Transcript 3rd CPG on Management of Tuberculosis

Case Discussion 4 –
TB & H V
by
Dr. Anuradha P. Radhakrishnan
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History
• 45 y.o./female
• Productive cough - 4/52
• LOA, LOW, night sweats
• Intermittent fever - 2/52
• Chronic diarrhoea - 3 months, 2 - 3x per day
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History (cont.)
• Has sought Rx at numerous GPs
– Several courses antibiotics given
• Cough & fever persists
• A CXR done at a
private clinic
- told to be normal
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Q1
• Does a normal CXR rule out TB?
A. Yes
B. No
C. Not sure
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A1
• A normal CXR may be seen in up to 15%
of patients with proven TB & HIV.
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Atypical CXR in Advanced HIV
•
•
•
•
•
•
Lower/middle lobe opacity
Interstitial or miliary pattern
Adenopathy (hilar, paratracheal)
Pleural effusion
Pericardial effusion
Normal chest radiographs – 15%
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Physical examination
•
•
•
•
•
•
Cachexic
Pale
No jaundice
Lungs - clear
Heart - DRNM
PA - soft, no mass
• Several anterior
cervical nodes,
discrete, largest 2x3
cm
• No rash
• Sa O2 - 98% in room
air
• Odynophagia
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History (cont.)
• Denies high risk behaviour
• Married for 20 years
• Late husband deceased 2 years ago fatal MVA
• Q2. What is the provisional diagnosis?
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A2
• Fever & cough for Ix, TRO PTB
• Oral thrush - HIV status should be
determined
(Esophageal thrush as patient has
odynophagia)
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TB- H V Interaction
• HIV-positive patients have more than 2x risk
of primary MDR-TB.1,2
• Risk of mortality is 2.6x higher in HIV-positive
patients who develop TB compared to those
who do not.3
1Conaty
SJ et al., Epidemiol Infect, 2004
et al., PLoS ONE, 2009
3Straetemans et al., PLoS ONE, 2010
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2Suchindran S
Laboratory investigations
General:
• Full blood count
• Liver & Renal
function
• Hepatitis Bs Ag
• AntiHep C Ab
• VDRL/TPHA
• HIV
Specific:
• CD4/CD8
• Blood C&S
• Stool C&S/FEME
• Sputum AFB DS
• Sputum MTB C&S
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Diagnostic Challenges
Many HIV-TB co-infected patients:
• Have no cough & negative sputum
AFB smears
• Have lower AFB { } in sputum
– AFB density in sputum decreases with
decreasing CD4
• Have normal CXR even in cultureconfirmed PTB
• Have less cavitary disease on initial
CXR
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Laboratory Ix - results
•
•
•
•
•
Hb - 10 g/dL
WCC - 5x109/L
Platelet - 105x109/L
Urea - 5 mmol/L
Creat - 78 µmol/L
• ALT - 10 U/L
• ALP 98 U/L
• Bilirubin - 5 µmol/L
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Laboratory Ix - results
• Sputum AFB 1+
• Sputum MTB C&S - pending
• Stool FEME/C&S - NAD
• Blood C&S - no growth
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Laboratory Ix - results
• HIV PA/Elisa - reactive 1st sample
• Hep B/C serology - NR
• VDRL - NR
• CD4 - pending
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Treatment
• Commenced on:
– EHRZ + B6
– Syrup nystatin - 5 mls TDS, swish & swallow
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INH, rifampin, PZA & ethambutol
(4 drugs, 10 pills once a day)
Q3. How to reduce pill burden?
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A3
• Fixed-dose combination
 Less pill burden
 Improved compliance
 Less prescription errors
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Q4
• Is there any additional medication
needed in TB-HIV co-infected patients?
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A4. CO-TRIMOXAZOLE (CTX) PROPHYLAXIS IN
TB-H V CO-INFECTION
• A RCT showed that CTX prophylaxis in TB-HIV co-infected
adults was associated with a 21% reduction in all cause
mortality.1
• CTX is generally safe & well-tolerated.1,2
• CTX should be initiated as soon as possible & given
throughout TB treatment.3
1Nunn
2Boeree
AJ et al., BMJ, 2008
MJ et al., Trop Med Int Health, 2005
3WHO, 2010
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Treatment
• Odynophagia - possible esophageal
candidiasis
• Fluconazole > itraconazole > syrup nystatin for
mycological cure
• Itraconazole has increased drug interaction
with rifampicin
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Treatment
• Fluconazole - 200 mg OD for 2 weeks
• Co-trimoxazole - 1 tab OD
Q5. Do we need to rule out EPTB?
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TB- H V INTERACTION
PTB (44.0 - 79.5%)
EPTB (14.0 - 18.8%)
Both PTB & EPTB (2.7 - 3.0%)
Zhou J et al., BMC Infect Dis, 2009
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TB Pattern &
HIV-related TB Survival
PTB
EPTB
Both
Days from diagnosis of TB
Source: Whalen C, Horsburgh CR Jr, Hom D, Lahart C, Simberkoff M, Ellner J. Site of disease and opportunistic infection
predict survival in HIV-associated tuberculosis. AIDS. 1997 Mar 15;11(4):455-60.
Risk of EPTB
• Q6.
– Is there a need to investigate for
lymphadenopathy?
– Is USG abdomen necessary?
• Blood for MTB culture to look for bacteraemic
TB
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Common Sites of EPTB
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•
•
•
•
•
•
Lymphatic System
Pleura
Pericardium
CNS
GI
Kidney
Bone
• Seen with lower
CD4 count
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EPTB
• Bacillary load - low
• Sampling - difficult
• Diagnosis - challenging
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TB Cultures
• Sputum/BAL TB cultures should be obtained in
all TB suspects with a normal CXR, particularly
HIV-positive persons.1
• Any biopsy specimen from extrapulmonary
sites should be sent for TB culture.
1Pepper
T et al., Int J Tuberc Lung Dis, 2008
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Multivariate Analysis of Risk Factors for Clinically Significant BSI Caused by Mycobacterial or Other Bacterial Infection in HIV-infected
Outpatients, Thailand, Cambodia, and Vietnam, September 2006–July 2008*
Fine Needle Aspiration Cytology
(FNAC)
• Cytology alone provides reliable diagnosis in
72% of patients.1
• Combining cytology with microbiology (smear
& culture) increases diagnostic yield from 67%
to 91% in clinically suspected tuberculous
lymphadenitis.2
1Mittal P
et al., Diagn Cytopathol, 2011
2Asimacopou;us EP et al., Int J Tuberc Lung Dis, 2010
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USG Abdomen
• Features suggestive of abdominal TB:
– ascites (79%)
– enlarged LN (35%)
– omental thickening (29%)
– bowel wall thickening (25%)
Khan R et al., World J Gastroenterol, 2006
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History (cont.)
• Patient refused FNAC
• USG abdomen appt - 2 months away
• MTB blood culture bottle - not available
32
Q7. When To Start Highly Active
Antiretroviral Therapy (HAART)?
Do We Wait For CD4 Or
Rely On WHO Clinical Staging?
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A7
• Counseled regarding HAART
• Planned for HAART after complete one month
of intensive phase as CD4 not available
• Continue EHRZ/cotrimoxazole
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WHO Clinical Staging - Clinical Stage 4
16. HIV wasting syndrome
17. PCP
18. Toxoplasma of the brain
19. Cryptosporidiosis with
diarrhea
20. Isosporiasis with
diarrheoa
21. Extrapulmonary
cryptococcosis
22. Cytopmegaloviral disease
of an organ other than
liver,spleen, or lymph
node
23. Herpes simplex virus
infection
24. PML (progressive multifocal
leukoencephalopathy)
25. Any disseminated endemic
mycosis
26. Candidiasis of the
esophagus, trachea,
bronchi, and lungs
27. Atypical mycobacteriosis
28. Non-typhoid Salmonella
septicemia
29. Extrapulmonary TB
30. Lymphoma
31. Kaposi’s sarcoma
32. HIV encephalopathy
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History (cont.)
• 2 weeks later:
– CD4 - 30
• Patient contacted for HAART commencement
– EHRZ day 17
– Tolerating medications well
– Mild rash over the back
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A7.Timing of HAART
CD4 count
(cells/µl)
Timing of HAART initiation
<50
2 weeks after starting intensive phase of
antiTB treatment
>50 but
<350
After completion of intensive phase of
antiTB treatment
>350
Continue antiTB treatment & monitor
CD4. Commence HAART if CD4 drops
<350 cells/µl.
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A7.Timing to Initiate HAART
• In HIV-associated TB meningitis,
immediate HAART is associated with an
increase in Grade 4 adverse events 
safer to defer HAART1
1Torok
ME et al., Clin Infect Dis, 2011
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Q8. Which HAART regimen?
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A8
Antiretroviral Regime
Antiretroviral drugs
Interactions with rifampicin
NRTIs
No clinically significant interaction
NNRTIs
Efavirenz: the preferred NNRTI
Nevirapine:
 can be continued if already on a
nevirapine-based HAART with close
monitoring of LFT;
 if need to start, please d/w ID physician
PIs
Referral to an ID Physician if patient already
on PI-based regimen
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History (cont.)
• Patient informed to come to TB clinic
earlier to commence HAART
– Stavudine/lamivudine/efavirenz
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History (cont.)
• 4 weeks after HAART:
– Left neck swelling
– Fever on & off
– Good appetite
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Q9. What is the diagnosis?
A. Patient is not taking the antiTB
medication
B. Patient has MDR-TB
C. Patient develops IRIS
D. Patient has lymphoma
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IMMUNE RECONSTITUTION
INFLAMMATORY SYNDROME (IRIS)
• An augmented inflammatory
response that occurs in
patients started on HAART &
antiTB
• Usually occurs within 3
months of TB treatment
o typically within 2 to 12 weeks
after the initiation of HAART
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IRIS
• The major manifestations of IRIS are fever &
lymphadenitis.1
• HAART & antiTB treatment should not be
stopped while managing IRIS.
1Dibyendu
D et al., Braz J Infect Dis2011
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History (cont.)
• Patient agrees for FNAC
• Left neck swelling fluctuant & mildly
tender
• Lymph node aspirate - no AFB seen,
numerous inflammatory cells
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A9
• Mild TB IRIS
– Patient given a course of NSAIDS for a week
– Lymph node swelling subsides in one week
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History (cont.)
• Patient reviewed in integrated HIV/TB clinic:
– Day 56 antiTB
– Fever subsides
– Tolerating efavirenz
– Occasionally dizzy
– Otherwise gaining weight
Q10. What is the duration of RH maintenance ?
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A10. ANTITB FOR TB-H V CO-INFECTION
• Prolong the continuation phase if:– there is a slow or suboptimal response
(e.g. cultures are still positive after 2 months of
therapy)
– patients with EPTB
• All HIV patients should receive DAILY TB
treatment in maintenance phase.
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History (cont.)
• Review in TB clinic at 4 months of RH:
– Gaining weight
– But c/o numbness tips of finger/soles of
feet
• Q11. Is the symptom secondary to stavudine
or INH?
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HAART & ANTITB TREATMENT
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A11.
• Isoniazid & stavudine can cause
peripheral neuropathy even with B6
supplements.
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Q12. How to treat peripheral neuropathy?
A. Stop INH
B. Stop stavudine
C. Increase pyridoxine dosage
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A12. Peripheral neuropathy
• Maintenance - RH 217 doses
+ Vitamin B6 50mg od
• Continue stavudine/lamivudine /stocrin
• Cotrimoxazole - 1 tab OD
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History (cont.)
• Day 217 RH
– CD4 - 126
– VL<20
– Hb - 12
– Adherent to medications
– AntiTB ceased
– Numbness of fingers persists
Q13. Should stavudine/lamivudine/efavirenz
be continued?
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A13
• Switch to zidovudine/lamivudine/efavirenzbased regime to prevent worsening
neuropathy secondary to stavudine
• Switching to a single drug only done if HIV
viral load is suppressed
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Q14
• When should cotrimoxazole be ceased?
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A14
• Cease cotrimoxazole:
– In patient with
CD4 counts >200 on 2 separate occasions or
sustained viral suppression ( VL<20 )
• Continue HAART lifelong
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THANK YOU
[email protected]
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