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Monitoring for Adverse Events During LTBI

Helene M. Calvet, MD

Health Officer and TB Controller

Long Beach Department of Health and Human Services

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Reported Tuberculosis Cases By YearCity of Long Beach, 1997-2009

Department of Health and Human Services

100

57

88

64

50

59

65

54 53

39 39

4744

0

20

40

60

80

100

120

1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009

Count Year

Nu

mb

er

of C

ase

s

2009 TB Case rates: CA = 6.4, LB = 8.9

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Current TB Screening and LTBI RxLong Beach TB Control Program

• Historically, TB screening limited to certain high-risk groups (contacts, B-1 immigrants, some drug treatment facilities and homeless programs)

• Routine, low-risk TB screening (school, employment) done in our Walk-In clinic for a fee

• Previously, any patients with positive TST and indication for treatment were offered LTBI treatment through TB clinic (~600/yr)

• Currently, due to budget shortages and staffing cutbacks, only contacts and B-1 immigrants are treated through our program (~150/yr), and others are referred for Rx to PMDs or community clinics

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LTBI Baseline AssessmentLong Beach TB Control Program

• Baseline LFTs obtained on all over age 35, and those under 35 who have hx liver disease, are pregnant or less than 3 months post-partum, HIV+, EtOH or drug abuse

• If baseline LFTs > 3x ULN, risk-benefit assessment done and w/u for etiology of increased LFTs (Hep B and C)

• After orders signed off by MD, PHN does “INH Start” visit and educates patient on signs/symptoms of INH adverse effects

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LTBI Follow-Up Assessment Long Beach TB Control Program

• All patients (or responsible adult if patient is a minor) are seen on a monthly basis by RN or PHN for refill, assessment of symptoms and review of compliance

• Repeat LFTs done on those who had baseline lab assessment monthly for the first 3 months; further labs as ordered by MD

• LFTs done on any patient complaining of symptoms of hepatitis

• If follow-up LFTs increase, reviewed by MD with decision to continue or hold INH

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Case #1

• 11/2005: 14 y.o. Hispanic male, arrived in US from Honduras 4 years prior, needing TB screening for school

• TST negative x 2 in past (2002, 2003); current TST positive at outside clinic 10 mm

• No known TB exposure

• CXR normal, no symptoms of TB, no past medical history, but c/o sore throat x 3 days; referred to outside clinic for sore throat

• INH started 12/16/05

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Case #1• Mother returns on Jan 13, 2006 for refill

• States patient has decreased appetite and feeling tired since November 2005 (before starting INH, but was not mentioned on INH start visit)

• Also learned that patient not been in school since January 2005

• Mother given INH refill but advised to bring patient in for evaluation ASAP

• Home visit by Spanish-speaking community worker later that day to investigate social situation and to reiterate need to bring patient in

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Case #1• 1/30/06: patient still had not come in for

evaluation; referred to field nursing

• Field PHN finds that patient is still taking INH, c/o itching after taking medicine and vomited x1 two days ago; PHN advised mother to stop giving medication and to bring patient to clinic the next day

• No show to clinic

• 2/14/06: TB PHN spoke to patient’s mother, who now says patient looks pale yellow; advised to bring patient in immediately

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Case #1Drug-Induced Liver Toxicity (DILI)

• 2/17/06: patient finally comes in, grossly icteric

• C/o fatigue and vomiting x 2 weeks, weight loss of 5 lbs

• Mother continued giving patient medication until 4 days prior, despite advice to d/c meds over 2 weeks previously

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Case #1: DILI

• Sent to hospital; admission LFTs: AST 3750, ALT 2876, T.bili 26, INR 2.47

• Work-up done for other causes: negative hepatitis panel, CMV neg, EBV IgG +/IgM neg

• Patient denied taking Tylenol, EtOH, illicit drugs or herbal meds

• Patient stayed in hospital 1 month; d/c labs AST 94, ALT 111, T. bili 30, INR 1.13

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Isoniazid-Induced HepatitisComparison of “Old” and “New” Data

N=13,838

HepatitisAge (yr) Cases/1000

<20 0.020-34 3.0

35-49 12.0

50-64 23.0

>65 8.0

N=11,141

HepatitisAge (yr) Cases/1000

0-14 0.0

15-34 0.8

35-64 2.1

≥65 2.8

Nolan CL et al. JAMA 1999;281:1014Kopanoff et al. Am Rev Resp Dis 1976;117:991

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Case #1: DILILessons Learned

• Parent of a 14 y.o. who has not been in school for one year is not a “responsible adult”

• No longer give INH refills to parents if any symptoms reported

• Learned to follow-up on no-shows to clinic more aggressively

• INH toxicity to this level is extremely rare, but can affect anybody (even adolescents with no identified risk factors), and is more common when INH continues to be administered after symptoms develop

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LTBI TreatmentRisk/Benefit Analysis

• Will offer treatment to any patients meeting CDC’s criteria for treatment

• If patient at increased risk for DILI (advanced age or underlying liver disease), will counsel patient about risk for TB and risk of DILI and allow them to make the choice

• If patient at increased risk for DILI, will follow more closely

• If patient opts not to Rx LTBI, will educate the pt to self-monitor for symptoms of TB

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Case #2: To Treat or Not to Treat?

• 65 y.o. Cambodian man, referred for TB screening 5/06 due to contact with patient with smear + pulmonary TB disease (index died of TB)

• Patient in country for 25 years, can’t remember any prior TST

• Hx of Hep C (on treatment) and partial lung resection in Cambodia in 60’s

• TST + 44 mm, c/o loss of appetite

• CXR reveals fibrolinear densities LLL, post-traumatic deformities left ribs, fibrocalcific density in L apex

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Case #1: To Treat or Not to Treat?

• Sputa x 3 obtained; one showed rare AFB, but all specimens culture negative except for one with M. chelonae

• 7/06: Pt decides to defer LTBI treatment until HCV therapy finished

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Case #1

• Pt returns 2/07: Liver PMD advises Rx LTBI with INH since pt likely transplant candidate

• Patient also admits to cough x 3 weeks; w/u for TB disease repeated

• Admitted with variceal bleed late 2/07

• Sputum cultures negative final 4/07, so INH started

• Baseline LFTs: AST 51, ALT 13, T. bili 1.6, Alb 2.7

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Case #1

• LFTs after one month: AST 82, ALT 22, T. bili 1.4; so far, so good!

• Near end of second month: patient c/o bloating and increased fatigue, INH held pending LFTs

• LFTs AST 114, ALT 36, T. bili 2.1

• Patient admitted with new-onset ascites 5 days later

• Although no evidence of DILI on admission, pt’s disease obviously progressing and risk/benefit ratio thought to be too high, so INH stopped

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Case #3

• 71 y.o Hispanic male with c/o lower abdo pain x 2-3 months admitted to hospital 2/4/09 because of hypercalcemia

• PMHx of Crohn’s disease, anemia, chronic kidney disease (CKD), and hx +TST

• CXR read as “no active lung lesion”, but CT chest showed “patchy inifltrate versus scarring right upper lobe, ?lytic lesions in thoracic vertebra”

• Bronchoscopy done and specimen sent for AFB; smear and culture negative

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Case #3

• Pt eventually diagnosed with multiple myeloma, and chemotherapy started

• Also diagnosed with liver disease, presumably due to prior EtOH abuse

• INH started by PMD, but stopped after one month due to increasing LFTs (no details available)

• Initial chemotherapy completed 6/09

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Case #3

• Patient readmitted to the hospital 11/3/09 with several month history of cough and 1 week history of altered mental status

• Admission CXR showed RUL infiltrate

• Ammonia level elevated, new onset ascites

• Sputa checked and now 3-4+ AFB

• TB meds started

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Case #3

• Patient continued to have alteration of mental status, progressive elevation of bilirubin

• CKD worsened after trial of aminoglycosides for TB

• Eventually developed multi-organ failure and expired 12/6/09

Important points to remember: TB can kill people, and INH does help to prevent TB disease!

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TREATMENT OF LATENT TB INFECTIONHow long is enough?

0 6 12 18 24

Months of Treatment

Cases per 100

5

4

3

2

1

0

Observed values

Calculated curveCalculated values

Comstock Int J Tuberc Lung Dis. 1999;10:847

• Lower TB rates among those who took 0-9 mo

• No extra increase among those who took >9 mo