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Chronic Infection Flashcards

1
Q

What is the prevalence of HIV?

A
  • 120,000 people in the Uk are thought to currently be living with HIV, however approximately 1/5 to 1/3 are throught to be unaware
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2
Q

What kind of virus is HIV?

A
  • HIV is a lentivirus which is a memeber of the retrovirusgroup
  • these are disease causing virusesthat typically cause long periods of disease or long periods of latency
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3
Q

What cells does HIV attack?

A
  • HIV virions have a viral protein cap consisting of GP120 and three GP41 anchoring stems
  • GP120 is the cell surface protein that causes attachment to the target cell
  • GP120 binds to CD4 ligands on CD4+ cells
    • i.e. HIV is able to infect CD4+ T-lymphocytes (helper T cells) macrophages and microglial cells
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4
Q

Explain briefly how HIV is able to infect cells:

A
  • An HIV virion binds to a CD4 ligand on a target cell. The viral envelope will then fuse with the target cell membrane and release the viral cell contents into the cell, this starting the infection cell cycle.
  • The single side viral RNA is reverse transcribed into complementary sense, antisense DNA molecules by the viral reverse transcriptase enzyme
    • Reverse transcription is an extremely error prone process and gives rise very rapidly to drug resistance due to its rapid mutation rate and rapid accumulation of point mutations.
  • Complementary DNA molecules then combine to form double stranded pro-viral DNA which is then integrated into the host chromosome by the viral integrase enzyme. Integrated viral DNA may lie dormant, which explains the long and variable latent period of HIV infection.
  • Transcription factors needed to produce viral copies are expressed by metabolically active cells, such as those currently fighting infection, or involved in other aspects of immune surveillance. From this combination of features you can start to see how HIV will slowly reduce the number of CD4 cells over time as well as reducing the functional capacity of existing but virally infected cells as these processes are directly toxic to the host cell and reduce their life expectancy.
  • During viral replication, pro-viral DNA is transcribed by the host cell back into RNA which is transported from the nucleus back to the cytoplasm where it is [….] into the various components required.
  • Before being released form the host cell, immature viral polyproteins are cleaved into functional components by the viral enzyme protease.
    • The three enzymes that we have just mention, reverse transcriptase, integrase and protease are very important in understanding the treatment for HIV as these are the enzymatic targets of current first-line combination antiretroviral therapy.
  • In the final step, mature virions are released to spread through the body either by cell free spread after release into the blood stream and tissues, or by direct cell to cell spread. The viral envelope is composed from lipid components derived from the host cell
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5
Q

Explain what happens during the serovconversion illness:

A
  • At time 0, our hypothetical person becomes infected.
  • At this time the viral load is zero, and a healthy CD4 count is between 500-1500 cells per mm3.
  • As with many acute viral infections there will be a transient dip in CD4 cells as the infection becomes established.
  • The rate of viral replication is rapid, and in established infection 100 million or more virions are being produced each day and the infected person rapidly becomes highly viraemic.
  • The symptoms of this stage range from mild and non-specific flu-like symptoms (myalgia, sweats and fever) to more outward signs (generalised lymphadenopathy which may be sustained and persistent, widespread macular rash, pharyngitis and occasionally CNS involvement with features such as Bell’s palsy or even seizures.
  • During these first few weeks, antibodies to the P24 viral capsid proteins start to be made, and this illness is often referred to as the seroconversion illness for this reason: the patient’s serum is converting from being antibody negative to being antibody positive.
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6
Q

What happens after the initial seroconversion illness?

A
  • for reasons unknown the viral load becomes suppressed following the seroconversion
  • the HIV will then remain latent for a variable period of time (median of 5 years) and then start to demonstrate obvious outward signs of immunocompromise
  • as the CD4 count continues to fall, a variety of clinical signs are seen with increasing frequency as the immune system starts to become dysregulated and ultimately to fail
  • CD4 counts:
    • 350-500 - bacterial pneumonias, oropharyngeal candidiasis, psoriasis and diarrhoeal illness including parasitic infections such as crytosporidium and microsporidiosis
    • <200 - opporunistic conditions such as PCP, Kaposi’s sarcoma and progressive multifocal leukoencephalopathy
    • <100 - more serious and invasive problems start to be seen, such as cerebral toxoplasmosis, retinitis or colitis due to reactivated CMV infection or invasive infection iwht non-tuberculosis mycobacteria such as mycobacterium avium complex (MAC)
    • below this there are increasing presentations with lymphoid malignancy such as primary CNS lymphoma
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7
Q

Presentations of HIV: seroconversion

A

The seroconversion illness often goes unnoticed by the patient and may be relatively asymptomatic, however patients can become unwell with it and need to be hospitalised. Usually, the illness goes along with a very characteristic HIV seroconversion rash, which looks very similar to the rash of EBV or CMV, or possibly measles. It is a viral exanthem rash which is diffuse and macular. There are few very specific diagnostic features but should always raise question of recent HIV infection and do we know their HIV status? If status is unknown, they should be offered an HIV test.

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8
Q

Presentations of HIV: persistent generalised lymphadenopathy

A

As part of the seroconversion illness, generalised lymphadenopathy is seen, and in some people this lymphadenopathy becomes persistent.

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9
Q

HIV presentations: oro-pharyngeal candida

A

This is also a common feature of early stages of immunosuppression due to HIV infection. Recurrent or refractory oropharyngeal candida should prompt the question do we know this patient’s HIV status? In more severe immunosuppression this candidiasis can become more invasive, and symptoms of dysphagia or odynophagia can sometimes potin to oesophageal candidiasis. If oesophageal candidiasis is found incidentally for example on endoscopy, then the question should again be asked: do we know this patient’s HIV status?

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10
Q

HIV presentations - psoriasis

A

Psoriasis is a relatively common skin condition, but it is not uncommonly triggered by HIV infection or immunosuppression. Also, if you ask more about their history, you will see they regularly would present to health services with a variety of problems, including troublesome skin conditions, in the year or two prior to diagnosis.

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11
Q

HIV presentations: varicella zoster (shingles)

A

Shingles is a common presentation in all age groups, but can also be seen in association with stress, exhaustion or acute illness, but recurrent or multi-dermatomal shingles should always raise the question of HIV. Notice how the rash does not cross the midline. This is the hallmark of shingles.

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12
Q

HIV presentations: Kaposi’s sarcoma

A

Kaposi’s sarcoma is an AIDS defining illness but sometimes is not as severe as in the picture shown in the introduction picture. Careful examination of the patient from top to toe, including mucosal surfaces in the oropharynx and elsewhere may reveal small lesions such as those seen in this patient. These are highly vascular, violaceous lesions often of rubbery appearance. If they are biopsied or accidentally lacerated can bleed heavily. Kaposi’s sarcoma generally retreats or resolves once the patient starts antiretroviral therapy but can affect the viscera in which case occasionally chemo or radiotherapy is necessary.

(HHV-8)

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13
Q

HIV presentations: oral hairy leukoplakia

A
  • phenomenon caused by EBV
    • the causative agent of infectious mononucleosis (glandular fever) and also associated with Burkitt’s lymphoma
  • not pathognomonic of HIV but is associated with immunosuppression in general
  • clinically is painless and cannot be scraped away from the tongue
  • this will regress as the immune system recovers with antiretroviral therapy
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14
Q

Define the four stages of HIV (according to WHO):

A
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15
Q

Describe the list of conditions that should prompt HIV testing:

A
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16
Q

Once a patient’s viral load is suppressed, will their CD4 count always recover?

A

The CD4 count will then recover to some extent, some to fully, sometimes less so. An early and prompt diagnosis and sustained access and adherence to effective treatment the patient can expect to have a normal life expectancy.

Patients with persistently low CD4 counts may need to stay on long term prophylaxis for opportunistic infections, such as PCP.

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17
Q

When should patients with HIV be offered treatment?

A
  • immediately, as the START study shows reduction in AIDS defining event and death by half when therapy was started immediately, as opposed to waiting until CD4 count drops to below 350
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18
Q

What is current first-line treatment for HIV?

A
  • generally two NRTI (nucleoside reverse transcription inhibitors) along with another agent from a different class
    • first-line NRTIs - tenofovir & emtricitabine
    • plus one of the following
      • dolutegravir
      • atazanavir boosted with ritonavir
      • elvitegravir boosted with cobicistat
      • darunavir boosted with ritonavir
      • raltegravir
      • rilpivirine

Other classes include:

  • protease inhibitors
  • non-nucleoside reverse transcription inhibitors
  • integrase inhibitors
  • fusion inhibitors
  • chemokine receptor antagonist
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19
Q

AIDS defining illness - crytococcal meningitis

Presentation

A
  • Symptoms of immunosuppression may be evident:
    • For example, history of recurrent shingles
    • Cachexia
    • Generalised lymphadenopathy
  • Severe headache
  • Possible fever, but can be afebrile
  • Neck stiffness and focal signs
  • Or may have a subacute course of malaise and headache without stiff neck over several weeks
  • May have classical signs of meningitis (photophobia, nausea, vomiting)
    • Symptoms of raised ICP – papilloedema, headache worse when lying down
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20
Q

AIDS defining illness - crytococcal meningitis

Investigations

A
  • Routine investigations, with WC differential (due to features of immunosuppression that will be present in an AIDS defining illness)
  • Protein counts – check MLE
  • CT head
    • To exclude space-occupying lesion – if symptoms of raised ICP this would be a differential
  • HIV test
    • If positive, then check viral load and CD4 count to quantify degree of immunocompromise
  • Lumbar puncture
    • Opening pressure may be raised, suggestive of marked inflammation of the CNS
    • Protein may be mildly elevated
      • Makes viral unlikely
      • Not massively elevated, which is often seen in TB and bacterial meningitis
    • CSF – may be slightly low, but not markedly as would be seen in bacterial meningitis
    • Raised WCC – mainly lymphocytes
      • Not specific to cryptococcal meningitis as viral, fungal, treponemal and mycobacterial infections and autoimmune or paraneoplastic syndromes are all causes of raised lymphocytes
  • Stains to confirm diagnosis
    • India Ink stain - shows presence of encapsulated yeast, which are typical of crytococcus
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21
Q

AIDS defining illness - crytococcal meningitis

Treatment

A
  • Liposomal amphotericin B and flucytosine (2/52) then oral fluconazole
  • Co-trimoxazole prophylaxis for PCP (480mg until CD4 sustained above 200)
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22
Q

What is immune reconsitution inflammatory syndrome?

A

This occurs as a failing immune system recovers and starts to mount more exaggerating inflammatory responses. These can be disordered and unpredictable at first.

There are two broad categories of IRIS: paradoxical and unmasking.

  • In paradoxical reactions, the inflammatory response to a known opportunistic infection may become more pronounced.
  • In unmasking reactions, there may be no overt evidence of opportunistic infection due to the body’s inability to mount a coordinated inflammatory response due to profound immunosuppression. As the immune system recovers new signs and symptoms may emerge that lead to the diagnosis of opportunistic infections that were there all along.

IRIS can generally be managed effectively with anti-inflammatory drugs such as NSAIDs, or with steroids, but can occasionally be dangerous.

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23
Q

Risk factors cryptococcus infections:

A

Risk Factors: T-cell deplete individuals (e.g. HIV, haematological disorders, iatrogenic immunosuppression), steroids, Hodgkin’s lymphoma

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24
Q

AIDS defining illness - Pneumocystis pneumonia

Presentation

A
  • History suggestive of chest infection
    • dry cough
    • fevers
    • malaise
    • weight loss
    • exertional dyspnoea/de-saturation
    • hypoxia beyond chest examination findings
  • Clinical features pointing to immunocompromise
  • Relatively good oxygenation at rest but marked SOBOE raises possibility of PCP
    • Walking around the department while wearing pulse oximetry – if quickly desaturates this is suggestive of PCP
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25
Q

AIDS defining illness - Pneumocystis pneumonia

Investigations

A
  • HIV, CXR, ECG, ABG, Ddimers,
    • ABG may show type I respiratory failure
    • CXR findings for PCP: bilateral perihilar interstitial infiltrates, no dense consolidation (batwing distribution)
  • To confirm diagnosis – deep sputum sample (either induced sputum or bronchoscopic alveolar lavage)
    • Sent for PCR or staining + fluoroscopic examination
  • Also blood culture to rule out any other infections
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26
Q

AIDS defining illness - Pneumocystis pneumonia

Treatment

A
  • High dose co-trimoxazole and steroids
  • if HIV positive - HAART in 2/52 and secondary prophylaxis
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27
Q

AIDS defining illness - cerebral toxoplasmosis

Presentation

A
  • In immunocompetent patients, toxoplasmosis may present as a ‘glandular fever-like’ illness, with myalgia and lymphadenopathy, or may not be noticed at all
  • It can then lay dormant and reactivate if the patient becomes immunosuppressed
    • focal neurology
      • signs consistent with UMN
    • potentially headache
    • weight loss, cachexia
    • can affect the eyes and cause chorioretinitis (particularly in immunocompromised)
  • If acquired in pregnancy, toxoplasma can cause congenital infection leading to miscarriages, still birth or severe disability in the child
  • In immunocompromised patients, toxoplasma can reactivate and most commonly causes CNS infection with space occupying lesions
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28
Q

AIDS defining illness - cerebral toxoplasmosis

What causes cerebral toxoplasmosis?

A

Toxoplasmosis is caused by Toxoplasma gondii – protozoan parasite. Cats are definitive host. Humans can acquire infection by:

  • Eating undercooked meat of animals harbouring tissue cysts
  • Consuming food or water contaminated with cat faeces or by contaminated environmental samples (such as faecally contaminated soil or changing the litter box of a pet cat)
  • Blood transfusion or organ transplant
  • Transplacentally from mother to foetus
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29
Q

AIDS defining illness - cerebral toxoplasmosis

Diagnosis

A
  • Contrast CT
    • Show ring enhancing lesions with surrounding oedema
      • Ring enhancement means there is oedema around the lesion, suggesting reactive inflammation
      • This points to metabolically active lesions such as abscesses, tumours or parasites
  • If CT is normal or inconclusive, MRI should then be offered (due to focal neurology)
  • Other differentials to consider would be tuberculoma however there would be other evidence of TB e.g. on CXR) or CNS lymphoma – both are common in advance HIV
  • For definitive diagnosis, a brain biopsy is required – this is high risk procedure
    • Trial of treatment for toxoplasmosis and repeat imaging in 2 weeks
    • If lesions decrease in size you can continue toxoplasmosis treatment
    • If they increase or fail to decrease they may require a brain biopsy to look for lymphoma
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30
Q

AIDS defining illness - cerebral toxoplasmosis

Other investigations to order

A
  • HIV test
    • CD4 count and viral load
  • Toxoplasma IgG
  • CXR and IGRA – TB
  • CT chest/abdo/pelvis – to look for evidence of TB or malignancy
    • May show mild lymphadenopathy
  • LP is often contraindicated in the clinical setting of cerebral toxoplasmosis with multiple intracranial lesions with perilesional oedema
    • If it is possible you could check toxoplasma PCR on CSF
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31
Q

AIDS defining illness - cerebral toxoplasmosis

Treatment

A
  • 2 weeks sulfadiazine and pyrimethamine
  • If immunocompromised – 6 weeks of treatment followed by secondary prophylaxis with lower doses of the same drugs until CD4 count improves
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32
Q

AIDS defining illness - Kaposi’s sarcoma

Presentation

A
  • Cancer of the skin
  • Associated with human herpes virus 8 (HHV8)
  • Previously a very rare cancer seen in older men of Mediterranean or eastern European descent.
  • Increased exponentially with the AIDs pandemic
  • Typically purple-brown raised lesions on lower limbs or head and neck but may occur anywhere
  • Visceral lesions can involve bronchial walls, causing haemoptysis/dyspnoea,
  • GI tract causing haematemesis, dysphagia, bowel obstruction and melaena
  • If there are skin lesions only, these may regress as HIV is controlled with antiretroviral medication
  • Chemotherapy is needed in visceral or more extensive skin disease.
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33
Q

AIDS defining illness - Kaposi’s sarcoma

Diagnosis

A
  • Biopsy – to confirm KS
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34
Q

AIDS defining illness - kaposi’s sarcoma

A
  • In the context of HIV
    • Usually self-resolves as CD4 count recovers
    • If not, need to consider surgery/chemo/radiotherapy
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35
Q

AIDS defining illness - crytosporidiosis

Presentation

A
  • Cryptosporidiosis can occur in the immunocompetent but is usually self-limiting
  • Persistent cryptosporidium infection is an AIDs defining illness
  • Cryptosporidium is a protozoan parasite
  • Infection is caused by drinking water contaminated by oocysts
  • Oocysts are not killed by chlorine so outbreaks may occur in swimming pools
  • In severe HIV can present as persistent diarrhoea and weight loss
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36
Q

AIDS defining illness - cryptosporidiosis

Treatment

A

First-line treatment -

  • Antiretroviral therapy
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37
Q

Decribe the natural history of syphilis:

A
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38
Q

What is primary syphilis?

A
  • Chancre(s) (sore) at the site of infection
  • Usually firm, round and painless
  • May go unnoticed esp. if not visible (e.g. in mouth, anus or vagina)
  • Without treatment the chancre disappears by 2-8 weeks
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39
Q

What is secondary syphilis?

A

Rash

  • Generalised, including palms and soles
  • Classically maculopapular and non-itchy
  • Condylmata lata – moist, warty lesions in genital area

Systemic illness

  • Fevers, fatigue
  • Lymphadenopathy, splenomegaly
  • Hepatitis
  • Alopecia
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40
Q

What is latent syphilis?

A

Asymptomatic infection following untreated or unrecognised primary and secondary syphilis.

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41
Q

What is early latent syphilis?

A
  • Within two years of infection
  • Risk of sexual and vertical transmission
  • 25% have recurrence of secondary syphilis
  • Can be treated with a single dose of penicillin
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42
Q

What is late latent syphilis?

A

Late latent

  • Diagnosed after more than two years of infection
  • Risk of vertical transmission
  • Requires longer treatment course
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43
Q

What is tertiary syphilis?

A
  • Gummatous
    • granulomatous lesion(s) with central necrosis
  • Cardiovascular
    • aortitis –> aneurysm, aortic regurgitation
  • 3o neurosyphilis
    • general paresis - progressive dementia
    • tabes dorsalis = a slow degeneration of the nerve cells and nerve fibers that carry sensory information to the brain
        • neuropathy, ataxia, pupillary changes
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44
Q

Described findings of ocular syphilis:

A

Uveitis

  • painful, red eyes
  • visual disturbances - floaters, flashing lights
  • may cause blindness
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45
Q

Describe findings of neurosyphilis:

A
  • asymptomatic
    • abnormal CSF findings
  • meningitis
  • altered behaviour
  • stroke - secondary to vasculitis
  • tertiary neurosyphilis
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46
Q

Describe findings in congenital syphilis and how to prevent congenital syphilis:

A
  • Adverse pregnancy outcomes
    • Miscarriage, stillbirth, prematurity
  • Early congenital syphilis
    • Hepatosplenomegaly, lymphadenopathy, desquamating rash
    • Severe anaemia, jaundice
  • Late congenital syphilis
    • Hutchinson’s triad – pegged teeth, keratitis, deafness
    • Others – saddle nose, bone and joint deformities developmental delay

Routine antenatal screening

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47
Q

How is syphilis diagnosed?

A

Direct detection (from swabs from a primary lesion)

  • Primary syphilis
  • Dark field microscopy
  • PCR

Treponemal tests

  • E.g. EIA, TPPA, IgM
  • Determine exposure to syphilis
  • Remain positive life-long

Non-treponemal tests

  • E.g. RPR, VDRL
  • Determine disease activity
  • Measure response to treatment

While direct tests (e.g., microscopy or PCR) are helpful in early syphilis, the mainstay of diagnosis remains serologic tests. The traditional algorithm using a nontreponemal test (NTT) followed by a treponemal test (TT) remains the standard in many parts of the world

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48
Q

How do you treat syphilis?

A
  • Penicillin by injection is first-line treatment for all stages (other antibiotics are less reliable)
  • Duration of treatment – depends on the syphilis stage
    • Early syphilis (primary, secondary, early latent) – single dose
    • Late syphilis (late latent, unknown, tertiary) – 3x weekly doses
    • Ocular and neurosyphilis – daily for 10-14 days
  • Monitoring efficacy
    • 4 fold decrease in non-treponemal test titre
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49
Q

What is the Jarisch-Herxheimer reaction?

A
  • triggered by penicillin treatment in patients infected by spirochetes (i.e. can happen in syphilis and lyme disease)
  • acute onset fever, muscle aches, flushing, rash and palpitations
  • managed conservatively; steroids used for prevention in neurosyphilis
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50
Q

What is the causative organism of syphilis?

A
  • Spirochaete
  • Treponema pallidum
  • Fragile
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51
Q

What is the epidemiology of syphilis?

A
  • disproportionately affects MSM
  • incidence in men increasing greatly
  • indicator disease for other STIs
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52
Q

How is syphilis transmitted?

A

Sexual

  • Only in early syphilis
  • 30-50% contacts infected
  • Vaginal, oral and anal sex

Blood-borne

  • Needle sharing
  • Blood transfusion – very rare

Accidental inoculation

  • E.g. healthcare workers

Transplacental

  • More common in early syphilis (higher bacterial load)
  • Cases occur despite maternal screening
53
Q

What does the contact tracing process for syphilis involve?

A
  • voluntary
  • primary syphilis: partners in the past 3/12
  • secondary/early latent syphilis: partners in the past 2 years OR 3/12 before last neg test
  • late: not infectious
54
Q

What are the management options for syphilis contacts?

A
  1. Testing and empirical treatment
  2. Testing now and at end of window period (12 weeks)
55
Q

What does MDR TB mean?

A
  • multi-drug resistant TB
    • resistant to isoniazid and rifampicin
56
Q

What organism causes tuberculosis?

A
  • The clinical syndrome of ‘tuberculosis’ in humans is caused by members of the Mycobacterium tuberculosis complex family
    • Genetically similar organisms
      • M. tuberculosis - commonest
      • M. bovis – ~30 cases in UK/year
      • M. africanum – 40% of pulm TB in central/west Africa
      • (M. carnettii) – rare, opportunistic
      • (M. microti) – rare, Horn of Africa
      • (M. caprae) – rare, Spanish domestic animals
57
Q

How is TB spread?

A
  • airborne droplet nuclei
    • coughing, singing, communal smoking
  • can remain suspended in air for hours
  • overcrowded living/prison
  • rarely, oropharyngeal/intestinal deposition (when you ingest the pathogens)
58
Q

What signs and symptoms can be seen in TB?

A
  • Dependent on site of infection but most commonly pulmonary (80-90%):
    • Cough – dry then productive (yellow) +/- blood
    • Fever
    • Night sweats
    • Malaise
    • Loss of appetite, weight loss ‘consumption’
    • Weeks to months (due to pathogens being slow growers, can grumble away in the background until you become unwell)
    • Sometimes pleurisy in pleural TB
  • Clinical signs dependent on site and extent of TB:
    • Often normal. Effusion, crackles, lymphadenopathy, clubbing (rare), hepatomegaly, CNS signs, abdominal masses, sinuses, skin TB
59
Q

What key investigations are needed in TB?

A
  • CXR
  • Bloods often not that helpful
  • Sometimes CT scan
  • Sputum/pleural fluid/urine, pus, biopsy/CSF for routine and TB culture (and histology) – as much as possible!
    • In terms of sputum: sputum x3 for AFB smear/TB culture and routine MC&S
60
Q

What sites can you find TB and how prevalent are these?

A
61
Q

Tell me about latent TB infection:

A
  • Of the 90-95% who ‘contain’ TB organisms and do not develop active disease, most will have latent TB infection
  • Lifetime risk of reactivating TB ~10%, highest in first 2 years after infection
  • Risk factors for reaction:
    • HIV infection
    • Immunosuppression – cancer, chemo, steroids, anti-TNF
    • Diabetes, renal failure, IVDU, malnutrition, GI surgery, silicosis, smoking, age and frailty
  • Can be treated with 3-6 months of isoniazid +/- rifampicin
62
Q

What TB drug causes the most problems with drug interactions and why?

A

Main drug is rifampicin because it is a liver enzyme inducer

63
Q

What drugs does rifampicin interact with?

A
  • Oestrogens – alternative methods of contraception must be advised, preferably use of an intra-uterine device and condoms, continuing for 4 weeks after stopping the rifampicin
  • Corticosteroids – normal prednisolone/dexamethasone doses must be doubled whilst on rifampicin
  • Blood phenytoin levels will be significantly reduced, so regular doses will need to be titrated up using phenytoin levels
  • Sulfonylureas e.g. gliclazide. BM control in diabetics may deteriorate and adjustments need to be made
  • Anticoagulants – warfarin, dabigatran, apixaban, rivaroxaban. Increased INR monitoring at initiation of therapy. Manufacturers of newer anticoagulants recommend monitoring for signs of thrombosis
64
Q

Who needs to be observed on treatment for TB?

A
  • do not adhere to treatment (or have not in the past)
  • have been treated previously for TB
  • have a history of homelessness, drug or alcohol misuse
  • are currently in prison, or have been in the past 5 years
  • have a major psychiatric, memory or cognitive disorder
  • are in denial of the TB diagnosis
  • have multidrug‑resistant TB
  • request directly observed therapy after discussion with the clinical team
  • are too ill to administer the treatment themselves
65
Q

How can you tell if a person is reinfected with TB or if it is recurrence?

A

This depends on how many single nucleotide polymorphisms the two isolates are apart:

  • M TB mean mutation rate is ~0.5 SNP/year
  • Therefore if 1 polymorphism different two years later then recurrence
66
Q

All TB meds are hepatotoxic, especially pyrazinamide (Z). What are the indications to stop treatment?

A
  • If ALT > 3 x baseline (with symptoms)
  • 5 x baseline (without symptoms)
  • If bilirubin rises

Unless patient so sick they need treatment, in which case use a non-hepatotoxic regimen.

67
Q

How do you go about re-starting treatment following a pause due to hepatotoxicity?

A

In people who have experienced a treatment interruption because of drug‑induced hepatotoxicity:

  • investigate other causes of acute liver reactions and –wait until aspartate or alanine transaminase levels fall below twice the upper limit of normal, bilirubin levels return to the normal range and hepatotoxic symptoms have resolved then
  • sequentially reintroduce each of the anti‑TB drugs at full dose over a period of no more than 10 days, starting with ethambutol and either isoniazid (with pyridoxine) or rifampicin.
68
Q

How would you go about altering a TB treatment regime for severe or highly infectious TB in patients who develop hepatotoxicity?

A
  • for hepatotoxicity, a combination of at least 2 anti‑TB drugs of low hepatotoxicity (such as ethambutol and streptomycin, with or without a quinolone, such as levofloxacin or moxifloxacin) and monitor with a liver specialist for further reactions
69
Q

How would you go about altering a TB treatment regime for severe or highly infectious TB in patients who develop cutaneous reactions?

A
  • for a cutaneous reaction, a combination of at least 2 anti‑TB drugs with a low risk of cutaneous reactions (such as ethambutol and streptomycin) and monitor with a dermatologist for further reactions.
70
Q

Why do mycobacteria required a different stain that regular gram staining?

A
  • Cell wall is different from non-mycobacterial species as it has mycolic acid (high molecular weight lipid), hence special stains are required in the lab for its detection
71
Q

How are direct smears prepared for direct microscopy (mycobacteria)?

A
  • Slide smears for TB: prepared from clinical specimens like sputum, broncho-alveolar lavage, pus from abscesses, CSF, lymph nodes
  • Smears are stained with special stains and examined under the microscope
  • Microscopy alone is unable to differentiate different types of mycobacteria. Culture is important for speciation
72
Q

What is an acid fast stain?

A
  • Acid fast stains: special stains that give bright red colour to the bacilli and a counter stain is used for the background
73
Q

Describe the Ziehl Neelson method for staining mycobacteria:

A
  • Hot carbol fuschin (dark red) is poured over the smeared slide, kept for a minute and then washed with acid-alcohol (the TB bacteria retains the red stain hence called ‘acid fast’). Smear is then counter stained with methylene blue to give other cells a blue stain and this results in a light blue background
  • Seen under a light microscope with oil-immersion lens
  • Mycobacteria are therefore called Acid Fast Bacilli (AFB)
74
Q

Describe the fluorescent staining method for staining mycobacteria:

A
  • Auromine-phenol stain is poured over the smeared slide, kept for 15 minutes and washed with acid-alcohol. It is then counter stained with thiazine red
  • Mycobacteria are seen under fluorescent microscope as fluorescent bright greenish yellow against a dark background. This makes it easy to spot
75
Q

Describe findings on culture for mycobacteria:

A
  • There are two ways of performing TB culture in the laboratory
  • Solid culture is done on solid medium which is agar and egg based
  • Most commonly used solid culture medium is Lowenstein-Jensen (LJ). The colonies on an average take about 3-4 weeks to grow. The medium has to be checked manually for growth
    • positive: rough, buff coloured colonies
  • Lipid culture is done in tubes filled with culture medium in liquid state which are placed in electrical cabinets (at correct incubation temperatures) with sensors that set of an alarm when growth is detected
    • positive: cord-like growth
76
Q

How do you identify species and susceptibility of mycobacterium?

A
  • Manual methods for identification and sensitivity testing are labour intensive and still very popular in TB labs around the world
  • Manual methods have rapidly moved to identification by Whole Genome Sequencing (WGS) in labs that have the means for high throughput
  • WGS also helps in identifying outbreaks of TB in the wider community by matching genomic profile of the mycobacteria
77
Q

PCR test for MTB:

A
  • Cepheid Xpert MTB/Rifampicin ultra-PCR test
  • Detects MTB and rifampicin resistance
  • It’s a 1.5-hour test in optimum circumstances – much quicker than the weeks it would take for manual testing
  • Can be performed on primary samples and positive culture isolate
78
Q

What key principles do you need to remember for TB treatment?

A
  • Start treatment with all 4 drugs + do not reduce until two months treatment AND drug sensitivities available
  • If fully sensitive AND better – change to Isoniazid and Rifampicin for further four months
  • In absence of drug sensitivity – can consider continuation 3rd agent if no recourse to re-sampling (i.e. of you cannot get more isolates for the lab
  • Only CNS involvement mandates 12 months Rx
    • May mean spinal/choroiditis as well as tuberculomas/CSF
  • Who should be notified: TB team e.g. TB nurse specialists, case notified to public health
  • How would you monitor response to treatment: gain in weight, improving cough and sputum, sputum smear and culture ‘conversion’ (i.e. sputum becomes smear then culture-negative). Patients often get paradoxically worse for 2-6 weeks before clinically improving. Radiological improvement lags behind clinical improvement
79
Q

How do you test for latent TB?

A
  • Latent TB infection can become full blown active TB if patient is commence on immunosuppressive drugs or corticosteroids for underlying conditions, therefore it is important to known who has latent TB
  • Interferon gamma release assays (IGRA): detects interferon gamma levels in blood which is a measure of cell mediated immune response to MTB bacteria in exposed individuals
  • Quantiferon test is one such method
80
Q

What is acute hepatitis?

A
  • Acute hepatitis = inflammation of the liver which has a duration < 6 months
  • Most acute hepatitis is self-limiting BUT complications include:
    • Acute liver failure = severe acute liver failure with encephalopathy and impaired synthetic function in a patient without cirrhosis or pre-existing liver disease
    • Progression to chronic hepatitis - persistent inflammation for >6 months, with potential progression to cirrhosis, chronic progression to cirrhosis, chronic liver failure and hepatocellular carcinoma
81
Q

Broadly what are the causes of acute hepatitis?

A
  1. Drugs (especially paracetamol)
  2. Infections (especially viral hepatitis)
  3. Others, e.g.
    1. autoimmune
    2. pregnancy related
    3. toxins
    4. ischaemia
    5. malignancy
    6. Budd-Chiari syndrome
    7. Wilson disease
82
Q

What are the common infectious causes of acute hepatitis?

A
83
Q

How is hepatitis A transmitted?

A
  • faeco-oral route
    • person-person spread
    • contaminated food and drink
84
Q

What are the risk factors for hepatitis A?

A
  1. No history of vaccination
  2. Recent travel
  3. In the UK specific outbreaks
    1. Among men who have sex with men
    2. Among PWID
    3. Associated with imported foods/shellfish
85
Q

Hepatitis A - clinical features

A

Prodrome

  • nausea, vomiting, anorexia, fever, abdominal pain, fatigue

Acute hepatitis after approx 10 days

  • jaundice
  • dark urine/pale stools
  • RUQ pain
  • hepatomegaly

Rarely progresses to acute liver failure

Full clinical recovery:

  • symptoms usually improve 1-3 weeks, but can persist up to 12 weeks
86
Q

Hepatitis A - investigations

A
  • Liver function tests
    • Raised serum aminotransferases (ALT and AST) – often > 1000 IU/dL
    • Raised bilirubin
    • Raised alkaline phosphatase
    • Check INR/albumin
  • Hepatitis A serology
    • Hepatitis A IgM - acute infection
    • Hepatitis A IgG – past infection or vaccination
    • Tested using serum (clotted blood) sample in virology laboratory
    • May confirm by PCR testing
87
Q

Hepatitis A - management

A
  1. Clinical management
    1. No specific treatment  supportive care
  2. Infection control:
    1. Infectious during incubation period and for approx. 1 week after onset of jaundice
    2. Side room, no food handling etc.
  3. Prevention of secondary cases:
    1. Notifiable infection  inform Public Health England
    2. Contact tracing
    3. Give close contacts hepatitis A vaccine or HNIG (Human Normal Immunoglobulin) to prevent infection
88
Q

Hepatitis A can be prevented by giving the vaccine. Who should get the vaccine?

A
  • Travellers to endemic areas
  • Men who have sex with men
  • IVDU
  • Chronic liver disease
  • Haemophilia
  • Occupation risk e.g. lab workers, sewage workers
  • Following exposure to infected individual
89
Q

Describe the two different types of hepatitis E infections:

A
90
Q

What are the clinical features of hepatitis E?

A
  • incubation period approx 40 days

Prodrome

  • nausea, vomiting, anorexia, fever, abdominal pain

Acute hepatitis after approx. 1 week

  • jaundice
  • dark urine/pale stools
  • RUQ pain
  • hepatomegaly

Full clinical recovery - <2-3 months

91
Q

Who develops chronic hepatitis E?

A

Only immunocompromised patients, genotypes 3/4

92
Q

Hepatitis E - investigations

A
  • Very similar to hepatitis A
  • Liver function tests
    • Raised serum aminotransferases (ALT and AST) – often >1000IU/dl
    • Raised bilirubin
    • Raised alkaline phosphatase
    • Check INR/albumin (check synthetic function of the liver)
  • Hepatitis E serology
    • Hepatitis E IgM – acute infection
    • Hepatitis E IgG – past infection
    • Hepatitis E PCR - current infection (confirmation or for chronic disease)
93
Q

Hepatitis E - management

A
  1. Clinical management:
    1. No specific treatment –> supportive care
  2. Infection control:
    1. Infectious during incubation period and for approx. 3 weeks after onset of jaundice
    2. Side room, no food handling etc.
  3. Prevention of secondary cases:
    1. Notifiable infection –> Inform Public Health England
    2. Contact tracing
  4. Vaccines
    1. Not widely available
94
Q

How is hepatitis B transmitted?

A
  • Via blood and body fluids – mainly
    • Through vaginal or anal intercourse
    • As a result of blood-to-blood contact through percutaneous exposure (e.g. sharing of needles and other equipment by people who inject drugs (PWID), ‘needlestick’ injuries, tattoos, blood products etc.)
    • Through perinatal transmission from mother to child (biggest cause world cause worldwide)
95
Q

Hepatitis B - clinical features

A

Asymptomatic/subclinical infection

  • >90% children
  • 70% adults

Symptomatic acute infection (most common in adults - 30% adults)

Prodrome

  • nausea, vomiting, anorexia, fever, abdominal pain

Acute hepatitis after <1 week

  • jaundice
  • dark urine/pale stools
  • RUQ pain
  • hepatomegaly

Important cause of chronic hepatitis.

96
Q

Hepatitis B serology

A
97
Q

Acute Hepatitis B - management

A
  1. Clinical management
    1. Most patients  supportive care
    2. Anti-hepatitis B drugs only usually given in patients with severe acute hepatitis (HBV drugs to be discussed in chronic infections) – e.g. INR >1.5, protracted course (persistent symptoms/marked jaundice > 4 weeks), signs of acute liver failure
    3. Screen for other blood-borne viruses (HIV, Hep C)
    4. Screen for hepatitis D co-infection (hep D only in patients with HBV)
  2. Prevention of secondary cases:
    1. Again notifiable infection  inform Public Health England ASAP
    2. Contact tracing
    3. Give close/sexual contacts Hepatitis B vaccinations +/- HBIG (hep B immunoglobulins) to prevent infection
  3. Follow up
    1. Most adults will spontaneously clear hep B infection. However, should be followed up to demonstrate clearance of infection (loss of Hep B surface antigen and Hep B surface antibody seroconversion)
98
Q

Hepatitis B - prevention

A
  1. Education re modes of transmission
    1. E.g. safer sexual practices, needle exchange programmes
  2. Increased testing
    1. E.g. blood products, antenatal screening, screening of at-risk groups
  3. Hepatitis B immunoglobulin (HBIG)
    1. Pooled blood product with high levels of anti-HBs  passive immunity
    2. Can be given after high-risk exposure to susceptible individuals to prevent HBV infection.
    3. E.g. Neonates born to highly infectious mothers, unvaccinated individuals who have definite exposure (e.g. needlestick/sexual) to HBV positive source, HBV vaccine non-responders who receive possible exposure.
  4. Hepatitis B vaccination
    1. Recombinant hepatitis B surface antigen
    2. Safe and highly effective
    3. Can be given both pre-exposure and post-exposure to prevent infection.
99
Q

Who should be vaccinated against Hep B?

A
  1. All neonates
    1. part of routine childhood immunisation schedule since 2017
  2. Anyone at increased risk of exposure to HBV – e.g:
    1. Close or household contacts of someone with HBV infection
    2. Travellers to intermediate or high prevalence areas
    3. Individuals who change sexual partners frequently
    4. PWID (people who inject drugs)
    5. People receiving regular blood products e.g. haemophilia
    6. People with renal failure who may require haemodialysis
    7. People in residential accommodation for those with learning difficulties
    8. Inmates of custodial institutions
    9. Occupational risk – e.g. healthcare workers, laboratory workers, etc
  3. Anyone at high risk of complications of disease e.g.
    1. Patients with HIV
    2. Patients with chronic liver disease
  4. Post-exposure vaccination – following a known/possible exposure to HBV e.g.
    1. Following needlestick injury
    2. Following sexual contact
    3. Neonates of HBV positive women
100
Q

What are the other common causes of acute viral hepatitis?

A
  1. Hepatitis C virus infection
    1. <20% acute hepatitis C infections symptomatic
    2. 60-80% of those infected become chronically infected –> will cover more in chronic infections.
    3. Acute hepatitis C presents similarly to acute hepatitis A/B/E
  2. Epstein-Barr Virus (EBV) infection
    1. Mostly associated with ‘Infectious Mononucleosis’ (fever, sore throat, lymphadenopathy, fatigue etc.)
    2. Mild hepatitis in up to 90%, but only 5-10% have clinical jaundice
    3. Increased risk of hepatitis in immunosuppressed patients.
  3. Cytomegalovirus (CMV) infection
    1. Like EBV infection, may cause ‘mononucleosis-like’ syndrome, with mild hepatitis.
    2. Important cause of hepatitis in immunosuppressed patients.
101
Q

What are the viral causes of chronic hepatitis?

A
  • B – Hepatitis B (HBV)
  • C – Hepatitis C (HCV)
  • D – Hepatitis D (HDV) – only in HBV infected patients
  • E – Hepatitis E (HEV) – only in immunosuppressed patients

Remember Hepatitis A only acute (not chronic) hepatitis.

102
Q

Describe the progression of hepatitis B infection to chronic hepatitis and it’s implications:

A
103
Q

Chronic hepatitis B pathogenesis:

A
  • NOT all patients with chronic hep B infection have active inflammation and hepatitis
  • NOT all patients with hep B develop cirrhosis
  • liver damage is mainly immune-mediated
  1. hepatitis B virus replicates within host hepatocytes
  2. host immune response to the virus –> helps to clear virus BUT also causes liver inflammation and hepatitis
  3. persistent inflammation and hepatitis –> liver fibrosis and damage
104
Q

Why do you stage chronic hepatitis?

A
  • Natural history of chronic hepatitis B infection has been divided into 5 stages
  • Helps with clinical assessment of patient and determines whether treatment is required
  • Relies upon:
    • Laboratory markers of liver function/inflammation
      • ALT
    • Laboratory markers of hepatitis B infection
      • HBsAg
      • HBeAg
      • Anti-HBe
      • HBV DNA
      • Anti-HBs
    • Assessment for presence of fibrosis/cirrhosis
      • Liver imaging
      • Liver biopsy
      • Non-invasive methods e.g. transient elastography
105
Q

What are the 5 stages of chronic hepatitis infection?

A
106
Q

Chronic hepatitis management

A
  • Referral to specialist viral hepatitis clinic for full assessment
    • Assessment of liver disease activity and severity and markers of HBV infection
  • General management
    • Prevent secondary cases:
      • Education re-routes of transmission
      • Testing and vaccination of contacts
    • Prevent further liver damage:
      • Test for other viruses e.g. hepatitis C, HIV
      • Vaccination against hepatitis A
      • Avoid/reduce alcohol
  • Treatment with anti-HBV drugs
    • Not everyone with hepatitis B infection requires treatment
    • Treatment can suppress viral infection, but only very rarely induces long-term clearance of infection.
    • Usually long-term
107
Q

Medical management of hepatitis B:

A

2 main goals:

  1. improve survival and quality of life by preventing disease progression and therefore development of cirrhosis/HCC
  2. reduce transmission of HBV

End-points of treatment

  • loss of seroconversion
  • suppression of HBV DNA
  • ALT normalisation

What drugs are used?

  1. nucleotide analogues
    1. usually entecavir or tenofovir
    2. oral tablets taken long term
  2. pegylated IFN-a
    1. induces longterm immunological control
    2. finite duration to treatment
    3. injection
    4. rarely used
108
Q

Hepatitis B - indications for treatment

A
109
Q

Hepatitis D

A
  • Infection only possible in patients with hepatitis B virus
    • Requires hep B virus for virus assembly and release
    • Co-infection = infection at the same time as HBV infection
    • Super-infection = infection after HBV infection
  • transmission - same as hep B
  • treatment
    • usually by treating HBV
  • if co-infection with HBV and HDV there is much quicker progression to cirrhosis
110
Q

How is hepatitis C transmitted?

A
  • Mainly parenteral
    • PWID – shared needles/injecting paraphernalia (England 23% PWID have current HCV infection)
    • Blood products (before 1991)
    • Needlestick injuries (3% risk)
    • Tattoos/acupuncture etc
  • Also sexual and vertical transmission (but lower risk than HBV)
111
Q

Why are genotypes of hep C important?

A
  • No cross-protection between genotypes
    • People can be co-infected by more than one genotype.
    • Reinfection with another genotype.
  • Treatment
    • Some treatments are genotype specific
    • Different response to treatments
112
Q

What are the similarities between HCV and HBV?

A
  • Acute infection –> chronic infection –> cirrhosis –> HCC
  • Again can cause extrahepatic manifestations
113
Q

What are the important clinical differences between HCV and HBV?

A
  • Acute infection:
    • Often asymptomatic (only 20% symptomatic)
    • Less spontaneous clearance than HBV - 55-85% progress to chronic infection (vs 5% HBV)
  • Chronic infection:
    • Slow development to cirrhosis (20-30% over 20-30 years)
  • NO reactivation:
    • Cure is possible - can NOT reactivate following immunosuppression
  • Multiple genotypes:
    • Reinfections possible and common
  • No vaccine
114
Q

How do you diagnose hepatitis C?

A

Sample of blood tested.

  1. Hepatitis C antibody
    1. Shows whether someone has ever had hepatitis C.
    2. Cannot differentiate current vs past hepatitis C infection
    3. Used as a screening test.
    4. May have false negatives in immunocompromised patients (esp. HIV) or be negative in acute HCV infections
  2. Hepatitis C RNA - PCR
    1. Detects actual viral RNA –> differentiates current from past infections.
    2. Used in immunocompromised patients
  3. Hepatitis C genotyping
115
Q

Describe the trend of blood markers of hep C during infection:

A
116
Q

What is the management of hepatitis C?

A
  • DAAs = Direct Acting Antivirals
  • Drugs that target specific non-structural proteins of HCV  disrupt viral replication and infection
  • All patients with hep C should be treated due to high rates of progression to chronic infection
    • current cornerstone of treatment is combination of 2 or more DAAs
      • drugs end in ‘svir’ (NS5A) or ‘uvir’ (NS5B)
117
Q

How do you know what DAAs to use in hepatitis C?

A
  • HCV genotype
    • Some specific genotypes
    • Some pan-genotypic
  • Drug interactions
  • Treatment history
  • Presence of cirrhosis
  • Cost
  • National/local guidelines

Endpoints of treatment:

  • Test HCV RNA at end of treatment
118
Q

WHO target for elimination of viral hepatitis by 2030 - how will this be achieved?

A
  • increased screening and testing
  • reduced stigma
  • increased awareness and education regarding modes of transmission
  • general public health - needle exchange, safer sex practiceds
  • screening of blood products
  • increasing HBV vaccination
  • obstetric services –> prevents vertical transmission
  • improved access to HBV and UCV treatment
    • DAAs very expenisve BUT some generic versions of these medicines now available
119
Q

When does chronic hepatitis E occur?

A
  • HEV usually causes acute hepatitis
  • Chronic hepatitis ONLY in immunosuppressed patients and ONLY genotypes ¾ (i.e. not travel associated cases)

Things to remember:

  1. Consider as a cause of chronic hepatitis in immunocompromised patients
  2. If a patient with acute hepatitis E is immunocompromised, they should be followed up to ensure clearance
  3. Occasionally treatment may be required (Ribavirin)
  4. Hepatitis E serology may be falsely negative in immunocompromised patients – diagnosis needs HEV RNA PCR
120
Q

What kind of tick transmits Lyme disease?

A
  • ixodes tick
121
Q

What is the causative pathogen of Lyme disease?

A
  • Commonest vector-borne disease is Northern hemisphere
  • Spirochete bacterium
  • Borrelia burgdorferi sensu lato (US)
  • Borrelia garninii, Borrelia afzelii (Europe)
    • although all three of these are important causes in the UK
122
Q

What is erythema migrans?

A
  • Increases in size and may sometimes have a central clearing
  • Is not usually itchy, hot or painful
  • Usually becomes visible from 1 to 4 weeks (but can appear from 3 days to 3 months) after a tick bite and lasts for several weeks
  • Is usually at the site of tick bite
  • May be associated with fever, headache, ‘flu-like’ symptoms
123
Q

What are the less common features of early Lyme disease?

A
  • Neurological symptoms (weeks to months after exposure)
    • Facial palsy (may be bilateral)/other unexplained cranial nerve palsies
    • Lymphocytic meningitis
    • Mononeuritis multiplex or other unexplained radiculopathy
  • Cardiac problems:
    • Heart block (1st degree commonest)
    • Pericarditis, myocarditis
124
Q

What are the features of late Lyme disease?

A
  • Months to >1y after exposure
    • Joints (US infection):
      • Inflammation arthritis affecting 1 or more joints that may be fluctuating and migratory
      • Knee ‘always’ affected
    • Late cutaneous (European infections)
      • Acrodermatitisn chronica atrophicans
      • Lymphocytoma (clinically earlobe)
125
Q

What other non-specific findings of Lyme disease?

A
  • fever and sweats
  • swollen glands
  • malaise
  • fatigue
  • neck pain or stiffness
  • migratory joint or muscle aches and pain
  • cognitive impairment, such as memory problems and difficulty concentrating (sometimes described as ‘brain fog’)
  • headache
  • paraesthesia
126
Q

How do you diagnose Lyme disease?

A

Lyme disease suspected

  • is erythema migrans rash present?
    • Yes - diagnose Lyme disease and offer antibiotics
    • No - offer ELISA test
  • Positive ELISA test?
    • Yes - offer immunoblot test
    • No - review history consider alternative diagnoses
      • repeat after 4-6 weeks if ELISA test done within 4 weeks of onset of symptoms
      • if symptoms remain after 12 weeks offer immunoblot test
  • Positive immunoblot test?
    • Yes - diagnose Lyme disease and offer antibiotics
    • No - consider other diagnosis
      • contact specialist if symptoms persist
127
Q

What are the challenges in diagnosing Lyme disease?

A
  1. History of tick bite not always noted
  2. Not all patients have erythema chronicum migrans
  3. Some symptoms are very non-specific
  4. Differences in organisms and symptoms in US vs. Europe
  5. Early infection may show negative serology
  6. Early treatment may attenuate serological response
  7. No single diagnostic test has perfect sensitivity and specificity
  8. Availability of unvalidated private tests
  9. Over-testing in patients with low pre-test probability
  10. What is the significance of persistent symptoms after treatment? (‘chronic Lyme disease’ / ‘post-treatment Lyme disease’)
128
Q

How do you treat Lyme disease?

A
  • Early disease (e.g. ECM rash)
    • Oral doxycycline 21d (NICE) [evidence that 10dis sufficient]
  • Meningitis/radiculopathy/CN palsy
    • IV ceftriaxone 21d
    • Data suggest oral doxycycline equally effective
129
Q

What is the outcome of Lyme disease treatment?

A
  • How to define successful treatment?
    • ~30% have some post-treatment persistent symptoms for few months
    • But by 12+ months not statistically different to background population rate
  • There is no test for ‘active infection’
  • Role of re-treatment?
  • High quality (RCT) evidence that long antibiotic courses offer no additional benefit
    • E.g. 2w vs. 14w

CDM (7 decks)

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