LTBI in Alaska ALASKA...72 year-old Vietnam-born female seen in your clinic for routine primary...

Latent TB Infection (LTBI) Basics

Lisa Chen, MDNeha Shah, MD, MPH

LTBI in Alaska: What You Need to KnowNovember 8, 2018 1

LTBI in Alaska

Lisa Chen MD & Neha Shah MD MPH

Bethel, Alaska, November 2018

ALASKA

Disclosures

None

The findings and conclusions in this presentation are those of the presenter and do not necessarily represent the views of CDC.




Objectives

At the end of this session, participants will be able to:

1. Identify at least 3 groups who are at risk for tuberculosis and should undergo screening to prevent tuberculosis disease and transmission

2. Discuss pros and cons for the tuberculosis skin tests (TSTs) versus interferon-gamma release assays (IGRAs) and how they may apply to different risk groups to improve application in clinical practice

3. List four recommended treatment options for latent tuberculosis infection (LTBI) and describe the advantages versus disadvantages to each to inform clinical judgment in choosing the optimum regimen for patient care

Continuing Education Credits

To receive your continuing education hours, you must:

1. Sign-in2. Attend the entire training3. Complete the online evaluation by Thursday Nov. 15th

URL: bit.ly/BethelEvaluation

CME/CEU questions can be directed to [email protected]

Materials available online! URL: bit.ly/BethelTrainingMaterials

mailto:[email protected]




Why are we here?

We want to protect our

patients from developing TB in order for them to

lead happy, healthy lives

Key Points

Who should I test for LTBI?

Birth, travel or residence (>1 month) in a country 1 with an elevated TB rate

Immunosuppression

Close contact to someone with infectious TB disease during lifetime

Alaskan Native




Key Points

How should I test for LTBI?

IGRA (blood test) preferred for anyone aged 2 or older

Key Points

How should I treat LTBI?

12-dose Isoniazid (INH) +Rifapentine

§ 1 dose per week x 12 weeks

Rifampin (RIF) daily x 4 months

Isoniazid daily x 9 mo.

Safest HIV-infected individuals




Part 1: What is latent TB infection?

9

How do you explain LTBI?




What were your key words?

Spectrum of disease

12Dheda K, Lancet, 2016

A – ClearanceB – Latent infectionC – Pulmonary infectionD – Disseminated infection




Part 2: Why test?

14




Common patient beliefs about TB testing

I was vaccinated so I will be positive

I do not need to be tested, everyone is positive in my country

ASK: What have you heard about testing?

How do TB Cases Occur in California?

* France et al, Am J Epidemiol. 2015

16

13% RecentTransmission

7.5% Importation

CDC plausible source case method*

79.5% Activation of remote infection




LTBI Prevalence 2011-2015

M. Hadid, EID 2017

Spectrum of disease

18Dheda K, Lancet, 2016




10% TB Cases Die

More people die from TB in the world than any other infectious disease

(Global: 1.6 million TB deaths in 2017)

TB elimination




Part 3: Who to test?

21

What kind of workup would you do?

50 year-old Alaskan-born female who has been coughing and was treated with Z-pack for pneumonia without improvement.

72 year-old Filipino female immigrated 10 years ago seen in your clinic for routine primary care. Previous HbA1c = 6.0.

38 year‐old Native American male who is entering a substance treatment program for narcotics and heavy alcohol use.

1 year-old female who brings you a paper saying she needs TB testing for school entrance whose grandfather was just diagnosed with TB




What is targeted testing?

23


Immunosuppression


Alaskan Native

Risk Assessment




Why not test everyone?

Testing populations with low prevalence will result in many false-positive results

25

Prevalence of latent TB infection

Proportion of positive teststhat are false

U.S. born 2.8% 46%

Non-U.S. born 16% 12%

Part 4: When else should I think of TB?

28




Cases

45 year‐old homeless man with heavy alcohol use was identified as a close contact to a highly infectious TB case

Cough for last 1 week

Bilateral infiltrates

IGRA positive

What would you do?

Clinical history?

CXR

IGRA/TST

What would you do now?

What kind of workup would you do?

50 year-old Alaskan-born female who has been coughing and was treated with Z-pack for pneumonia without improvement.

72 year-old Filipino female immigrated 10 years ago seen in your clinic for routine primary care. Previous HbA1c = 6.0.

38 year‐old Native American male who is entering a substance treatment program for narcotics and heavy alcohol use.

1 year-old female who brings you a paper saying she needs TB testing for school entrance whose grandfather was just diagnosed with TB




Wait – one more time – what do you do if the TB test (TST or IGRA)

is positive?

Part 5: How to test?




What would you do in this situation?

72 year-old Vietnam-born female seen in your clinic for routine primary care. On prior diabetes screening was noted to have an HbA1c = 6.0 and was TST+

What would you use to test the following person?


45 year-old Alaska-born Native American individual who is HIV positive with CD4 of 200 and has a negative TST







24 year-old health care worker who just moved here from Wyoming with no risk factors but has a TST + test for employment screening

Testing Options

TB skin test




Testing Options

Interferon-Gamma Release Assays (IGRAs)➢Measure release of interferon-gamma

following stimulation by antigens unique to TB

Recommended for anyone 2 years of age or older

Testing Options

How to read: ➢ Measure induration (not erythema) at 48-72 hrs

➢ Record millimeters

Positive test:➢ ≥ 5mm for immunosuppressed including HIV,

recent contacts

➢ ≥ 10mm for all others with TB risk




Advantage of IGRA over TST

Not affected by BCG vaccination

Interpretation is more objective

No return visit needed for interpretation of test

Patients and providers may lack confidence in TST results

39

CDC, MMWR, 2010 | Pai, Clin Micro Rev, 2014

What if I am not confident the test results are correct?




Repeat Testing

Individual at high risk where missing LTBI has serious consequences

If initial test is negative, REPEAT

Person is considered infected if either test is positive.

Repeat Testing

Unlikely to be infected but testing required.

A second test if the initial is positive ➢Person is considered infected if both tests are positive.







24 year-old health care worker who just moved here from Wyoming with no risk factors but has a TST + test for employment screening

TSTs and IGRAs

19% of all confirmed TB cases have a negative skin test

39% of HIV-positive TB cases are TST negative

Negative IGRA or TST does NOT rule out TB!!!

• CDC, National TB Surveillance System, 2000–2011

• Auld, BMC Infectious Disease, 2013

• Sester, Eur Respir J, 2011




Summary

IGRA (blood test) preferred for anyone aged 2 years or older

Part 6: How to treat?

46




Treatment Regimens for Latent TB Infection

Medication(s) Frequency Duration Doses

Rifapentine (RPT) + INH Weekly 3 months 12

Rifampin Daily 4 months 120

Isonizaid (INH) Daily 6–9 months 180 - 270

47




INH-RPT INH

Administration Directly-observed therapy Self-administered therapy

Frequency/duration 12 weekly doses 9 months daily

Effectiveness 1.9 per 1,000 4.3 per 1,000

Completion rate 82.1% 69.0%

Hepatotoxicity 0.4% 2.7%

INH-RPT by Self-Administered Therapy

Self-Administered

Self-Administered with reminder texts

DOT

Completion rate 77.9% 76.7% 85.4%

Hepatotoxicity 0.9% 1.5% 0.3%

B. Belnap 2017




Mensies et al, 2018

Rifampin INH

Duration 4 months 9 months daily

Effectiveness 0.05 per 100 0.05 per 100


Hepatotoxicity 0.3% 1.5%




Rifampin INH

Duration 4 months 9 months daily

Effectiveness 0 cases of TB 1 case of TB


Serious Adverse Event

0 0

Isoniazid (INH)

When taken properly, very effective

Completion rates of 50% or less

Hepatotoxicity: Incidence of hepatitis estimated at 1 per 1,000 ➢ Also rash and neuropathies

Can be given to individuals on ARVs

• Nolan, JAMA, 1999

• Smieja, Cochrane Database Syst Rev, 2000

• Menzies, Ann Int Med, 2008




LTBI Treatment : INH – Why 9 months?

0 6 12 18 24

Months of Treatment

Cases per

100

5

4

3

2

1

0

Observed values

Calculated curve

Calculated values

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

• 9 months appears optimal

• 6 months less efficacious

• No significant gains if rx

extended to 12 months

Maximize medical benefits

Less hepatotoxicity & better completion

or vs.




Summary

Medication(s) Frequency Duration Doses

Rifapentine (RPT) + INH Weekly 3 months 12

Rifampin Daily 4 months 120

Isonizaid (INH) Daily 6–9 months 180 - 270

57

Part 6: Case Management

58




Commonly asked questions from patients

Can I infect my family?

Will I be able to work?

Will I die of this disease?

Will my community shun me?

Why should I bother with treatment if I feel fine?

Case Management

Monthly patient checks




Date: Dose/Month:

__/__/__0

Baseline

__/__/__1

__/__/__2

__/__/__3

__/__/__4

__/__/__5

__/__/__6

__/__/__7

__/__/__8

__/__/__9

__/__/__10

__/__/__11

__/__/__12

No adverse reaction ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐

Loss of appetite ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐

Nausea or vomiting ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐

Yellow eyes or skin ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐

Diarrhea ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐

Rash/hives ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐

Fever or chills ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐

Sore muscles or joints ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐

Numbness or tingling ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐

Fatigue ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐

Dizziness/fainting ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐

Abdominal pain ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐

(Other)-________________

☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐

Treatment stopped or held (complete AE report on last page) ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐




Summary

Key Points: Who to test?

Use a risk based approach to testing

Patients should be evaluated for TB risk factors regardless of age

64


Immunosuppression


Alaskan Native




Key Points: How to Test?

IGRA preferred for everyone over the age of 2 years

Positive test does not rule out active TB disease

How should I test for LTBI?

IGRA (blood test) preferred for anyone 2 years of age or older

Key Points: What to treat with?

Short course regimens have highercompletion rates and are lesshepatotoxic

Treatment of LTBI is key to TB Elimination

How should I treat LTBI?

12-dose Isoniazid (INH) +Rifapentine

§ 1 dose per week x 12 weeks

Rifampin (RIF) daily x 4 months

Isoniazid daily x 9 mo.

Safest HIV-infected individuals




Resources

tbfreecalifornia.org

currytbcenter.ucsf.edu

The findings and conclusions in this presentation are those of the presenter and do not necessarily represent the views of CDC.

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LTBI in Alaska ALASKA...72 year-old Vietnam-born female seen in your clinic for routine primary...

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