LTBI Conundrums - Curry International Tuberculosis …nid...LTBI Conundrums John Bernardo ... Health...

Tools for TB Elimination April 22, 2015 Curry International Tuberculosis Center

LTBI Conundrums: Illustrative Cases 1

LTBI Conundrums

John Bernardo Boston University School of Medicine Massachusetts Department of Public

Health

Objectives

• Review concepts of Infection, Latency

• Cases – Understand:

– How can new tools help the decision process?

– MDR exposures?

– What can be done to encourage adherence to treatment?

Adapted from: Shaler, CR, et al. Clin Dev Immunol. 2012

TB disease progression and major events leading to protection

“window” time time



Primary TB

- Delayed-type Hypersensitivity develops 8-10wk post-infection: TST or IGRA-positive

Latency of M. tuberculosis

• Environment of granuloma favors altered metabolism: • Low pO2 • Reduced CHO • High Fat

• Replication time >>> 20hr. • Loss of acid fast staining properties • Mechanism(s) unknown

• genetic switch?

• Potential for reactivation: TB Disease • Risk factors – 10% lifetime (overall)

- Tubercle bacilli - “dormant”

- Usually positive TST (or IGRA)

- No symptoms

- Normal Examination

- Normal chest radiograph

- NOT infectious

- Sputum smears and cultures are

negative

- Not a “case” of TB

Latent TB Infection



From: Flynn, J Immunol Res, 2011

Outcome of TB Infection

It’s as close as your back yard …

LYNN, Mass. (AP) — Over 30 Lynn Community Health Center employees & 800 patients being tested to determine if they were exposed to tuberculosis after center doctors confirmed a case …"not a reason to panic.“ • Case: 33 y/o physician, ill for 3 months, mis-diagnosed

with “pneumonia,” later diagnosed with pulmonary TB by culture report – Prior treatment with 6mos INH for LTBI (16 yr ago) – Traveled/worked overseas – Large practice, included > 100 children under 5 (+ siblings,

moms, etc.) seen during infectious period

September 9, 2014



Lynn CHC: Contact Investigation

• What do we know? – Patient was surprised!

• Did not even Think TB

– Smear negative/Culture positive • But that was 4 weeks ago (time spt was obtained for culture) • NAAT was not done

– Cavitary disease and coughing • Tried to limit cough when with patients

– DST pending • Recall travel, previous INH: Is this Drug Resistant disease?

– 17% of MA cases with isolates are resistant to at least 1 drug – 7 MA cases MDR in 2013

Special Considerations

• Only one MD at LCHC is trained in TB – Required collaboration and intervention by DPH

• Extensive Contact Investigation was announced – Family, patients and staff at health center: ?focus

• Children <5 y/o were of special concern – Often develop severe forms of TB forms with grave

consequences • e.g., hearing loss, blindness, mental impairment

– Screening included chest radiographs (PA and Lat)*, exams, and TB skin testing – AND preventive treatment

• Skin testing in young children - or IGRA?

• “Window prophylaxis” required - but which drug?

* < 11 y/o get 2 view

Primary TB in a Child



Molecular DST

• Molecular assays for INH, RIF most common • Detect polymorphisms associated with drug resistance

• Performed on clinical specimens or culture isolates

• TAT hours – versus days-to weeks for phenotypic (culture-based) DST

• In-house assays

• Molecular beacons - RT-PCR

• Whole genome sequencing

• Commercial assays • HAIN and INNO-LIPA line probe assays; Cepheid GeneXpert® MTB/RIF *

• Some Issues • Multiple mutations may confer resistance – not identified

• Silent mutations – flagged but not really resistant

* Approved by FDA July, 2013

Molecular Testing

• GeneXpert®MTB/RIF?

– TAT hours; reads MTB complex, Rif resistance (97%)

– Done automatically on smear-pos spt (State Lab)

• NOT done here (smear neg)

– NOT done on isolates

• CDC MDDR Service …

Molecular Detection of Drug Resistance (MDDR) Service at CDC

• Clinical/Program: available to providers

• Make rapid confirmation of MDR TB available • Make laboratory testing data available to clinicians

about second-line drug resistance in cases of Rif- resistant or MDR TB

• Development • Continuous correlation of molecular (genotyping)

results and DST (phenotypic) results • Addition of new drugs and alleles

• Research • Determination of mechanisms of resistance

B. Metchock, CDC



MDDR Service: Drugs and Genes for Panel

Drug Gene(s)

RIF rpoB

INH inhA, katG

KAN rrs, eis

AMK rrs

CPM rrs, tlyA

FQ gyrA

PZA pncA

EMB embB B. Metchock, CDC

Outcomes

• Initially started INH for window prophylaxis – Changed to Rif when prior history (travel, INH

treatment) revealed

• CDC MDDR Service – Results reported back within 5 days – No mutations detected – Confirmed pan-susceptible by culture-based DST

• Options for INH or Rif remained (window or infected)

• Little transmission – No converters in family!

• No new cases were identified

It’s All in the Family

• 31y/o software engineer from India diagnosed with TB – Arrived in US (CA) July, 2014; recently relocated to MA

(October, 2014)

– Presented Oct 2, Ill for 3 months; cough, night sweats, weight loss

• treated w Amoxicillin (CA), Levaquin (MA)

– CXR scattered nodular infiltrates w cavitations

– Sputum smear-POS, GeneXpert®MTB/RIF: Rif resistant

• Molecular susceptibility testing confirmed by CDC MDDR Service: MDR – However embB and gyrA mutations also detected

(EMB and FQN resistance)



10/22/14

Family?

• Lived with wife and infant son (10mos old) • At Home …

– Wife and child TST and IGRA negative (test 1)

• Infant evaluated: – Wife: No symptoms; exam normal, CXR (PA) neg – Child: No symptoms, thriving; exam normal, CXR (PA

and Lat) neg

• Treatment for Contacts? – Wife? – Infant?

Stay Cool …

• Molecular testing suggested High Level Moxi susceptibility – Treatment of MDR-infected contacts?

• CDC: 2 drugs to which isolate is susceptible …

• Treat – Wife? No – Child? ??? – and if Yes, with what? (MDR exposure* – at least!)

• Sputum culture: pos MTB – Phenotypic DST: confirmed MDR w 50% Cipro R at 2ug/ml

(by MIC-CDC); suscept to PZA, PAS, Cycloserine, injectables

* Mase IUATLD J. 18:912, 2014



So…

• Consultation with Pediatrics expert, RTMCC

– Child is ok: watch closely (weekly); no treatment

– Repeat TST, IGRA in 10wk

Done …

• January, 2015

– Child: remained well; repeat TST 4mm, IGRA neg

– Wife: 22mm TST

Just When You Thought It Was Safe…

• Wife (now TST-POS) – Denied symptoms of TB: Felt “fine”

– CXR: Nodular LUL infiltrate, new since 10/2014 film

– Admitted to respiratory isolation

– Sputum smear-POS (<1 organism/hpf), GeneXpert®MTB/RIF POS, Rif R

• Family support? – None; community associates and friends refused to

help (like care for child, …)



CT Same Day

What Now?

• Child (now 12 mos old)

– Had spent whole life with Mom (now sm POS; molecular test POS for Rif-R)

– NOT on treatment (TST now 4mm, IGRA neg)

– Looks and behaves well: Examination normal

– CXR (PA and Lat) negative

– TREAT??

– Repeat referral to RTMCC

• Continue to watch; repeat evaluation in 10 weeks

So?

• Child continued to be seen weekly – Remained well, no treatment – DPH arranged day care while Dad returned to work

• Laboratory – Confirmed Mom’s isolate as MDR TB, same DST as Dad’s

• At 10 weeks (March, 2015) – Examination: normal – CXR (PA and Lat): normal – TST and IGRA: negative

– Whew! (April, 2015) – We hope!! Child continues to be seen frequently



In the Beginning…In a TB Clinic Long, Long Ago…...

• 8 y/o Haitian female (USA-born) presents in the TB clinic 4/88

– Referral from a local NHC; school screening

• TST reported as “positive”

• No symptoms, normal examination

• CXR (PA and Lat) -negative

• Patient recommended for INH treatment

Follow-up…

• None; patient was non-adherent. Lost

• Returns to clinic two years later (3/90) to restart preventive therapy

• No symptoms, normal growth and development;

• No change in x-ray from previous film (4/88)

• Adherence issues reinforced

• Patient returns to clinic monthly and completes therapy in 6 months

Back to the Future……...

• November, 1997: Patient now 18 y/o presents in Pedi ED – Cough x one month, fever, night sweats

– CXR-RUL infiltrate

• Patient admitted to Pedi – Placed on respiratory Isolation

– Initial sputum AFB smears 4+ positive

– Culture +MTB • Pan-susceptible

• Refused to believe diagnosis of TB!



It Just Gets Better……..

• Family of household contacts agree to screening – Mother (TST- ) – Sister (6 y/o; TST-) – Girlfriend living with family (TST-)

• 3 m/o infant (TST 10mm)

• Infant evaluated at Clinic – Examination normal – CXR (PA and Lat) normal – Placed on INH - with DOT by PHN

• Suddenly…

– Girlfriend and infant disappear – Family have no knowledge of her whereabouts – Child was lost to follow-up UNTIL …

Two Years Later …

• Notified from Children’s Hospital (3/99) – 2 y/o girl admitted with TB meningitis

• Original 3 mos old household contact who moved

• RUL infiltrate

• Blind

– Her Mom • Cough x 2 months

• CXR: RUL infiltrate and cavity

• Child and Mom started on treatment – Relocated to another state

Classic Approach to TB Prevention

• Scheduled initial appointment at TB Clinic – Patients have no prior understanding of TB prevention – Process

• Intake – Personal information; risk assessments

• Medical evaluation – Chest x-ray; physical examination

• Treatment recommendation – I am the doctor; you are the patient – 1 month supply of medications; ? Costs, co-pays

• Monthly follow-up visits – Usually at-convenience of clinic

• Lots of defaults (DNKA) – Low completion rates



TB Prevention in the Private Sector

• Providers are not well-educated about TB – Unfamiliar with current standards

• Varying links to expertise in TB and public health – Many non-U.S. trained physicians hold native beliefs about TB

and its prevention (e.g. BCG) • TB prevention is not a priority

– Other health issues usually prevail • Few resources are available to patients

– Most lack health insurance coverage for TB prevention • Coverage for CXR, drugs, …

– Varying links to public health • Poor acceptance of principles of TB prevention among

providers and community

Cultural Approach to TB Prevention

• Tailoring approaches to health care to accommodate community beliefs, perceptions, and needs can be successful – AIDS and community approaches (Africa) – Cultural case management of LTBI (Seattle)

• Hypothesis: Improving community acceptance of TB prevention will result in increased numbers of infected persons completing treatment for LTBI – This will translate to lower incidence of disease in the

community

Cultural Approach to TB Prevention

• Understanding

• Trust

• Accessibility



Community-Based TB Prevention, Boston

Original model; utilized community health centers in neighborhoods with high rates of TB – 75 - 80% of Massachusetts TB cases are non-U.S. born

– Multi-cultural approach, relied on health center staff to provide community link

– Based on program of • assessment of community understanding, beliefs, health practices

• assessment of health center needs, systems of operation

• continuous provider education/training

• community education and information

• patient referral to the public health clinic, and

• monitoring of therapy in the community

1996; TBAA, NHLBI HL-33035

158

51

24

25

21

16

14

Tuberculosis in Boston, 1999 Cases per 100,000 population*

* Based on 1990 US Census Data

6

(Boston 11/100,000)

The Community: Trust and Access

• Identify trusted allies

• Assess Community Needs – For the community and for providers – CBO, church, social club, health center

• Provider education – Didactic sessions and workshops

• Public education: Provide context – Radio, TV shows – Teaching materials in native language; Posters for Community – Presence at health fairs, and – Training of community health educators

• Support Local Clinical Services: BE AVAILABLE!! – Resources, access to specialists



It always comes down to….

• EDUCATION…

• EDUCATION…

• EDUCATION…

Community-Based TB Prevention

Neighborhood Health Center BMC-TB Clinic

PPD + Evaluation

- Chest Radiograph

- Medical evaluation by Pulmonary MD, BUSM

- Baseline LFT’s

- TB/HIV education (HIV counseling/testing)

- Follow-up appointment at NHC

Monthly follow-up at NHC

- Assess adherence

- Evaluate for side effects

- Address other health care issues

- Reinforce TB education

- Dispense medications (DOPT if necessary)

- Forward documentation to TB Program Monitor

- Monthly evaluations, provide medications

- Completion of therapy for LTBI

- Feedback to NHC

- Education program for NHC staff

1996; TBAA, NHLBI HL-33035



Completion of Treatment for LTBIBMC vs NHC

n: BMC: 187; NHC:187

BMC NHC

Site

0

20

40

60

80

Pe

r C

en

t C

om

ple

tio

n

(73)

(136)

Challenge: TB in Boston’s Haitian Community

• High-risk population in Boston-metro area – Represent 9 - 13% of Massachusetts cases annually

• Many failed to complete treatment of LTBI in past

• Divergent health belief systems – Use of folk healers, herbal treatments common

• Frequent travel to Haiti to address health issues

– Distrust of Western medicine • Favored use of private (ethnic) providers

– Prevention of disease not within health framework

• TB is highly stigmatized – Avoidance of association with TB/TB programs

Goals

• Educate the Haitian community and its health providers – To provide current information about TB, clinical TB services

to the community • Utilize accepted channels of communication

– To improve health providers' awareness about TB • Targeted education

– To reduce stigmatization of TB within the community • Create dialog between community and providers

• Encourage providers to screen more high-risk people for TB infection

• Encourage completion of treatment for LTBI



Selected Findings: Metro Boston’s Haitian Community

• TB is more stigmatizing than AIDS – Often viewed as a curse or a test from God

• No framework for “latent infection” – Treatment without symptoms = experimentation

• Translated words may carry different semantics – “Positive” PPD is common in Haiti; is a good thing

• Indicates that BCG is working

• Medications are dangerous – Not “natural;” represent pollutant chemicals – Liquid “safer” than pills – US medicines are appropriate for Americans, not for them

• Mistrust of American physicians/systems – Blood test for LTBI (QFT) may be accepted if presented by their doctor

• Health belief system is complex; poor health literacy – Secular, religious, mystical/supernatural forces

Selected Findings: Metro Boston’s Haitian Community

• Acceptance of program’s objectives by Haitian Community, providers

– Focus group findings: Annie E. Casey Foundation

• Acceptance translates to CHC model

– Focus group findings: TBESC Task Order 12

• Need to re-approach model

– In order to improve TB prevention in high risk communities

Rocket Science?



TB and the Homeless

Priorities

• Early diagnosis of infectious cases – Remove suspects from environment

– Early treatment of active cases: Shattuck Hospital

• Identification of high-risk infected persons: targeted testing – Case contacts, medical co-morbidities

• Treatment of MTB infection – Prioritize effective treatments and settings: TB Clinic,

Primary Care

Principles

• Take it to the clients –

– On their turf and their terms: Education, clinical

• Listen to their concerns and priorities

– Structure interventions around their life activities

• Treat people with respect

– Develop a dialog; understand their problems

• Public Health is Personal!



Clinical Services • Bi-Weekly TB clinic staffed with

2 TB Providers – Pulmonologist – Nurse Practitioner

• Patients referred primarily by nurses – Based on +TST status and/or

assessment of respiratory symptoms and “cough log”

• Radiology/Laboratory services available on-site

• Electronic Medical Record: BHCHP

30 Pine Street Homeless cases 1990; 0 cases since 2010

Num

ber

of

Cases

Quarter

It’s Not Over Homeless Cases by TB Report Date

Springfield, 2009-2014

MDPH: ISIS

Oops!



Work the Problem!

• Work as a TEAM!

• Understand your patients!

• Nurses and staff become the “eyes” and “ears” of TB

• Show consistency with provision of services by credible and recognizable team

• Have an accessible TB team to problem solve and screen potential suspect cases -- available 24/7

• Provide on-going education and training of shelter staff

• Collaborate with practicing PCP’s, nursing staff, and shelter counselors to identify potential patients at risk

• Clients understand TRUST and RESPECT

LTBI Conundrums - Curry International Tuberculosis …nid...LTBI Conundrums John Bernardo ... Health...

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