17 - TB, HIV, STIs Flashcards
What is the pathophysiology of TB infection?
- Mycobacterium Tuberculosis
- Spread by aerosol droplets causing pulmonary infection
- Pulmonary infection can then spread haematogenously in the body
What is the difference between active and latent TB?
Latent: Asymptomatic due to containment of TB in granulmoa. Will have positive skin testing but they are not infectious and no x-ray findings.
Lifetime reactivation of 10-15%
Active: Can be due to primary infection or reactivation. Patient is symptomatic and contagious
What are the different types of active TB?
Classified by the site affected e.g:
- Pulmonary TB
- Lymph node TB
- TB meningitis
- Milliary TB
What are some causes of latent TB reactivation?
- HIV
- Immunosuppression
- Increasing age
- Organ transplant
- Drug use
- Malnutrition
- Immigrating to UK from endemic areas
Latent TB is asymptomatic so how is it diagnosed?
Screening with:
- CXR
- Interferon gamma testing (quantiFERON or T-spot)
- Tuberculin skin testing (Mantoux)
How do the following tests for TB work:
- Tuberculin Skin Testing
- QuantiFERON
- T-spot test
NO TEST CAN DISTINGUISH BETWEEN ACTIVE AND LATENT!
Mantoux: Intradermal injection of PPD tuberculin, size of skin induration determines positivity. If positive cannot distinguish between latent, active or BCG
QuantiFERON: Blood test where T-cells are mixed with TB antigen to see how much interferon gamma they release. Pre-exposed T-cells release more. Negative in BCG. Cannot tell difference between active and latent
T-Spot Test: Same as above but instead of whole blood, isolate lymphocytes. Good if patient has low amount of lymphocytes
What is the cause of a false negative QuantiFERON test?
Immunosuppression as not enough T cells to release interferon gamma!
What people are offered screening for latent TB?
Asymptomatic patients with high risk for TB:
- Immigrants from high prevalence countries
- Close contacts e.g family
- Healthcare workers
- HIV positive
- Starting immunosuppressive therapy
- Prisons and homeless
How is latent TB treated?
Balance between risk of developing active disease and side effects of treatment (hepatotoxicity)
If >35 high risk of hepatotoxicity so only treat if risk factors of reactivation e.g HIV, immunosuppressants
If risk of hepatotoxicy use 3 months of isoniazid (with pyroxidine) + rifampicin
OR 6 months of just isoniazid (with pyroxidine)
What are some of the signs and symptoms of active TB?
Symptoms:
- Non-resolving cough
- Low grade fever
- Night sweats
- Weight loss
- Haemoptysis
- Pleurisy
Signs:
- Clubbing
- Cachexia
- Lymphadenopathy
- Hepatosplenomegaly
- Erythema nodosum
- May be pericardial rub
What general investigations should you do if you suspect pulmonary TB?
Imaging: CXR, CT, MRI
Samples: 3 early morning sputum smear , sputum cultures as gold standard, NAAT
Biopsy: lymph nodes
What could you find on imaging of acitve TB?
CXR: mediastinal lymphadenopathy, cavitating pneumonia, pleural effusion
CT: lymphadenopathy
MRI: leptomeningeal enhancement in TB meningitis
How long do sputum cultures, sputum smears and NAAT tests for TB take?
Sputum Culture: takes 6 weeks so start ATT before samples back, GOLD STANDARD
Sputum Smear: 3 early morning sputum samples for AFB. If positive then isolate. Takes 1-2 days
NAAT: PCR takes 8 hours due to DNA/RNA amplification. Can also detect drug sensitivities
What would you see histologically on a biopsy of a TB infected lymph node?
Granulomas with caseating central necrosis
Once the results are back for the sputum smear for TB, in a suspected case of TB, what is the management?
Smear positive: indicates high bacterial load so high infectivity so needs ATT immediately
Smear negative: Bronchoscopy +/- EBUS (biopsy of pulmonary lymph nodes). Once these samples are taken and sent for AFB test then start ATT
What investigations should you do if you suspect extra-pulmonary TB?
NAAT: any sterile body fluid so lumbar puncture or pericardiocentesis if suspect meningeal/pericardial TB
AFB: take biopsies of lymph nodes, pleura, colon and send for AFB staining, histological exam and culture
Why is there a paradoxical reaction at the start of Anti-TB therapy?
As bacteria die there is an increase in inflammation causing worsening symptoms
If TB is in sites where additional swelling cannot be tolerated e.g meningeal, pericardial, then give steroids at the start of ATT
How does a patient with CNS TB/TB meningitis present and what should you do to diagnose this?
Presentation: INSIDIOUS ONSET, personality change, headache, meningitic, comotose over several weeks
Diagnosis:
- Lumbar puncture: high protein, low glucose, lymphocytosis
- MRI: leptomeningeal enhancement
- Everyone with milliary TB needs LP to exclude TB meningitis
Why is it important to know if a patient has TB meningitis before starting ATT?
Need to give steroids when starting treatment as paradoxical reaction can be fatal!
Also need 12 months of treatment not 6
How might pericardial TB present and what is the importance of this?
- Often pericardial effusion so pericardial rub and Kussmaul’s sign
- Can get pericarditis
- Need to give steroids at start of ATT as paradoxical reaction can lead to tamponade
How do you know a patient has milliary/disseminated TB and how do you treat it?
- CXR/CT shows foci of granulomas throughout the lung, heart, joints etc
- Need to have neuroimaging and LP to exclude CNS involvement
- Do not withold treatment whilst awaiting biopsies, start ATT as soon as you know no CNS involvement
What are some symptoms of the following extrapulmonary TB:
- Spinal
- Skin
- Genitourinary
- GI
Spinal: local pain and bony tenderness
Skin: lupus vulgaris, apple jelly nodules
Genitourinary: dysuria, frequency, haematuria, infertility, genital ulceration
GI: colicky abdominal pain and vomiting
How is active TB treated?
Treat all TB the same apart from CNS, Pericardial, MDR
2 months quadruple therapy:
- Rifampicin
- Isoniazid (+Pyroxidine)
- Pyrazinamide
- Ethambutol
4 more months: (10 more months if CNS)
- Rifamipicin
- Isoniazid (+Pyroxidine)
When should you suspect MDR TB and what should you do wit this?
- Previous incomplete TB treament
- Birth or resident in country with MDR TB
- Need to do NAAT if high risk of resistance to check for resistance
- Need good infection control in negative pressure room and masks/PPE
- Specialist advice treatment with at least 6 agents using
How does the treatment regime change for pericardial TB, CNS TB and MDR TB?
Pericardial: need steroids at start of treatment
CNS: need steroids at start of treatment and 12 months instead of 6
MDR: Use second line drugs and at least 6
What are the side effects of each of the ATT drugs?
Rifampicin: hepatitis + , urine/tears turn orange
Isoniazid: peripheral neuropathy, colour blind, hepatitis ++
Pyrazinamide: hepatitis +++
Ethambutol: optic neuropathy/reduced visual acuity
What monitoring needs to be done before and during ATT to combat the side effects?
Before: baseline LFTs and visual acuity
During: LFTs (if they derange can stop and gradually reintroduce or use liver-friendly regime but this takes 24 months), monthly visual acuity
What are the infection control measures on the ward with a new TB case?
- Nurse in negative pressure side room until 2 weeks of treatment, need to wear mask when leaving room
- If ward has immunocompromised patients (e.g HIV), need to be in side room for whole stay on ward
- Smear positive patients can go home but need to quarantine until 2 weeks of treatment
- Only need to wear FFP3 mask/aprons if MDR TB or aerosol generating procedures
How should you take a sexual history?
Symptoms: discharge, genital skin problems, pain, dysparaunia, unusual PV bleeding, anal symptoms
Exposure: sexual contacts in past 3 months including what sex is the partner and what type of sex (oral, anal, vaginal), contraceptive method, type and duration of relationship, ask men if ever had sex with man, STI history
Other: LMP, last smear, HPV vaccine history, consensual sex
How does syphillis present?
Treponema Pallidum
Primary: macule then papule then painless ulcer
Secondary: maculopapular rash, mucous patches, lymphadenopathy, hepatitis, headache, fatigue
Tertiary: neurosyphillis, cardiovascular, gumma
How is syphillis diagnosed and treated?
Dx: PCR and Serology
Mx: IM benzylpenicillin
What are the following for Chlamydia Trachomatis:
- Presentation
- Diagnosis
- Treament
- Complications
- Presentation: often asymptomatic, urethral discharge, dysuria, intermenstrual bleeding, dysparaunia
- Diagnosis: NAAT on first pass urine or vulvovaginal swabs
- Treament: Azithromycin or Doxycycline, Partner tracing, avoid sexual contact until treatment complete
- Complications: Reactive arthritis, epididymo-orchitis, PID, ectopic prefnancy, infertility
What are the following for Neisseria Gonorrhoeae:
- Presentation
- Diagnosis
- Treament
- Complications
Presentation: urethral/vaginal discharge, dysuria, asymptomatic
Diagnosis: NAAT on first void urine or vaginal swab, can also culture
Treatment: IM Ceftriaxone, contact tracing, avoid sex during treatment
Complications: prostatitis, epididymitis, reactive arthritis, PID
What are the following for non-gonococcal urethritis:
- Presentation
- Diagnosis
- Treament
- Complications
Caused by C.Trachomatis, Mycoplasma Genitalium, Trichomonas Vaginalis
How does HIV get into the body to cause infection?
Sexual transmission, sharing needles, blood tranfusions, vertical transmission etc
HIV binds to CD4 receptors on helper T cells to get in
How does early HIV present?
Usually 2-4 weeks after infection:
- Flu like symptoms
- Rash
- Myalgia
- Persistent generalised lymphadenopathy
What are some tests you can do for HIV?
ELISA blood test: Used to test blood at 4 weeks after exposure and takes a few days. Looks for p24 antigen and HIV antibodies. If positive need serological confirmatory test.
Rapid point of care testing: Uses finger prick or mouth swab and rapid results. Need confirmatory test. Can only use 3/12 post exposure
Once someone has had a positive test for HIV, what are some oher baseline investigations that should be done?
(NB - read image)
- Confirmatory HIV test
- CD4 count
- HIV viral load
- HIV resistance profile
- HLAB*5701 (for abacavir sensitivity)
- Serology for Hep A/B/C and Syphillis
- Toxoplasm IgG, Measles IgG, Varicella IgG, Rubelle IgG
- FBC, U+Es, LFTs, bone profile lipid profile
- Annual cervical cytology
What is the risk of HIV transmission from a needle-stick injury from a person not on ART and what measures should take place after this injury?
1 in 300!
- Bleed wound and put under running water
- Seek advice from occupational health
How do the following opportunistic infections in HIV present and how are they treated:
- Pneumocystis Jirovecii
- Candidiasis
- Cryptococcus Neoformans
- Toxoplasma Gondii
Opportunistic infections that occur when CD4<200
How do the following opportunistic infections in HIV present and how are they treated:
- CMV
- Cryptosporidum
- Kaposi’s Sarcoma
- Lymphoma
What are some infection/malignancies HIV patients are more suspectible to?
- Latent infections: CMV, EBV, HSV, Varicella Zoster
- Candida
- Pneumocystis Jirovecci
- Lymphoma
- Kaposi’s sarcoma
- TB
What are the 5 different drug classes involved in ART and what is their mechanism of action?
- CCR5 antagonsits: inhibt entry of HIV into cell by blocking CCR5 coreceptor
- NRTI/NNRTI: inhibit reverse transcriptase so viral RNA cannot be converted into DNA so cannot be integrated into nucleus
- ISTI: inhibit integrase so stops HIV DNA integrating into nucleus
- Protease inhibitors: stops protease and maturation of virus particles
- Pharmacokinetic enhancers: increase effectiveness of ARV drugs allowing lower doses to be used
What monitoring is done during ART?
- Viral Load
- CD4 counts: see if need prophylaxis for opportunistic infections
- Check adherance
- Chest for adverse effects: LFTs and Glucose
What are the side effects of each class of drug in ART?
- NRTI: GI disturbance, anorexia, pancreatitis, hepatic dysfunction, decreased bone mineral density, avoid abacavir in CVD, avoid tenofovir if eGFR<30
- PI: hyperglycaemia, insulin resistance, dyslipidaemia, jaundice, hepatitis
- NNRTI: CNS toxicity, suicidal thoughts, rash, GI disturbance
- Integrase Inhibitor: rash, GI disturbance, insomnia
Why is adherance important in ART and how can it be improved?
To prevent resistance and disease progression
- Explore reasons for non-adherance
- Simplify dosage regime with dossette box
- Link taking medication to regular daily activity
- Explain risks of not adhering
What prophylaxis is offered to patients with a low CD4 count and why?
CD4<200: Offer daily co-trimoxazole to prevent P.Jirovecii Pneuomonia
CD4<50:
Offer Azithromycin weekly to protect against MAI.
Also refer to opthamology for dilated fundoscopy to check for CMV retinitis
When is the diagnosis of AIDS given?
CD4<200
What drug is given for PEP?
Truvada (tenofovir/emtricitabine) for 28 days then do a test 8-12 weeks after exposure
Can be given up to 72h after exposure e.g needlestick, unprotected sex
