10/11/19 Outline La Laten ent t Tuber ubercul ulosis Infec - - PDF document

▶
10 11 19
SMART_READER_LITE
LIVE PREVIEW

10/11/19 Outline La Laten ent t Tuber ubercul ulosis Infec - - PDF document

Jun 01, 2023 305 likes •451 views

10/11/19 Outline La Laten ent t Tuber ubercul ulosis Infec ecti tion n (LTBI BI) Background 101 101 Screening (Who to T est) T esting Janice Louie, MD, MPH LTBI Treatment Medical Director San Francisco Tuberculosis

slide-1
SLIDE 1

10/11/19 1

La Laten ent t Tuber ubercul ulosis Infec ecti tion n (LTBI BI) 101 101

Janice Louie, MD, MPH Medical Director San Francisco Tuberculosis Prevention and Control Program

1

Slide 2

§ Background § Screening (Who to T est) § T esting § LTBI Treatment

Outline 2 TB TB Epi Epidem demiology gy-U. U.S. (2017)

  • US: 9,105 active TB

cases* (2.8 per 100,000 population)

  • California is a

hotspot (5.3 per 100,000)

  • San Francisco is

super hot (13.1 per 100,000)

*Centers for Disease Control and Prevention TB Data and Statistics: https://www.cdc.gov/tb/statistics/default.htm

3

Sa San Franci cisco

  • TB Cases: 2018
  • Incidence rate of 13.1 per 100,000 (n=118)
  • Non-US Born: 86%
  • Most common countries of origin outside
  • f the US: China, Philippines, Vietnam
  • Median age: 64 years (range 3-95)
  • 49% were ≥65 years of age
  • The median age of TB cases in San

Francisco is increasing.

  • Most of these cases are preventable!

50.352.751.3 56.452.454.550.1 57.258.1 59 59.6 60 64 1 5 2 5 3 5 4 5 5 5 6 5 7 5 2 0 0 6 2 0 0 7 2 0 0 8 2 0 0 9 2 0 1 0 2 0 1 1 2 0 1 2 2 0 1 3 2 0 1 4 2 0 1 5 2 0 1 6 2 0 1 7 2 0 1 8 Age (Years)

TB Case Age Trend Over Time

Me di a n Age

2018 TB Cases by Country of Origin

4

slide-2
SLIDE 2

10/11/19 2

He Health h di dispa parity in n TB: API San n Franc nciscans ns

The TB case-rate in Asian-Americans is 10.8X that in Non-Hispanic White populations

5

~2 ~2.4 m million C Californians w with th l latent T t TB i infecti tion- most are unaware and untreated

1.8M

20% 12%

0.0 0.5 1.0 1.5 2.0 2.5 LTBI preva lence Aware of LTBI Treat ed f or LTBI Millions of persons

U.S.-born Foreign-born

NHANES 2011-2012 applied to California population 6

Estimated 65,111 San Franciscans with LTBI

(2017, CDPH TBCB Report)

6

Slide 7

TB TB Disease vs. (Latent) Tuberculosis Infection (LTB TBI)

Active TB disease Latent TB infection

Cough, fever, weight loss, night sweats No symptoms Abnormal chest x-ray Normal chest x-ray Infectious Not infectious May progress to active TB disease

7 Na Natur ural History y of TB TB

8

Latent TB (LTBI)

(Dormant or “sleeping”)

Active TB disease

Exposure to infectious TB Rapidly develop active TB disease (~1-5%)

  • Children <5 years
  • Immunocompromised/HIV
  • Recent converters

years

Not infected

5-10% over lifetime, depending on risk factors

8

slide-3
SLIDE 3

10/11/19 3

  • Background
  • Screening (Who To Test)
  • Testing
  • LTBI Treatment

Outline 9 10

Risk of false positives is high in a low incidence population

11 12

slide-4
SLIDE 4

10/11/19 4

86% of TB cases in SF are non-US

  • born. Countries
  • f origin for

most cases

  • utside of US

include: China, Philippines and Vietnam. HIV patients have exceptionally high rate

  • f reactivation (7-10%

per year); screen annually

13

Routine testing of persons without risk factors is not recommended and may result in unnecessary evaluation and treatment because of false positive results Note: Age not considered in this assessment, however younger adults have more years of expected life. Some clinicians may choose to prioritize younger non-US born persons

14

Watch out! Patients with abnormal CXR and report that says “lesions consistent with old TB, no evidence of active TB”

15

  • Risk of developing active TB is

up to 19-fold higher

  • TST or IGRA may be negative
  • Check sputa and await culture

results before starting LTBI treatment

  • Data still unclear on what are

best regimens

  • At SFDPH we use INH+ RIF x

4 months or INH x 9 months

Ra Radiog

  • graphic

c lesion

  • ns “con
  • nsistent

t with th inacti ctive TB TB” 16

slide-5
SLIDE 5

10/11/19 5

LTBI with abnormal chest X-ray: 3 cases

A B C

  • Non- US born
  • Asymptomatic
  • QFT+
  • CXR report: “BUL nodules, calcified,

consistent with old granulomatous

  • disease. No active disease.”

What do you do?

Check sputa! Sputa preliminary results:

  • Smear neg x 3, geneXp neg x 1
  • Await cultures (8 weeks)

17

Culture results

A B C Å Yes, Active TB, pan-sensitive Å No, TB 4 (old granulomatous disease, LTBI treatment with INH and rifampin) Å Yes, Active TB, pan-sensitive

18

Pathophysiology of TB lesions: a dynamic state A radiographic interpretation of “old” TB on chest X- ray does NOT rule out active disease

19 20

slide-6
SLIDE 6

10/11/19 6

Ri Risk Fact ctor

  • rs for
  • r Develop
  • ping Acti

Active TB 21 22

  • Children <5 years at high risk
  • f disseminated TB/TB

meningitis

  • Active TB in children is

usually pauci-bacillary:

  • Asymptomatic or atypical

symptoms

  • CXR abnormalities non-

specific: look for infiltrate in lower lobes, mediastinal lymphadenopathy

  • Sputum typically non-

diagnostic, need gastric aspirates x 3 (geneXp often not available)

  • Exposure history important
  • Infants and children <5 yrs

are “sentinels of transmission”

23

§ Background § Screening (Who to T est) § T esting § LTBI Treatment

Outline 24

slide-7
SLIDE 7

10/11/19 7

25 Tu Tuberculin Skin Testing 26

> 5 mm of induration > 10 mm of induration* Considered positive in:

  • Persons with HIV or immunosuppression
  • Recent contacts to an active case of

pulmonary or laryngeal TB

  • Persons with fibrotic changes on chest X-ray

consistent with old TB Considered positive in all other persons recommended for TB screening

Ca Califor

  • rnia TST interpretati

tion

  • n guidelines

27 28

slide-8
SLIDE 8

10/11/19 8

History of BCG vaccination

29

ESAT-6, CFP-10, and proprietary CD8 antigens (absent from all BCG strains and from most nontuberculous mycobacteria with the exception of M. kansasii, M. szulgai, and M. marinum)

30 31

Repeat testing provided valid result (positive or negative) in 68% (Banach Int Jl TB Lung Dis 2011)

32

slide-9
SLIDE 9

10/11/19 9

33

73% false positive rate 12% false positive rate

34 35

§ Background § Screening (Who to T est) § T esting § LTBI Treatment

Outline 36

slide-10
SLIDE 10

10/11/19 10 LT LTBI Treatment Options

Normal CXR

  • Rifampin x 4 months
  • INH + rifapentine x 3 months
  • INH x 6 months
  • INH x 9 months (gold standard)- immunocompromised/HIV

TB-4 (Radiographic evidence of old TB disease)

  • INH + Rifampin x 4 months*

*Jasmer et al. Twelve months of isoniazid compared with four months of isoniazid and rifampin for persons with radiographic evidence of previous tuberculosis: an outcome and cost- effectiveness analysis. Am J Respir Crit Care Med 2000 Nov;162(5):1648-52.

37 Fi First Line: e: Rifam ampin

Multi-center Phase 3 RCT: N= 3443 Rifampin x 4 months vs INH x 9 months Study sites: Australia, Canada, Benin, Brazil, Ghana, Guinea, Indonesia, Korea, Saudi Arabia Findings:

  • Rifampin x 4 months was non-

inferior to INH x 9 months for the prevention of active TB at 28 months

  • f follow-up
  • Higher rate of treatment completion
  • Lower rate of adverse events and

hepatotoxicity

38 39 40

slide-11
SLIDE 11

10/11/19 11

41 First Line: 3-HP by Directly Observed Therapy 42

Multi-center RCT (n=8053) 3HP DOT x 12 weeks vs INH x 9 months Study Sites: U.S., Canada, Brazil and Spain

  • 3HP was non-inferior to INH x

9 months for the prevention of active TB at 33 months of follow-up

  • Higher rate of treatment

completion

  • Lower rate of hepatotoxicity

Prevent TB Study 43

Sel Self Adm dmini nister ered ed-3H 3HP

  • Recommended by CDC June 2018*
  • Based on study of 1000+ adults in Denver, median age 36 years
  • SFDPH protocol:

Inclusion criteria:

  • All adults, who upon mutual assessment by MD and nursing, can be compliant
  • Children <18 years who are able to swallow pills (without crushing) and can be monitored by

a parent Exclusion criteria:

  • Any patient who requires DOPT
  • Any adult where noncompliance is a concern
  • Children who need crushed pills or liquid formulations
  • Children (including adolescents and teenagers) where parents do not agree or are unable to

monitor compliance *MMWR Weekly / June 29, 2018 / 67(25);723–726

44

slide-12
SLIDE 12

10/11/19 12

“52 weeks of INH prevented the most tuberculosis, but 24 weeks prevented the most tuberculosis per case of hepatitis caused.”

Second line- Isoniazid x 6 months

(Use when rifamycin is not tolerated or contra-indicated)

45

*But increased hepatoxicity as duration of INH increases

Second line- Isoniazid x 9 months

Recommended for immunocompromised/HIV

46 Is Isonia iazid id Adverse Events

  • Hepatitis
  • Uncommon in age <20 years
  • Increased risk with older age: ~2% in ages 50-64 years
  • Increased risk with ETOH abuse or chronic liver disease
  • Asymptomatic transaminitis (20%)
  • Peripheral neuropathy (<0.2%); supplement with B6 50 mg
  • Rash
  • Mild CNS effects
  • Note drug interactions: increase Dilantin, carbamazepine and

Antabuse levels

47 Mo Monthly Mo Monitoring

  • Adherence
  • Symptoms:
  • Fatigue, anorexia, nausea/vomiting, abdominal pain
  • Icterus, jaundice, dark urine
  • Rash, itchiness
  • Peripheral numbness
  • LFTS:
  • History of liver disease or ETOH use
  • HIV
  • Pregnancy/post-partum (<3 months)
  • Other hepatotoxic meds (e.g. statins)
  • Age> 50

ATS/CDC LTBI Guidelines 2000 Hold medications if:

  • Symptomatic and LFTS >3X ULN
  • Asymptomatic and LFTS >5X ULN

48

slide-13
SLIDE 13

10/11/19 13

Dosing recommendations in children vary: https://www.cdc.gov/tb/topic/treatment/ltbi.htm

49 50

Ta Take-Ho Home Messages

Targeted Testing takes into account differing risks in populations. Do test:

  • Foreign-born, especially those with medical risk factors for progression to active TB
  • Immunocompromised
  • Contacts
  • Converters
  • Residents of congregate settings
  • Abnormal CXR concerning for old or active TB

Diagnosis

  • IGRA is more specific; preferred in non-US born
  • TST is cheaper, reasonable to use in US born (but beware misinterpretation)

Treatment Options: Short courses are now the standard of care

  • Rifampin x 4 months
  • 3-HP x 3 months
  • INH x 6 months (9 months if immunocompromised)
  • INH x 9 or RIF/INH x 4 months if CXR suggests old TB (rule out active TB first)

51

SF SFDPH TB Preventi tion

  • n and Con
  • ntr

trol

  • l Prog
  • gram

Re Resources

Physician/RN questions

  • Phone: 628 206-8524
  • E-consult
  • E-mail: janice.louie@sfdph.org or Rocio.agraz-lara@sfdph.org

Felix Crespin, Surveillance

  • Questions about possible active case or hospitalization discharge

approval

  • 628 206-3398

52

slide-14
SLIDE 14

10/11/19 14

Qu Questions?

Questions? 53