Tuberculosis Flashcards
Risk factors for TB infection
- living in urban areas
- residents of prisons, homeless shelters, nursing homes
- close contact with someone with pulmonary TB ( the more prolonged the contact, the greater the risk )
- elderly ( Reactivation of infection acquired years earlier)
- co infection with HIV
Risk factor for active diseases TB
- Lifetime risk of developing active disease ~10% (highest risk during first 2 years after infection)
- Extremes of age (<2yrs and >65 years)
- underlying immune suppression
( disease-related : Renal failure , cancer)
( Drugs ) - co- infection with HIV (annual risk ~10%; ~29X more likely to develop active disease)
Clinical presentation of TB
- gradual onset
- SNS
WT lost Fatigue Fever Productive cough Night sweats Hemoptysis
- Physical examination
Dullness on percussion
Rales/rhonchi - X-ray
Infiltrated in apical regions
Cavitary lesions
Granulomas
Clinical presentation of TB
In
HIV patient
Elderly
Extrapulmonary TB
Military TB
HIV infected patients
- may not manifest typical symptoms
- higher incidence of extra-pulmonary TB
- screen for TB.
Elderly
- weight loss
- altered mental status
- have a high index of suspicion
Extrapulmonary TB
- bones
- joints
- spine ( Pott’s disease)
- meningitis
- adrenal glands
Military TB
- disseminated form of disease
- rapidly progressive
- mortality up to 33%
Key to preventing spread of TB is early identification of infected individuals
Key to preventing spread of TB is early identification of infected individuals
Latent TB infection
(LTBI) definition
Presumptive infection with
M tuberculosis as evidenced by a positive tuberculin skin test and or positive gamma interferon release assay without clinical or radiologic manifestation of disease.
Screening criteria LTBI
Implement selective testing based on risk of progression to active disease
Indicated only for those willing to undergo treatment with a positive test result.
CLEAR indication for screening
- children and young adults with recent close contact
- hiv infected individuals
- candidates for tumors necrosis factor antagonist therapy
- dialysis patients
- organ/ hematologic transplant patients
Controversial groups for screening for LTBI
Vary from country to country
Immigrants from country with high incidence of TB
Healthcare workers
Prisoners
Homeless
Injection drug user
Detection of latent TB infection
Tuberculin skin test
Detection of Latent TB Infection
Tuberculin skin test/Mantoux test/PPD test
- Singapore practice
- 0.1mL tuberculin purified protein derivative (PPD)
- Injected intra-cutaneously on volar aspect of forearm
Read after 48 – 72 hours by experienced person
Area of induration important, not area
Interpretation depends on risk group and history of BCG vaccination
Biggest limitation is low specificity
- Does not distinguish between infection with M. tuberculosis, prior BCG vaccination, or environmental contact with non-tuberculous mycobacteria
BCG vaccinated population
No universally accepted criteria
- UK NICE guidelines → ≥ 15mm induration
Recent vaccination can result in false positive test
Given in infancy → response wanes in ~ 5 yrs
Given later in life → can persist > 10 yrs
Detection of LTBI gamma interferon release assays
Detection of Latent TB Infection
Gamma interferon release assays
Detect gamma interferon released by sensitized T cells (mainly CD4) in response to antigens specific to M. tuberculosis
Can be used in people with prior BCG vaccination
Quantiferon® and T-Spot ® tests
As good as, or even better, than skin testing
Recommended as an alternative in any situation where skin testing would be used
Results within a few hours
Suspicion of active TB disease
Active Disease
Suspect based on
History
— Risk factors or exposure
Clinical presentation
Physical exam findings
Chest X-ray findings
Confirm with microbiological tests to identify/isolate organism
Sputum microscopy of TB
Sputum Microscopy
Expectorated sputum sample or induced with aerosolized hypertonic saline
WHO recommendations
—Send 2 specimens → increased yield
—Can send 2 specimens on the same day
Ziehl-Neelsen stain for acid fast bacilli (AFB)
Lower limit of detection = 8,000 – 10,000
organisms/mL
— Can be smear negative but still grow on culture
Staining cannot determine species of Mycobacterium
Cannot determine if organisms in original specimen were alive (viable) or dead
If sputum is AFB positive → start treatment
Sputum culture TB
Sputum Culture
Solid media
—Takes 4 – 8 weeks to grow and get confirmation
of TB
—Another 4 – 6 weeks for drug susceptibility testing results
Liquid culture systems
— Can detect growth of M. tuberculosis within 1 – 3 weeks
— Another 1 – 2 weeks for drug susceptibility testing
— Can test first-line and second-line drugs
— Can be partially or fully automated
— Recommended by WHO as standard practice
Molecular methods
— Real-time PCR assay
Xpert MTB/RIF®
— Detect M. tuberculosis and determine rifampin resistance < 2 hours
— WHO recommendations
—
Confirming extrapulmonary TB
Extrapulmonary TB Can perform AFB staining and culture on Draining fluid Bone biopsy specimen Tissue samples Cerebrospinal fluid (CSF)
Treatment LTBI principle
Treatment – LTBI
Primary goal is to reduce the risk of progression to active disease
Treatment reduces lifetime risk of active disease from ~10% to ~1%
Must first exclude active disease
Weigh risk of not treating (i.e., progression to active disease) vs. risk of adverse effects from treatment (i.e., primarily hepatotoxicity)
Patients are asymptomatic and non-infectious
Monotherapy is effective
Lower bacterial burden vs. active disease
Low risk of selecting out resistant organisms
LTBI treatment regimens first line
Treatment Regimens – LTBI Isoniazid First-line for HIV positive and HIV negative 5 – 10mg/kg daily (preferred) Adults = 300mg standard dose
Duration
9 months → better efficacy
6 months—
Treatment regimens LTBI alternative First line
Treatment Regimens – LTBI
Isoniazid plus rifapentine
Rifapentine
— Long-acting rifamycin derivative
—
Treatment regimens LTBI
For isoniazid resistance / cannot tolerate
Rifampin Adults 600mg daily Duration US guidelines = 4 months UK NICE guidelines = 6 months
Suspect isoniazid resistance or contacts of isoniazid-resistant active TB
Cannot tolerate isoniazid
Treatment regimens LTBI second line alternative
Isoniazid plus rifampin
Alternative second-line
Duration = 3 – 4 months
Rifampin plus pyrazinamide
No longer recommended due to high rates of hepatotoxicity
Isoniazid 300mg (5-10mg/kg/ day) Rifampin 600mg daily
Drug induced hepatotoxicity definition
Definition
ALT > 3X upper limit of normal (ULN) with symptoms
OR
ALT > 5X ULN without symptoms
Rank order of drug for hepatotoxicity
Risk of Hepatotoxicity Rank order 1. Pyrazinamide 2. Isoniazid 3. Rifampin 4. Ethambutol
Second-line drugs
—
Risk factors for drug induced hepatotoxicity
Risk Factors Combination therapy Increasing age (> 35 years) Female Underlying liver disease Heavy alcohol use Higher doses (pyrazinamide) Antiretroviral therapy
Hahcifu
Monitoring to avoid or detect hepatotoxicity for latent TB
Before tx
Monitoring to Avoid or Detect Hepatotoxicity
Latent TB infection
— Screen for risk factors before starting treatment
— no risk factor —> start tx (no need chk Baseline)
W risk factor
- chk Baseline LFT
- normal —> start TX
- abnormal —> defer tx
N/V, abdominal discomfort, unexplained fatigue = stop Tx
Monitoring to avoid or detect hepatotoxicity
Active disease
Monitoring to Avoid or Detect Hepatotoxicity
Active disease
— No risk factors
1) Baseline LFT’s
2) Re-check only if develop signs and symptoms
with risk factor
- check Baseline LFT
- recheck q 2-4 weeks
- > 35yo = RF(?)
What to do if develops hepatotoxicity
With Hepatotoxicity
Stop current treatment
If severely ill and unsafe to completely stop
TB treatment
— streptomycin , ethambutol, FQ
OR
Wait till SNS resolve and LFT normalize
- restart drug 1 at a time
- first drug - rifampin
- monitor SNS and LFT
- 3-7 days later at Isoniazid
- if necessary, restart pyrazinamide
- if symptoms it LFT abnormalities recur —> last drug added should be stopped
Treatment regimens for hepatotoxicity
WHO Guidelines on Treatment Regimens
Rifampin implicated
— Isoniazid + ethambutol + streptomycin x 2
months, then isoniazid + ethambutol x 10 months
Isoniazid implicated
— rifampicin + pyrazinamide + ethambutol x 6-9months
both Isoniazid and rifampin cannot be used
- streptomycin + ethambutol + FQ x 18 - 24 months
Acute TB treatment regimen
Overall regimen no dose
Six month TB treatment
- 2 month intensive phase
- daily Ethambutol , isoniazid, rifampicin and pyrazinamide
Followed by
- 4 month continuation phase of daily
- rifampicin and isoniazid
( can be doses 3x weekly; dose for isoniazid be adjusted to 15mg/kg)
For patients who are unlikely to tolerate pyrazinamide (eg elderly, liver disease)
- 9 month regimens
- ethambutol, rifampicin, isoniazid for 2 months
Followed by
- rifampicin and isoniazid for 7months
Dose for first line TB drugs active TB
Isoniazid
>= 15yo
- 5mg/kg/day, MAX 300mg/day
- 15mg/kg, MAX 900mg 3x/week
<15yo
- 10-15mg/kg daily, MAX 300mg/day
- 20mg/Kg, MAX 900mg 3x/week
Rifampicin
>=15yo
- 10mg/kg, MAX 600mg daily or 3x/week
<15yo
- 10-20mg/Kg daily, MAX 600mg daily
- 20mg/kg, MAX 600mg 3x/week
Ethambutol
>=15yo
- 15-20mg/kg daily for 1st two months then 15mg/kg daily
MAX: 1600mg/day
<15yo
- 15-25mg/kg, MAX 1600mg/ day
Pyrazinamide
>=15yo
- 25mg/kg daily, MAX: 2g/day
<15yo
- 25-35mg/kg MAX 2g/day
Streptomycin IM
>=15yo
- 15mg/kg daily, MAX 1g/day in person <= 59yo
- 10mg/kg daily, MAX 0.75g/day in persons > 59yo
<15yo
- 15-20mg/kg, MAX 1g daily.
Latent TB hepatotoxicity during tx
During tx No risk factor for hepatotoxicity - no need chk LFT routinely - monitor SNS - develops SNS —> stop TX and check LFT
Options (if develop hepatotoxicity)
- stop Tx completely
- restart Isoniazid after ALT <2x uln
- switch to rifampicin x4 months
With risk factor
- monitor LFT q2-4weeks
