TUBERCULOSIS IN SAN DIEGO DIAGNOSTIC WORKUP AND LTBI … · After this lecture, the participant will be able to: Describe local epidemiology of tuberculosis in San Diego County and

Susannah Graves, MD, MPH

Chief and Medical Director

Tuberculosis Control and Refugee Health

County of San Diego Health and Human Services Agency

San Diego Civil Surgeons: New Mandatory TB Requirements

Webinar│September 17, 2019 1

TUBERCULOSIS IN SAN DIEGO

DIAGNOSTIC WORKUP AND LTBI TREATMENT





DISCLOSURES

No conflicts of interest to disclose







OBJECTIVES

After this lecture, the participant will be able to:

Describe local epidemiology of tuberculosis in San

Diego County and CA State

Appropriately work up a possible case of tuberculosis

Prescribe short-course treatment for latent TB

recommended by CDC

TB INCIDENCE RATES, SAN DIEGO COUNTY, CALIFORNIA, US, 1987-2018

Cas

es

pe

r 1

00

,00

0

Year

San Diego County

California

United States

0.0

2.0

4.0

6.0

8.0

10.0

12.0

14.0

16.0

18.0

20.0

1987 1993 1998 2003 2008 2013 2018







TB INCIDENCE RATES BY ZIP CODE, SAN DIEGO COUNTY, 2015-2017

0

0.1-3.1

3.2-5.2

5.3-8.5

8.6-43.5

<5000 population

Incidence per 100,000

(3-yr average)

TIP OF THE ICEBERG

Estimated 150,000 – 180,000 (approx 5%) residents in San

Diego have LTBI

Lifetime risk of progression to active disease without

treatment is 5-10% and depends on age and medical

comorbidities

80% of active disease in California is reactivation of latent

infection







CALIFORNIA BURDEN OF LATENT TB

California Department of Public Health, Tuberculosis Control Branch, Report on Tuberculosis in California, 2018

https://www.cdph.ca.gov/Programs/CID/DCDC/CDPH%20Document%20Library/TBCB-TB-Fact-Sheet-2018.pdf

At risk for TB

Treated for LTBI

Untreated population with LTBI

Gap = opportunity

WHO SHOULD YOU TEST FOR TB?

Risk assessment for all patients is recommended by:

American Academy of Pediatrics

U.S. Preventive Task Force

CDC

Your local TB Control Branch

Test those at elevated risk of infection, or progression

“Test to treat”







RISK FACTORS FOR EXPOSURE

• Contact with TB case anytime in your life

• Foreign birth (from a high-prevalence country)

• Binational residence / lifestyle

• Unpasteurized dairy (raw milk, queso fresco)

• Homelessness*

• Incarceration*

• Drug abuse*

*Or children who are exposed to individuals in these circumstances

75% of TB cases in California

TB INCIDENCE RATE BY BIRTH COUNTRY, SAN DIEGO COUNTY, 2015-2017

2.5

22.720.5

46.4 47.7

0

10

20

30

40

50

60

US Outside the US Mexico Philippines Vietnam

No

. cases p

er

100,0

00







RISK FACTORS FOR DISEASE

• Recent contact to a TB case

• Cancer

• Diabetes

• HIV infection

• Renal failure, on dialysis

• Transplant

• Malnutrition / gastric bypass

• Other immune-suppression

• Smoking

FIRST – EXCLUDE ACTIVE TB

Symptoms:

• cough 2wk or hemoptysis

• night sweats

• fevers

• chills

• weight loss

• fatigue

• lymphadenopathy

Obtain Chest X-ray

Careful exam (LNs)

Other diagnostic tests based on

Symptoms, exam, X-ray:

• Biopsy (mass or lymph node)

• 3 sputa for AFB smears and culture

o Send one of these for PCR

(GeneXpert)

• DO NOT TREAT LTBI until cultures

are finalized (6-8 wk)

• If unsure, call TB Control:

619-692-8610







THEN: TEST FOR LTBI

Interferon Gamma Release Assay (IGRA)

Required TB test for all applicants age 2 years or older

Does not cross-react with BCG vaccination

Tuberculin skin test (TST, Mantoux)

Only use for children <2 years when indicated

May cross-react with BCG vaccination

WHAT IS BCG VACCINE ANYWAY?

Bacille Calmette-Guérin (BCG) is a live bacteria, closely

related to Mycobacterium tuberculosis

Administered to infants and children in high-prevalence

countries

not used routinely in the United States

80% effective against TB meningitis and dissemination

Less effective at preventing LTBI and pulmonary TB

Source: CDC

https://www.cdc.gov/tb/topic/basics/va

ccines.htm







IMPORTANT!

IGRA and TST cannot distinguish between latent TB infection

and active TB disease AND

Approximately 10-20% of active TB cases test negative

Patients with symptoms or a positive IGRA/TST should be

evaluated for active TB disease and risk for progression

Medical history

Symptom screen

Chest radiograph (Xray)

FURTHER EVALUATION TO RULE OUT ACTIVE DISEASE

If symptoms or chest Xray abnormal, collect sputum x3:

AFB smear microscopy and culture

TB PCR (eg GeneXpert)

Remember: if culture is sent

Either start empiric multi-drug treatment for active disease

Or await final culture results to rule out active disease before

starting monotherapy (or 2-drug therapy) for LTBI treatment







TREATMENT OF LATENT INFECTION

*Consider administration via DOT

Medication(s) Frequency Duration Doses

Rifapentine

(RPT) + INHWeekly 3 months* 12

Rifampin Daily 4 months 120

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

“While all the regimens are effective, healthcare providers should prescribe the

more convenient shorter regimens, when possible. Patients are more likely to

complete shorter treatment regimens.”

https://www.cdc.gov/tb/topic/treatme

nt/ltbi.htm

RIFAMPIN DAILY (4 MONTHS)

Advantages:

Less hepatotoxicity (~5x less than isoniazid)

Greater adherence (78% rifampin vs. 60% isoniazid)

Disadvantages:

Multiple drug interactions including: Warfarin, oral contraceptives,

methadone, protease inhibitors, tenofovir alafenamide (TAF, many others

Providers may have less experience using rifampin to treat LTBI

May be more expensive for self-pay patients (approx $40/month)

References:

1. 1. Villarino, Am J Respir Crit Care Med, 1997

2. 2. Menzies, Ann Intern Med, 2008

3. 3. Hong Kong Chest Service/Tuberculosis

Research Centre, Am Rev Respir Dis, 1992







WEEKLY ISONIAZID + RIFAPENTINE

Children (≥2 yrs)

Non-inferior to 9 months of isoniazid

HIV

Non-inferior to 9 months of isoniazid

Unable to receive anti-retroviral therapy in first 90 days

Self-administered therapy (SAT)

Non-inferior to 3 months of weekly isoniazid + rifapentine DOT

Villarino, JAMA Pediatrics, 2015

Belknap, CROI, 2015

Sterling, CROI, 2015

WEEKLY ISONIAZID – RIFAPENTINE

Advantages:

Less hepatotoxicity (~ 7x less than isoniazid)

Greater adherence (82% isoniazid-rifapentine vs 69% isoniazid)

Disadvantages:

Multiple drug interactions (similar to rifampin)

Large pill burden once a week

Flu-like / hypersensitivity syndrome (2.2 – 3.8%)

Very expensive for uninsured (approx. $400/month)

Bliven-Sizemore, IJLTD, 2015

Sterling, CID, 2015







PRIORITIZATION

Local epidemiology and prioritization of resources will determine who

should be tested.

San Diego County prioritization:

1. Contacts to infectious cases and recent immigrants (high-burden countries)

2. HIV/AIDS

3. Children <5 years and adolescents

4. Diabetes, dialysis, and other medical risk factors for progression

5. Exposure to high-risk congregate settings (nursing home, shelter, prison)

6. Adolescents

SPECIAL CONSIDERATIONS

Pregnancy/Breastfeeding

Isoniazid preferred

immediately if high risk

OR postpone treatment until 2-3

months postpartum

Children under age 2

use rifampin (4 months) or

isoniazid (6-9 months)

REPORT TO TB CONTROL

Renal insufficiency

Consider dose-adjustment

administer post-dialysis

Contact to resistant case

If INH-resistant treat with rifampin

x4 months

If MDR – quinolone x6-12 months if

sensitive (expert opinion),

otherwise consult an expert

CDC Guidelines

https://www.cdc.gov/tb/publications/ltbi/treatment.htm







TREATMENT MONITORING

Baseline lab tests for:

Liver disease, alcohol use, pregnancy, HIV

Repeat / monitor liver function tests

Abnormal baseline labs

symptoms of hepatitis – hold medication if liver enzymes are >3x upper

limit of normal

OK to continue treatment in asymptomatic patients if liver enzymes are

up to 5x upper limit of normal.

Latent Tuberculosis Infection: A Guide for Primary Health Care Providers

https://www.cdc.gov/tb/publications/ltbi/default.htm

TB ELIMINATION INITIATIVE

INITIATIVE GOAL

Decrease the incidence of active TB cases to

1 case per million by 2040







WHY TB ELIMINATION NOW?

• Better diagnostic methods: IGRA

• Better treatments: short course therapy

• New guidelines: risk-based testing

• Mobilization at global, federal, state and local levels


BUILDING THE PUBLIC HEALTH FRAMEWORKFEDERAL

CDC Division of TB Elimination

National TB Controllers Association

STATE

California Department of Public Health

California TB Controllers Association

California TB Elimination Action Committee

LOCAL

Partners in TB Elimination







ELIMINATION GOALS IN SAN DIEGO COUNTY

ACTIVE DISEASE TARGETS

0

50

100

150

200

1985 1995 2005 2015 2025 2035

-16% per year

Target Rate Target Year

Current Status

California 53 per million 2018

San Diego 68 per million 2018

Pre-elimination <10 per million 2025

Elimination <1 per million 2040

Cas

es

pe

r m

illi

on

Year

TB ELIMINATION STAKEHOLDERS & ROLES

•Interrupt transmission

•Leadership and consultation

•Dissemination of best practices

Public Health Department

•Risk assess

•Diagnose, treat and reportHealthcare Providers

•Advocacy and support

•Includes persons with TB and LTBI experiences and their representativesCommunity

•Educate regarding risk and resourcesSchools and Universities

•Screen and treatShelters, Correctional

Facilities

•Leadership, consultation, collaboration

•Reporting of binational and transnational cases (CureTB)

•Shared strategies for tuberculosis treatment and control

Border and Binational Partners

•Research and development of new tools

•Funding of implementation pilotsPharma & Biotech








Initial meeting of planning group

October 2, 4:00- 5:30pm – contact us if interested to attend

Goal: evidence-based approach to implement risk-based TB screening and LTBI

treatment

Areas of focus (meeting 1):

Get an overview of populations at risk and initiative goals

Define work groups for different stakeholders & set timeline to define goals and

work plans.

Stakeholders include: occupational health, civil surgeons, primary care, military,

schools, universities, shelters and drug treatment programs, correctional facilities

Questions?








Chief, Tuberculosis Control and Refugee Health

[email protected]

Marti Brentnall, MPH

Education and Outreach Coordinator

[email protected]

Surveillance Reporting and Advice Line

619-692-8610

Tuberculosis Control and Refugee Health Branch


THANK YOU!

SUPPLEMENTARY INFORMATION

mailto:[email protected]

mailto:[email protected]

Documents

TUBERCULOSIS IN SAN DIEGO DIAGNOSTIC WORKUP AND LTBI … · After this lecture, the participant will be able to: Describe local epidemiology of tuberculosis in San Diego County and