tuberculosis in san diego diagnostic workup and ltbi … · after this lecture, the participant...
TRANSCRIPT
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
Susannah Graves, MD, MPH
Chief and Medical Director
Tuberculosis Control and Refugee Health
County of San Diego Health and Human Services Agency
DISCLOSURES
No conflicts of interest to disclose
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 2
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
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 3
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
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 4
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”
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 5
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
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 6
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
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 7
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
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 8
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
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 9
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
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 10
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
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 11
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
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 12
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
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 13
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
TB ELIMINATION INITIATIVE
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
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 14
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
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 15
TB ELIMINATION INITIATIVE
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?
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 16
Susannah Graves, MD, MPH
Chief, Tuberculosis Control and Refugee Health
Marti Brentnall, MPH
Education and Outreach Coordinator
Surveillance Reporting and Advice Line
619-692-8610
Tuberculosis Control and Refugee Health Branch
County of San Diego Health and Human Services Agency
THANK YOU!
SUPPLEMENTARY INFORMATION