Evaluation and Management of the Patient with Latent Tuberculosis Infection (LTBI) CURTIS FOWLER MPT,PA C ASSISTANT CLINICAL PROFESSOR UNIVERSITY OF THE PACIFIC Learning objectives Recognize the appropriate screening population for LTBI. Determine the most appropriate screening method based on patient risk and history. Correctly interpret findings of LTBI testing. Understand the benefits of treatment for LTBI. Review current treatment recommendations for LTBI. Disclosures none
Source information WHO,CDC,IDSA http://www.who.int/publications/guidelines/tuberculosis/en/ http://www.idsociety.org/guidelines/patient_care/idsa_practice_guidelines/inf ections_by_organism/bacteria/tb_in_adults_and_children/ https://www.cdc.gov/tb/publications/guidelines/default.htm Mycobacterium Tuberculosis (TB) Worldwide 1/3 of the world is infected (latent). i.e., 1/3 of the worlds population is acting as a reservoir for TB 5 10% lifetime risk of developing active infection. 5% in the first 2 years after infection Another 5% at some point in their lives. 8 million new cases of TB per year worldwide. 2 million deaths worldwide per year WHO,2011 https://commons.wikimedia.org/wiki/file:globe.svg Mycobacterium Tuberculosis (TB) United States More than 11 million people in the United States have LTBI. 4% of the total population In 2015, a total of 9,536 new active TB cases were reported in the United States. 80% were related to untreated LTBI U.S. Preventive Services Task Force Recommendation Statement: Screening for Latent Tuberculosis Infection (LTBI) in Adults Centers for Disease Control and Prevention Division of Tuberculosis Elimination September 2016 https://commons.wikimedia.org/wiki/file:united_states_on_the_globe_(north_am erica_centered).svg
Mycobacterium Tuberculosis (TB) California In 2016, California reported 2,062 new active TB cases. 80% were due to reactivation of LTBI 13% resulted from recent transmission 7% were imported from outside the United States Tuberculosis Control Branch, Report on Tuberculosis in California, 2016. California Department of Public Health, Richmond, CA. August 2017 http://www.erasepoverty.org/taxonomy/term/261/all Mycobacterium Tuberculosis (TB) California LTBI is not a reportable condition in CA. Only a handful are aware, and even less have been treated. Tuberculosis Control Branch, Report on Tuberculosis in California, 2016. California Department of Public Health, Richmond, CA. August 2017 Why screen for LTBI? The goal of WHO and Stop TB partnership is to eliminate TB as a public health problem by 2050. To do so requires elimination of TB reservoir. Screening and treatment of LTBI are critical components. 90% efficacy of first line treatments for LTBI If taken properly. However, only 50 65% complete the course properly. 1.Jasmer RM, Saukkonen JJ, Blumberg HM, Daley CL, Bernardo J, Vittinghoff E, King MD, Kawamura LM, Hopewell PC. Short course rifampin and pyrazinamide compared with isoniazid for latent tuberculosis infection: a multicenter clinical trial. Ann Intern Med. 2002;137(8):640 647 2.Horsburgh CR, Goldberg S, Bethel J, Chen S, Colson PW, Hirsch Moverman Y, Hughes S, Shrestha Kuwahara R, Sterling TR, Wall K. et al. Latent TB infection treatment acceptance and completion in the United States and Canada. Chest. 2010;137(2):401 409. doi: 10.1378/chest.09 0394 3.WHO. 2006. The global plan to stop TB 2006 2015: Stop TB partnership. Geneva, Switzerland: World Health Organization
The screening dilemma ANNIE ANAYA https://www.flickr.com/photos/kartaba/32433753580/ https://commons.wikimedia.org/wiki/file:geethuanna.jpg The screening dilemma 27 year old female. Immigrated from India 5 years ago. Software engineer who travels to china regularly for work. I just need a chest x ray, I am always positive ANAYA https://commons.wikimedia.org/wiki/file:geethuanna.jpg The screening dilemma ANNIE 26 year old female. Moved here from Utah 5 years ago. Works part time staging homes for a real estate agency. Has never been outside of the country. https://www.flickr.com/photos/kartaba/32433753580/
Screening for LTBI DESPITE CDC RECOMMENDATIONS TO THE CONTRARY: TESTING IS OFTEN DONE TO MEET ADMINISTRATIVE OR LEGAL REQUIREMENTS PERSONS MEETING ENTRANCE REQUIREMENTS FOR CERTAIN SCHOOLS AND WORKPLACES. INDIVIDUALS WHO ARE NOT CONSIDERED TO HAVE AN INCREASED POSSIBILITY OF INFECTION IDEALLY SCREENING WOULD BE TARGETED BASED ON INDIVIDUAL RISK. ALL TESTING ACTIVITIES SHOULD BE ACCOMPANIED BY A PLAN FOR FOLLOW-UP CARE. Screening for LTBI INDIVIDUALS AT RISK FOR NEW INFECTION DUE TO TUBERCULOSIS EXPOSURE: CLOSE CONTACT WITH KNOWN ACTIVE TB INITIAL, AND THEN REPEAT 8-12 WEEKS AFTER EXPOSURE HAS ENDED HEALTHCARE WORKERS WHO CARE FOR PATIENTS AT INCREASED RISK FOR TB BASELINE 2 STEP, AND THEN ANNUALLY Screening for LTBI INDIVIDUALS WITH AN INCREASED RISK OF PROGRESSION TO ACTIVE DISEASE DUE TO UNDERLYING CONDITIONS THOSE ON IMMUNOSUPPRESSIVE MEDICATIONS. HIV PROGRESSION FROM LTBI TO TB DISEASE IS 7-10% PER YEAR WITH UNTREATED HIV. ANTIRETROVIRAL THERAPY REDUCES THE RISK OF PROGRESSION. IV DRUG USERS
Screening for LTBI INFANTS, CHILDREN AND ADOLESCENTS EXPOSED TO ADULTS WHO ARE AT INCREASED RISK. PEOPLE WHO LIVE OR WORK IN HIGH-RISK SETTINGS. FOR EXAMPLE: CORRECTIONAL FACILITIES, LONG-TERM CARE FACILITIES OR NURSING HOMES, AND HOMELESS SHELTERS PEOPLE FROM A COUNTRY WHERE TB DISEASE IS COMMON MOST COUNTRIES IN LATIN AMERICA, THE CARIBBEAN, AFRICA, ASIA, EASTERN EUROPE, AND RUSSIA Risk assessment tool http://www.cdc.gov/tb/ Adapted from a form developed by Minnesota Department of Health TB Prevention and Control Program Should they have been screened? ANNIE ANAYA https://www.flickr.com/photos/kartaba/32433753580/ https://commons.wikimedia.org/wiki/file:geethuanna.jpg
TUBERCULIN SKIN TEST (TST) A.K.A PPD Screening tests for LTBI PREFERRED TB TEST FOR CHILDREN UNDER THE AGE OF 5. INTERFERON-GAMMA RELEASE ASSAY (IGRA) QUANTIFERON -TB GOLD-IN-TUBE TEST (QFT-GIT) T-SPOT TB TEST PREFERRED TEST FOR: INDIVIDUALS WHO HAVE RECEIVED BCG IGRA DOES NOT GIVE FALSE-POSITIVE RESULTS BECAUSE OF PRIOR BCG VACCINATION OR SENSITIZATION TO NONTUBERCULOUS MYCOBACTERIA INDIVIDUALS WHO MAY HAVE A DIFFICULT TIME RETURNING FOR TST TO BE READ. Screening tests for LTBI THERE IS NO NEED TO PERFORM BOTH TESTS. FEEL COMFORTABLE USING EITHER TEST IF IT IS THE ONLY ONE AVAILABLE. Interpreting skin reaction with TST Measure 48 72 hours after injected to be valid Measure the induration The amount of erythema is not measured. Recorded in millimeters (mm).
Interpreting skin reaction with TST > 15 MM: INDURATION. OR VESICULATION > 10 MM: IN THE FOLLOWING POPULATIONS: RECENT IMMIGRANTS FROM HIGH PREVALENCE AREAS (<5Y) IV DRUG USERS RESIDENTS AND STAFF OF HIGH RISK SETTINGS CHILDREN < 4 CHILDREN EXPOSED TO HIGH RISK ADULTS LAB STAFF WORKING WITH MYCOBACTERIA Interpreting skin reaction with TST >5MM: IMMUNOSUPPRESSION E.G., ESRD, ORGAN TRANSPLANTS, METHOTREXATE USE, LONG TERM STEROID USE HIV RECENT CONTACT WITH ACTIVE TB CXR WITH FIBROTIC FINDINGS CONSISTENT WITH PRIOR INFECTION. PERSONS WITH EVIDENCE SUGGESTIVE OF HEALED, PRIMARY TB DISEASE (I.E., CALCIFIED SOLITARY PULMONARY NODULES, CALCIFIED HILAR LYMPH NODES, AND APICAL PLEURAL CAPPING) ARE NOT AT INCREASED RISK FOR TB DISEASE. Interferon gamma release assay (IGRAs) MEASUREMENT OF THE IMMUNE RESPONSE TO TB ANTIGENS: WHOLE BLOOD IS MIXED WITH ANTIGENS DERIVED FROM M.TUBERCULOSIS. WHITE BLOOD CELLS RECOGNIZE THE ANTIGENS, AND RELEASE INTERFERON-GAMMA. IGRA INTERPRETATIONS ARE BASED ON: THE AMOUNT OF IFN-G THAT IS RELEASED. THE NUMBER OF CELLS THAT RELEASE IFN-G. REPORTED AS BOTH A QUALITATIVE AND QUANTITATIVE.
QUANTIFERON TB GOLD IN TUBE TEST (QFT GIT) Interpreting IGRA T SPOT.TB TEST (T SPOT) Positive Negative Indeterminate Positive Negative Indeterminate Borderline https://www.accesalabs.com/quantiferon Gold TB Blood Test www.oxforddiagnosticlaboratories.eu/wp content/media/form 10 012.01 v6.pdf
The screening dilemma continues But I had BCG!!! All my family has a positive skin test!!! I just need a chest x ray A chest x ray is not an adequate test ANAYA https://commons.wikimedia.org/wiki/file:geethuanna.jpg Bacillus Calmette Guérin (BCG) Vaccine Produced from mycobacterium Bovine, BCG is used in many countries that have a high prevalence of TB. (IGRAs use M. tuberculosis specific antigens that do not cross react with BCG, and therefore, do not cause false positive reactions in BCG recipients). TST reactivity caused by BCG vaccine generally wanes with the passage of time. periodic skin testing may boost reactivity in vaccinated persons. https://www.cdc.gov/tb/publications/ltbi/diagnosis.htm Bacillus Calmette Guérin (BCG) Vaccine A person with a history of BCG vaccination can be tested with TST and treated for LTBI if they react. TST reactions should be interpreted based on risk stratification regardless of BCG vaccination history. https://www.cdc.gov/tb/publications/ltbi/diagnosis.htm
Barriers to treatment Patient Adherence and buy in Involves: Motivation Understanding of the diagnosis and risk Availability of medications Ability to follow through with treatment plan Provider inertia Is it really a problem? Concern over the length of treatment Concern over side effects Concern over monitoring Barriers to treatment General Treatment Guidelines Determine if the individual is a candidate for treatment: Appropriate screening? Level of commitment Potential for adherence Adequate resources Once the decision to treat is made: Establish a plan to ensure adherence Evaluate for treatment barriers Discuss risks/benefits of treatment Review side effects
Treatment options for LTBI Treatment regimens for (LTBI) include one or more of the following: isoniazid (INH) rifapentine (RPT) rifampin (RIF) Treatment choice dependent on: Susceptibility of source (if known) Coexisting medical illness Drug to drug interactions and known allergies Daily treatments can be self administered. Directly observed therapy (DOT) : Suspected of nonadherence Intermittent dosing regimen LTBI treatment regimens CDC Division of Tuberculosis Elimination website http://www.cdc.gov/tb Ann Intern Med. 2017;166(3):ITC17 ITC32. DOI: 10.7326/AITC201702070
Rx issues RIF or RPT will cause orange discoloration of body fluids including urine and tears. Contact lens use is not recommended Pyridoxine/vitamin B 6 is not routinely recommended except during pregnancy, or if symptoms of neuropathy develop. Neuropathy develops in approximately.4% Some interactions to note: Rx issues INH increases blood levels of phenytoin (Dilantin) and disulfiram (Antabuse) RIF and RPT decrease blood levels of: oral contraceptives, warfarin, sulfonureas, and methadone RIF and RPT are contraindicated in HIV infected individuals being treated with: protease inhibitors and most nonnucleoside reverse transcriptase inhibitors. Follow up Monthly Evaluation for: Adherence Signs and symptoms of TB disease Signs and symptoms of adverse effects hepatitis jaundice, loss of appetite, fatigue, and/or muscle and joint aches Peripheral neuropathy Labs?
Laboratory Monitoring Routine laboratory monitoring during treatment of LTBI is recommended only for: Abnormal baseline liver function tests. Individuals at risk of hepatic disease should have baseline testing. HIV Postpartum women ETOH Chronic hepatitis B or C Laboratory Monitoring Symptomatic patients should be evaluated for hepatotoxicity. Withhold INH if: Liver enzymes exceed 3x the normal limit with symptoms of hepatotoxicity. 5x the upper limit of normal in an asymptomatic individual. Treatment Completion Give documentation of: TST or IGRA results medication, duration, and treatment completion dates. Remind them that treatment reduces the risk of progression to ITB, but does not eliminate it. Review the signs and symptoms of TB disease: Advise to seek medical attention if these occur.
Take home message Identification and treatment of LTBI is the cornerstones of efforts to control TB in the U.S. Proper screening with intention to treat positive results. INH is going to be the drug of choice for most individuals. Appropriately test and treat individuals who have had BCG. https://pixabay.com/en/question mark question help 2314106/