TB Infection Diagnostics and Treatmentnid... · Sharing the Care: Working Together on LTBI...

Sharing the Care: Working Together on LTBI Treatment and ManagementWebinar

September 24, 2014

Curry International Tuberculosis Center1

TB Infection Diagnostics and Treatment

1

Neha Shah MD MPH

Field Medical Officer

Tuberculosis Control Branch

California Department of Public Health

Centers for Disease Control and Prevention

Curry International Training Center

September 24, 2014

Outline

TB diagnostics

TB Infection treatment Review of TBTC Trial 33

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Experiences from the National Implementation Project

Experiences from California

Innovative ways to provide DOT

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Testing


September 24, 2014


Testing Options

Tuberculin Skin Test (TST)

Interferon‐Gamma Release Assays (IGRAs)In vitro blood tests of cell‐mediated immune response

Measure release of interferon‐gamma following stimulation by antigens unique to TB

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unique to TB

Both TST and IGRAsAre surrogate markers of LTBI

Cannot distinguish between LTBI and active TB disease

TST and IGRAs

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Sensitivity of IGRAs from low- and middle-income countries

6Metcalfe J Z et al. J Infect Dis. 2011;204:S1120-S1129


September 24, 2014


TB Diagnostics Test Characteristics

Specificity (95% CI)

TST with BCG 59 (46–73)

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TST without BCG 97 (95–99)

QFT‐GIT 96 (94–98)

• Menzies, Ann Intern Med, 2007

• Pai, Ann Intern Med, 2008

IGRA vs. TST

Advantages over TST• Not affected by BCG vaccination• No return visit needed for interpretation of test• Not affected by most non‐tuberculous mycobacteria (NTM)

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• Interpretation is more objective

• CDC, MMWR, 2010.

Reading QFT‐GIT Results

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• Source: Dr. Meza


September 24, 2014


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!!!

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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.

TBI Treatment

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Options for treatment of TB infection

Daily 9 months of INH

Daily INH and rifampin for 3 – 4 months

Daily Rifampin for 4 months

Once weekly rifapentine and INH for 3 months (12 doses)

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September 24, 2014


Isoniazid (INH)

Can be used with any HAART regimen

Adherence: Completion rates of 50% or less

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

• Nolan, JAMA, 1999

• Smieja, Cochrane Database Syst Rev, 2000

• Menzies, Ann Int Med, 2008

Rifampin

Can be given as 4 month daily

Efficacy data limited but ongoing study comparing 4RIF to 9INH Recent network meta‐analysis suggests 4RIF

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efficacious compared to placebo

Better completion rates and lower rates of hepatoxicity

• Menzies, 2011 IJMR

• Ziakas, CID 2009

• Staff, Annals Internal Medicine 2014

Rifampin and INH

Rifampin 600mg plus INH 300 mg daily for 3 – 4 months

Limited data on efficacy but likely same as 6INH or

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but likely same as 6INH or 9INH

Possible higher likelihood of side effects

• Menzies, 2011 IJMR

• Ziakas, CID 2009

• Staff, Annals Internal Medicine 2014


September 24, 2014


INH and Rifapentine

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INH‐RPT INH

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• Sterling, N Engl J Med, 2011

No. of patients 3,986 3,745

Administration Directly‐observed therapy Self‐administered therapy

Frequency Weekly Daily

Duration 12 weeks 9 months

Prevent TB Study Results

INH‐RPT INH P‐value

Effectiveness 1.9 per 1,000 4.3 per 1,000 Non‐inferior

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Completion rate 82.1% 69.0% P<0.001

Hepatotoxicity 0.4% 2.7% P<0.001

• Sterling, N Engl J Med, 2011


September 24, 2014


National 3HP Implementation Project

PurposeDetect adverse effects in non‐research settingsMeasure adherence and treatment completion

Assess program impact

Find and characterize breakthrough TB cases

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Find and characterize breakthrough TB cases

Post‐Marketing Surveillance Project Sites

22 volunteer sites participated in study design3 from California: Sacramento, Santa Clara, UCSD

Patients treated from July 2011 –

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Patients treated from July 2011 December 2013

Some type of DOT was used at all sites

(dated 5/24/2013)

National Post‐Marketing Implementation ProjectForms for Doses, Symptoms, and Outcomes

Final Disposition: ☐ Completed INH‐RPT treatment

☐ Stopped INH‐RPT treatment

Date __/__/__

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☐ Lost to follow‐up☐ Died☐ Other☐ Adverse event ☐ Pending Completion of

Alternate Regimen

• Slide adapted from Ho IAULTD 2014


September 24, 2014


National Post‐Marketing Implementation ProjectForm for Adverse Events

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National Post‐Marketing Implementation ProjectData as of October 2013

2134

started therapy

23 Excluded

Active TB, TB 0, index case INH‐resistant

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on treatment

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2061

eligible to complete treatment

1745 (85%)

completed

316 (15%)

Discontinued

179 (57%)

discontinued with symptoms

137 (43%)

discontinued without symptoms


National Post‐Marketing Implementation Project*Side Effects

Symptom# reported SE who had ≥1 dose

N= 2143 %

Any symptom 730 34

Nausea/vomiting 306 14

Fatigue 193 9

Sore muscles/joints 148 7

Fever/Chills 126 6

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Rash/hives 108 5

Abdominal pain 107 5

Dizziness/fainting 102 5

Loss of Appetite 90 4

Numbness/tingling 90 4

Diarrhea 82 4

Other 350 16



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National Post‐Marketing Implementation ProjectSevere Adverse Events

Severe AE: any patient who was hospitalized or died while on therapy

17 reports of hospitalizations 6 on‐site CDC investigations complete

10 in estigations in progress

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10 investigations in progress No deaths

No serious or permanent medical sequelae

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California

3HP is being used in 21 CA jurisdictions

Health department clinics only – 8 (38%)

Private/community providers only – 4 (19%)

Both health department clinics and community providers – 7 (33%)

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p y p ( )

Unspecified – 2 (10%)


September 24, 2014


National Post‐Marketing Implementation ProjectSacramento

MethodsProviding in‐clinic and field DOTMonthly lab monitoring

Results: 95 patients started at time of data collection (now more than 200)

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p ( )

80% completed to date

SE: malaise, gastric discomfort, headache, myalgia lasting 1 ‐2 hours post dose, rare pruritis

Medically managed side effects

One discontinuation due to elevated liver function tests

National Post‐Marketing Implementation ProjectUniversity of California in San Diego

MethodsSeveral alternatives for providing DOT: video, phone, email

Results37 students started therapy

Side Effect #reportingeventamongthosecompleting

therapyN=23

Percent

Nausea 5 13.5

Fatigue 2 5.4

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92% completed to date

1 experienced flu‐like symptoms

Muscle aches 3 8.1

Menstrual irregularities (females, n=20)

3 13.6

Diarrhea 2 5.4

Headache 2 5.4

Other 2 5.4

National Post‐Marketing Implementation ProjectSanta Clara Corrections

MethodsDOT provided at the medication administration window

Baseline and monthly liver function and complete blood count tests

Any adverse event12‐dose therapy

(N=91)

Hepatotoxicity* 1 (1.1)

Dizziness 4 (4.4)

Fever or chills 5 (5 5)

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Results91 patients started therapy85% of these patients completed treatment

18% experienced a side effect 2 discontinued due to drug side effects

Fever or chills 5 (5.5)

Rash/hives 4 (4.4)

Abdominal pain 1 (1.1)

Numbness or tingling 2 (2.2)

Nausea 3 (3.3)


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Alternative Directly Observed Therapy Options

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Options

Video DOT

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Wireless DOT

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Study 33 iAdhere

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Pharmacy‐based DOT

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Community Resources

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Summary

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Summary

IGRAs are good diagnostic tool but be aware of limitations

Short course therapy for TB infection is being implemented nationally with good results and limited side effects California has had good experiences with using this new regimen

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New and improved ways to provide directly observed therapy

TB elimination impossible without treating for TB infection

[email protected]

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

TB Infection Diagnostics and Treatmentnid... · Sharing the Care: Working Together on LTBI...

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