ID Flashcards
Definition of HIV Treatment failure
Viral load persistently >200 copies/ml after 24 weeks of Tx
Confirmed on 2nd test within 3-6 months
Adherence support between measurements
• Non-tuberculous mycobacterial (NTM) infection
-insidious, with a chronic cough usually productive of purulent sputum
MAC (Mycobacterium Avium Complex)
PJP prophylaxis in HIV
CD4 count <200
Bactrim daily
Toxo prophylaxis in HIV
CD4 count <200 and positive serology
Bactrim double strength daily
MAC prophylaxis in HIV
CD4 <50
Azithromycin 1g weekly or clarithromycin BD
Latent TB in HIV
TST >5 mm or positive IGRA
Isoniazid with pyridoxine for 9 months
HIV Transmission Risk factors for seroconversion in needlesticks
o Patient with untreated HIV and high viral load
o Deep injury (Odds ratio 15)
o Device visibly contaminated with patient’s blood (Odds ratio 6.2)
o Needle placement in a vein or artery (Odds Ratio 4.3)
o Terminal Illness in the source patient (Odds ratio 5.6)
Timing of PEP and duration
Within 1-2 hours of exposure up to 72 hours for most effect, but can be up to one week post exposure
Duration: 4 weeks
PEP Regimen
Tenofovir DF + Emtricitabine + Dolutegravir
Tenofovir DF + Emtricitabine + Raltegravir
Abacavir Hypersensitivity Gene - SJS
HLA B5701
Dolutegravir in pregnancy?
Safe in pregnancy as per WHO study in July 2019
Glycoproteins on HIV virus that aid its entry into CD4 T cells and macrophages
GP120, GP41, P24 antigen (viral capsid protein - can also be used to test for early detection)
Coreceptors on CD4 T cells HIV uses for cell entry
CCR5 and CXCR4
HIV Incubation period
2-4 weeks, up to 10 months
HIV Seroconversion Sx
Can be asymptomatic
Constitutional symptoms – Fever, fatigue, myalgia
Adenopathy – occasional hepatosplenomegaly
Sore throat
Mucocutaneous ulceration
Generalised rash
Headache – retro-orbital pain
Rarely - opportunistic infection - candidiasis
Protective mutation against HIV
CCR5 delta 32 mutation - no CCR5 expression on T cell
HIV Diagnosis testing
- 1st-3rd generation - HIV antibody only
- 4th generation – HIV antibody + HIV p24 antigen (can be detected 1-2 weeks after virus exposure)
- -4th generation >99% sensitivity and specificity for chronic infection
- -Only 80-90% for acute HIV
- -If suspecting acute HIV should also test HIV RNA as routine
NRTIs (Names)
nucleoside reverse transcriptase inhibitors (NRTIs)
Tenofovir -disoproxil fumarate(TDF) -alafenamide(TAF) Abacavir (ABC) Zidovudine (ZDV/AZT) Emtricitabine (FTC) Lamivudine (3TC)
NNRTIs (Names)
non-nucleoside reverse transcriptase inhibitor
Efavirenz (EFV)
Nevirapine (NVP)
Rilpivirine
Etravirine
PIs (Names)
Protease Inhibitors (PIs): “Navirs”
Atazanavir (ATV)
Darunavir
Lopinavir (LPV)
Ritonavir (RTV)
ISTIs (Names)
Integrase Strand Transfer Inhibitors (ISTIs): “Gravirs”
Raltegravir
Elvitegravir
Dolutegravir
*Bictegravir- licenced 2018
Entry Inhibitors
Maraviroc
Enfuvirtide
HIV Treatment Regimes
Usually 2 NRTIs and one other class.
Commonly:
- Raltegravir / tenofovir/emtricitabine
- Dolutegravir /tenofovir/emtricitabine
NRTI MOA
Mechanism: Inhibit viral replication through competitive binding to reverse transcriptase
NRTIs active against Hep B
Tenofovir, lamivudine and emtricitabine
NRTI SE
Side effects – historically MITOCHONDRIAL TOXICITY
Peripheral neuropathy, pancreatitis, lipoatrophy and hepatic steatosis
Now uncommon with current NRTIs
TAF interaction with rifampicin
reduces level of tenofovir
TDF Side effects
Renal failure: Characterised by raised creatinine, proteinuria, glycosuria, hypophosphatemia, and acute tubular necrosis – FANCONI syndrome – proximal renal tubular acidosis. Caution if eGFR <60
Bone loss - decreased bone mineral density - usually stabilizes with continued use
TAF – less toxicity than TDF
Abacavir SEs
Hypersensitivity reaction
May worsen CAD
Lamivudine SE
Pancreatitis
Emtricitabine SE
skin discolouration usually as hyperpigmentation on palms and/or soles
NNRTI MOA
Mechanism: different separate from target site of NRTIs. Bind to a hydrophobic pocket causes a stereochemical change in the protein, which reduces the ability of naturally occurring nucleosides to bind to the active site pocket
Efavirenz SE
Potent inducer of hepatic cytochrome P450
CNS toxicity, psychiatric – vivid dreams, confusion, dizziness
QTc prolongation
Elevated hepatic transaminases
PIs MOA
Competitively inhibit the cleavage of the Gag-Pol polyproteins in HIV-infected cells
Production of immature virions – non-infectious
What should be administered with a PI?
Should be administered with a pharmokinetic booster: Ritonavir or cobicistat
Increases trough plasma drug concentrations, and maximum plasma concentrations
Enables lower and less frequent dosing of the parent drug=decreasing pill burden
PI SEs
Nausea, diarrhoea!
Insulin resistance, hyperglycemia, diabetes, hyperlipidemia, lipodystrophy, hepatotoxicity
Interactions: Rifampicin!
ISTIs MOA
Integrase enzyme catalyzes the process by which viral DNA is integrated into the genome of the host cell
Target the strand transfer step of viral DNA integration
Prevent or inhibit the binding of the pre-integration complex (PIC) to host cell DNA
M184V mutation
HIV mutation often the first to appear.
REsistance to lamivudine and emtricitabine, BUT hypersusceptibility to TDF/TAF
IRIS definition
Collection of inflammatory disorders associated with paradoxical worsening of pre-existing infectious processes following the initiation of antiretroviral therapy (ART) in HIV-infected individuals
Crusted Scabies occurs in which populations
AIDS, human T cell lymphotropic virus type 1 (HTLV-1) infection, leprosy, and lymphoma
Treatment of Scabies
Topical permethrin and oral ivermectin
MOA Permethrin
Topical synthetic pyrethroid agent that impairs function of voltage-gated sodium channels in insects, leading to disruption of neurotransmission
Cause of Neurocystiercosis
Taenia solium -Pig tapeworm
How does IGRA work
IGRAs are in vitro assays that measure T-cell release of interferon-γ in response to stimulation with highly tuberculosis-specific antigens ESAT-6 and CFP-10 (QuantiFERON-TB Gold In-Tube and T-SPOT TB test).
Factors that increase the risk of developing active TB
HIV Immunosuppression Genetic factors Smoking Vit D deficiency Diabetes/renal impairment Low BMI
Which immune cells are involved in forming a TB granuloma
T cells and macrophages
Limitations of Tuberculin skin testing
- Responses nor read
- Inaccuracy of measuring induration
- False positives due to sensitisation with related bacteria (BCG vaccine)
IGRA Specificity and Sensitivity
- QFT: High Specificity: 96-100%
- QFT: Sensitivity: 80-85%
IGRA limitations
o Does not differentiate between latent and active TB
o May remain positive after successful treatment
o Negative IGRA does not exclude active TB
TB in CSF findings
– Lymphocytic pleocytosis, low glucose (DDX Cryptococcal meningitis)
o Recommendations for commencing ART in patients with TB
Risk of IRIS
If CD4 < 50 – Early ART (<2 weeks)
If CD4 > 50 then ART by 8 weeks after starting TB therapy
Treatment for TB meningitis
HRZM (moxifloxacin better than Ethambutol) 9-12 months
Dex reduces mortality
Standard TB treatment
2HRZE/4HR = 98% Cure
(H) Isoniazid – Most helpful with initial fast multiplying TB
(R)Rifampicin – Usually daily therapy, but can be 3-5 x/wk; most effective on resistors (TB bugs that are hard to kill)
(Z) Pyrazinamide – Slow multiplying TB – works in acidic environments
• If not used then therapy is for 9 months instead of 6 months
(E)Ethambutol
Isoniazid SEs
Hepatitis, rash, neuropathy
Rifampicin SEs
Drug interactions, hepatitis
Pyrazinamide SEs
Hepatitis, skin, joint (gout)
Ethambutol SEs
Optic Neuropathy
Order of TB drugs that cause the most hepatitis
o Pyrazinamide >Isoniazid»_space;Rifampicin
Mx of TB drugs in setting of derranged LFTs
o If 2-5x normal + asymptomatic = monitor closely
o If >5x normal or >3 x and symptoms = cease
Most common mono-drug resistance in TB?
Isoniazid
MDR TB definition
Resistance to INH + RIF +/- any other resistance
XDR TB definition
MDR TB + resistance to quinolones and injectables (1 of amikacin, kanamycin, or capreomycin)
- fever
- cough/coryzal Sx
- Conjunctivitis
- Koplik’s spots (bluish green elevations in buccal mucosa)
- erythematous, maculopapular, blanching rash, which classically begins on the face and spreads cephalocaudally and centrifugally to involve the neck, upper trunk, lower trunk, and extremities
Measles
Incubation period for Typhoid
1-2 weeks
Clinical features of typhoid
- rising (“stepwise”) fever and bacteremia
- “rose spots” (faint salmon-colored macules on the trunk and abdomen)
- fever with headache, arthralgia, myalgia, pharyngitis, and anorexia
- hepatosplenomegaly, intestinal bleeding, and perforation due to ileocecal lymphatic hyperplasia of the Peyer’s patches
Incubation period of Dengue
3-14 days; Sx typically 4-7 days after transmission
Diagnosis of Dengue with warning signs
Diagnosis made as defined in previous column + any one of the following:
- Abdominal pain/tenderness
- Persistent vomiting
- Clinical fluid accumulation (ascites/pleural effusion)
- Mucosal bleeding
- Lethargy/restlessness
- Hepatomegaly >2 cm
- Increase in haematocrit concurrent with rapid decrease in platelet count
Diagnosis of Dengue without warning signs
Diagnosis made in the setting of travel to endemic area + fever + 2 of the following:
- N+V
- Rash
- Headache, eye pain, muscle ache, or joint pain
- Leukopenia
- Positive tourniquet test (Tourniquet inflated midway between sys and dys BPs for 5 mins and skin below is examined 1-2 mins post deflation – if 10 or more new petechiae in one sq inch, it is positive
Diagnosis of severe Dengue
Diagnosis made as defined in previous column + at least one of the following:
- Severe plasma leakage leading to shock or fluid accumulation with resp distress
- Severe bleeding
- Severe organ involvement (AST or ALT >1000 units/L; Impaired consciousness; organ failure
What time period of symptoms should you monitor for warning signs
Day 3-7
What is the critical phase of dengue
o Present in Dengue Hemorrhagic fever and Dengue Shock Syndrome, but not Dengue Fever
o Involves systemic plasma leakage, bleeding, shock, and organ impairment
o Lasts for 24-48 hours
o Initially have adequate circulation, but then compensation occurs with pulse pressure narrowing
o Moderate to severe thrombocytopenia may occur with a nadir of platelets <20, which improves rapidly in the recovery phase
What is a clinical feature of entering the convalescent phase Dengue
“WHITE ISLANDS IN THE SEA OF RED”
Diagnosis of Dengue
Reverse transcriptase PCR (positive in first 5 days of illness)
NS1 (Viral antigen nonstructural protein 1) - positive in first 5 days
Dengue Serology - IgM dectected as early as 4 days after onset
- Primary: IgG up in 7 days
- Secondary: IgG in 4 days
Fever in Returned Traveller Incubation <10 Days
Dengue Influenza Yellow fever Chikungunya Plague Paratyphoid fevers Legionella
Fever in Returned Traveller Incubation up to 21 days
Malaria Viral haemorrhagic fever Q fever African trypanosomiasis Typhoid fever Brucellosis Leptospirosis Relapsing Fever
Fever in Returned Traveller Incubation > 21 days
Malaria Viral hepatitis HIV Rabies Visceral leishmaniasis Amoebic liver abscess Filariasis TB Q Fever Acute schistosomiasis
Mx of Nec Fasc
Carbapenem + agents against MRSA + Clindamycin
Role of Clindamycin in Nec Fasc
antitoxin and other effects against toxin-elaborating strains of streptococci and staphylococci
Septic arthritis, tenosynovitis, vesicular pustules, negative synovial fluid culture and stain
Disseminated gonnococcal infection
Ix of Orbital cellulitis
Blood cultures
CT of sinuses
Mx of orbital cellulitis
3-14 days IVABx
-Cefotaxime OR Ceftriaxone +Fluclox
Followed by 10 day PO tail of Aug DF
Surgical Drainage if abscess found
Features of C. Diff suggesting need for early surgical referral
o Hypotension
o Fever ≥ 38.5
o Ileus or significant abdominal distension
o Peritonitis or significant abdominal tenderness
o Altered mental status
o WBC > 20 cells/mL
o Lactate > 2.2 mmol/L
o ICU admission
o End organ failure
o Failure to improve after 3-5 days of maximal medical therapy
Mx of C. Diff
Mild to Mod: PO Metro TDS for 10 days
Severe: PO Vanc QID for 10 days/Fidaxomicin
Complicated: PO Vanc and IV Metro
When to retest stool for C. Diff
IF needed to test, must be >6 weeks post treatment
Recurrent C Diff Mx
FMT if recurred 3x despite adequate treatment
Causes of infective bloody Diarrhea
SEECSY = Bloody Diarrhea Doesn't Sound Sexy S=Salmonella E=E Coli EHEC, ETEC E = Entamoeba C = Campylobacter S=Shigella Y=Yersinia
Which malria screening test allows for accurate speciation?
Thick blood films check for parasite burden, thin films allow for speciation
CAuse of painful genital ulcers vs painless
painful: herpes much more common than chancroid
painless: syphilis more common than lymphogranuloma venereum
Aciclovir and Ganciclovir MOA
inhibits the viral DNA polymerase
Amantadine MOA and Indication
Inhibits uncoating (M2 protein) of virus in cell. Also releases dopamine from nerve endings
Influenza, Parkinson’s
HIV Patient
CT: usually single or multiple ring enhancing lesions, mass effect may be seen
Thallium SPECT negative
Toxoplasmosis
Tx of Toxoplasmosis
sulfadiazine and pyrimethamine
HIV Patient
CT: single or multiple homogenous enhancing lesions
Thallium Spect Postive
CNS lymphoma
typically prodrome: fever, malaise
causes pyrexia of unknown origin, atypical pneumonia, endocarditis (culture-negative)
Q Fever
Coxiella burnetii, a rickettsia
Q fever
Bartonella henselae
Cat Scratch Disease
S. pneumoniae
Gram stain
gram positive diplococci/chain
E. coli
Gram Stain
gram negative bacilli
H. influenzae
Gram Stain
gram negative coccobacilli
L. monocytogenes
Gram stain
gram positive rod
Neisseria meningitis
Gram stain
gram negative diplococci
Fluctuating temperatures, transient arthralgia and myalgia, hyperhidrosis with a ‘wet hay’ smell. The clue in the history is his exposure to unpasteurised cheese.
Brucellosis
Cutaneous leishmaniasis
- spread by sand flies
- caused by Leishmania tropica or Leishmania mexicana
Mucocutaneous leishmaniasis
caused by Leishmania braziliensis
skin lesions may spread to involve mucosae of nose, pharynx etc
Visceral leishmaniasis (kala-azar)
mostly caused by Leishmania donovani
occurs in the Mediterranean, Asia, South America, Africa
fever, sweats, rigors
massive splenomegaly. hepatomegaly
poor appetite*, weight loss
grey skin - ‘kala-azar’ means black sickness
pancytopaenia secondary to hypersplenism
the gold standard for diagnosis is bone marrow or splenic aspirate
Jarisch-Herxheimer reaction
the Jarisch-Herxheimer reaction is sometimes seen following treatment of syphillus
- fever, rash, tachycardia after the first dose of antibiotic
- in contrast to anaphylaxis, there is no wheeze or hypotension
- it is thought to be due to the release of endotoxins following bacterial death and
- typically occurs within a few hours of treatment
- No treatment is needed other than antipyretics if required
BCG vaccine
live