case 5 - headache & fever Flashcards
What 2 measures of clinical sign accuracy are characteristics of the test?
Sensitivity, specificity
What is the sensitivity of a clinical test?
The proportion of people with disease who have a positive test (true positive)
What is the equation for the sensitivity of a clinical test?
a/(a+c)
What is the specificity of a clinical test?
The proportion of people without a disease who have a negative test (true negative)
What is the equation for the specificity of a clinical test?
d/(b+d)
What are the predictive values of a clinical sign?
The likelihood that person with a certain test result has the correct result
What are predictive values of a clinical test affected by?
The prevalence of the disease and therefore the pretest probability of having the disease
What is the positive predictive value of a clinical test?
The proportion of patients with a positive test that are correctly identified as having the disease
What is the negative predictive value of a clinical test?
The proportion of patients with a negative test who do not have the disease
What is the pre-test probability in a clinical test?
The chance that a patient has the disease, based on the proportion of people in the community that have the disease (the prevalence)
What is the equation for the positive predictive value of a clinical test?
a/(a+b)
What is the equation for the negative predictive value of a clinical test?
d/(c+d)
What does the letter a represent in a 2 by 2 table for a clinical test?
true positives
What does the letter b represent in a 2 by 2 table for a clinical test?
false positives
What does the letter c represent in a 2 by 2 table for a clinical test?
false negatives
What does the letter d represent in a 2 by 2 table for a clinical test?
true negatives
When performing a number of tests one after the other for the same disease, are the tests dependent or independent?
Independent
In 2 consecutive clinical tests, how is the prior predictive value of the second test calculated?
As the positive predictive value of the first (if 1st test is positive), or the negative predictive value minus 1 (if the test is negative)
What are the 3 key acute phase proteins measured in patients with acute inflammation.
Coagulation proteins, Alpha-1-Antitrypsin, C-Reactive Protein
What happens to levels of coagulation proteins in the acute inflammatory response?
Typically elevated
What is the function of the acute phase protein Alpha-1-Antitrypsin?
protects the body from inflammatory agents by binding to elastase
What happens to Alpha-1-Antitrypsin levels in response to acute inflammation?
Elevated
What is the key role of CRP in acute inflammation?
Activation of the complement system
What are the 4 key stimuli that trigger acute inflammation?
Pathogens/microorganisms, chemical agents, inappropriate immunological response, tissue death
How do pathogens/microorganisms trigger acute inflammation?
Viruses cause cell damage, while bacteria produce endotoxins, which is detected by immune cells
How does tissue damage trigger acute inflammation?
Dead, necrosed cells release cellular contents, which includes proteins and chemicals hat attract phagocytes and other leukocytes to the area.
What are the gross changes in coagulation necrosis?
Pale area
What are the gross changes in gangrenous necrosis?
Black area
What are the gross changes to the brain/meninges in meningitis?
congestion (redness, blood vessels), swelling (widening of gyri, narrrowing of sulci), pus accumulation
What are the 2 key microcopic responses occuring in the acute inflammatory response?
Vascular response, cellular response
What are the processes occuring in the vascular component of the acute inflammatory response?
blood vessel dilation, increased vessel permeability, vascular congestion, increased blood viscosity (incr. RBC conc.), white blood cells slowing down
What are the processes occuring in the cellular component of the acute inflammatory response?
leukocytes leave the vasculature and enter the site of inflammation to participate in phagocytosis and degranulation, releasing chemical mediators to attract more cells to the area.
What are the 6 steps through which leukocytes leave the vasculature and enter the site of inflammation?
Margination, rolling, adhesion, transmigration, chemotaxis, activation
What is exudate, and what is its function?
A protein rich fluid formed due to increased vascular permeability to fluid, that aids in the local inflammatory responses
What does exudate deliver to the site of inflammation?
Immune plasma proteins, chemical mediators, leukocytes
What are cytokines released by?
macrophages
What are the key pro-inflammatory cytokines (3)?
IL-1, IL-6, TNF alpha
What is the role of TNF alpha in the acute inflammatory response?
vasodilation, vascular leakage, fever, hyperalgesia, leukocyte recruitment to site of inflammation
What is the role of IL-1 in the acute inflammatory response?
fever, hyperalgesia, leukocyte recruitment to site of inflammation
What is the role of IL-6 in the acute inflammatory response?
fever, hyperalgesia, leukocyte recruitmenr
What are the systemic inflammatory processes that proinflammatory cytokines trigger?
fever, inflammation, pain, tissue destruction
What is the key bacteria causing meningococcal disease?
Neisseria meningitidis
What are the major causative organisms of meningitis in infants?
E. coli, Strep. agalactiae, Listeria monocytogenes
What are the major causative organisms of meningitis in children up to 10 years old?
Heamophilus influenzae, neisseria meningitidis, strep. pneumoniae
What are the major causative organisms of meningitis in adolescents?
Neisseria meningitidis, viruses
What are the major causative organisms of meningitis in adults?
Neisseria meningitidis, strep. pneumoniae,
What are the major causative organisms of meningitis in the elderly?
Strep. pneumoniae, listeria monocytogenes
What are the 2 key presentations of meningococcal disease?
septicaemia, meningitis
What are the key steps in the pathogenesis of bacterial meningitis?
1.) microorganism enters CSF
2.) bacteria multiply in the CSF and release chemicals that trigger an acute inflammatory response
3.) subarachnoid space becomes expanded as blood vessels are congested, and becomes infiltrated with neutrophils, resulting the purulent exudate (pus)
4.) intracranial pressure increases leading to physical signs of meningitis
What are the 3 ways bacteria can enter the CSF?
Crossing the nasopharyngeal epithelium and entering the blood (then spread haematogenous), direct inoculation, haematogenous spread
What is haematogenous spread of bacteria in meningitis?
When bacteria spread to CSF via the bloodstream
What are the steps in the pathogenesis of meningococcal septicaemia?
1.) bacteria enter the bloodstream and multiply, releasing toxins
2.) systemic inflammatory state triggered leading to endothelial cell activation.
3.) activation leads to vasodilation, increased vascular permeability, DIC
4.) shock, oedema, organ failure, rash, etc. occurs
What is DIC in septicaemia?
Disseminated Intravascular Coagulation
What are the 3 key effects of Endothelial Cell activation in septicaemia?
vasodilation, increased vascular permeability, DIC
What are the effects of DIC on organ systems?
Renal failure, ecchymotic rash, adrenal haemorrhage
What is the first line pre hospital antibiotic for suspected bacterial meningitis?
Intramuscular ceftriaxone
What is the second line pre hospital antibiotic for suspected bacterial meningitis?
Intramuscular Benzylpenicillin
What is the hospital empiric antibiotic treatment for bacterial meningitis?
Intravenous Ceftriaxone
What is the antibiotic treatment for meningitis caused by N. meningitidis?
Intravenous Ceftriaxone
What is the antibiotic treatment for meningitis caused by H. influenzae?
Intravenous Ceftriaxone
What is the antibiotic treatment for meningitis caused by S. pneumoniae?
Intravenous penicillin, or Intravenous Vancomycin + Ceftriaxone (for resistant strains)
What is antibiotic prophylaxis?
Administration of antibiotics to prevent, rather than treat, bacterial infections, particularly in those with possible exposure to an infected person or source.
What is the purpose of antibiotic prophylaxis in contacts of bacterial meningitis cases?
To eradicate nasopharyngeal colonisation to prevent spread of harmful bacteria to the blood or CSF
What are the 2 possible preventative treatments for close contacts of bacterial meningitis cases
antibiotic prophylaxis, vaccination
What are the 3 antibiotics used in prophylaxis for close contacts of bacterial meningitis cases?
Rifampicin, Ceftriaxone, Ciprofloxacin
What is the meningitis prophylaxis used for contacts who are children?
Rifampicin
What is the meningitis prophylaxis used for contacts who are adults that are not pregnant of lactating?
Ceftriaxone
What is the meningitis prophylaxis used for contacts who are adults?
Ciprofloxacin
What is the process of a lumbar puncture?
A needle is used to extract CSF from arachnoid mater. It is put between two lumbar vertebrae and penetrates the dura mater and arachnoid mater
What are the key parameters measured in the CSF?
protein, cells, glucose, colour/opacity, gram stain, culture, PCR
What does the CSF in bacterial meningitis typically look like?
Purulent, cloudy
What type of leukocyte is found in the CSF in bacterial meningitis?
Neutrophil
What do the blood tests of a patient with bacterial meningitis typically show?
Elevated WBC (especially neutrophils), culture can show bacteria
What are the results of a lumbar puncture in bacterial meningitis?
high cell count, increased protein, decreased glucose, gram stain positive for bacteria, culture positive for bacteria
What are the relative levels of cells in a lumbar puncture of a patient with bacterial meningitis?
Increased
What are the relative levels of protein in a lumbar puncture of a patient with bacterial meningitis?
Increased
What are the relative levels of glucose in a lumbar puncture of a patient with bacterial meningitis?
decreased
What tests are done on CSF to determine the underlying bacteria in meningitis?
Gram stain, culture, (maybe PCR)
What are the relative levels of cells in a lumbar puncture of a patient with viral meningitis?
Increased
What are the relative levels of protein in a lumbar puncture of a patient with viral meningitis?
Moderately increased
What are the relative levels of glucose in a lumbar puncture of a patient with viral meningitis?
normal
What are the results of a gram stain and culture of the CSF of a patient with viral meningitis?
Negative for bacteria
What testing of CSF can be used to determine the virus causing meningitis?
PCR (detects viral genome)
What type of cell is elevated in the CSF in bacterial meningitis?
Neutrophils
What type of cell is elevated in the CSF in viral meningitis?
lymphocytes
What are the prodromal symptoms of bacterial meningitis?
Fever, headache, lethargy/malaise, vomiting/diarrhoea, myalgia/arthralgia
What are the characteristic symptoms of bacterial meningitis?
neck stiffness, photophobia, headache, papilloedema, altered mental state, seizures, cold extremities, non-blanching rash
What is the key characterisitc of the rash in bacterial meningitis?
Non-blanching
What are the 2 signs used in the diagnosis of bacterial meningitis?
Kernig’s sign, Brudzinski’s sign
What is a positive Kernig’s sign?
Knee cannot be fully extended when hip is flexed to 90 degrees
What is a positive Brudzinski’s sign?
Passive flexion of neck causes flexion of both legs and thighs
What is the purpose of vaccinations?
Prevent the spread of infectious disease by preventing individuals from acquiring disease and reducing its severity if it is acquired
What is the programme under which vaccines are funded and administered in New Zealand?
New Zealand Immunisation Schedule
What meningitis vacciantion is adminsitered to infants under the New Zealand Immunisation Schedule?
Meningococcal B
How many does of the Meningococcal B vaccination do infants receive under the New Zealand Immunisation Schedule?
3
What vaccinations are available for the Varicella Virus under the New Zealand Immunisation Schedule?
Chicken Pox vaccination t 15 months, Shingles vaccination at 65 years
What are the environmental & socio-economic factors that influence the spread of disease?
public sanitation, access to healthcare, healthcare resourcing/funding, public health education, health habits, air/soil/water quality, deprivation, inequity, economic climate
How is infectious disease surveillance carried out in NZ?
MOH contracts Institute of Environmental Science and Research to undertake surveillance, with reporting by doctors and then follow up by public health officials.
What is the legislation surrounding Meningococcal disease reporting in New Zealand?
Doctors are mandated to inform the Medical Officer of Health of any cases of meningococcal disease
What is the criteria in NZ for a close contact of a meningococcal disease case?
unprotected contact with URT droplets in the 7 days before illness onset to 24 hours after treatment onset.
What are the issues involved in vaccine development?
pathogen biological complexity, pathogen immunity, manufacturing scaling, finding therapeutic dose, cost/time of clinical trials
What are the issues in implementation of vaccination programmes?
cost, harm/benefit, vaccine efficacy, workforce, priority for certain diseases, equity, misinformation, logistics of storage/transport
