosts inflammatory response
A localised infection is caused by spread of EBs to adjacent cells when they are released by infected cells at the end of their replicative cycle. They also have the ability to spread to distant sites via the lymphatic system or in blood
Gonorrhoea Physiology
- Attachment to hosts mucosal surface by pili (surface projections)
- Local penetration or invasion
- The bacteria is engulfed by the body’s parasite-directed endocytosis - Local proliferation
- Neisseria gonorrhoea then multiply within intracellular vacuoles, where they are protected from the host immune response (they also induce a local inflammatory) - Local inflammatory response or dissemination
- Which causes damage to the host as a result of this gonococcal-induced inflammatory response
Syphilis physiology
- Evades the host immune response
- Some may present with an initial painless ulcerative lesion (known as a chancre) known as primary syphilis
- Our body initially appears to have a variety of effective immune responses (which cause the resolution of the chancre) even in the absence of treatment
- Can develop secondary syphilis shown as disseminated rash and generalised lymphadenopathy
- Then becomes latent syphilis which can have no further complications (72%) or can lead to tertiary syphilis (28%)
- Can develop into tertiary syphilis which can lead to symptoms such as gumma (bacteria leading to mass of dead and swollen fibre like tissue often in liver), cardiovascular symptoms and neurological complications (psychosis)
Symptoms of Chlamydia females vs males
As a summary, the symptoms that are common in chlamydia infection of females include;
- Cervicitis
- Crampy abdominal pain
- Menstrual change
- Pain on urination
- Bleeding / Spotting
- Pain during or after sex
- Change in vaginal discharge
Males with chlamydia infection typically show the following clinical signs;
- Urethritis (most common cause of Non-Gonococcal Urethritis/NGU)
- Penile discharge (mucoid or watery discharge)
- Epididymitis
- Prostatitis
- Pain on urination
- Swollen and sore testes
- Proctitis (genital serovarts or LGV serovars)
Symptoms of Gonorrhoea male vs female
- Males (symptomatic)
- Urethral discharge
- Urethritis, epididymitis
- Proctitis (purulent discharge, common in men who have sex with men)
- Dysuria (painful or difficulty of urination)
- Complications are rare in males - Females (asymptomatic)
- 50% of female cases are mild or asymptomatic but are still infectious (major reservoir of infection)
- Cervicitis
- Vaginal discharge
- Untreated gonorrhoea in females can lead to PID, Infertility, chronic pelvic pain and disseminated infection
Diseases causing genital ulcers
HSV, chancroid, syphilis, lymphogranuloma venereum. The ulcers may cause a point of entry for HIV, and testing for HIV should be performed.
Diseases with discharge
bacterial vaginosis (commensal flora replaced with a mix of anaerobic Gram neg rods and Gardnerella vaginalis), trichomoniasis (Trichomonas vaginalis). Candida may produce a discharge, but is not considered an STI. Infection is usually associated with discharge, vaginal itching and sometimes an odour. Frequently co-infections with gonnorhoea.
Diseases with cervicitis or urethritis
Neisseria gonnorhoea, Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma genitalium. Inflammation of the urethra with a purulent discharge and painful urination is typical of urethritis. Females may be asymptomatic or have mild symptoms, but may develop PID if untreated.
Diseases with genital warts
human papilloma virus (HPV), syphilis. Some types of HPV can cause genital warts and cervical cell dysplasia. Persistent infections with these high risk HPV types are associated with cervical cancer. Gardasil 9 provides fully vaccinated people with protection against nine types of HPV including
Explain the testing procedures for the three major sexually transmitted bacterial pathogens: Chlamydia, Gonorrhoea
A lab diagnosis of both chlamydia and gonorrhoea is achieved by the following procedures;
1. Swab for PCR
- Can be used for both male and female
- Of the affected genital, rectal, throat or eye areas
- Should be done with a dry swab or commercial collection kit (not a bacterial swab as they have gel in the bottom of them which interferes with the viral PCR)
2. Urine for PCR
- Can be used for both male and females
- First catch is best (first 10 – 50ml of urine)
3. Swab for Microscopy, Culture and Sensitivity
- Are important for monitoring the development of antimicrobial resistance
Syphilis lab diagnosis
SYPHILIS – SEROLOGY DIAGNOSIS
- Screen the blood using the Syphilis total Antibody Test (EIA) which detects IgM and IgG
- If the antibody test is positive perform an RPR (indicates whether they have current infection or not)
- Then perform a TPPA test once for each total antibody positive patient (a back up for the total antibody test to ensure its correct). In other words it is a confirmatory assay
SYPHILIS – TREPONEMAL TESTS
Are the syphilis-specific tests used
They are a high-throughput screening assay for qualitative measurement of antibody to T. Pallidum in serum
These tests are specific for syphilis, remain positive for many years, even after antibiotic treatment and so can be used to confirm exposure (advantages)
They cant be used to follow treatment efficacy (disadvantage)
Examples include Treponema pallidum particle agglutination assay (TPPA test) and Treponema pallidum haemagglutinin assay (TPHA test)
They detect antibodies against T pallidum
SYPHILIS – NON-TREPONEMAL TESTS
These are positive at 4 – 6 weeks post infection and are useful for monitoring progress of disease and therapy
They are not specific for syphilis
A biological false positive can occur when tissue damage has occurred due to other processes e.g. old age, pregnancy, autoimmune disease, tuberculosis, malaria
Understand the predisposing
factors to UTI’s
Kidney stones, Diabetes, Catheter
Sexually active, birth control, pregnancy, menopause,
enlarged prostate, old age, unprotected sex
Recognise the main structural
differences between two
groups of pathogens covered:
bacteria and fungi
BACTERIA CELL STRUCTURE
Bacteria are prokaryotes, simple structure
Some important structural differences in bacterial cells is their cell wall, and their lack of membrane bound inclusions
There are 2 main types of bacteria. These are;
1. Gram-Positive
2. Gram-Negative
or acid fast
FUNGI STRUCTURE
Fungi are Eukaryotes
1. Unicellular (yeasts)
2. Multicellular (fungi)
The problem with treating a eukaryotic infection is that our cells are also eukaryotic cells, so they share a number of structures
Correlate structural differences
between pathogens and the
eukaryotic host with
mechanisms of drug actions
and toxicity
The problem with treating a eukaryotic infection is that our cells are also eukaryotic cells, so they share a number of structures
Because of this we don’t typically have many drugs which can treat systemic fungal infections (those that we do have cause all sorts of side effects as they can’t differentiate between the target and host)
It is important to note that fungal infections do not typically cause systemic infections as our immune system should be able to fight them off. If a patient does however, it may indicate some sort of immunodeficiency
What are the two portals for microbial entry
There are 2 main overarching portals of microbial entry. These are;
1. Endogenous entry
- Is achieved by organisms already present either on or within the body
2. Exogenous entry
- Is used by organisms within the external environment
- Examples of exogenous entry include: Inhalation, Ingestion, Direct contact, Nosocomial, breach of skin / epithelium / conjunctiva (e.g. Trauma from surgery or burns or by vector injection from mosquitos or ticks)
- The below diagram outlines the various protective mechanisms / innate barriers that the body has against invading organisms
- Individuals with altered defence mechanisms are at higher risk of disease by exogenous entry e.g. smoking destroys the mucociliary elevator increasing their risk of respiratory infections
- Host factors for exposure include: occupation (healthcare worker), lifestyle (camper) and geography/travel
Name some virulence factors of microbes
- Capsule
- Coats an organism, hiding away the non-self-antigen that the host uses to trigger an immune response against the pathogen
- They are made of a very non-immunogenic polysaccharide matrix that successfully hides the organism away, meaning the host isn’t aware of the infection until much later on, giving the organism plenty of time to multiply and grow - Adhesins
- Allows an organism to attach to the host upon entry - Flagella
- Is a tail like structure, that allows a pathogen to move
- i.e. towards a food source or away from a chemical source like an antibiotic - Toxins
difference between exotoxins and endotoxins
EXOTOXINS
Is a toxin actively produced and excreted by a live organism / pathogen
As exotoxins are actively secreted, the organism must be live
One of the most important examples of exotoxins are superantigens, which are produced and secreted by gram positive bacteria
When released into the body, superantigens produce an overwhelming immune response by overriding the normal MHC – TCR molecule interaction so that instead of a few highly specific T Cells reacting, there is an overwhelming cytokine storm leading to shock
ENDOTOXINS
endotoxins exist as a structural component of Gram-Negative bacterial cell walls (LPS)
Endotoxins are released during cell lysis and death of gram-negative organisms (because it is apart of the cell wall itself so only released upon breakdown. In other words, the component that causes the damage is only available to cause damage to the host when the organism dies)
A key example is the Lipopolysaccharide (LPS) which produces a very similar set of symptoms as exotoxins (fever and shock as a result of excessive cytokine induction and release)
mechanisms of microbial transmission
- Airborne
- The organisms must be able to survive outside of the host (bacteria and fungus can, virus cannot) - Waterborne transmission
- Commonly associated with natural disasters - Foodborne transmission
- Spoilage, food processing or compliance issues can all cause transmission by food - Horizontal transmission (person to person)
- Aerosols transmission between respiratory tracts (e.g. coughing)
- Saliva transfer or oropharyngeal transfer
- Faecal / oral transfer between gastrointestinal tracts
- Sexual contact leading to transmission between genital tracts
- Direct contact between skin
- Transmission by needles and insect bites between blood - Zoonotic transmission (between animals and humans)
difference between gram negative and gram positive
- Gram Positive
- Contain a thick peptidoglycan layer that makes up over 50% of the cell wall
- More commonly found in the environment as this huge cross-linked unit of sugars (glycans) and amino acids (peptido) give the cell wall an incredibly strong rigid structure that allows them to resist drying out - Gram Negative
- Contains only a small peptidoglycan layer (makes up only 5 – 15% of the cell wall), as well as an extra outer lipopolysaccharide layer (LPS)
- It is in this LPS that endotoxin sits, which when released causes endotoxic shock upon death of the organism (whilst embedded in this layer it is not toxic to the host)
gram staining process
The actual process of gram staining is as follows;
1. Crystal violet
- Is added to the specimen smear
- It will cause both gram-positive and gram-negative cells to stain purple or blue
2. Iodine
- Adding iodine makes dye less soluble so it adheres to cell walls better
- It will cause both gram-positive and gram-negative cells to remain purple or blue
3. Alcohol
- Decolorizes and washes away the stain from gram negative cell walls
- It will cause gram-positive cells to remain purple or blue
- It will cause gram-negative cells to become colourless
4. Safranin
- Is a counterstain that adheres to gram-negative cells
- It will cause gram-positive cells to remain purple or blue
- It will cause gram-negative cells to appear pink or red
name some of the normal flora of the body
Identify the main structural
features of the three groups of
pathogens covered: viruses,
prions and parasites
VIRUS
VIRUS STRUCTURE
As a very general overview of the structure of viruses, the following is true
The below diagram gives an example of the general structure of a virus (not all viruses look like this), which consists of the following structures;
1. Spikes
- Cover the outside of the virus
- Are the first structures to come into contact with the host cell
- Allow the virus to attach to specific cell surfaces
- It is against these spikes that the human immune system produces targeted antibodies against
2. Envelope
- Some, but not all viruses have this lipid envelope
- Not an essential structure (depends on the type of virus)
- Is acquired by the virus when budding out of the host cell
- Protein Coat
- Is a structure which encases the nucleic acid, giving structure to the virus - Nucleic acid
- Is the genetic code of the virus
- Can be DNA or RNA
Discuss the major replication
strategies of DNA and RNA
viruses, including integration
into the host genome
VIRUS infection lifecycle
- Entry
- Specific attachment
- Internalisation and Uncoating
- Replication
- Virus assembly
- Release
Correlate different viral
infection and replication
strategies with disease
outcome
HOW VIRUSES persist
MECHANISMS OF PERSISTENCE
- Antigenic variation
- Viruses have the characteristic ability to evolve their antigens
- This means that as their antigens change, a host’s memory T Cells are unable to recognise them if reinfected, allowing them to survive - Immune tolerance
- For a number of reasons, a host’s immune system may tolerate a virus, meaning it won’t launch an attack against it - Restricted gene expression
- A virus may reduce the number of genes it expresses so as to avoid detection by the immune system
- HSV is the perfect example of this - Immune response modulation by virus
- Some viruses may release factors which modulate the immune response against them - Infection of immunoprivileged sites
- Immunoprivileged sites are those areas in our body that are not accessible to by our immune system
- So, by infecting these areas viruses are able to avoid detection and destruction by our immune system - Direct infection of immune cells
- Some viruses (e.g. HIV) may even be able to directly affect the normal function of our immune cells
- For example, HIV actually destroys our CD4 T Cells
Correlate lifecycles of major
parasitic organisms to
geographic occurrence, public
health control programs and
vaccine design
PARASITES – PROTOZOA
They are most commonly found within the tropics and subtropics, which intuitively is where the majority of protozoa infections are found
Infection acquired through;
- Ingestion of contaminated food or water
- Insect vectors
- Occasionally via vertical transmission (transmission from mother to an embryo, foetus or baby during pregnancy or childbirth)
PARASITES – HELMINTHS
Infection by helminths occur worldwide but are most common in the tropics and subtropics
Transmitted via ingestion of eggs/larvae (faecal/oral route), penetration of skin by larvae
The most important helminths in regard to helminth infection include;
1. Tapeworms (cestodes) – flat bodies with hooks/suckers for attachment
2. Flukes (trematodes) – same structure as tapeworms
3. Roundworms (nematodes) – long, worm like bodies with no hooks
PARASITES – ARTHROPODS
Are the largest of the 3 groups of parasites and are usually visible to the naked eye
In terms of human infections, the most important are Insects (e.g. body lice), Ticks, Mites
1. Directly
- By feeding on the host which leads to irritation and then scratching
- E.g. scabies and head lice
2. Indirectly
- By transmitting infections
- E.g. Mosquitos transferring dengue, ticks transferring plague
Identify the main structural
features of the three groups of
pathogens covered: viruses,
prions and parasites
PRIONS
Are misfolded proteins that have the ability to transmit their misfolded shape onto normal variants of the same protein
They are not viruses, but instead a proteinaceous particles that do not have a genome, and are modified forms of normal cellular proteins
- They are simply a misfolded form of a naturally occurring protein on the surface of nerve cells
- When prions come in contact with normal proteins, they cause them to transform and become misfolded (eventually leading to chain reactions that lead to accumulations of the prion proteins in lymphoid tissue and the brain)
- A prion infection has an incredibly long incubation period, which eventually results in huge deposition of misfolded prion proteins and the development of large intracellular vacuoles containing them
Identify the main structural
features of the three groups of
pathogens covered: viruses,
prions and parasites
PARASITES
PROTOZOA
Are the smallest type of parasites. They are single celled and between 2 – 100nm in size
HELMINTHS
The eggs and larvae of helminths are small, but the adults can be quite large
– ARTHROPODS
Describe the role of LPS in the
development of sepsis
Gram-negative bacteria
1. LPS stimulates and activates macrophages (by TLR-4 binding tightly to macrophages CD14 receptor) which then start to produce and secrete cytokines. These cytokines have a broad spectrum of effects on the body;
- IL-1 and TNF stimulates T lymphocytes to release more cytokines to perpetuate the process (making the cascade self-perpetuating meaning it can continue even after treatment)
- IL-1 and TNF also activates endothelial cells to cause vasodilation, which increases their vascular permeability resulting in leakage of fluid out of the vessels resulting in hypotension and shock
- IL-1 and TNF also cause fever through their action of the hypothalamus
- IgE acts on mast cells to cause degranulation and thus the release of mediators
- At the same time, the LPS stimulates the coagulation cascade resulting in DIC (disseminated intravascular coagulation) thrombosis formation
- Not only does this cause clotting issues in patients, but it also means that the increase in vascular permeability is not counteracted by our clotting factors, leading to increased leakage of blood into the periphery (which is evident as petechiae in patients) leading to hypotension and shock - As a result of the increase in vascular permeability (caused by both points 1 and 2) the patients blood volume drops (as it moves into the periphery) and they will become hypotensive. Their heart will then try and pump faster to no effect, eventually leading to shock (the state of not having enough blood to flow to the tissues of the body)
- At the same time, the patient will experience a range of organ dysfunctions. This is because the blood that is full of cytokines and mediators is flowing through them
- For example, one of the classic symptoms of sepsis is the inability to breath. This is because cytokines are causing the release of fluid that is moving in and clogging the airways, preventing the gas exchange from occurring
- Issues happen in multiple organs
Describe the role of
superantigens in the
development of sepsis
- Gram-positive bacteria
- Use superantigens that bind to the MHC-2 complex on CD4 T lymphocytes overriding their specificity to cause huge release of IL-1, IL-2 and IFN-gamma which both perpetuates T lymphocyte proliferation and activates macrophages to release IL-1 and TNF-alpha
- They also use exotoxins to elicit the same effect
Illustrate the burden of RHD and
describe the management
When treating RHD, the following should be performed;
1. Antibiotic therapy
- Broad spectrum antibiotics should initially be used, which should then be focused after the causative organism is isolated
- Broad spectrum antibiotics should continue to be used if cultures are negative
2. Cardiac surgery on valve
- Should be performed as soon as possible if the infection is uncontrolled and / or is life-threatening
- Can be performed later on if the valve damage is progressive
3. Supportive therapy
4. Prevention
- Prophylactic antibiotics for at risk patients
Apply a process to identify the
infectious cause of sepsis
- Blood culture
- Sepsis is caused by an infection that has spread through the blood, as such there is a 80 – 90% chance of getting a positive blood culture
- Should involve a gram stain, catalase test and a coagulase test
- This will provide information as to what organism caused the sepsis - Urine for Microscopy / Culture / Sensitivity
- Used if the patient has a urinary tract infection - Imaging
- Used to identify primary and secondary foci of infection
Apply a process to identify the
infectious cause of endocarditis
- Patients with abnormal / damaged valves
- Oral streptococci
- Staphylococcus aureus - Patients that are IV drug users
- Staphylococcus aureus
- Oral streptococci
- Gram negative (enteric) bacteria) - Patients with a prosthetic valve (New valve)
- Is more likely to be caused by complications with surgery (hospital acquired infections)
- Coagulate negative staphylococci
- Staphylococcus aureus
- Gram negative (enteric) bacteria
- Oral streptococci - Patients with a prosthetic valve (Older valve)
- Is more likely to be caused by bacteria found in the community
- Oral streptococci
- Coagulase negative staphylococci
- Gram negative (enteric) bacteria
- Staphylococcus aureus
- Should involve a gram stain, catalase test and a coagulase test
What are
Genera Staphylococcus and how are they further classified
Is a gram-positive cocci in clusters
There are a number of different staphylococcus organisms, some of which are highly virulent and some of which only have low virulence
There are two groups of staphylococcus bacteria, which are separated based on whether or not they produce coagulase;
1. Coagulase positive
- Staphylococcus aureus (is the only clinically relevant coagulase positive staphylococcus)
2. Coagulase negative (CoNS)
- Staphylococcus epidermis
- Most staphylococcus bacteria are in this group
Define the virulence factors
and pathogenic mechanisms of
the organisms within the
Genera Streptococcus
(1) M protein and lipoteichoic acid for attachment; (2) a hyaluronic acid capsule that inhibits phagocytosis; (3) other extracellular products, such as pyrogenic (erythrogenic) toxin, which causes the rash of scarlet fever;
STREP what are they
Streptococci are Gram-positive cocci in chains
Streptococci are catalase negative
STAPH what are they
Staphylococci are Gram-positive cocci in clusters
Staphylococci are catalase positive
STAPH what are they
Staphylococci are Gram-positive cocci in clusters
Staphylococci are catalase positive
Interpret the aetiology
and pathophysiology of
common upper
respiratory infections
♦ colds and
rhinovirus
NON-ALLERGIC RHINITIS (THE COMMON COLD)
Is characterised by inflammation of the nasal mucosa that is caused by a virus (not by an allergy)
The symptoms of non-allergic rhinitis include;
- Copious watery nasal discharge
- Nasal obstruction (blocked nose)
- Sneezing
- Mild sore throat
- Cough
- Little or no fever
Whilst non-allergic rhinitis itself is usually an extremely mild-illness, the damage that it causes can predispose patients to Otitis Media or Sinusitis
The pathogens that cause non-allergic rhinitis are all viruses, and include;
1. Rhinovirus (50% of cases)
2. Coronavirus (15% of cases)
3. Other uncommon viruses include;
- Enteroviruses
- Parainfluenza viruses
- Adenoviruses
Correlate normal
bacterial flora of the URT
with disease in the host
Interpret the aetiology
and pathophysiology of
common upper
respiratory infections
♦ pharyngitis
PHARYNGITIS and TONSILLITIS
Pharyngitis is inflammation of the pharynx (a sore throat)
Tonsillitis is caused by the inflammation of the tonsils at the back of the throat
These two infections can be caused by both viruses and bacteria. The most common causative organisms of these states are;
1. Bacterial: Streptococcus pyogenes
- Highest rates between 5 and 15 years of age
- Transmission occurs via infected droplets
- 10 – 30% of the population are asymptomatic carriers of the bacteria
- Invasive disease can occur as a result of Streptococcus pyogenes if dissemination from the skin or throat occurs to other sites (can also be caused by impetigo)
2. Viral (70% of cases)
- Adenovirus
- Cytomegalovirus (CMV)
- Epstein Barr Virus (EBV)
- Herpes Simplex Virus (HSV)
It is important that microbiology is interpreted with caution (as there are tonnes of organisms that live in these regions that have the potential to cause disease states)
Because of this, it is not possible to determine the cause by inspection (as all of them cause the same acute inflammation of the pharynx and tonsils)
Interpret the aetiology
and pathophysiology of
common upper
respiratory infections
♦ mumps
MUMPS: PAROTITIS
Parotitis is the swelling of your parotid glands
The most common presentation of parotitis is mumps, caused by infection of the parotid glands by the mumps virus
The mumps virus is spread by airborne droplets, salivary secretions and potentially urine
Virus is shed in the saliva prior to any clinical illness, meaning you can infect people without knowing your unwell
The peak incidence occurs between 5 – 14 years of age
It is highly preventable by MMR Vaccine (is around 80 – 90% immunoprotective)
It is important to note that people who have been vaccinated can still get mumps (particularly in settings where there is close contact)
The virus itself is highly neurotropic, and can also cause Orchitis in adults (inflammation of the testicles)
Interpret the aetiology
and people at risk of
common upper
respiratory infections
♦ oral candidiasis
ORAL THRUSH: CANDIADIASIS
Candidiasis in the mouth or throat is uncommon in healthy adults
People at higher risk include:
- Babies > 1 month
- Older people who wear dentures
- Those with diabetes, cancer, HIV/AIDS
- Those on antibiotics or corticosteroids including inhaled corticosteroids for conditions like asthma
- Those who take medications that cause dry mouth or have medical conditions that cause dry mouth
Interpret the aetiology
and pathophysiology of
common upper
respiratory infections
♦ epiglottitis
EPIGLOTTITIS
Is the inflammation of the epiglottis (the flap at the base of the tongue that keeps food from going down your trachea)
Because of the anatomical location, inflammation of the epiglottis is extremely serious
In terms of the clinical presentation, patients will typically present with;
- High fever
- Sore throat
- Pain on swallowing
- Inspiratory stridor and hoarseness
- Respiratory difficulty within 24 hours
Intubation is required to secure the airway
It is important to differentiate epiglottitis from croup (croup is viral and has a barking cough with no fever, can only symptomatically treat) as epiglottis will become a medical emergency
A patient with epiglottis will have a fever, no cough, sore throat, dysphagia (difficulty on swallowing) and they will drool. A patient with croup will have none of these***
Epiglottis is caused by the following bacteria;
1. Haemophilus influenzae (type B) – decreased due to vaccination
2. Streptococcus pneumonia
3. Staphylococcus aureus
The causative bacteria should be confirmed by blood and throat cultures
Interpret the aetiology
and pathophysiology of
common upper
respiratory infections
♦ otitis media
Is an infection of the middle ear (the air-filled space behind the eardrum)
Cases of Otitis media are typically preceded / caused by non-allergic rhinitis (some sort of viral URTI). The reasons for this are outlined below;
- Between your nasopharynx and middle ear is a structure known as the Eustachian tube (auditory tube or pharyngotympanic tube)
- If a person gets the common cold, they will experience inflammation and fluid build-up within the nasal mucosa, which inevitably builds pressure within the nasopharyngeal area
- Eventually, this negative pressure will force any pathogens and nasopharyngeal commensal flora up and into the middle ear (via the Eustachian tube)
Otitis media is most common in infants and young children (highest rates between 6 – 18 months) because they simply have narrower airways to begin with meaning it requires less inflammation to force pathogens into the middle ear
Around 50% of the cases are viral (most common is by Respiratory Syncytial Virus)
If the cause is bacterial, it is usually preceded by a viral Upper Respiratory tract infection (for the above outlined reason). The most common bacteria that cause otitis media are;
1. Streptococcus pneumoniae (35% of cases)
2. Haemophilus influenza (25% of cases, are non-typable, as they don’t have a capsule)
3. Moraxella catarrhalis (15% of cases)
In terms of the clinical presentation of otitis media, clinical features are variable;
- Infants typically experience fever, vomiting, diarrhea and irritability
- Older children experience severe ear pain (less of other stuff)
- Fluid may persist for weeks to months (glue ear)
Interpret the
aetiology and
pathophysiology
of common
lower respiratory
infections
♦ pneumonia
PNEUMONIA
Is an infection characterised by air sacs filled with purulent material in one or both lungs
cough, purulent sputum and fever
The physical or radiological changes are compatible with consolidation of the lung
The pathogens that cause pneumonia are partly determined by age and by risk factors
There are a few different types of pneumonia;
1. Bacterial Pneumonia (General Pneumonia)
- Is the most common type of pneumonia
- It is a major cause of death in elderly populations (older than 70 years old)
- The most common bacterial agents are: Streptococcus Pneumonia, Staphylococcus aureus (often as a secondary infection following influenzae), Klebsiella pneumoniae, Haemophilus influenzae and Burkholderia pseudomallei (melioidosis)
- Bacterial pneumonias often occur after a viral infection which damages the airways, allowing the bacteria to venture deeper into the airways
2. Primary Viral Pneumonia
- Very rare
- Is uncommon in adults
- Is very important cause in young children and in the immunocompromised
- The most common viral causes include: RSV, hMPV, Parainfluenza, Infleunza (is very dangerous), Adenovirus
- Hospital acquired pneumonia
- Is caused by gram-negative bacteria like Klebsiella pneumonia, Serratia or Pseudomonas (especially if the patient is ventilated) - Cystic Fibrosis
- Because they have a compromised mucociliary escalator mechanism, these patients experience mucus build up in their airways resulting in colonisations of bacteria
- Common bacterial causes include Staphylococcus aureus, Haemophilus influenzae, Pseudomonas and Burkhoderia cepacia - Atypical Pneumonia
- Mycoplasma pneumoniae
- Chlamydia pneumonia
- Legionella species
Outline the
testing
procedures for
the major
respiratory
pathogens
Be aware of the
common respiratory
pathogens causing
pneumonia
- Bacterial Pneumonia (General Pneumonia)
- Is the most common type of pneumonia
- It is a major cause of death in elderly populations (older than 70 years old)
- The most common bacterial agents are: Streptococcus Pneumonia, Staphylococcus aureus (often as a secondary infection following influenzae), Klebsiella pneumoniae, Haemophilus influenzae and Burkholderia pseudomallei (melioidosis)
- Bacterial pneumonias often occur after a viral infection which damages the airways, allowing the bacteria to venture deeper into the airways - Primary Viral Pneumonia
- Very rare
- Is uncommon in adults
- Is very important cause in young children and in the immunocompromised
- The most common viral causes include: RSV, hMPV, Parainfluenza, Infleunza (is very dangerous), Adenovirus
Identify the vaccine
preventable
respiratory infections
Bordetella pertussis, Streptococcus pneumoniae, Haemophilus influenzae type B, Corynebacterium diphtheriae, measles virus, and influenza virus
Interpret the aetiology
and pathophysiology of
common upper
respiratory infections
♦ Bronchitis
Is a common chest infection in young children caused by viral infection and inflammation of the bronchioles leading to mucus build up in the airways
Patients with bronchiolitis will show;
- Rapid and laboured breathing
- Cough
- Expiratory wheezing
- Cyanosis
- Atelectasis (complete or partial collapse of a lung)
- Marked emphysema
It is most often caused by the Respiratory Syncytial Virus (over 75% of cases), as well as Human Metapneumovirus, Parainfluenza and Influenza
The disease itself is restricted to children under 2 years of age
It is very severe in young infants; its peak mortality is around 3 months (because they only have extremely narrow respiratory airways meaning it doesn’t take much to block them)
It is believed to be a contributor of SIDS
Interpret the
aetiology and
pathophysiology
of common
lower respiratory
infections
♦ influenza
INFLEUNZA VIRUSES
Is apart of the Orthomyxoviridae family (is a negative sense RNA)
Its genome is made up of 8 segments which means there is significant variability between influenzas viruses which are RNA
The virus has a viral envelope which contains two very important glycoproteins, Haemagglutinin (HA) (which is involved in attaching and entering into the host cell) and Neuraminidase (NA) (which Is involved in the release from the host cell after viral replication has occurred)
These glycoproteins are the first point of contact between our body and the virus, meaning that it is these antigens that our immune response targets (if these antigens change, we lose immunity)
There are a number of different types of Infleunza viruses;
1. Infleunza A
- Affects numerous animals (including humans)
- There is a huge reservoir in bird species
- It is a major cause of epidemics and pandemics
2. Influenza B
- It is a human pathogen only
- It generally only causes localised outbreaks
3. Infleunza C and D
- Is rare
- Only causes mild illness
Interpret the
aetiology and
pathophysiology
of common
lower respiratory
infections
♦ human
metapneumovirus
HUMAN METAPNEUMOVIRUS (hMPV)
Is another virus apart of the Paramyxoviridae family (has an RNA genome)
It is an important human respiratory pathogen in infants, the elderly and the immunocompromised
The peak incidence of infection by hMPV is during winter (similar pattern to influenza and RSV)
Infection by hMPV causes a broad spectrum of illness that ranges from mild infection, to bronchiolitis and pneumonia (it causes a similar disease state to RSV)
It is the second most common cause of bronchiolitis and pneumonia in children under 5 years of age
Infections in humans is almost universal by 5 years of age, however reinfection can occur throughout life
Difference between antigenic shift and drift
- Antigenic Drift
- Occurs in both Influenzas A and Influenza B
- Are small and cumulative mutations that occur frequently and commonly
- It is usually associated with point mutations that affect all antigens within the virus
- If they occur in the HA and NA glycoproteins, it may result in a new Flu Subtype that has the ability to evade the hosts immune response
- This results in repeated re-infection of hosts - Antigenic Shift
- Occurs only in Infleunza A
- Are sudden, major changes in the viruses H or N antigens that occurs randomly
- This may result in new strains that are antigenically different enough to cause pandemics
- Antigenic shift is caused by exchange of genetic material between 2 different strains of Influenza A (when they co-infect a single cell)
- For example, A duck passes an avian strain to an intermediate host like a pig. A human then passes a human strain to the same pig, resulting in the pig host cells being infected by two strains at once. As a result the genes from the two strains can mix producing a new strain of daughter virus. If this new strain has a pathogenic advantage it will then spread between humans potentially causing a pandemic
- Antigenic shift can also occur without undergoing any genetic change. Instead an avian strain can infect a person straight up, which may then develop and evolve in the human to be able to spread from person to person
- The same could also occur in an intermediate host
Interpret the
aetiology and
pathophysiology
of common
lower respiratory
infections
♦ pertussis
PERTUSSIS (Whooping Cough)
Is a highly contagious respiratory disease caused by the bacterium Bordetella Pertussis characterised by uncontrollable, violent coughing which makes breathing difficult
The classic clinical presentation is a paroxysmal cough with inspiratory whoop. However, it is important to note that this may be minimal or absent in very young infants. Sometimes the only symptom is apnoea or cyanosis
The highest risk of severe infection is in young infants (younger than 3 months), which can develop into pneumonia, seizures, hypoxic encephalopathy and even death
Neither natural infection or vaccination against Bordetella pertussis provides long term protection meaning that reinfection can often occur
A lab diagnosis is achieved by Nasopharyngeal swab for PCR, or by blood for serology (not as accurate as NP swabs)
Interpret the
aetiology and
pathophysiology
of common
lower respiratory
infections
♦ melioidosis
MELIOIDOSIS
Is an infectious disease caused by the Burkholderia pseudomallei bacteria, which is found in the soil of endemic areas like SE Asia and tropic Australia
It is quite an uncommon infection, and usually presents as pneumonia (with or without septicaemia) and can be rapidly fatal
2/3 cases have a predisposing medical condition
Treatment of melioidosis is with specific antibiotic therapy
Sputum and blood cultures are required for diagnosis
Interpret the
aetiology and
pathophysiology
of common
lower respiratory
infections
♦ TB
TUBERCULOSIS
Is an infectious disease caused by Mycobacterium tuberculosis (Mtb)
Transmission occurs via droplet spread
Mycobacterium tuberculosis usually causes respiratory infections, but can also affect a number of other areas of the body
Mtb usually survives and multiplies within alveolar macrophages;
The symptoms of respiratory tuberculosis are listed below;
- Weight loss
- Night sweats
- Fever
- Cough
- Haemoptysis
- Can also be asymptomatic in a latent form
It is important to note that many of the symptoms of tuberculosis infection are due to the hosts immune response
It can lay dormant in a patient’s lungs, and be reactivated later on in life
Microbiological diagnosis is achieved by sputum for M/C/S
Because they have such a thick cell wall, a special acid-fast bacilli stain known as Ziehl-Neelsen stain is required in conjunction with a prolonged culture using specialised media
How to test for U and L RT infections
the first thing we do is take a nasopharyngeal swab (NP swab). This is because it is in the nasopharynx that the viruses often replicate
NP swabs are then taken and put through a Polymerase Chain Reaction (PCR), which tests for the specific corresponding genetic code of viruses.
The standard panel used in a multiplex PCR is Flu A, Flu B, Parainfluenza 1 – 4, RSV, Adenovirus, hMPV and Rhinovirus (can look for Bordetella Pertussis and Mycoplasma Pneumoniae if specifically requested)
Technological advancements have also developed GeneXpert, which is a system that can provide rapid molecular detection of respiratory viruses within the hour (after processing). The process of GeneXpert testing is as follows;
- A Nasopharyngeal sample is taken and mixed with a viral transport media
- The tube is then vortexed and added into a test cartridge
- The test cartridge is put into the GeneXpert instrument
- A result is provided in 32 minutes
- Only checks for Influenza A, Influenza B or RSV (nothing else)
This Rapid Diagnostic Testing for Influenza and RSV is only recommended for high-risk patients where a rapid result will affect clinical management (e.g. ICU patients, immunocompromised patients, inpatients and ED patients with flu like symptoms)
Differentiate the symptoms, time frames and causes of food associated infection from food poisoning
- Salmonella
- Incubation period between 16 hours – 2 days
- Infectious dose required: 1000
- Is able to spread systemically (typhoid fever) or uncomplicated gastroenteritis
- Transmission is acquired in food or drinks contaminated with human faeces
- Diagnosis is through stool culture and treatment by fluid replacement and symptom management. If becomes systemic antibiotics are required - Campylobacter
- Incubation period between 16 hours – 2 days
- Infectious dose required: 500
- Are invasive, and therefore cause dysentery with abdo pain, fever and N/V
- Transmission is usually through consumption of contaminated animal products (birds) – reservoir species - Shigella
- Incubation period between 1 – 4 days
- Infectious dose required: 10 (meaning touch is able to transfer enough organisms to cause infection) – low infectious dose
- Mainly person to person transmission (incidence doesn’t tend to change with environment) and invades colonic epithelium to hide from immune system
- Are invasive, and therefore cause dysentery or watery diarrhoea (less common) - Escherichia Coli
- Incubation period between 16 hours and 3 days
- Infectious dose required: up to 106
- Toxins cause osmotic imbalances in the gut - Vibrio Cholerae
- Incubation period between 2 – 3 days
- Infectious dose required: up to 108
- Toxins cause osmotic imbalances in the gut
Be aware of the causes and clinical significance of diarrhea verses dysentery
- Diarrhoea
- Is the passage of three or more loose or liquid stools per day (or more frequent passage than is normal for the individual)
- Is usually associated with some sort of pathology in the small intestine - Dysentery
- Diarrhoea containing blood, +/- pus and mucous (indicating some sort of damage to the enterocytes)
- It is associated with pain, fever and abdominal cramps
- Is usually associated with some sort of pathology in the large intestine
defences in GIT to prevent infection
HOST DEFENCES
It makes sense that infections of the gastrointestinal system are going to be caused by infectious agents that are ingested (faecal oral transmission)
The gastrointestinal system has a number of defences to prevent this transmission. Some of these defences include;
1. Peristalsis (moves the organisms through preventing attachment)
2. Normal Flora (provide a natural barrier)
3. Mucous (provide a natural barrier and can also trap invading organisms for disposal)
4. Gastric acidity (the stomach has an extremely low pH which kills the large majority of pathogens)
5. Digestive enzymes (destroy bacteria)
6. Bile (inhibitor to growth of many bacteria)
7. Secretory IgA (are antibodies present on the mucosal surfaces of the gut)
OESOPHAGEAL INFECTIONS
The most common type of oesophageal infection is by the yeast Candida (the same fungus that causes thrush)
It usually occurs in immunocompromised patients e.g. diabetics and HIV positive
It is also associated with Gastric or abdominal surgery, however if a patient has candida you should look for some sort of underlying immunocompromising condition
STOMACH INFECTIONS
Because of the acidic pH of the stomach, 90 – 99% of all organisms that are ingested are destroyed very quickly
The exception to this is the gram-negative, spiral bacteria Helicobacter pylori
Helicobacter pylori is able to survive the low pH for a number of reasons;
1. It does not have a lipid envelope and so is not destroyed by the acid
2. It also has the unique ability to burrow into the mucous layer of the stomach (which protects the stomach from the acid)
3. It is able to produce an enzyme known as Urease, which is able to convert the high levels of UREA present in the stomach into ammonia (a basic molecule which increasers the pH of its local environment)
Infection by helicobacter pylori causes gastritis, gastric ulcers (75%) and duodenal ulcers (90%)
Diagnosis of an infection by Helicobacter pylori can be achieved by a breath test which picks up the excessive amounts of Urease produced by the bacteria (the breath test contains radiolabelled Urea, which is broken down if Urease is present indicating infection by helicobacter pylori)
FOOD POISONING
- Staphylococcus aureus
- Incubation period of 1 – 6 hours
- Lasts for around 8-24 hours, affecting the CNS and causes severe vomiting
- Common in ham and cream filled pastries - Bacillus cereus (2 forms)
- Incubation period of 15mins – 6 hours
- Lasts for around 12-24 hours and these cause endospores
- Common in fried rice (likes starch as it requires it for growth)
CHOLERA
Is an infection of the small intestine by Vibrio cholerae that is characterised by severe diarrhoea and dehydration
The pathology of cholera is caused by the release of exotoxin. The complete infectious processes is outlined below;
- Vibrio cholerae is ingested in large numbers
- Because it is sensitive to stomach acid, an extremely large infectious dose is required to cause disease (unless they are achlorhydric meaning they don’t produce HCL or taking antacids)
- The bacteria then continues on and colonises the small intestine, where it starts to produce exotoxin
- This exotoxin then enters into the enterocytes and Ribosylates the G-Proteins sticking it in the locked position, and increases the production of cAMP (disrupting the osmotic potentials of the cells)
- As a result the enterocytes start to pump out irons and liquids, in other words a mass loss of fluid and electrolytes
ESCHERICHIA COLI
ESCHERICHIA COLI
There are 6 pathotypes of E. Coli (e.g. Enterotoxigenic E. Coli / ETEC, Enterohaemorrhagic E. Coli, Enteropathogenic E. Coli etc.)
Has fimbriae and adhesins so is able to colonise the intestinal tract
It is a leading cause of children’s diarrhea and travellers’ diarrhea
There is currently no licensed vaccination against E. Coli
The pathology caused by E. Coli is caused by 2 main enterotoxins;
1. Heat Labile Enterotoxin
- Mimics cholera
- It does this by elevate intracellular cAMP or cGMP levels in host epithelial cells to cause water and fluid hypersecretion, and therefore eventually watery diarrhea
- Heat labile means it becomes inactivated at high temperatures
- Heat Stable Enterotoxin
- Has a similar action to the Shiga toxin (released by Shigella)
- Heat stable means that it is able to maintain its form, structure and function at high temperatures
ENTERIC FEVER-TYPHOID
Is a systemic bacterial disease caused by Salmonella typhi and Salmonella paratyphi that is characterised by fever and abdominal pain
Transmission is achieved by person to person contact (therefor hygiene is incredibly important)
A person can carry the organism without clinical symptoms for months or years, and can even become a chronic carrier (Typhoid Mary)
Enter fever-typhoid is a systemic infection as the bacteria is able to penetrate through the gut mucosa and into the intestinal lymph nodes. Once here the bacteria is carried by macrophages into the blood stream
The incubation period is around 10 – 14 days
A patient will typically first present with fever, followed by rose spots (non-blanching spots on the trunk), delirium and then abdominal pain (caused by perforation of the bowel)
Can be fatal
LISTERIOSIS
Is a systemic bacterial infection caused by the gram positive coccobaccillus listeria monocytogenes
Listeriosis is widespread in animals and in the environment
Listeria monocytogenes is able to replicate at 4°C, making it common in uncooked foods like pates and soft cheeses (foods that are not recooked)
Because this infection can become systemic, there is increased risk to pregnant women and the immunocompromised
Pregnant women are advised from foods that can become infected by listeriosis as it can pass through the placenta
Infection of a pregnant lady can cause, maternal, foetal and neonatal disease;
- Maternal listeriosis during pregnancy presents as mild febrile illness
- Foetal listeriosis has a high mortality rate of 25 – 35% (depending on the gestational age at the time of infection)
- Neonatal listeriosis presents as sepsis or meningitis with severe sequalae (evidence of previous disease) and high case fatality rate of 20%
If the mother is treated it prevents foetal disease
HEPATITIS A
HEPATITIS A
Is the most common of the two viral hepatitis. It is a single stranded RNA virus apart of the picornavirus family
It is associated with poor sanitation, hygiene, a lack of safe water and within day care centres in Australia (due to the high contact between children)
Transmission is via person to person contact via hand contact, contaminated food and water, sexual contact and household contacts
The incubation period is around 3 -5 weeks; however the virus is present in faeces up to 1 – 2 weeks before symptoms appear (infectious before symptoms)
There is an extremely high amount of virus excreted in faeces (around 108 per gram)
There is no chronic state of infection, patients usually get over it in a couple of days
It is rarely fatal, and infection provides lifelong immunity (therefore not typically seen in adults)
Detection is based on serum IgM levels
There is a formaldehyde-inactivated vaccination available (typically used by travellers)
Symptoms include;
- Nausea
- Vomiting
- Diarrhea
- Jaundice
- Fever
- Abdominal pain
HUMAN CALICIVIRUS
Is also known as Norovirus or Norwalk-like virus
It is the most common cause of adult diarrhea worldwide (20% of cases)
It is highly infectious and spreads rapidly. It is also common in the hospital setting
Symptoms typically present 12 – 48 hours after initial exposure to the virus and last around 1 – 3 days
It is able to withstand hot and cold temperatures, as well as most disinfectants making it very difficult to eradicate
One of the factors that make norovirus so infective is the fact that it can bind to the cell surface carbohydrates of histocompatibility-blood group antigens, meaning there is a plethora of cells throughout the body that it can easily bind to and infect
It is the causative virus behind cruise ship infections, on plains etc.
It is often associated with sewage contaminated shellfish
PROTOZOAN INFECTIONS
Some examples of the more common protozoan infections include;
1. Giardia
- The trophozoite stage is able to adhere to the brush border of the small intestine
- They completely cover the small intestine causing a malabsorptive state (resulting in explosive flatulence, fatty stools etc.)
- It then develops into a cyst, which is environmentally stable
- The cyst is able to pass out in stools and infect people (the stage found in stool samples)
2. Entamoeba histolytica
- Causes amoebic dysentery by burrowing into the gut wall causing destruction of the enterocytes
- The trophozoite can live harmlessly in the Large Intestine (around 10% of the population are asymptomatic carriers)
- Cryptosporidium hominis
- Differs as the asexual and sexual phase occurs in the same host
- Transmission is typically by ingestion of cysts in water
All 3 of the above are typically water associated
ASCARIS LUMBRICOIDES (ROUNDWORM) LIFECYCLE
The lifecycle of the roundworm is as follows;
1. Somebody who has the worm defecates on the ground
2. The eggs are swallowed orally (in contaminated water, contaminated food or by scratching your bum)
3. The eggs then go into the intestine, and the larvae hatch and penetrate the intestinal mucosa
4. These then travel through the blood stream into the liver where they develop and mature
5. These then travel to the lung and are coughed up, and then swallowed
6. Once the adults are in the intestine again, they produce eggs
7. The process starts again
ANCYLOSTOMA DUODENALE (HOOKWORM)
The lifecycle of the hookworm is as follows;
1. Somebody who has the worm defecates eggs on the ground
2. The eggs of the worm are then present on the ground, and therefore develop into larvae
3. After 2 – 3 weeks of development through larvae stages, the larvae penetrate intact skin of a person walking by barefoot (can cause a skin rash where penetration occurs)
4. The larvae then travel via the blood stream, mature in the liver and finish up in the capillary bed of the lungs
5. They then wiggle into the alveoli and develop further, where they eventually cause a cough and a wheeze
6. Because of the cough, they are expelled from the lungs, up the respiratory tract where they are then swallowed back into the gastrointestinal system
7. Once in the intestine, the adults live and lay eggs, at which point the cycle continues
Clinical features include;
- Anaemia (pallor and fatigue)
- Poor growth
- Cough
STRONGYLOIDES
Unlike other worms, this worm can reinfect you after only 1 exposure
This is because whilst some eggs develop in the soil, others can develop into auto infective larvae in the colon
As a result of this, the worm load persists and or increasers even if there is no further exposure
The lifecycle of the threadworm is the same as the hookworm, however it also includes the ability to autoinfect
Usually the body can handle it. However if someone that is immunosuppressed (on corticosteroids etc.) experiences infection by Strongyloides, they can invade numerous organs and have accelerated growth causing issues
If the worms become widely disseminated there is a morality of 90%
Clinical features include;
- Burning pain around abdomen
- Anaemia
- Weight loss
Describe the mechanisms used
by pathogens to invade the
CNS
- Direct Cytotoxic effect
- Streptococcus pneumoniae secretes a pore forming toxin that forms pores within the endothelial cells that line the various barriers, dysregulating their function
- As a result of the toxins some organisms secrete, they cause an overwhelming response of host inflammatory mediators which damages the area (inflammation increases permeability of the various barriers allowing organisms to enter) e.g. Sepsis which permeases the barrier allowing organisms to enter - Passive/transcellular passage
- Can be transported across in intracellular vacuoles (Streptococcus pneumoniae does this as well) known as transcytosis
- Microbes can grow in the endothelial cells/neurons and then into the astrocytes or choroid plexus (e.g. Polio which infects the neuromuscular junction and then grows back along the nerve) - Paracellular passage
- Moving between cells by disrupting the tight junctions (e.g. Neisseria meningitidis) - Carried by inflammatory cells
- Often referred to as the trojan horse type mechanism
- Cells infect inflammatory cells which can then migrate into the brain and meninges
- Once inside the infected cells lyse and release the organism
- Also known as leukocyte mediated CNS invasion
Be able to differentiate
between bacterial and viral
infection based on blood
biochemistries
Be aware of the difficulties and
limitations of antimicrobial use
for CNS infections
limit drugs getting into the CNS to treat infections within the brain and spinal cord. We currently only have a few drugs that are able to penetrate through these protective mechanisms to heal these infections
Describe the different clinical
symptoms of meningitis,
Sudden high fever.
Stiff neck.
Severe headache that seems different from normal.
Headache with nausea or vomiting.
Confusion or difficulty concentrating.
Seizures.
Sleepiness or difficulty waking.
Sensitivity to light.
Describe the different clinical
symptoms of
encephalitis
Is an inflammation of the brain commonly caused by infection (most commonly by viruses)
Characteristic signs of encephalitis are cerebral dysfunctions like;
- Abnormal behaviour
- Altered mental status (confusion)
- Motor or sensory deficits (hemiparesis, flaccid paralysis, paraesthesia’s)
- Speech or movement disorders
- Seizures
- Nausea
- Vomiting
- Fever
Describe the different clinical
symptoms of brain abscess
BRAIN ABSCESS
Is basically a space occupying lesion within the brain that is caused by infection
Basically an infectious organism gets into the brain and the immune system walls it off forming a purulent filled space. As the lesion grows the patient experiences more and more neurological symptoms as a result of increased pressure on blood flow, nerves etc.
The most common causative organisms in non-IC populations are streptococci and staphylococci
Brain abscess are typically caused by infectious agents that enter the brain through the following mechanisms;
1. Direct introduction
2. Local extension (e.g. mastoiditis or sinusitis)
3. Haematogenous spread (e.g. heart, lungs, tooth extraction)
Do not perform a lumbar puncture due to increased ICP so increased risk of brain herniation
Describe the different clinical
symptoms of neurotoxins
Are toxins produced by bacterial infections that can affect the CNS
The main two we are concerned with are;
1. Tetanus
- Produced by clostridium tetani
- Anaerobe that produces endospores
- Toxin is carried to the CNS in peripheral nerve axons
- Causes muscles to spasms due to lysis of neurotransmitter inhibitor (GABA)
2. Botulism
- Produced by clostridium botulinum
- Anaerobe that produces endospores
- Pre-formed toxins are typically ingested in food which is then passed from the gut into the blood (common in canned foods)
- Wound contamination with spores
- Causes flaccid paralysis as neurotransmitter (Ach) release is blocked
Understand the diagnostics of
Hep B and the link to stages of
clinical disease
Correlate HIV diagnostic tests
with stages of disease
progression
HIV – DIAGNOSIS
A diagnosis of Infection by HIV is achieved a HIV Ag/Ab combination test (which is an automated enzyme immunoassay or Automated EIA) from a blood sample from the patient (HIV results are gained very rapidly)
Any HIV positive samples are then referred for confirmation testing which is achieved by;
1. P24 Ag Test (p24 is a detectable HIV viral antigen)
2. HIV Western Blot
- Proteins for HIV are separated out on the basis of molecular weight and embedded into strips
- The patient’s serum is then applied to the strip
- If the patient has antibodies to the specific HIV antigens on the strip, there will be a colour reaction, indicating which of the viral proteins the person has antibodies for
- This is particularly useful as the combination of antibodies present in the patient’s sample can indicate whether it is definitely HIV, whether it is an indeterminant result or at what stage of the disease process the person is at
- An indeterminant result is when is does not show HIV Antigens, but it is too early since exposure to determine
This confirmation testing is repeated twice to ensure the result is correct, where it is then referred to Brisbane for further testing
Other tests available include;
1. HIV viral load (test efficacy of treatment)
2. HIV genotyping (determine what type of treatment would be effective)
3. HIV proviral DNA (Detects viral DNA in the host genome, can be useful in testing whether or not newborns have HIV)
These can be used not only to assist with the diagnosis, but also for the treatment and monitoring of the HIV positive patient
Point of care testing are also available, they are particularly useful in resource poor settings
Correlate the principles of viral
replication with the
therapeutic drugs used for HIV
Differentiate between the
pathogenesis of
Hepatitis C
HEPATITIS C VIRUS (HCV)
Is a flavivirus with a single stranded positive sense RNA genome
There are 6 main genotypes or strains of HCV, each of which have numerous subtypes (a, b or c). The distribution of genotypes varies across the world
Transmission of HCV is through exposure to blood from an infected individual. This typically occurs as a result of;
1. IVDU (more than 80% of cases)
2. Contaminated blood/blood product acquired prior to 1990 (5% of cases)
3. Other means (12%)
- Non sterile tattooing / body piercing
- Non sterile medical procedures / vaccinations
- Needle stick injuries
- Household exposure
- Other blood to blood contact
The incubation period is 2 – 6 weeks (typically 4 weeks)
About 20 -25% of patients exposed to HCV clear the virus completely within this time period (but they remain HCV Ab Positive), whilst 75 – 80% develop chronic HCV
Of this 75 – 80% with chronic HCV;
- 20% are asymptomatic but remain infectious
- 40 – 50% develop liver damage and symptoms (after 15 years)
- 10 -20% of those with liver damage develop cirrhosis (after 20 years)
- 2 – 5% develop liver failure or hepatocellular carcinoma
Whilst the exact molecular mechanisms are not fully understood, HCV directly invades hepatocytes where it is cytotoxic and induces an early innate immune response, but HCV seems to be resistant resulting in chronic infection in 75 – 80% of cases. Over the course of 10 – 20 years of chronic infection it causes extensive scarring of the liver (fibrosis and cirrhosis) and in some cases can cause the development of hepatocellular cancer
The biggest risk factor for development of cirrhosis or liver cancer is the duration of infection. Other risk factors of chronic disease complications include;
- Age at time of HCV infection (faster disease progression if infected after 40 yo)
- Male gender
- Alcohol
- Co-infection of HBV and/or HIV
- Obesity
Differentiate between the
pathogenesis of Hepatitis B
HBV – PATHOGENESIS
Once a person has acquired the infection, HBV travels to the liver via the bloodstream
Once here, they enter into the hepatocytes (liver cells) which is the main site of HBV replication
The exact mechanisms by which HBV infects hepatocytes is not yet well understood, however once they do, the virus triggers an immune response against the infected hepatocytes by cytolytic T-Cells, resulting in the destruction of the liver (that is, Hepatitis B is an immune mediated disease)
In terms of the disease itself, there are 2 different types; Acute and Chronic
An HBV infection is considered acute during the 1st 6 months following infection, if HBsAg persists for longer then the infection is considered chronic (longer than 6 months is chronic)
In other words, if a person fails to mount an effective immune response during the acute HBV infection, chronic infection develops which will result in progressive liver disease and fibrosis (chronic HBV infection can be lifelong)
The clinical symptoms of the two types of HBV infection are outlined below;
1. Acute
- Often asymptomatic, patients can be unaware that they are infected (especially in children) as it is quite non-specific
- Loss of appetite
- Nausea and vomiting
- Tiredness
- Abdominal pain
- Muscle and Joint pain
- Jaundice (usually occurs approximately 12 weeks post infection)
- A small portion of cases may develop fulminant hepatitis (a rare syndrome of massive necrosis of the liver parenchyma and reduction in liver size)
2. Chronic
- Most cases are asymptomatic, patients can be unaware that they are infected
- Tiredness, depression, irritability
- Right Upper Quadrant pain
- Jaundice
- Nausea and vomiting
- Loss of appetite
- Joint aches and pains
HIV replication
HIV REPLICATION
On the outside of HIV is a number of molecules which interact with molecules of the host cell to gain entry into the cell
Gp120 on the HIV interacts with CD4 receptors (T Cells, macrophages, dendritic cells) on host cells as well as various other cofactors (which differ between host cells) facilitating entry into the cell
The HIV then moves into the host cell nucleus, where the RNA reverse transcriptase (one of the 3 essential enzymes HIV carries with it) transcribes the viral RNA into a double stranded copy producing viral DNA
Another viral enzyme (one of the 3 essential enzymes HIV carries with it) Integrase then integrates the double stranded DNA into the host cell genome (it is in there for life)
Now whenever that host cell replicates, the viral DNA is replicated
From this Viral DNA proteins are produced as well as new viral RNA
These products assembly at the surface of the host cell, at which point new viruses bud off acquiring their lipid envelope, gp120 antigens and other host antigens
The new virus particle then matures, at which point the whole process starts again
describe the principle of ‘selective toxicity’ and use this to explain the major cellular targets of antimicrobial drugs
Another important concept is selective toxicity, which is when the drugs are toxic to invading microorganisms while having minimal adverse effects on the host. This is done by exploiting the biochemical differences between the infecting organism and the host (as some of these processes are common, whilst others are specific to one)
Using this selective toxicity, 4 classes of antibacterial therapies have been developed that target different biochemical mechanisms specific to bacteria. These are outlined below;
1. Agents that affect peptidoglycan bacterial cell wall synthesis
2. Agents that affect bacterial protein synthesis
3. Agents that affect bacterial nucleic acid synthesis
4. Agents that disrupt bacterial cell membrane function
Combination therapies of these classes of drugs are common to reduce the likelihood a bacteria is able to develop mutations that overcome a specific class resulting in the development of resistance
describe the mechanism of action of each major class of antibacterial drugs: beta-lactams (penicllins, cephalosporins)
- Beta-Lactams
- Inhibit the final transpeptidation step
- They do this by forming covalent bonds with penicillin binding proteins, which prevents the formation of crosslinks
- E.g. penicllins and cephalosporins
- It is important to note that some of these agents can be destroyed by bacterial enzymes (Beta-lactamases and amidases), which is the basis of one of the main types of antibiotic resistance
describe the mechanism of action of each major class of antibacterial drugs: glycopeptides,
- Inhibit the release of the building block unit from the carrier
- This therefore prevents the addition of the new building block onto the growing end of the peptidoglycan chain, stopping cell wall synthesis
Gram negative Spiral rods Helicobacter
Gram positive
Coccus
Staphylococcus (catalase-positive)
Gram positive
Spirillum chains
Streptococcus (catalase-negative)
Gram negative
Bacillus
E. coli, Pseudomonas aeruginosa,
Gram Negative
Coccus (sphere)
Diplococci Dyptheria
Acid fast staining
TB
Look at the additional slide of Candida albicans. In which taxonomic grouping is this organism placed?
Fungus due to budding and grouping of it- yeast (unicellular)- eukaryote
Normal skin bacteria
URT normal bacteria
GIT normal flora
Ecoli
Enterococcus
streptococci species
Q2. Describe what the following terms mean and the appearance on a blood agar plate
α -haemolysis
β -haemolysis
γ-haemolysis
α -haemolysis
an organism will only partially break down a red blood cell
β -haemolysis
an organism will completely break down a red blood cell
γ-haemolysis
an organism that will cause no haemolysis
COPD pathophysiology and why they are immunocompromised.
Outline the major differences found in CSF samples between bacterial and viral meningitis with respect to the below criteria.
Starting with the bloodstream as a portal of entry, describe the events that lead to the development of acute bacterial meningitis (pathophysiology) caused by S. pneumoniae.
Is a gram-positive diplococcus
Enters the CNS by inducing sepsis
Transcellular
Describe the normal flora of the vagina of a young adult female
Name 2 viral antigens that can be detected during acute and chronic infection with Hepatitis B.
What are the possible long-term outcomes of chronic HCV infection and how common are they?
