Diagnosing and Treating TB Infection: A Brief Overviewnid]/6...Diagnosing and treating TB infection:...

Diagnosing and treating TB infection: a brief overview 1

Diagnosing and TreatingTB Infection: A Brief Overview

Ann Raftery, RN, PHN, MSOakland October 2019

Latent TB Infection DefinitionsCDC The presence of M. tuberculosis organisms (tubercle bacilli)

without signs and symptoms or radiographic or bacteriologic evidence of TB disease.

WHO A state of persistent immune response to stimulation by

Mycobacterium tuberculosis antigens without evidence of clinically manifested active TB.


Risk Factors for TB InfectionThe chance of INFECTION Increases when… The concentration of TB bacteria circulating in

the air is greater Coughing; smear-positive; cavitary disease Poor ventilation; small enclosed space

More time is spent with the infectious person (frequency and duration)

Exposure occurs in an area where the bacteria can easily survive (no UV light)

Risk Factors for Progression of Infection to TB Disease


Risk Factors for Progression of Infection to TB Disease (2) Recent infection (within 1-2 years of infection)

Conditions/treatment that impairs immune control of M.tb

Ai J-W, et al. Emerging Microbes and Infections (2016) 5, e10; doi:10.1038/emi.2016.10

Condition (partial list) TB riska

HIV/AIDS 10 - 100

Organ-transplant recipients 20 - 70

Chronic renal failure requiring dialysis 6.9 - 52.5

Taking TNF-alpha blockers 1.6 - 25.1

Silicosis 2.8

Fibronodular disease on CXR 6 - 19

Diabetes mellitus 1.6 - 7.83

Smoking 2 – 3.4a Relative risk of TB compared to the general population

“Unfocused population-based testing is not cost effective or useful and leads to unnecessary treatment. TB testing activities should be conducted only among high-risk groups, with the intent to treat if LTBI is detected” – CDC’s Guide for Primary Health Care

Providers

Target TB Testing


TB Risk Assessment

https://www.cdph.ca.gov/Programs/CID/DCDC/Pages/TB-Risk-Assessment.aspx


Testing for LTBI


Oxford Immunotec, T-SPOT.TB

Qiagen, QFT

Available Test Options

TST= Tuberculin skin test; IGRA = Interferon-gamma release assay

Correct Administration of TST 0.1 ml of 5 TU PPD Intradermal: Hold the needle

(bevel up) almost parallel with the skin

– Hold the skin taut above the injection site

– Insert needle at a 5-15 degree angle just beneath the surface of the skin (into the dermis)

– 27-gauge needle

Wheal 6 - 10mm diameter

If no wheal, place again.

Do not cover site.


Immune System’s Response to TST

Immediate erythema or other hypersensitivity reactions to the ingredients of tuberculin PPD may occur at the injection site.

These reactions disappear by 24 hours, and should not be confused with delayed-type hypersensitivity reactions.

Document hypersensitivity reactions.IGRA’s can be used in place of TST for

these individuals.

• Read at 48 to 72 hours• Measure induration

– Not erythema

• Record in millimeters– Not “negative” or “positive”

• 3 cut off points to determine if the TST is positive (≥ 5mm, ≥ 10mm, ≥ 15mm) based on risk factors

You can read a positive reaction after

72 hours, but not a negative. Repeat if not read within 72 hours.

Reading TST Result


Induration of ≥ 5mm HIV positive persons Recent contacts of TB

cases Fibrotic changes on CXR

consistent with prior TB Patients with organ

transplants or other immunosuppression Prednisone therapy

(15mg/day > 4 weeks) TNF-alpha antagonists

Induration of ≥10mm Recent arrivals from high prevalence countries IVDU Residents/employees - high-risk congregate

facilities (health care, prisons, shelters. . .) TB lab personnel Children < 4 years of age Children exposed to adults in high risk

categories Persons with “high-risk” medical conditions

Silicosis - Diabetes - Gastrectomy Chronic Renal Failure - Jejunal Bypass Hematologic Disorders/ Leukemia/

Lymphoma Cancers, particularly Head/neck and Lung Low body weight <10% below ideal body

weight

Induration of ≥15mm• Persons with no risk factors

Interpreting TST Result

TST Performance - BCG

Bacille Calmette-Guerin (BCG) A vaccination given usually shortly after

birth

Impact of BCG vaccination on TST result is strongly associated with age of BCG vaccination: Greatest when BCG given after 1 year

of age BCG in infancy has little effect on TST

>10 years after vaccination

BCG World Atlas http://www.bcgatlas.org/index.php

Image credit: WHO

Source: Farhat M, Greenaway C, Pai M, Menzies D.(2006) IJTLD.10(11):1192-1204


IGRAs (2011) QFT T-Spot

Initial Process Process whole blood within 16 hours

Process peripheral blood mononuclear cells within 8 hrs (30hr if T-Cell Xtend used)

MTB Antigen Single mixture of synthetic peptides representing ESAT-6, CFP-10, & TB7.7

Separate mixtures of synthetic peptides representing ESAT-6 & CFP-10

Measurement IFN-g concentration Number of IFN-g producing cells (spots)

Possible Results

Positive, negative, indeterminate Positive, negative, indeterminate, borderline

https://www.cdc.gov/tb/publications/factsheets/testing/igra.htm

Tuberculin Skin Test (TST)Pros: Inexpensive Low tech; can be done anywhere

Cons: Patient must return in 48-72 hrs Skill required for placing, reading and

interpreting Relatively more staff time required May cross react with BCG or non-

tuberculosis mycobacteria (NTM) False Negatives:

• Immunosuppressed

Interferon Gamma Release Assay (IGRA)Pros:- Only one visit needed- Results can be ready within 24 hours- No Cross reactivity with BCG Vaccine- Less Cross reactivity with other NTMs

Cons:- May be expensive- Blood samples must be processed 8-30 hours after collection (logistics required)

- Errors in collecting, transporting, running, or interpreting assay can decrease accuracy of test result

- Indeterminates

NOTE: A negative test does not exclude the diagnosis of LTBI or TB disease!

Which Test to Use?


Test Selection Guidance IGRAs are preferred method of testing for:

Groups of people who have poor rates of returning to have TST read

Persons who have received BCG vaccine

TST is the preferred method of testing for: *Children under the age of 2

* As per American Academy of Pediatrics (2019)

http://www.tstin3d.com/en/calc.html


Treatment for Latent TB Infection

Rule Out Active Disease Before Treatment

1. Symptom screen

3. Sputum collection

2. Chest x-ray

• Cough• Hemoptysis• Weight loss• Fevers/night sweats• Extreme fatigue

• Infiltrate• Cavitary lesion• Nodule• Effusion• Hilar lymph adenopathy

• AFB smear & culture• MTB PCR/NAAT

Images: 1. MedlinePlus.gov 2. Adobe Stock Images 3. CDC.gov, TB 101 for Healthcare Workers


Recommended Regimens for LTBI

Drug(s) Duration Abbr Interval # DosesIsoniazid & Rifapentine

3 months 3HP Once weekly 12

Rifampin 4 months 4R Daily 120

Isoniazid 9 months 9H Daily 270

Twice weekly 76

6 months 6H Daily 180

Twice weekly 52

Adapted from: CDC, Targeted Tuberculosis (TB) Testing and Treatment of Latent TB Infection slideset (9/2016)

IMPORTANT! Completion of therapy is based on the total number of doses taken, not duration alone

Special Situations: Fibrotic Lesions Extremely important to rule out active TB prior to

initiating treatment for LTBI Send sputum for AFB smear and TB culture

Acceptable regimens include: 3 months of INH and Rifapentine (12-doses once weekly) 4R (with or without INH) 9 months of INH

If high TB5, some will treat with RIPE and reevaluate after M2. If cultures obtained at baseline are negative and CXR unchanged:

LTBI treatment complete


Special Situations: HIV co-infection

Consult an expert in managing HIV and TB INH regimen is preferred; 9 mo’s instead of 6 mo’s is

optimal (270 doses w/in 12 months) 4R or 3HP* are accepted alternatives BUT… Assessment for potential drug-drug interactions is essential

prior to treatment initiation in patients on HAART RIF and RPT are generally contraindicated for persons

taking protease inhibitors Rifabutin with dose adjustments can sometimes

be substituted for Rifampin Seek expert consultation

* MMWR. June 29, 2018 / 67(25);723–726; MMWR 2011;60:1650–3

Special Situations: Pregnancy Women at high risk for progression to TB

disease should not delay LTBI treatment HIV, close contact, converter Monitor carefully - hepatotoxicity risk

INH daily or twice weekly (with B6) is preferred regimen

If cannot take INH, consult with TB expert (4R or wait?)

Breast-feeding not contraindicated B6 for baby?

*Not necessary unless baby also taking INH

*Red Book, 3rd ed. (2017). pg. 678


Special Situations: Pediatric

Table source: American Academy of Pediatrics (2019).aDosage from CDC. Recommendations for use of an isoniazid-rifapentine regimen with direct observation to treat latent Mycobacterium tuberculosis infection. MMWR Morb Mortal Wkly Rep. 2011;60(48):1650–1653.

Special Situations: Drug-Resistance

Contact to MDR-TB Consult an MDR-TB expert Follow closely for 2 years after last exposure

Contact to infectious INH-resistant TB 4R for all ages


Case Management for LTBI Treatment

Case Management: LTBI Treatment

Conduct an initial assessment

Provide patient education at each encounter

Ensure monthly face-to-face visit with a clinician Assess adherence

Assess for side effects/adverse effects

Refer for further clinical evaluation when indicated

Coordinate care including referral for other support services as indicated

Outreach between visits to encourage adherence with clinic appointments and for follow-up

Closing the case


Communicating the Value of Treatment and Addressing Patient Questions/Concerns

2) talk to my doctor about treatment

Yes. It is most likely your test result means you are

infected with TB. The good news is, we have several treatment options for TB

infection…


Communicate the Value of Treatment and Address Patient Questions/Concerns

Common Questions “I don’t feel sick.

Why should I take this medicine?”

Messages to Relay You are infected with TB germs.

TB germs can hide in the body for years. People with hidden (latent) TB do not feel sick; however, TB germs can “wake up”, make you ill, and can spread to loved ones…

“Why do I have to take the medicine for so long?”

TB is a slow-growing germ, so treatment of TB infection takes longer than antibiotics you take for other infections…

LTBI Treatment: Monitoring*Routine baseline/follow-up laboratory testing not required EXCEPT… HIV co-infection Pregnancy or early postpartum History of liver disease Regular alcohol use

References: *ATS/CDC. Targeted tuberculin testing and treatment of LTBI (2000). MMWR

• Baseline LFTs• Repeat LFTs if

abnormal baseline or if at risk for hepatic disease

Consider also for those > 50 y/o taking a statin drug Baseline hep serology – those from high-incidence areas

for Hep B and C

Injection drug use Use of medications with known possible interactions

**3HPAlso:

**Borisov AS, Bamrah Morris S, Njie GJ, et al. Update of rec’s for use of once-weekly INH-RPT regimen... MMWR 2018;67:723–726.


LTBI Treatment: Monitoring (2) Face-to-face assessment monthly for: Treatment adherence Symptoms of hepatitis or other side effects Anorexia, nausea or vomiting RUQ abdominal pain Fatigue or weakness Dark urine Rash Peripheral neuropathy

Managing Missed Doses Extend or re-start treatment if interruptions were

frequent or prolonged enough to preclude completion

Completion of treatment for LTBI: 3HP - 12 doses w/in 16 weeks 4R – 120 doses w/in 6 months 6H – 180 doses w/in 9 months 9H – 270 dose completed w/in 12 months

When treatment interruption is >2 months, patient should be reexamined to rule out TB disease

Recommend and arrange for DOPT or VDOPT as needed

References: *ATS/CDC. Targeted tuberculin testing and treatment of LTBI (2000). MMWR


Drug Information

RIF Side Effects & Patient InfoSide Effects Pruritus +/- rash ~ 6%

Less common: Hepatotoxicity ~ <1%-2.7%

(↑ w/INH, PZA) Hyperbilirubinemia ~ 0.6% GI upset, flu-like syndrome

(more common with intermittent dosing)

Hypersensitivity ~ 0.3% Hemolytic anemia and

thrombocytopenia ~ <0.1%

Patient Info/Counselling Body fluids (tears, sweat, urine)

will turn orange; this is expected and not harmful

Report any experience of: Rash Flu-like symptoms (fever/chills) Unusual tiredness Loss of appetite (LOA) GI upset

Best taken without food but small amount food is ok

Many drug-drug interactions!! IMPORTANT: Avoid oral hormone-

based birth control


Drug-Drug Interactions Resources

https://www.heartlandntbc.org/products/

TB Drug-related Resources TB Free CA

https://www.cdph.ca.gov/Programs/CID/DCDC/CDPH%20Document%20Library/Latent%20TB%20Starter%20Kit%20for%20Providers/3HP_drug_interactions.pdf

DHHS AIDS-info (HIV-specific)https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent- arv/27/tb-hiv

Heartlandhttps://www.heartlandntbc.org/products/


RPT Side Effects & Patient InfoSide Effects* Hepatotoxicity Flu-like symptoms Thrombocytopenia Hypersensitivity Hypotension Hyperbilirubinemia

Rash and arthralgia

Patient Info/Counselling Body fluids may turn orange; this is

expected (caution re. staining of contact lenses or dentures)

Report any experience of: Rash, fever or chills Unusual tiredness or LOA Dizziness or fainting

Drink plenty of water on the days you take this medicine

Small amt food with medicine is ok Drug-drug interactions similar to

RIF IMPORTANT: Avoid oral hormone-

based birth controlPill burden!*Reference: Egelund EF & Peloquin CA. Rifapentine for the treatment of latent tuberculosis, (2016). Expert Rev Clin Pharm, 9:10, 1253‐1261

Most common

INH Side Effects & Patient InfoSide Effects Asymptomatic ↑ ALT ~12-15% Rash ~ 2% Fever ~ 1.2% Overt hepatotoxicity

~ 1% -2.7% (↑ w/RIF, PZA) Discontinue if transaminases ↑

> 3 X ULN with symptoms; OR

↑ > 5 X ULN Neuropathy ~ <0.2%

(B6 supplement 25-50mg/day) CNS ~ (restlessness, insomnia,

dysarthria, seizures) Lupus-like syndrome

Patient Information This medicine interacts with

other medicines so it’s important to know what other medications or OTC/herbal medicines you may be taking

Report any experiences of: LOA, tiredness or weakness

Stomach pain, N/V Numbness or tingling (hands/toes)

Dark urine, yellow skin or eyes

Blurred vision or eye pain


Drug-Drug Interactions - INHINH

Hypoglycemics Monitor glucose, may ↑ BG

Acetaminophen ↑ hepatotoxicity

Anticoagulants ↑ anticoagulant effect

Benzodiazepines ↑ toxicity

Anti-epileptics ↑ toxicity of carbamazepine and phenytoin

Disulfiram (Antabuse) Psychotic episodes

Haloperidol ↑ toxicity antipsychotics

Ketoconazole ↓ efficacy of ketoconazole

Dilantin ↑ toxicity antiepileptic

Theophylline ↑ toxicity theophylline; monitor levels

Valproate ↑ hepatic and CNS toxicity

LTBI-Related Resources for Community Providers


LTBI Videos for Healthcare Providers

Available at: https://www.currytbcenter.ucsf.edu/products/latent-tb-videos-healthcare-providers

Other topics: Why should I get

tested for latent TB?

Why do I need treatment for latent TB?

CDC LTBI Resources https://www.cdc.gov/tb/publications/ltbi/ltbiresources.htm


Patient Information Resources

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

Nursing Guide for Managing SE’s

Designed as a reference guide so nurses can quickly: Identify symptoms that may

indicate a drug-related side effect

Assess for severity as well as potential contributors

Intervene appropriately in order to: minimize patient discomfort,

reduce side effect progression, and

ultimately support successful treatment completion


Summary Many resources available to assist providers with diagnosis and

treatment of latent TB infection

Important to rule out active TB prior to initiating treatment for latent TB infection

Anti-TB drugs have associated adverse effects that require some monitoring and management. Drug interactions are numerous for RIF (RPT) and many for INH; careful medication history is important prior to LTBI treatment start

TB consultation available through state, local health and TB Centers of Excellence: Curry International TB Center = (877) 390-6682

Rutgers Global TB Institute = (800) 482-3627

Heartland National TB Center = (800) 839-5864

Southeastern National TB Center = (800) 482-4636

Acknowledgements Cherie Stafford, MSN, MPH

TB Nurse Coordinator, Arizona Department of Health Services

Shereen Katrak, MD, MPHMedical Officer, CDPH/TB Control BranchAssistant Clinical Professor, Div of Infectious Disease, UCSF

Rupali Jain, PharmD, BCPSUniversity of Washington Medical Center

Chis Keh, MDPublic Health Medical Officer, CDPH/TB Control BranchAssistant Clinical Professor, Div of Infectious Disease, UCSF

Lisa Chen, MDPI/Medical Director, Curry International TB Center, UCSF

Centers for Disease Control and Prevention

Diagnosing and Treating TB Infection: A Brief Overviewnid]/6...Diagnosing and treating TB infection:...

Documents

Transcript of Diagnosing and Treating TB Infection: A Brief Overviewnid]/6...Diagnosing and treating TB infection:...