Infectious disease Flashcards

Question

name some of the normal flora of the body

Answer 1

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 3. Protein Coat - Is a structure which encases the nucleic acid, giving structure to the virus 4. Nucleic acid - Is the genetic code of the virus - Can be DNA or RNA

Answer 2

1. Entry 2. Specific attachment 3. Internalisation and Uncoating 4. Replication 5. Virus assembly 6. Release

Answer 3

MECHANISMS OF PERSISTENCE 1. 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 2. 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 3. 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 4. Immune response modulation by virus - Some viruses may release factors which modulate the immune response against them 5. 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 6. 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

Answer 4

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

Answer 5

 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

Answer 6

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

Answer 7

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 2. 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 3. 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) 4. 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

Answer 8

2. 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

Answer 9

 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

Answer 10

1. 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 2. Urine for Microscopy / Culture / Sensitivity - Used if the patient has a urinary tract infection 3. Imaging - Used to identify primary and secondary foci of infection

Answer 11

1. Patients with abnormal / damaged valves - Oral streptococci - Staphylococcus aureus 2. Patients that are IV drug users - Staphylococcus aureus - Oral streptococci - Gram negative (enteric) bacteria) 3. 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 4. 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

Answer 12

 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

Answer 13

(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;

Answer 14

 Streptococci are Gram-positive cocci in chains  Streptococci are catalase negative

Answer 15

 Staphylococci are Gram-positive cocci in clusters  Staphylococci are catalase positive

Answer 16

 Staphylococci are Gram-positive cocci in clusters  Staphylococci are catalase positive

Answer 17

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

Answer 18

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)

Answer 19

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)

Answer 20

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

Answer 21

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

Answer 22

 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)

Answer 23

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 3. Hospital acquired pneumonia - Is caused by gram-negative bacteria like Klebsiella pneumonia, Serratia or Pseudomonas (especially if the patient is ventilated) 4. 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 5. Atypical Pneumonia - Mycoplasma pneumoniae - Chlamydia pneumonia - Legionella species

Answer 24

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

Answer 25

Bordetella pertussis, Streptococcus pneumoniae, Haemophilus influenzae type B, Corynebacterium diphtheriae, measles virus, and influenza virus

Answer 26

 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

Answer 27

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

Answer 28

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

Answer 29

1. 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 2. 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

Answer 30

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)

Answer 31

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

Answer 32

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

Answer 33

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)

Answer 34

1. 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 2. 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 3. 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) 4. Escherichia Coli - Incubation period between 16 hours and 3 days - Infectious dose required: up to 106 - Toxins cause osmotic imbalances in the gut 5. Vibrio Cholerae - Incubation period between 2 – 3 days - Infectious dose required: up to 108 - Toxins cause osmotic imbalances in the gut

Answer 35

2. 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 3. 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

Answer 36

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)

Answer 37

 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

Answer 38

 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)

Answer 39

1. 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 2. 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)

Answer 40

 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

Answer 41

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 2. 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

Answer 42

 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

Answer 43

 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

Answer 44

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

Answer 45

 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

Answer 46

 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) 3. 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

Answer 47

 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

Answer 48

 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

Answer 49

 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

Answer 50

1. 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 2. 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) 3. Paracellular passage - Moving between cells by disrupting the tight junctions (e.g. Neisseria meningitidis) 4. 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

Answer 51

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

Answer 52

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.

Answer 53

 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

Answer 54

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

Answer 55

 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

Answer 56

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

Answer 57

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

Answer 58

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

Answer 59

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

Answer 60

 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

Answer 61

1. 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

Answer 62

- 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

Answer 63

 E.g. Doxycycline  The mechanism of action of these drugs is outlined below; - These drugs reversible bind to the 30S subunit of bacterial ribosomes - This prevents the amino-acycl tRNA from binding to the A site, preventing bacterial protein synthesis  These drugs are bacteriostatic  These drugs can cause some adverse effects including; 1. Tooth discolouration and enamel dysplasia in children 2. GI damage  They can also undergo chelation (combination) reactions with calcium and antacids (therefore don’t take these drugs with milk or antacids as they combine and lose their effect)

Answer 64

 E.g. Roxithromycin  These drugs work by binding to the 50S ribosomal subunit which prevents the ribosome moving along the mRNA, preventing translocation from the A site to the P site  These drugs are bacteriostatic  These drugs have some immunomodulatory effects and anti-inflammatory effects  These drugs often cause GI effects like nausea, vomiting and diarrhoea  Some of them are also potent inhibitors of CYP3A4  Often used as an alternative for patients with penicillin allergies

Answer 65

 E.g. Gentamycin  The mechanism of action of these drugs is outlined below; - These drugs bind to the aminoacyl site of the 16S subunit RNA within the 30S ribosomal unit - This leads to misreading of the genetic code, and inhibition of protein synthesis  These drugs are bactericidal  Adverse effects of these drugs include; 1. Nephrotoxicity - Probably due to interfering with phospholipids in the tubules - Probably the most important drug around nephrotoxicity - Be wary of using this drug in patients with kidney disease 2. Ototoxicity

Answer 66

 Is a drug on its own class that targets protein synthesis  It works by preventing protein chain elongation by inhibiting the enzyme peptidyl transferase that is present in bacterial ribosomes (inhibits the transpeptidation step)  This drug is bacteriostatic  This drugs have some very rare but severe adverse effects including; 1. Bone marrow suppression 2. Aplastic anaemia (trashes the hematopoietic stem cells)  This drug also inhibits CYP2C19 and CYP3A4

Answer 67

 e.g. Ciprofloxacin  These drugs work by blocking DNA gyrase and topoisomerase IV to inhibit bacterial DNA synthesis - DNA gyrase is involved in uncoiling super coiled DNA for replication - Topoisomerase IV is involved in untangling super coiled DNA for replication, repair and transcription  These drugs may cause rash and GIT issues

Answer 68

 E.g. Rifampicin  These drugs exert their antimicrobial effect by inhibiting bacterial RNA synthesis  The complete mechanism of action is outlined below; - These drugs bind to the beta subunit of DNA-dependent RNA polymerase (also DNA polymerase) - By blocking this enzyme, these drugs block RNA transcription  These drugs have shown a tendency to develop resistance against them, so they are usually used in combination with another drug  These drugs can cause hepatotoxicity  One of the main drugs used to treat TB

Answer 69

 E.g. Metronidazole  These are prodrugs, meaning they are metabolised to active metabolites  These drugs covalently bind to DNA, disrupting its helical structure which inhibits nucleic acid synthesis  These drugs are bactericidal and antiprotozoal  These drugs are used as radiation sensitizers (makes radiation therapy more effective)  These drugs do cause GIT issues and sometimes hypersensitivity reactions

Answer 70

- (PABA – Folate – tetrahydrofolate – thymidine synthesis – DNA) - Sulfonamides are competitive analogues of PABA - Trimethoprim blocks the effect of dihydrofolate reductase (differentially effective on bacterial forms as opposed to human forms)  These drugs are often used in combination (trimethoprim with sulfamethoxazole) as hitting two points in the synthesis pathway is better than one

Answer 71

ANTI-FUNGAL DRUGS  Instead of cholesterol (like humans), fungal cells have sterols within their cell membrane (which do not exist in any prokaryotes). The most important of these sterols is ergosterol - The formation of this sterol ergosterol involves a number of important enzymes AZOLES  These drugs inhibit 14-alpha-demathylase enzyme which is responsible for converting lanosterol into ergosterol for use in the fungal cell membranes  This inhibition causes cell leakage and death (by lytic activity of host defences) TERBINAFINE  This drug works by inhibiting the enzyme squalene epoxidase  Squalene epoxidase is responsible for converting squalene into lanosterol to form ergosterol for the fungal cell wall  Thus by blocking this enzyme we stop the formation of the fungal cell wall  Accumulation of squalene is also toxic to the cell POLYENES  These drugs bind to ergosterol in fungal cell membranes and alter their permeability. This allows leakage of intracellular components from the cell causing death

Answer 72

BETA LACTAMS are usually well tolerated, but can cause hypersensitivity reactions, diarrhoea (antibiotics alter the microbiome) and rash in some patients  They also can interact with oral contraceptives GLYCOPEPTIDES 1. Nephrotoxicity 2. Ototoxicity (hearing loss) 3. Red man syndrome (occurs if drug is administered IV at a rapid rate, causes a huge release of histamine) TETRACYCLYNES 1. Tooth discolouration and enamel dysplasia in children 2. GI damage  They can also undergo chelation (combination) reactions with calcium and antacids (therefore don’t take these drugs with milk or antacids as they combine and lose their effect)

Answer 73

 There are two different types of resistance; Intrinsic resistance (due to intrinsic properties of the bacterium, many gram negative bacteria) and Acquired resistance (occurs when bacteria that were previously susceptible become resistant)  Acquired resistance can be spread amongst bacteria through; - Transfer of resistance bacteria between people - Transfer of resistance genes between bacteria (usually plasmids) - Transfer of resistance genes between genetic elements within bacteria, on transposons  The actual biochemical processes or mechanisms that occur within bacteria that leads to resistance against anti-microbial agents are outlined below (expect you to remember this); 1. Production of enzymes that inactivate the drug - Beta-lactamases - Acetyltransferases - Kinases 2. Alteration of drug-binding sites - Aminoglycosides - Erythromycin - Penicillin 3. Reduction of drug uptake by the bacterium (they can develop pumps to kick drugs out) - Tetracyclines 4. Alteration of the enzyme pathway - Trimethoprim

Answer 74

ANTIBIOTIC STEWARDSHIP  Is about being a good prescriber of antibiotics  Appropriate prescribing is important for 3 main reasons; 1. Optimising clinical outcomes 2. Minimising adverse effects 3. Reducing development of resistance  Antibiotic stewardship is a collective set of strategies to improve the appropriate use of antibiotics and reduce antibiotic resistance  It is a systemic effort to educate and persuade prescribers to follow evidence-based prescribing in order to stem antibiotic overuse and thus antimicrobial resistance

Answer 75

 Arboviruses is another term used for Arthropod-borne viruses, which is any virus transmitted by an arthropod  There are a number of different type of Arboviruses, this week we are going to particularly focus on the 2 most common groups; 1. Flaviviruses - Dengue - Zika Virus - Murray Valley Encephalitis Virus - Kokobera - Kunjin Virus - Japanese Encephalitis Virus 2. Alphaviruses - Ross River Virus - Barmah Forrest Virus - Chikungunya

Answer 76

 Laboratory diagnosis however are able to provide a definitive diagnosis (quickly and accurately) using the following tests; 1. PCR (Detects virus/viral antigens) 2. Viral Antigen Test (Detects virus/viral antigens) 3. Serological Test (Detects antibodies to the virus) 4. Point of Care Test  In order for these laboratory investigations to be performed, the lab requires a serum sample (as well as urine for Zika)  Direct methods look for evidence of the virus, indirect methods look for evidence of an immune response

Answer 77

To do with public health survalience: Use insect repellents any time you are outdoors. Wear long-sleeved clothing. Schedule outdoor activities to avoid the hours from dusk to dawn during peak mosquito season. Repair damaged window and door screens.

Answer 78

TICKS  Ticks may be vectors of rickettsia, borrelioses (limes disease) and arboviruses  Prolonged feeding may cause painful skin lesions which can become secondarily infected with bacteria

Answer 79

SCRUB TYPHUS  Infection caused by rickettsia bacteria (Orentia tsutsugamushi) transmitted by bite of mites (chiggers, which is the larvae form of mites, the only form that transmits this bacteria)  Symptoms usually occur within 1 – 2 weeks, and typically involve; - Eschar (a bite site that ulcerates and becomes red with a central black scab) - Fever and headache - Muscle aches - Malaise - Dull red rash  Diagnosis is by serology and PCR. Treatment is with Doxycycline (for about 7 days)  Prevention is by reducing exposure to vectors via stopping bites, wearing long sleeves and shoes, stay away from problematic areas

Answer 80

Q FEVER  Pathogen that causes Q fever is bacteria known as Coxiella burnetti  Transmission is via vector-borne (ticks) and inhalation  50% are asymptomatic. But those who are symptomatic show; - Fever - Chills and sweats - Fatigue - Severe headache - Myalgia - Rash - Acute or chronic disease (proteins from bacteria may note dgrade leading to chronic immune reaction)  It is rarely fatal and complications include subacute endocarditis  Diagnosis is via clinical history (exposure to cattle i.e. farmer, vet, abattoir) serology (rising tire of IgG) and PCR (paired samples)  Treatment is with doxycycline  Prevention is via immunisation

Answer 81

POLYMERASE CHAIN REACTION (PCR)  Is a molecular method of detection that works by detecting viral RNA/DNA in a clinical sample (serum or urine in zika)  They are able to isolate and detect a unique region of the viral genome, indicating the viruses present and therefore infection has occurred and by what  There are a number of advantage and negatives to PCR testing; 1. Advantages - Highly sensitive and highly specific - Rapid (doesn’t take a long time to perform) 2. Disadvantages - Very complex - Requires specialised staff and facilities - Is very expensive

Answer 82

VIRAL ANTIGEN DETECTION  Works by detecting specific viral antigens in a serum  This type of detection is only available for Dengue viruses so far, in a test known as the Dengue NS1 Antigen Test  NS1 is a highly conserved NS protein produced by all dengue serotypes that circulates in high concentration in the serum of individuals with dengue  Available in commercial EIAs and POCTs  A microtiter plate is coated with antibodies that specifically react with the NS1 antigen, thus if your patient’s serum reacts, the conjugate will bind. You then wash away the excess, add your conjugate and if there is a reaction a colour change will occur (wells with no colour are negative)

Answer 83

SEROLOGICAL DIAGNOSIS  Works by detecting virus-specific IgM antibodies  This testing is suitable for testing large numbers of samples  Its sensitivity is great, but it has some specificity issues (as antigens in dengue, JE, Zika etc. are very similar meaning their can be cross reactivity in serological testing) thus you require multiple tests

Answer 84

POINT-OF-CARE TESTS (POCT)  Works by detecting antibodies +/- viral antigens  They are rapid and simple to perform  Specificity usually reliable but they have some sensitivity issues  Are very useful for low resource settings, and for low volume/sporadic testing and for remote settings

Answer 85

HEALTHCARE ASSOCIATED INFECTION (HAI)  Is an infection not present or incubating prior to admittance to the hospital, but generally occurring 48 hours after admittance  They are also known as nosocomial infections  Basically a HAI is an infection someone gets in hospital  Over 200,000 HAIs occur in Australian hospitals every year  The sources of these hospital infections are fundamentally either people (patients, hospital staff or visitors) or by the environment (from contaminated objects, food, water or air)  Human sources can include people who are infected themselves, someone who is incubating an infection or a person who is a healthy reservoir carrier  There are 2 main types of HAIs; Primary and Secondary infection

Answer 86

Misuse and overuse of antimicrobials are the main drivers in the development of drug-resistant pathogens. Lack of clean water and sanitation and inadequate infection prevention and control promotes the spread of microbes, some of which can be resistant to antimicrobial treatment. - overuse - not completing the course - misdiagnosis

Answer 87

STANDARD INFECTION CONTROL MEASURES  Standard precaution are the minimum infection prevention and control practices that must be used at all times for all patients in all situations  Standard precautions consist of the following practices; 1. Hand hygiene before and after all patient contact 2. Use of PPE (e.g. gloves, impermeable gowns, plastic aprons, masks, face shields and eye protection) 3. The safe use and disposal of sharps 4. Use of aseptic technique for all invasive procedures 5. Re-processing of reusable instruments and equipment 6. Routine environmental cleaning 7. Waste management 8. Respiratory hygiene and cough etiquette TRANSMISSION INFECTION CONTROL MEASURES  Are used in addition to standard precautions when standard precautions alone may be insufficient to prevent the transmission of infection  These measures are used for patients known or suspected to be infected or colonised with drug resistant or highly transmissible pathogens

Answer 88

Gram negative Spiral rods Helicobacter

Answer 89

Gram positive Coccus Staphylococcus (catalase-positive)

Answer 90

Gram positive Spirillum chains Streptococcus (catalase-negative)

Answer 91

Gram negative Bacillus E. coli, Pseudomonas aeruginosa,

Answer 92

Gram Negative Coccus (sphere) Diplococci Dyptheria

Answer 93

Acid fast staining TB

Answer 94

Fungus due to budding and grouping of it- yeast (unicellular)- eukaryote

Answer 95

S. Aureus S. Faecalis

Answer 96

Neisseria gonorrhoeae Neisseria meningitidis

Answer 97

Clostridia Listeria

Answer 98

Rickettsia Escherichia

Answer 99

Endospores are formed mainly by two genera of Gram-positive bacteria: Bacillus, the aerobic sporeformers, and Clostridium, the anaerobic sporeformers. Both genera contain pathogens, and the endospores produced by these bacteria invariably play some role in the toxicity, transmission or survival of the pathogen. allows the bacterium to produce a dormant and highly resistant cell to preserve the cell's genetic material in times of extreme stress. Disposable equipment

Answer 100

Endospores are formed mainly by two genera of Gram-positive bacteria: Bacillus, the aerobic sporeformers, and Clostridium, the anaerobic sporeformers. Both genera contain pathogens, and the endospores produced by these bacteria invariably play some role in the toxicity, transmission or survival of the pathogen. allows the bacterium to produce a dormant and highly resistant cell to preserve the cell's genetic material in times of extreme stress. Disposable equipment

Answer 101

The key difference between bacterial endospores and fungal spores is the cellular organization of the two types of spores. Bacterial endospores are dormant structures present in prokaryotic bacteria. Fungal spores are reproductive structures present in eukaryotic fungi.

Answer 102

Clostridium tetani binds to the presynaptic membrane of the neuromuscular junction, is internalized and transported retroaxonally to the spinal cord. The spastic paralysis induced by the toxin is due to the blockade of neurotransmitter release from spinal inhibitory interneurons.

Answer 103

Staphylococcus aureus (staph) bacteria bacterial toxins act as superantigens, activating very large numbers of T cells and generating an overwhelming immune-mediated cytokine avalanche that manifests clinically as fever, rash, shock

Answer 104

Haemophilus influenzae type B (Hib) bacterial meningitis, pneumonia, epiglottitis, septic arthritis and cellulitis. Streptococcus pneumoniae (pneumococcus) Pneumococcal disease Neisseria meningitides (meningococcus) meningococcal disease

Answer 105

Ecoli Enterococcus streptococci species

Answer 106

Image result for Briefly outline the concept of viral tropism Viral tropism is the ability of a given virus to productively infect a particular cell. For many viruses, tropism is determined by the availability of virus receptors on the surface of a host cell.

Answer 107

Quasispecies: population structure of viruses with a large number of variant genomes due to high mutation rates and faulty RNA polymerase enzymes This high rate of mutation comes from the lack of proofreading ability in RNA polymerases. These enzymes make mistakes, but they can't correct them. Therefore the mutations remain in the newly synthesized RNA.

Answer 108

Quasispecies theory predicts that a replicating viral population will contain a large number of unique mutants, so there is a probability that an active viral infection will already have resistant mutants upon time of RNAi treatment, which could rapidly become the dominant mutation when placed under selection

Answer 109

Viruses that spend their entire life cycle in the cytoplasm do not have access to host polymerases and thus need to encode their own polymerases for transcription and replication.

Answer 110

The integration of the HIV provirus into the host genome is a key characteristic of retroviruses and an essential step in the HIV life cycle that enables viral persistence

Answer 111

HSV:trigeminal ganglia VZV:trigeminal and dorsal root ganglia EBV: B cells, epithelial cells and natural killer/T cells CMV: bone marrow stem cells and myeloid cells

Answer 112

Restricted gene expression - A virus may reduce the number of genes it expresses so as to avoid detection by the immune system

Answer 113

Antigenic shift is caused by exchange of genetic material between 2 different strains of Influenza A (when they co-infect a single cell)

Answer 114

transmission of viruses can occur through two pathways: horizontal and vertical transmission. In horizontal transmission, viruses are transmitted among individuals of the same generation, while vertical transmission occurs from mothers to their offspring. rickettsiae driven diseases (like typhus), which are contracted by a body louse's fecal material being scratched into the bloodstream.

Answer 115

- 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

Answer 116

- Is a degenerative brain disorder that leads to dementia and death - It is a very rare chronic encephalopathy that occurs world wide - We still don’t know exactly why it occurs in all cases (some cases are familial due to inherited mutated prion gene) - Can be caused by medical / surgical procedures, spontaneous mutations (most common) or it can be inherited - There is also variant CJD (vCJD) which occurs from consumption of BSE-infected food from cows

Answer 117

A hardy, thick-walled stage of the life cycle of coccidian parasites. This is the stage that is shed in the feces of people infected with parasites

Answer 118

- 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)

Answer 119

The definitive host is the one which harbors the adult parasite and where the parasite reproduces sexually. The intermediate host is the host which harbors the larval stage or the asexual forms of the parasite.

Answer 120

Catalase enzyme. Positive for staph, negative for strep which catalyzes the decomposition of hydrogen peroxide to water and oxygen. It is a very important enzyme in protecting the cell from oxidative damage by reactive oxygen species (ROS)

Answer 121

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

Answer 122

α -haemolysis Viridians streptococci Oral strep β -haemolysis Streptococcus pyogenes RF γ-haemolysis Enterococcus Bacteraemia

Answer 123

LPS stimulates and activates macrophages (By TLR) which then start to produce and secrete cytokines. - Ige released activates mast cells LPS also stimulate the coagulation cascade resulting in DIC causing thrombus formation - Increased vascular permeability not countered by clotting factors leads to increased leakage of blood into the periphery Increased activation of neutrophils build up in organ.

Answer 124

Endotoxins: Released by the organism when dead (LPS) Exotoxins: Released by the organism when alive as a virulence factor

Answer 125

Furthermore, it is important that when choosing an antibiotic for treatment you don’t choose one that acts on the outer membrane of the bacteria as it would cause a sudden release of LPS into the host as you will push them into shock

Answer 126

A: Neisseria Meningitidis B: Pseudomonas C: Escherichia coli

Answer 127

Gram-negative bacteria have peptidoglycan between membranes. Penicillin works best on gram-positive bacteria by inhibiting peptidoglycan production, making the cells leaky and fragile.

Answer 128

A: Endocarditis in IV drug users - Staphylococcus aureus B: Endocarditis in patients with prosthetic heart valves - Staph epidermididus

Answer 129

A: Hemolysins: lipids and proteins that cause lysis of red blood cells by disrupting the cell membrane. B: Enterotoxins : kill cells by altering the apical membrane permeability of the mucosal (epithelial) cells of the intestinal wall.

Answer 130

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)

Answer 131

Streptococcus pneumoniae: is a Gram-positive, spherical bacteria, alpha-hemolytic. They are usually found in pairs Haemophilus influenza: Gram-negative coccobacillus. The cultured organism can be further characterized using catalase and oxidase tests, both of which should be positive. Moraxella catarrhalis: gram-negative diplococcus

Answer 132

- The tympanic membrane bursts as a result of acute otitis media leading to acute otorrhea (ear discharge draining from the ear) - Continuous exposure and lack of adequate treatment means infections persist leading to chronic suppurative otitis media - Chronic suppurative otitis media is characterised by discharge through a perforated tympanic membrane for at least 6 weeks

Answer 133

Cilia propel a liquid layer of mucus that covers the airways. The mucus layer traps pathogens (potentially infectious microorganisms) and other particles, preventing them from reaching the lungs.

Answer 134

- Infleunza - Parainfluenza - Coronavirus - Rhinovirus

Answer 135

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 Polymerase Chain Reaction (PCR), which tests for the specific corresponding genetic code of viruses.  Most large labs can offer multiplex PCR 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)

Answer 136

SARS-COV-2  Spike proteins interact with ACE-2 cells in the respiratory tract  RNA genome so more prone to mutations due to lack of proof-reading proteins INFLEUNZA PATHOGENESIS  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)

Answer 137

 It is most often caused by the Respiratory Syncytial Virus (over 75% of cases), as well as Human Metapneumovirus, Parainfluenza and Influenza

Answer 138

 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

Answer 139

 Neither natural infection or vaccination against Bordetella pertussis provides long term protection meaning that reinfection can often occur

Answer 140

found in the soil of endemic areas like SE Asia and tropic Australia and usually presents as pneumonia Transmitted via contact with the bacteria. Wet season

Answer 141

 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

Answer 142

- Mycoplasma pneumoniae - Chlamydia pneumonia - Legionella species - Pneumocystis (especially in immunocompromised patients)

Answer 143

PNEUMONIA 1. Infleunza Viruses 3. Human Metapneumovirus 4. Parainfluenza virus HAEMOPHILUS INFLUENZA PERTUSSIS (Whooping Cough) SARS-COV-2

Answer 144

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 2. 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

Answer 145

- Transmission is acquired in food or drinks contaminated with human faeces chicken, turkey, beef, pork, eggs, fruits, sprouts, other vegetables,

Answer 146

Salmonella bacteria invade and destroy the cells that line your intestines. This makes it hard for your body to absorb water, which can give you stomach cramps. The water leaves your body in the form of diarrhea.

Answer 147

Contact with contaminated fomites (object that carries infection)  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

Answer 148

- 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)

Answer 149

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

Answer 150

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

Answer 151

2. 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) 3. Paracellular passage - Moving between cells by disrupting the tight junctions (e.g. Neisseria meningitidis) 4. 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

Answer 152

1. Blood Brain Barrier - Separates the lumen of the brain capillaries from the brain parenchyma itself - The main structure which reduces permeability and excludes exogenous organisms from the brain parenchyma is the tight junctions between endothelial cells that line the capillaries - Astrocytes also form a continuous layer around the capillaries adding another layer of protection 2. Blood-CSF Barrier - Exists within the choroid plexus (where the cerebrospinal fluid in the ventricles is produced) of each ventricle of the brain - Functions is similar to the BBB, however has a different structure - Unlike the capillaries in the BBB, the capillaries in the Blood-CSF barrier has no tight junctions and are also fenestrated - The Blood-CSF barrier is instead made up of epithelial layers of the choroid plexus that are joined by tight junctions (counters invading organisms to some extent) - This varied structure does make the Blood-CSF barrier more permeable to invading organisms then the BBB

Answer 153

 Is a gram-positive diplococcus  Enters the CNS by inducing sepsis Transcellular

Answer 154

pneumococcal capsule and surface proteins as well as secreted proteins. Bacterial interactions with the host and the subsequent development of bacterial meningitis are promoted by a high level of bacteremia

Answer 155

Having a weakened immune system increases the risk of developing chronic meningitis.

Answer 156

1. Japanese encephalitis (vaccine is now available) 2. Kunjin 3. Dengue virus - 4. Murray valley encephalitis -

Answer 157

 Rhabdovirus gets into the CNS through the following mechanism; - An infected animal bites another transferring saliva into the wound - The rhabdovirus replicates in the muscle, before moving through the neuromuscular junction and up the dorsal root ganglion into the spinal cord and then into the brain Therefore giving IgG starts fighting virus before body makes own IgM and IgG

Answer 158

 The most common causative organisms in non-IC populations are streptococci and staphylococci

Answer 159

 Do not perform a lumbar puncture due to increased ICP so increased risk of brain herniation

Answer 160

- Pili: Are surface projections that facilitate attachment (prevent them from being washed away by vaginal secretions or by urine) and antigenic diversity - Por proteins: Penetration of host cells - Opa proteins: Facilitate binding - Lipo-oligosaccharide (endotoxin): Endotoxin activity - IgA protease: Destroys IgA1, allowing it to avoid immune destruction - Capsule: resits phagocytosis

Answer 161

1. Males - Usually transient and self-limited infection (lasting for a few weeks) - Commonly causes urethritis 2. Females - Without treatment, the infection can last for months or even years - Can lead to ectopic pregnancies, preterm deliveries, infertility, vaginitis (causing frothy discharge in heavy infections)

Answer 162

- 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)

Answer 163

A: Chlamydia trachomatis and B: Neisseria gonorrhoea 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 C: Trichomonas vaginalis  PCR is the most commonly used detection method in Australia. This is because they are; - Excellent for screening large numbers of specimens rapidly - Highly sensitive and specific - Submit same specimen / specimen types as for CT and NG PCRs  Wet preparations are also commonly performed (in large and small laboratories, remote health centres and sexual health clinics). This is done by; - Smearing the wet sample on a glass slide - Add a drop of sterile saline - Add coverslip - Examine for motile trophozoites D: Mycoplasma genitalium  A lab diagnosis is done via a swab or urine for PCR F: Syphilis 1. Serology - Is the method of choice for syphilis diagnosis (looks at blood) to look for Abs - Treponemal tests (is a syphilis specific test): Treponemal total Ab test, TPPA test - Non-Treponemal (non-specific tests e.g. lipids): RPR, VDRL 2. T. Pallidum PCR - Is via a swab of a lesion 3. Darkfield microscopy - Is rarely used

Answer 164

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

Answer 165

 Wet preparations are also commonly performed (in large and small laboratories, remote health centres and sexual health clinics). This is done by; - Smearing the wet sample on a glass slide - Add a drop of sterile saline - Add coverslip - Examine for motile trophozoites  The advantages of using wet preparations is that they are simple and quick, however they are quite subjective

Answer 166

 The genome of HIV has 2 identical copies of ssRNA in its nucleus, and 3 essential enzymes (protease, integrase and reverse transcriptase) all required for viral replication  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

Answer 167

An inactive viral form that has been integrated into the genes of a host cell.

Answer 168

Viral attachment Chemokine receptor antagonists On the outside of HIV is a number of molecules which interact with molecules of the host cell to gain entry into the cell Viral fusion and entry Inhibitors of viral fusion 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 Viral genome replication Reverse transcriptase inhibitors 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 Viral assembly Inhibitors of viral integrase 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 Viral exit Protease inhibitors 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

Answer 169

Combined antigen and antibody tests show a higher sensitivity for the detection of primary HIV infection than conventional tests in urban centers with high HIV incidences and prevalences - Reduces detection time by 16 days

Answer 170

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

Answer 171

This is usually seen in asymptomatic infections: no definitive diagnosis is seen if a western blot turns up tow or more reactive bands. If there is one or several uneven bands, this is indeterminate.

Answer 172

in highly endemic areas, hepatitis B is most commonly spread from mother to child at birth (perinatal transmission) or through horizontal transmission (exposure to infected blood),

Answer 173

1. Vertical transmission (during pregnancy and delivery) - Exposure to breast milk and during delivery 2. Blood exposure - Parenteral and mucosal exposure to blood - IVDU - Needlestick injuries

Answer 174

She failed to seroconvert and create antibodies

Answer 175

HIV needs a higher viral load for transmission to occur

Answer 176

1. Screening test - EIA for HCV Ab (EIA is an Enzyme Linked immunoassay) + 2nd EIA for confirmation - HCV Ag test if required 2. HCV PCR - Quantitative test of the HCV genome (testing the viral load which can be useful for monitoring of response to antiviral treatment) 3. HCV genotyping - Was previously important for treatment considerations as some genotypes were resistant to treatment (some wouldn’t even respond to treatment)

Answer 177

- Rash - Fever - Headache - Fatigue - Arthralgia - Myalgia

Answer 178

 Severe disease is extremely uncommon, however there are a number of potential neurological and auto-immune complications including; 1. Microcephaly (Is a birth defect caused by infection of zika of a pregnant women) 2. Intracranial calcification 3. Guillain-Barre Syndrome (GBS) (Is an autoimmune disorder that affects peripheral nerves)

Answer 179

In the bloodstream, the merozoites invade red blood cells (erythrocytes) and multiply again until the cells burst. Then they invade more erythrocytes. This cycle is repeated, causing fever each time parasites break free and invade blood cells.

Answer 180

If not promptly treated, the infection can become severe and may cause kidney failure, seizures, mental confusion, coma, and death.

Answer 181

Pregnant women infected with malaria usually have more severe symptoms and outcomes, with higher rates of miscarriage, intrauterine demise, premature delivery, low-birth-weight neonates, and neonatal death. They are also at a higher risk for severe anemia and maternal death.

Answer 182

- Dengue - Kunjin Virus - Japanese Encephalitis Virus - Malaria - Dengue - Kunjin Virus - Japanese Encephalitis Virus 1. PCR (Detects virus/viral antigens) 2. Viral Antigen Test (Detects virus/viral antigens) 3. Serological Test (Detects antibodies to the virus) 4. Point of Care Test

Answer 183

NS1 Ag assay is a useful early diagnostic marker for dengue fever but cannot be used as an early predictor of severe dengue infection

Answer 184

Non-specific take time costly

Answer 185

POINT-OF-CARE TESTS (POCT)  Works by detecting antibodies +/- viral antigens  They are rapid and simple to perform  Specificity usually reliable but they have some sensitivity issues  Are very useful for low resource settings, and for low volume/sporadic testing and for remote settings

Answer 186

defined as infections not present and without evidence of incubation at the time of admission to a healthcare facility.

Answer 187

Standard precautions are the minimum infection prevention and control practices that must be used at all times for all patients in all situations. Standard precautions consist of the following practices: hand hygiene before and after all patient contact; the use of personal protective equipment, which may include gloves, impermeable gowns, plastic aprons, masks, face shields and eye protection; the safe use and disposal of sharps; the use of aseptic “non-touch” technique for all invasive procedures, including appropriate use of skin disinfectants; reprocessing of reusable instruments and equipment; routine environmental cleaning; waste management; respiratory hygiene and cough etiquette

Answer 188

The polysaccharide biofilm matrix acts as an adhesive foundation and a defence barrier that protects the embedded cells against detachment from the surface. Once it becomes mature, the biofilm is difficult to clear by either the host immune response or antimicrobial therapies. Bacteria living in biofilms exhibit 100- to 1000-fold increase in their antibiotic tolerance in comparison to free-living bacteria, as the matrix traps and concentrates extracellular enzymes such as β-lactamases.

Answer 189

If drug resistance is suspected then cases should remain in isolation with airborne precautions in place until susceptibility results are confirmed. If sputum remains smear positive, a decision about hospital discharge should be made in consultation with a specialist physician with experience in managing TB and taking into account the social circumstances at home, such as the potential to expose new contacts and the presence of children under 5 years of age.

Answer 190

Antimicrobial stewardship (AMS) programs have developed as a response to the global issue of antimicrobial resistance (AMR). As a systematic approach to optimising antimicrobial use, AMS aims to minimise the unnecessary use of antimicrobials and promote the appropriateness of antimicrobial prescribing, resulting in improved patient outcomes, cost-effective therapy and reduced adverse consequences of antimicrobial use, including AMR.

Answer 191

Airborne precautions are indicated for all patients where pulmonary TB is suspected or proven. Ideally patients with pulmonary TB should be accommodated in negative pressure rooms with ensuite. All staff should wear a correctly fitted P2/N95 respirator mask prior to entering the patient-care area. If the patient is ventilated, a filter must be present on the expiratory circuit Close household contacts should be assessed for active tuberculosis prior to visiting the facility. Children should be discouraged from visiting infectious patients. Close household contacts should wear the same PPE as hospital staff during patient visits. People who are vulnerable for disease following TB infection e.g. preschool children and the immunosuppressed, should not visit Patients should remain isolated in a negative pressure room with airborne precautions applied until criteria are met. In principle these criteria should include: • a reduction in or absence of cough; • reduced smear burden or smear negativity; • assured treatment by direct observation; and • an appropriate discharge plan

Infectious disease Flashcards

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