Week 15 - Infectious Diseases Flashcards
What type of virus is HIV?
RNA Retrovirus
What is the primary route of HIV transmission?
Genitourinary, rectal and oral mucosa
Which T cells are targeted by HIV?
CD4 T cells that express the receptor CCR5
What are the stages of HIV infection?
Acute - appears as clinically mild systemic viral infection. Can be flu-like.
Asymptomatic - CD8 cells rise in numbers to help combat the reduction of CD4 cells.
Late Stage (AIDS)
What are the main strains of HIV?
HIV1 - most common
HIV2 - less common and lower rate of transmissibility.
Where are high levels of CD4 T cells found in the body?
In the lamina propria of the gut - large numbers needed to keep bacteria at bay.
What are the two measures of how far a HIV infection has progressed?
Viral load
CD4 count
What is the latent reservoir in HIV infection?
The CD4 cells infected with HIV that are in a quiescent stage (G0).
Is problematic as you can treat active cells with a HIV infection but is very difficult to treat quiescent infection.
What types of HIV tests are available?
Nucleic acid test (NAT) - looks for HIV RNA
Antibody test - looks for HIV ABs
Combined antigen antibody test (most common) - ELISA test (Assay) - looks for IgM and IgG ABs for HIV but also looks for HIV protein (HIV p24)
What is the eclipse period of an HIV infection?
The time between the P being infected and the time when the RNA is at detectable levels
What is HAART?
Highly Active Antiretroviral Therapy - combination antiretroviral therapy - 3 more drugs that attacks the virus life cycle in different places - avoids the virus being put under selective pressure.
When do you need to start medication for a HIV infection?
As soon as possible
What are
- PrEP
- TasP?
PrEP = Pre-exposure Prophylaxis - given to Ps at very high risk of HIV
TasP = Treatment as Prevention - provided to Ps with HIV+ to reduce the viral load to undetectable levels - where they cannot transmit the virus
What is pyrexia of an unknown origin defined as?
Fever >38.3 lasting >3w with no clear diagnosis despite investigations.
What are the top 3 causes of pyrexia of unknown origin (PUO)?
1 = Infective cause
2 = Inflammatory cause - vasculitis or AI
3 = Neoplastic cause
Which systemic illnesses can cause a PUO?
Toxoplasmosis
EBV
Cytomegalovirus
HIV primary
Burcellosis
Lyme disease
What are the B symptoms of malignancy?
Fever, drenching night sweats and loss of more than 10 percent of body weight over six months
What inflammatory or AI conditions can cause PUO?
SLE
Granulomatosis with polyangiitis
Giant cell arteritis
Polymyalgia
Still’s disease
Periodic Fever Syndromes
Which drugs can cause PUO?
Penicillins
Cephalosporins
Anti-TB meds
Phenytoin
What Qs do you need to ask a P with PUO?
What clinical signs should you look for with a P with PUO?
Start with A-E assessment
What do you not want to do when managing PUO?
Give blind ABx or steroid therapy - can mask the underlying cause of infection
What are the S&S of cellulitis?
Redness
swelling
Pain
Tenderness
Fever
Malaise
What are the differentials of cellulitis?
What are the RF of cellulitis?
Immunosuppression (DM, HIV, drugs)
Broken skin
Athletes foot
Lymphodema
Previous Hx
Obesity
Which are the most common causative organisms of cellulitis?
Staph aureus
MRSA
Streptococcus
What ABx can be given for cellulitis?
Flucloxacillin
Penicillin
Cephalosporin
Fucidic acid
What complications can arise from cellulitis?
Bacteraemia
Sepsis
Endocarditis
Osteomyelitis
TSS
Nec fasc
How is HIV transmitted vertically?
Birth
Breastfeeding
Which are the common co-infections of HIV?
Hep B
Hep C
Human Herpes Virus 8 (HHV8)
What are the stages of HIV infection by CD4 count?
Stage 1 = Early stage = CD4 >500
Stage 2 = Intermediate stage = CD4 200-500
Stage 3 = Advanced stage = CD4 <200
How long can Ps stage in the secondary asymptomatic stage for?
Approximately 10 years
What is Primary HIV Infection?
Early phase of infection to 1-4 weeks later when there are sufficient ABs to be detected by a test (usually after 12 weeks of infection).
AKA Acute seroconversion illness
What is a late and very late diagnosis defined as?
Late = CD4 <350
Very late = CD4 <200
What Sx can present in Ps during the acute seroconversion phase?
May also have lymphadenopathy
What is the difference between the eclipse period and the Window period?
The eclipse period is the time between infection and when RNA becomes detectable
The window period is the time between initial infection and when the virus is detected by a test - e.g. ELISA test = 45 day window
If you find out a P has HIV - what other diseases should you screen for?
Hep A, B & C
Measles
Varicella
STIs
Syphyllis
What haematological complications can arise from HIV?
Anaemia of chronic infection (normochromic and normocytic)
Lymphoenia
Isolated thrombocytopenia in early infection
When is antiretroviral therapy started in a HIV infection?
When the P is ready - usually shortly after diagnosis.
More urgent if primary HIV, CD4 <200, have aids defining infection, HIV related malignancy or nephropathy or there is coinfection with Hep B / C
What infections are considered to be HIV associated?
What causes pneumocystis pneumonia (PCP)?
Pneumocystis jirovecii
When should you suspect PCP?
If an immune suppressed P (esp with HIV) has clinical SorS of pneumonia
How is PCP diagnosed?
Induced sputum sample or bronchoalveolar lavage
What treatment is given for PCP?
Co-trimoxazole
Can be given in low dose as PCP prophylaxis
How does PCP present on imaging?
Can get multifocal patchy opacities on CXR - if CD4 <200 then should be suspicious of HIV
Can get interlobular septal thickening, ground glass opacities and pneumatocoels (air cavitating lesions on CT).
What is the most common cause of an intracerebral mass lesion in Ps with HIV?
Toxoplasmosis
Which organism causes toxoplasmosis?
Toxoplasma gondii
How can toxoplasmosis present?
Multifocal cerebritis - causing diffuse and focal Sx
How does toxoplasmosis present on imaging?
Multiple ring enhancing lesions - likes the cortex and basal ganglia.
How is a diagnosis of toxoplasmosis confirmed?
Usually CT changes + resolution with appropriate therapy (no sampling is done!)
What differential can be given for brain lesions in HIV Ps?
Lymphoma - can get lots of oedema surrounding the lesion.
Which respiratory diseases would make you Q whether the P also has a HIV diagnosis?
TB
PCP
Bacterial pneumonia
Aspergillosis
Which neurological diseases would make you Q whether the P also has a HIV diagnosis?
Toxoplasmosis in cerebrum
Cryptococcal meningitis
Primary CNS lymphoma
Aseptic meningitis
Which dermatological diseases would make you Q whether the P also has a HIV diagnosis?
Kaposi’s sarcoma
Severe / recalcitrant psoriasis
Severe seborrhoea dermatitis
Multidermatomal or recurrent shingles
Which GI diseases would make you Q whether the P also has a HIV diagnosis?
Persistent cryptosporidiosis
Oral candidasis
Oral hairy leukoplakia
Hep B and C
Which cancers would make you Q whether the P also has a HIV diagnosis?
NHL
Anal
Lung
Head and neck cancer
What part of the coronavirus stricture is important for transmission?
The spike protein
Which cell protein interacts with the COVID spike protein?
ACE2
Only when the spike protein is in the up/open position can it bind to ACE2. However it is detectable by the immune system when this happens. How does COVID try to overcome this?
Hides it in sugars = viral glycan shielding
What is it called when viruses change part of their proteins to try and avoid detection?
Antigenic drift
What is the link between HIV and CVD?
HIV inc the risk of CVD - need to have close monitoring of bloods and lipids.
What should female Ps with HIV have done yearly?
Cervical smear test - risk of HPV is increased by HIV
Which vaccinations should Ps with HIV be given?
Annual influenza
Pneumococcal (5-10 years)
Hep A & B
Tetanus, diphtheria and polio
DO NOT GIVE THEM LIVE VACCINES
When should post exposure prophylaxis to HIV be given?
ASAP = but no longer than 72 hours
What causes malaria?
Plasmodium family of protozoans
Transmitted by female Anopheles mosquito
Which is the most severe strain of malaria?
Plasmodium falciparum
Where are the majority of malaria cases found?
Sub-Saharan Africa
What types of plasmodium are there?
Plasmodium falciparum
P. Vivax
P. Ovale
P. Malariae
P. Knowlesi
Each have different lifecycles and can make Ps ill at different intervals
How do Ps get ill with malaria? (What is the lifecycle of malaria?)
Ps are bitten my female anopheles mosquitos. Infected blood is sucked up by the mosquito - the malaria then reproduces in the mosquito’s gut producing thousands of sporozites (malaria spores).
That mosquito then bites again and injects sporozoites into the host - these travel to the LIVER of the infected person. There they mature into merozites - which attack RBCs. They reproduce inside RBCs for 48 hours or so and then rupture the RBC - releasing lots more merozites into the blood => causes HAEMOLYTIC ANAEMIA
This is why you get fever spikes every 48 hours or so.
In which types of malaria can Sx lie dormant for years?
P. vivax
P. ovale
Plasmodium vivax and Plasmodium ovale sporozoites enter into a dormant hepatic phase, where they are called hypnozoites.
Hypnozoites don’t divide - instead they snooze for a period of time before entering the process of schizogony, causing a long delay between the initial infection and symptoms from the disease.
What are malaria spores called?
Sporozites
What are the S&S of malaria?
Fever, sweats and rigors
Malaise
Myalgia
Headache
Vomiting
Diarrhoea
Cough
Pallor (anaemia)
Hepatosplenomegaly
Jaundice (bilirubin released during rupture of RBCs)
Which membrane protein expressed by plasmodium on the surface of infected RBCs?
Plasmodium falciparum Erythrocyte Membrane Protein
(PfEMP-1)
What is it called when two or more uninfected red blood cells (rbc) bind to an infected rbc to form clusters of cells?
Rosetting
What is the incubation period of malaria?
At least 6 days
Which type of malaria is most likely to occur within 3 months of return?
Falciparum
What types of malaria are there?
Asymptomatic
Uncomplicated
Severe
Depending on immunity of the host
What is the mortality of severe malaria?
10-40% in first 24 hours
Is a medical emergency
Which protein has a role in the cytoadherence of infected RBCs to the endothelium of cerebral capillaries - which can lead to blocking and hypoxia?
PfEMP1
What are the S&S of severe anaemia?
Oliguria
Acidosis
Hypoglycaemia
Pul oedema or ARDS
Severe anaemia <80
DIC
Shock
Haemoglobinuria
Which is the most common malaria that presents in the UK?
P. falciparum
Being Duffy blood group negative protects you from which strain of malaria?
P. vivax
Which blood illnesses help ward off malaria infections?
Sickle Cell Anaemia
Thalassemia
G6PD deficiency
Both mean that infected RBCs are more likely to die from oxidative stress - therefore limiting the infection.
How often do fevers occur in Ps with different types of malaria?
Malariae = every 72 hours (quartan)
Vivax & Ovale = every 48 hours (tertian)
Knowlesi = every 24 hours
Falciparum - pattern varies - can be terrain or daily.
How does p. falciparum avoid being destroyed by the spleen?
Sticky proteins cause the RBCs to clot together (cytoadherence) - stops the cells entering the spleen (but also stops blood reaching vital organs as well). Causes ischaemic damage
What is malaria called when it affects the
= brain
= liver?
Cerebral malaria (altered mental status, seizures and coma)
Bilious malaria (diarrhoea, vomiting, jaundice, liver failure)
What is the difference between a thick and thin smear?
Thick smear = identifies the presence of parasites
Thin spear = identifies which species of plasmodium is involved
How can bloods present in malaria?
Thrombocytopenia
Elevated LDH (due to haemolysis_
Normochromic, normocytic anaemia
Hypoglycaemia
Low HCO3
Elevated BUN and creatinine
Low Hb
Elevated PT and PTT
What is used to diagnose malaria in endemic countries?
Rapid Diagnostic Tests (RDTs)
How often do you need to repeat blood smears to confirm diagnosis?
Repeat every 12-24 hours for 3 days to confirm diagnosis. If no plasmodium appears after 3 days you can rule out malaria.
How are severe and uncomplicated malaria differentiated?
How is uncomplicated malaria managed?
ACT
Atovaquone-Progaunil or
Quinine plus doxycycline
If severe malaria is left untreated - what is the mortality rate?
Almost 100%
Why was IV quinine stopped as treatment for severe malaria?
What is given for severe malaria?
IV Artesunate
Which bacteria can cause respiratory infections?
Streptococcus pneumoniae
Haemophilus influenzae
Mycoplasma
Mycobacterium TB
What removes debris and pathogens from the lungs?
The mucociliary escalator and alveolar macrophages
How does IgA interfere with viruses?
Prevents adherence and viral assembly
What are the commensals found in the mouth?
Staph aureus
Streptococcus pneumoniae
Anaerobes
Bacteroides
What commensals are found in the sinuses and nasal passages?
Strep. pneumoniae
Staph aureus (MRSA)
Rhinovirus
Haemophilus Influenzae
What commensals are found in the throat?
MRSA
Strep pyogenes
Candida (thrush)
Which viruses attack the respiratory tract?
Adenovirus
Cytomegalovirus
Influenza
Rhinovirus
Coronavirus
Parainfluenza
Respiratory Syncytial Virus (RSV)
What is the most common cause of colds?
Rhinoviruses
What is the most common cause of tonsillitis?
Strep A
What are the commonest causes of sinusitis and otitis media?
Strep pneumoniae
Haemophilus influenzae
What are the commonest causes of bronchitis?
Strep pneumoniae
Haemophilus influenzae
Moraxella catarrhalis
What are the commonest causes of bronchiolitis in infants?
RSV
What are the commonest causes of pneumonia?
Strep pneuomoniae
Haemophilus influenzae
Legionella pneumophila
Mycoplasma pneumoniae
What is the incubation period of colds?
2-3 days
How are colds transmitted?
Droplet or direct contact
What causes a sore throat and nasal congestion in a cold?
Release of bradykinin = vasodilation
What causes the colour change in mucus in a cold?
Myeloperoxidase (released by Ns)
How can you differentiate between colds and influenza?
What are the S&S of influenza?
Abrupt onset of fever
Cough
Headache
Myalgia
Malaise
Sore throad
Nasal discharge
Who is at risk from influenza?
Risk groups = immunosuppressed, chronic conditions, pregnancy, 2 weeks PP, <2, >65, BMI>40
What are potential complications of influenza?
Complications – 1° viral pneumonia, 2° bacterial pneumonia, CNS disease, death
Which two viral proteins in influenza are responsible for the greatest antigenic shift and drift?
Haemagglutinin (binds to host cells)
Neuraminidase (allows escape from host cells)
What Rx can be given for influenza?
How does it work?
Tamiflu
Neuraminidase inhibitor and prevents replication of the virus
What is pneumonia?
Infection of the lung parenchyma
Alveoli become full of inflammation - reducing O2 transfer
What is the commonest cause of T1RF?
Pneumonia
What are the S&S of pneumonia?
Symptoms = fever, breathlessness, cough, sputum, pleuritic chest pain – elderly may not have such symptoms as their immune system may not be able to mount a response – instead = confusion, unwell, loss of appetite, dehydrated.
Signs = Tachypnoea, ↑ RR, reduced chest expansion and breath sounds, consolidation (dullness on percussion, ↑TVF & VR – unlike Pl Eff) + bronchial breathing. Severe – can lead to hypoxia.
What classifications of pneumonia are there?
CAP
HAP
Healthcare Associated
Ventilator Associated (VAP)
Aspiration Pneumonia
What are the Sx of CAP?
What are the clinical signs of CAP?
How does pneumonia appear on CXR?
Consolidation
May have obscured heart borders or diaphragm
Which are the commonest bacteria involved in CAP?
Strep pneumoniae (commonest)
Haemophilus influenzae
Mycoplasma pneumoniae
Legionella pneumoniae
Staph aureus
What type of organism is Strep pneumoniae? What Rx is given for this organism?
Gram positive cocci
Rx = Amoxicillin, Clarithromycin or Co-Amoxiclav in severe CAP
What type of organism is Haemophilus influenzae?
What Rx is given for this organism?
Gram negative anaerobe
Rx = Tetracycline (Doxycycline)
What is the commonest cause of walking pneumonia?
Mycoplasma pneumonia
What type of organism is mycoplasma pneumonia?
What Rx is given for this organism?
Mycoplasma = Lacks a cell wall! Resistant to penicillin. Cannot be grown on normal lab plates.
Rx = Macrolides or Tetracycline
How can you diagnose legionella pneumophilia?
Urinary legionella antigen (doesn’t grow on routine cultures).
What is the Rx for legionella pneumophilia?
Macrolides or Quinolones
What score is used to assess the severity of CAP?
CURB-65
Confusion
Urea
Respiratory Rae
BP
What is the management of CAP?
O2 if T1RF
Abx
What is the definition of HAP?
Pneumonia that develops >48hours after admission to hospital (in a P who did not have pneumonia on admission)
Which organisms are more commonly associated with HAP?
E. coli
Klebsiella pneumoniae
Pseudomonas aeruginosa
MRSA
Why is HAP important to recognise?
Has a much higher morbidity and mortality than CAP - often between 30-70%.
Multi drug resistance is also common.
What is infection & pus in the pleural space called?
Empyema
What are the RF for empyema?
Elderly
Immunocompromised
Alcoholics
DM
How does empyema present on pleural aspiration?
Pus
Low pH
Exudate
Bacteria
What is Light’s criteria?
Transudate - protein ratio <0.5 and LDH <0.6
Exudate - protein >0.5 and LDH >0.6
What is the management of empyema?
Long course ABx
Streptokinase
Drainage
Poss surgery
Which organisms can cause opportunistic respiratory infections?
PCP
Atypical mycobacteria
Fungal - aspergillus, candida, histoplasmosis, cryptococcus
Viral pneumonia - CMV
How doses pneumocystis jiroveci appear on CXR?
Bilateral, interstitial ground glass shadowing in a bat’s wing appearance
What is the Rx for pneumocystis jiroveci?
Co-trimoxazole
Give an example of a live attenuated vaccine
MMR
Give an example of an inactivated vaccine?
Meningococcal B & C
What is the difference between active and passive immunisation?
- Active Immunisations: cause the organism to mount an immune response as if a real infection was happening. Use the organism itself in either an attenuated or inactivated version.
- Passive Immunisations: provide the organism with a ‘manufactured’ immune response. Dont provide the immune system with lifelong memory - rather short term immunity by giving either antitoxins or immunoglobulins for the disease.
Give an example of an anti-toxin?
Diphtheria
Give an example of immunoglobulins given as passive immunisation.
Varicella zoster IG
Rabies IG
The answers are 3 and 4 because active immunizations, such as attenuated vaccines, use live organisms (or in the case of inactivated vaccines) include organisms that are ‘intact’ enough that immune system can still recognize it and make a protective antibody response. Furthermore, passive immunisation can reduce the severity of infection if contracted before vaccination.
Q1, 2, and 4 are correct because inactivated vaccines often produce less vigorous immune responses that live attenuated vaccines. Therefore they may need several doses, they are shorter lasting and often need an adjuvant.
What are the advantages and disadvantages of active immunisation with live vaccines?
Advantages:
* Strong immune response evoked
* Single dose often sufficient to induce long-lasting immunity
* Local and systemic immunity produced
Disadvantages:
* Potential to revert to virulence
* Contraindicated in immunosuppressed patients
* Poor stability
What are the advantages and disadvantages of active immunisation with inactivated vaccines?
Advantages:
* Stable
* Unable to cause the infection
* Cannot spread infection to others
Disadvantages:
* Need several doses
* Shorter lasting immunity
* Local reactions common
* Adjuvant needed
What are the advantages and disadvantages of passive immunisation?
Advantages:
* Provides immediate protection for those at high risk
* Takes several days to respond to a vaccine and not everyone able to receive vaccine
* May reduce severity of infection even if does not prevent
Disadvantages:
* Expensive
* Often in short supply
* Potential risk from blood product
* Only have limited time period in which they can be given to be effective
Short lived protection
How is DNA transported in a vaccine?
Viral vectors (e.g. adenovirus)
How is RNA transported in a vaccine?
Liposome
Are DNA and RNA vaccines stable at room temperature?
DNA - yes
RNA - no
How do RNA vaccines work?
Which MHC class is found on
- CD8 cells
- CD4 cells
CD8 = MHC Class I (Cytotoxic)
CD4 = MHC Class 2 (Helper cells)
Which nucleotide used to synthesis mRNA molecules was found to initiate a strong immune response?
Pseudouridine
How do DNA vaccines work?
What type of organism is mycobacterium tuberculosis?
Aerobic
Cell wall but no outer PL membrane = weak G+ve
What are the RF for TB?
How is TB transmitted?
Aerosol droplets
What’s the clinical presentation of TB?
T – troublesome cough (productive – not responding to usual Abs)
H – haemoptysis
I – involuntary weight
N – night sweats and fevers
K – known exposure
T - tiredness
B – breathlessness
Also – weight loss and pain.
In 5% of Ps - TB infection can present with initial hypersensitivity. What are the signs of this?
Erythema nodosum
Phlyctenular conjunctivitis
What is disseminated TB called?
Miliary TB
Miliary TB is a potentially fatal form of disseminated TB characterized by millet-seed-like granuloma formation in various organs. Miliary TB often arises from a primary pulmonary infection that spreads hematogenously.
What is the presence of granulomas + enlarged lymph nodes called?
Gohn complex
What are the three types of TB?
Latent TB
Cavitary TB
Military TB
What is it called when you have a granuloma with an area of central caseation and surrounding fibrosis in the lungs that is calcified with a few dormant bacteria?
Gohn focus
Which part of the lung does TB prefer?
The upper lobe - due to the increased O2 levels
How can we diagnose TB?
CXR
x3 early morning sputum samples
Bronchoalveolar lavage if no sputum
Mantoux (Tuberculin test)
IGRA T-spot test
Nucleic acid amplification
PCR
Signs & symptoms of TB + abnormal CXE + positive Mantoux/IGRA + culture of mycobacterium = diagnosis of TB.
How long does it take to get TB cultures?
6-8 weeks
Which stain can you use for TB?
What should you always test for in Ps with TB?
HIV
How does the Mantoux test work?
> 5mm = positive
15mm = strongly positive
May be falsely negative in the severely ill or immunosuppresed individuals
How can MTB appear on CXR?
What is the difference between primary TB and latent infection?
5% of cases - the bacilli overcome the immune system soon after the initial infection.
In 95% - latent disease will occur - no Sx and not infectious.
10% of these will later progress to active TB. Usually within first 2 years - changes of this happening decreases after 2 years.
What are the differentials for TB?
Bilateral hilar lymphadenopathy
Sarcoidosis
Lymphoma
How can disseminated miliary TB present?
Where can you develop extra-pulmonary TB?
Pericardium
Skeleton
GUI
Eye
GI
CNS
What are the first line drugs for TB?
Isoniazid & Rifampicin
What are the SEs of Rifampicin?
Hepatotoxicity
Red urine & tears
How is multi-drug resistant TB treated?
A prolonged course of 2nd Lind drugs - up to 24m
Third line may also be required
What treatment should be given for latent TB?
3m of Rifampicin + Izoniazid
6m of Izoniazid
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