Infectious Disease AS Flashcards
What are the different stages of TB?
Primary TB
Primary Progressive TB
Latent TB
Secondary TB
What is Primary TB
Childhood or naive TB infection.
- Organisms multiples @ pleural surface (Ghon focus)
- Macros take TB to LNs ( Nodes + lung lesion = Ghon complex).
- Mostly asymptomatic: may –> fever + effusion
- Cell mediated immunity/ DTH control infection in 95%.
(Fibrosis of Ghon complex –> calcified nodule (Ranke complex). - Rarely may –> primary progressive TB (immunocompromised).
Primary Progressive TB?
- Resembles acute bacterial pneumonia
- Mid and lower zone consolidation, effusions, hilar LNs.
- Lymphohaematogenous spread –> extrapulmonary
Latent TB?
Infected but no clinical or x-ray signs of active TB
Non-infectious
May persist for years
Weakened host resistance –> Reactivation
Secondary TB?
- Usually reactivation of latent TB due to decreased host immunity.
- May be due to reinfection
- Typically develops in the upper lobes
- Hypersensitivity –> tissue destruction –> cavitation and formation of caseating granuloma.
What are the pulmonary features of TB?
Cough, sputum Malaise Fever, night sweats, weight loss Haemoptysis Pleurisy Pleural effusion Aspergilloma/mycetoma may form in TB cavities
Features of meningitis TB?
Headache, drowsiness Fever Vomiting Meningism Worsening over 1-3 weeks CNS - Papilloedema - CN palsies
What are the lymph- node features of TB?
- Cervical lymphadenitis: scrofula
- Painless neck mass: no signs of infection (cold).
What are the genito-urinary features of TB?
Frequency, dysuria, loin/back- pain, haematuria, sterile pyuria.
What are the other involved systems in TB?
Bone TB: vertebral collapse and Pott’s vertebra
Skin: Lupus vulgaris (jelly-like nodules)
Peritoneal TB: abdominal pain, GI upset, ascites
Adrenal: Addison’s disease
What is the diagnosis of latent TB?
Explain the investigation results and interpretation
- Tuberculin Skin Test/Mantoux test
<6mm = negative - no significant hypersensitivity (previously unvaccinated individuals may be given BCG).
6-15 mm = Positive - hypersensitive to tuberculin. Should not be given BCG. May be due to previous TB infection.
> 10mm = positive result = implies previous exposure. Need erythema and induration.
> 15mm - Strongly positive - suggests TB infection.
- If +ve –> IGRA (for prior exposure)
Interferon Gamma Release Assay - Pt lymphocytes incubated with M.tb specific antigens. IFN-y production if previous exposure.
- Either active or latent TB.
- Will not be positive if just BCG (uses M.bovis)
e.g Quantiferon Gold.
Used when mantoux is positive, people where a tuberculin test may be falsely negative.
Tests for Active TB
All patients with suspected TB require a HIV test. Often pushed into active disease by immunosuppression.
- CXR
- Upper lobe cavitation
Active TB
* Sputum samples (Acid fast bacilli will be seen)
* Culture (GOLD STANDARD TEST)
* sputum smear and stain : Stain Ziehl Neelson
Latent TB
* Tuberculin tests (Montoux test) -> Shows active/latent/BCG vaccinated
If the patient has not had the BCG vaccine then this test can be used.
* Inteferongamma release assay (IGRA) -> Shows active/latent
This is used if the patient has had the BCG vaccine. The titre levels of this tells us if the TV has been treated. ,
What would give a false positive in the Mantoux test?
BCG, other mycobacteria, previous exposure.
What would give a false negative in the Mantoux test?
Immunosuppression.
Miliary TB Sarcoidosis HIV Lymphoma Very young age (< 6 months)
What is the pre-assessment investigations of TB?
NB: manage without culture if clinical picture is consistent with TB.
- Continue even if culture results are negative.
- Stress importance of compliance
- Check FBC, liver, renal function
- Creatine Clearanc 10-50ml/min –> decreased R dose by 50% ,avoid E.
- Test visual acuity and colour vision
- Give pyridoxine throughout management.-> This is because Isonazid has a chance to cause peripheral neuropathy
Therefore check LFTs cos all are hepatotoxic, test U+E for electrolyte disturbance + elevation of creatinine.
Baseline visual assessment for ethambutol for vision.
FBC baseline - assess for platelets.
Do not need URine dip.
What is the initial phase of management (RIPE)
Last 2 months
- Rifampicin: hepatitis, orange urine, enzyme induction.
- Isoniazid (nerves = ice for ice): hepatitis, peripheral sensory neuropathy, decrease PMN. (+ pyridoxine). Due to Vit B6 deficiency.
- Pyrazinamide: arthralgia (CI: gout, porphyria)
- Ethambutol: Optic neuritis.
All are hepatotoxic
don’t forget Pyridoxine
What is used in the continuation phase in TB?
4 months
- Rifampicin and Isoniazid
Management of TB Meningitis?
RIPE: 2 months
RI: 10 months
± dexamethasone
What is the management of latent TB?
RI For 3 months
or
Iso (+ pyridoxine) for 6 months.
What is directly observed therapy in TB?
- 3x a week dosing regimen may be indicated in certain groups
- Homeless people with active TB
- patients who are likely to have poor concordance
- all prisoners with active or latent TB.
What are the other TB disease?
Leprosy
MAI (Mycobacterium avium-intracellulare infection)
Buruli Ulcer
Fish Tank Granuloma
What is Leprosy/Hansen’s disease?
Pathogenesis
- Transmitted via nasal secretions (not very infectious)
- M.leprae
What are the classifications of leprosy? 2
Tuberculoid
- Less severe (paucibacillary)
- Th1 mediated control of bacteria
- Anaesthetic hypopigmented macules
- Symmetrical nerve involvement
Lepromatous
- Weak Th1/2 –> Multibacillary
- Skin nodules
- Nerve damage (esp ulnar and peroneal)
- Asymmetrical nerve involvement
What are the clinical features of Leprosy?
- Hypopigmented, insensate plaques (slow over 5 years).
- Trophic ulcers
- Thickened nerves (nerve damage + reduced sweating). Neuropathy + disfigurement.
- Keratitis
What is the management of Leprosy?
Tuberculoid: 6 month
- Rifampicin monthly
- Clofazamine daily
Lepromatous: 2 yrs
- Rifampicin months
- Clofazamine + dapsone daily.
What is MAI?
MAI (Mycobacterium avium-intracellulare infection)
- Complicates HIV infection
- Widely disseminated: Mainly in the lungs/GIt
- Fever, night sweats, weight loss
- Diarrhoea
- Hepatomegaly
What is a Buruli Ulcer? + what is it caused by
M.ulcerans
Australia and the Tropics
Transmitted by insects
Nodule –> ulcer
What is fish tank granuloma + what is it caused by?
M.marinum
Skin lesion appearing ~3 weeks after exposure
What is the pathophysiology of influenza?
Spread: droplet
Incubation: 1-4 days
Infectivity: 1d before symptoms start to 7d after
Immunity: only strains which have already attacked pt.
What is the presentation of influenza?
Fever Headache Malaise Myalgia N/V Conjunctivitis
Complications of Influenza?
Bronchitis Pneumonia: esp Staph Sinusitis Encephalitis Pericarditis
Reyes; Rash, vomiting, Increased LFTs in children given aspirin.
What investigations do you do for influenza?
Bloods: Paired sera (takes 14 days), lymphopenia, thrombocytopenia
Culture: 1 week from nasal swab
PCR: takes 36hrs
DNA: Up to 15-20mins
Management of influenza?
Bed rest and paracetamol
If severe
- Manage in ITU
- Cipro and co-amoxiclav: prevent Staph and Strep
Oseltamivir
- Neuraminidase inhibitor active vs flu A and B.
- May be indicated if >1yr with symptoms of >48hrs
Zanamivir
- Inhaled NA inhibitor vs influenza A and B
Prevention of influenza?
Good hygiene Trivalent vaccine - >65 yrs old - DM, COPD, Heart, renal, liver failure - Immunosuppression: Splenectomy, steroids - Medical staff
Oseltamivir
- Prophylactic use if influenza A/B is circulating and >1 yr old and <48hr since exposure.
What is the immunology of HIV? what is the structure of the virus?
HIV binds to gp120 to CD4 - Th cells, monocytes, macrophages, neural cells.
- CD4 + cells migrate to lymphoid tissue where virus replicates –> infection of new CD4 cells.
- Deplection + impaired function of CD4+ cells –> immune dysfunction
RNA retrovirus
- After entry - viral reverse transcriptase makes DNA copy of viral RNA genome.
- Viral integrase enzyme integrates this with host DNA
- Core viral proteins synthesised by host and then cleaved by viral protease into mature subunits.
- Completed virions released by budding.
What is the natural history of HIV?
- Acute infection (asymptomatic)
Then - Seroconversion (transient illness 2-6 weeks after
exposure, fever, malaise, myalgia, pharynitis, macpap rash (symmetrical maculopapular rash) , rarely meningoencephalitis).
then
asymptomatic infection (but 30% will have PGL (persistent generalised lymphadenopathy) - Nodes >1cm in diameter, >2 extra-inguinal sites, >3 months.
then
AIDS-related complex - prodrome with constitutional symptoms + minor opportunistic infections (oral candida, oral hairy leukoplakia, recurrent HSV, seborrheic dermatitis).
Then AIDS.
- CD4 usually <200
What are the other effects of AIDS?
Complications?
Osteoporosis
Dementia
Neuropathy
Nephropathy
How do you diagnose HIV?
HIV antibody test
- ELISA: detect serum (salivary) anti-HIV Abs
- Western Blot: for confirmation
Most develop antibodies 4-6 weeks but 90% do by 3 months)
Testing for HIV in asymptomatic patients should be done at 4 weeks after possible exposure.
If recent exposure, may be window period (usually 1-3 weeks. Can be 3-6 months)
- therefore must to HIV infection test** at 12 weeks**.
Test requested = antibodies and p24 antigen. (HIV-1 and HIV-2).
- PCR: Can detect HIV virions in the window period
- Rapid Antibody Test: false positives are a problem and results should be confirmed by Western Blot.
- p24 antigen test - usually positive by 1 week to 3-4 weeks.
Other investigations for HIV?
- HIV diagnostic tests
-Drug resistance studies
E.g genotyping - Mantoux test
- Toxo, CMV, HBV, HCV, Syphilis test
What is used to monitor HIV?
- CD4 count
- Viral load (HIV RNA)
- FBC, U+E, LFTs, Lipids, glucose.
Indications for HAART?
Highly active anti-retroviral therapy - at least 3 drugs.
For a newly confirmed infection - ART is strongly recommended, regardless of CD4 count.
What are the regimens for HAART?
At least 3 drugs -
1) typically two nucleoside reverse transcriptase inhibitors (NRTI) + either a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI)
Typical regimen (1 NNRTI + 2 NRTI)
NNRTI = Efavirenz NRTI = emtricitabine + tenofovir (Truvada) Atripla = efavirenz + emtricitabine + tenofovir.
Typical regimen (PI + 2 NRTI)
PI = Lopinavir (+lose dose ritonavir + Kaletra)
NEver tea
Examples of NRTI?
Zidovudine Tenofovir Stavudine Abacavir Lamivudine
General NRTI side-effects = peripheral neuropathy
Examples of NNRTI?
Nevirapine, efavirenz
Side effects: P450 enzyme interaction (nevirapine induces), rashes.
Examples of protease inhibitors?
Navir tease a pro.
Indinavir
Nelfinavir
Ritonavir
Side effects: diabetes, hyperlipidaemia, buffalo hump, central obesity, P450 enzyme inducer.
Examples of integrase inhibitors?
It’s grave/great you integrate.
Raltegravir
Elvitegravir
Dolutegravir
What prophylaxis do you give at CD4 count 200 and for what?
CD4 count of less than <200 - give co-trimoxazole. PCP.
This is for prophylaxis.
What prophylaxis do you give at CD4 count 100 and for what?
Give co-trimoxazole for Toxo
What prophylaxis do you give at CD4 count 50 and for what?
MAC Mycobacterium Avium Complex- azithromycin
What is HIV exposure management?
- Seroconversion post-needle-stick = ~0.3%
- Report to Occupational health
- Immunise against Hep B (active + passive)
- Test blood from both parties: HIV, HBC, HCV
- Repeat recipient testing @ 3 and 6 months).
When to use PEP?
- Post-exposure prophylaxis.
- Start PEP in high-risk exposure from HIV or unknown source
- Start ASAP as possible
Continue for at least 28 days. Can be started within 1-2 hrs, but may be started up to 72hrs following exposure. - Serological testing at 12 weeks.
- E.g Truvada + Kaletra.
What are the major AIDS-defining illness? Between 500-200? (4)
Between 500-200 CD4 Count
- Oral thrust (Candida)
- Shingles (HSV)
- Hairy Leukoplakia (EBV) - white streaky plaque that is present only on the side of the tongue.
- Kaposi sarcoma (HHV-8)
What are the major AIDS-defining illness? Between 200-100? (5)
- Cryptosporidiosis (most common cause of diarrhoea)
- Cerebral Toxoplasmosis
- Progressive Multifocal leukoencephalopathy - JC virus
- Pneumocystis jirovecii pneumonia
- HIV dementia
What are the major AIDS-defining illness? Between 100-50? (4)
Aspergillosis
Oesophageal candidiasis (manage with fluconazole, itraconazole)
Cryptococcal meningitis
Primary CNS lymphoma (EBV)
What are the major AIDS-defining illness? Between <50?
CMV retinitis - 30-40% of patients
Mycobacterium avium-intracellulare infection
TB and HIV?
- Increased risk of latent TB, and increased risk of disseminated TB.
- Higher bacterial loads but increased false -ve smears.
- False -ve skin test (T cell anergy)
- Absence of characteristic granulomas
- Increased toxicity combining anti-TB and anti-HIV drugs.
- IRIS: HAART –> increased CD4 –> paradoxical worsening of TB symptoms.
What is PCP?
P.Jiroveci: fungus
Presentation
- Dry cough
- Exertional dyspnoea
- Fever
Extrapulmonary manifestations
- Hepatosplenomegaly
- Lymphadenopathy
- Choroid lesions
CXR: bilateral perihilar interstitial shadowing
Exercise-induced desaturation
DX: visualisation from sputum, BAL or lung biopsy
Rx: High-dose co-trimoxazole IV or pentamidine (severe)
Prophylaxis if CD4 <200.
What can CMV cause in HIV?
Retinitis
- Decreased acuity
- Eye pain, photophobia
- Pizza sign on fundoscopy
- Manage with ganciclovir eye implant.
Cotton-wool spots, infiltrates and haemorrhages - pizza pie appearance on fundoscopy.
Remember central retinal vein occlusion = stormy sunset.
Toxoplasmosis and HIV?
- Posterior uveitis
- Encephalitis
- Focal neurology
Diagnosis with toxoplasma serology + LN or CNS biopsy.
Gondii parasite.
Antibody test or Sabin-Feldman dye test.
CT/MRI: Ring-shaped contrast enhancing lesion.
Differentiating between toxo and lymphoma is hard.
Toxo = multiple lesions, ring or nodular enhancing. Thallium SPECT negative.
Lymphoma = Single lesion, solid enhancement, Thallium SPECT positive.
Rx: pyrimethamine + sulphadiazine + folate for at least 6 weeks.
Candidiasis + HIV?
Features and management
Oral: nystatin syspension Oesophageal - Dysphagia - Retrosternal pain - Manage: itraconazole PO.
Cryptococcal Meningitis HIV?
Ix?
Treatment?
Presentation
- Chronic history
- Headache
- confusion
- Papilloedema
- CN lesions
Ix
- India ink CSF stain
- Increased CSF pressure
- CrAg in blood and CSF.
Management
- Amphotericin B + flucystosine for 2 weeks then fluconazole for 6 months/until CD4 >200.
Affects HIV positive patints.
PML and HIV?
- Progressive mutlifocal leukoencephalopathy
- Demyelinating inflammation of brain white matter caused by JC virus.
- Presentation
Weakness
Paralysis
Visual loss
Cognitive decline
Ix: JC viral PCR
Manage: HAART, mefloquine may halt progression.
Kaposi’ Sarcoma
Neoplasm derived from capillary endothelial cells or fibrous tissue
Caused by HHV8 infection.
Presentation
- Purple papules
- May have visceral involvement
Children present with generalised lymphadenopathy
Management
- HAART
- Radiotherapy or Chemo
What are the different types of Herpes infections?
Persist in DRG with mucocutaneous spread.
- HSV 1 - Oropharyngeal/primary stomatitis. Severe painful ulceration + submandibular lymphadenopathy. Severe and painful.
Gingivostomatitis = oral aciclovir, chlorhexidine.
Cold sores: topcial aciclovir.
- HSV2 - Meningitis/Encephalitis. Flu-like prodrome, headache, focal neuro, fits, odd behaviour.
CSF: increased lympho, normal gluc, CSF PCR, MRI.
Genitals Herpes
- HSV-2. Flu like prodrome, Dysuria, inguinal LNs, painful ulcers, sacral radiculomyelitis –> urinary retention + sacral sensory loss (elsbry syndrome).
Manage with oral aciclovir.
Herpes Gladiatorum
Herpetic Whitlow - Painful red fingers.
Eczema Herpeticum - Herpes infection at the site of skin damage.
Herpetic Keratitis - Unilateral//bilateral conjunctivitis + pre-auricular LNs (may make a corneal ulcer - dendritic ulcer
Remember, syphilis, lymphogranuloma venereum (caused by chlaymdia) (doxycycline) and granuloma ingiunal (caused by Klebsiella granulomatis) all cause painless genital ulcers.
Behcets causes painful genital ulcers but herpes simplex is more likely.
How do you treat all Herpes infections?
Aciclovir (PO, IV, or topical)
Varicella Zoster types?
CP?
S?
Ramsay hunt?
- Spread by Droplet or contact
replication in LN, then liver and spleen.
Chickenpox = varicella zoster = Flu-like prodrome. Non contagious after lesion scab. Droplet spread. May lead to pneumonitis, haemorrhage, encephalitis. Treat with calamine lotion (sometimes aciclovir).
Shingles (herpes zoster). Zoster reactivation due to decreased immunity/stress. Painful vesicular rash in dermatomal distribution. Thoracic and ophthalmic most commonly. Multidermatomal in immunocompromised. May progress to post-herpetic neuralgia (severe dermatomal pain) . Manage with aciclovir PO/IV, Famciclovir and Valciclovir.
Ramsay Hunt = ear zoster, facial palsy, decreased taste and hearing.
EBV types of disease?
Glandular fever/Infectious mononucleosis.
Burkitt’s Lymphoma
Post transplant lymphoproliferative disease
Oral hairy leukoplakia (non-malignant)
Primary brain lymphoma
Nasopharyngeal Ca
What is Infectious mononucleosis?
Fever, malaise, sore throat, cervical LN+++. Splenomegaly, hepatitis (–> hepatomegaly, jaundice).
Present with malaise, palatal petechiae, splenomegaly, hepatitis, transient rise in ALT, lymphocytosis.
Maculopapular, pruritic rash develops in 99% of patients who take amipillin/amoxicillin.
Complications: splenic rupture, CN lesion, ataxia, GBS, pancytopenia.
Diagnosis: lymphocytosis, atypical lymphocytes.
+ve heterophiles Abs (Monospot).
Increased LTFs.
Management
- Rest during early stages, drink plenty of fluid, avoid alcohol.
- Simple analgesia
- Avoid contact sports for 8 weeks after glandular fever.
Burkitt’s Lymphoma
Jaw or abdo mass. Endemic in africa/malaria. Can occur in immunodeficiency.
Starry sky appearance. t98:14).
What is oral hairy leukoplakia?
Painless shaggy white plaque along lateral tongue border.
HIV 500-200 cd4 cells
What are the false +ve for heterophile abs
Hepatitis, parvovirus, leukaemia, lymphoma, SLE, pancreatic Ca.
What is CMV?
Mucocutaneous spread
Infected cells become swollen
B-epitheliotropic.
Primary infection - 80% asymptomatic. Flu-like illness
Reactivation: Immunocompromised.
HIV: retinitis > colitis > CNS disease
Renal transplant: pneumonitis > colitis > hepatitis > retinitis.
Pneumonitis = bilateral interstitial infiltrates.
Diagnosis: owl’s eye intranuclear inclusions, atypical lymphocytes.
manage with ganciclovir, foscarnet, cidofovir.
How to prevent BMT CMV reactivation?
- Do weekly PCR for first 100d
- If viraemia +ve –> ganciclovir IV
- Use CMV -ve irradiated blood products.
Solid organ transplant
- seroneg recipient + seropos donor
- Renal tx prophylaxis = valganciclovir
What are the 5 types of Hepatitis?
ABCDE
What is the spread of Hepatitis A
FAeco-oral. Caused by Seafood (abroad)
What is the spread of Hep B
IV - Blood, body fluids, babies.
What is the spread of Hep C
Mainly blood. Less vertical can HCV
What is the spread of Hep D
Dependent on prior HBV infection
What is the spread of Hep E?
FAEco-oral - developing world.
What is the presentation of Hep A?
Presentation - incubation 2-4 weeks. Not associated with chronic liver disease.
- Prodromal Phase (fever, malaise, arthralgia, nausea, anorexia.
- Distaste for cigarettes.
Icterical phase
- Jaundice, HSM, Lymphadenopathy, cholestatis.
What are the investigations for Hep A?
Increased ALT, increased AST (AST:ALT <2)
IgM + ~25 days after exposure = recent infection
IgG +ve for life
Management of Hep A?
Supportive
Avoid Alcohol
IFN-a for fulminant hepatitis (rare)
No risk of hepatocellular carcinoma!
Vaccination for Hep A?
- People travelling or going to reside in areas of high or intermediate prevalence -
- People with chronic liver disease
- MSM
- Injecting drug users.
Hep B presentation?
Incubation: 1-6 months
Presentation - Prodromal phase and icteric phase as for Hep A - Extra-hepatic features due to immune complexes. Urticaria or Vasculitic rash Cryoglobulinaemia PAN GN Arthritis
Investigations for Hep B?
HBsAg +ve = current infection (+ve >6 months = chronic disease). Normally implies acute disease or chronic.
Anti-HBs = cleared infection or vaccinated. NEGATIVE in immunity.
Anti-HBc IgM = recent infection
Anti-HBc IgG = past infection
Anti-HBc = caught - negative if immunised.
HBeAg +ve = high infectivity
HBV PCR: monitoring response to Rx.