Diagnosis and Medical Management of TB Infection Lisa Y. Armitige, MD, PhD September 12, 2017 TB Nurse Case Management September 12 14, 2017 EXCELLENCE EXPERTISE INNOVATION Lisa Y. Armitige, MD, PhD has the following disclosures to make: No conflict of interests No relevant financial relationships with any commercial companies pertaining to this educational activity 1
Diagnosis and Medical Management of TB Infection Lisa Y. Armitige, MD, PhD Medical Consultant Heartland National TB Center Associate Professor Internal Medicine/Pediatrics University of Texas HSC Tyler Nurse Case Management Heartland National TB Center, San Antonio September 12, 2017 EXCELLENCE EXPERTISE INNOVATION TB INFECTION 2
TB EXPOSURE Your patient and someone who has active pulmonary TB have been sharing airspace CHARACTERIZING THE EXPOSURE Frequency and duration of exposure Dilution effect (volume of air) Ventilation Exposure to ultraviolet light AJCCRM. 2005: 170;1169 1227. 3
RISK OF TB TRANSMISSION AJCCRM. 2005: 170;1169 1227. TB INFECTION The TB organism has breached the barriers set up by the immune system and has caused infection Outcome of TB Infection Latent TB Infection (LTBI) (90%) No Active TB Disease Active TB Disease (10%) 50% Primary Progression in first 2 years 50% Reactivation later in life 4
Clinical Presentation of LTBI No symptoms or signs of infection Positive tuberculin skin test or IGRA Chest x ray may be normal, or show granulomata, pleural or parenchymal scarring NOT infectious LTBI ACTIVE TB DISEASE Recent infection HIV infection Chest x ray abnormality Underweight by >10% Intravenous drug use Immunosuppression ATS CDC. Am J Respir Crit Care Med 2000;161:S221 5
LTBI ACTIVE TB DISEASE Immunosuppression HIV Hematologic cancers Medical Co morbidities Medications TNF α inhibitors Prednisone >15 mg, > 4 weeks Chemotherapy Other immunosuppressive drugs (e.g. other biologics, anti rejection medications) LATENT TB INFECTION What s really happening? The bacteria that cause disease are dormant (metabolically inactive). For reasons that are not clear, they wake up and start to divide. OR Bacteria are metabolically active and dividing, but the infection is somehow controlled by the immune system. i.e. disease develops when immunity is somehow compromised 6
Latent Tuberculosis Infection (LTBI) Latent Tuberculosis Infection (LTBI) 7
TB Infection Diagnosis Who Should be Tested for TB Infection? Targeted Testing for TB Infection The simplified version: Persons who are at increased risk for M. tuberculosis infection Persons at increased risk for progression to active disease if infected with M. tuberculosis (even if not at increased exposure risk) And those who tend to be tested in addition: Persons tested for administrative reasons (e.g., mandatory employment testing) Persons with symptoms of active TB disease (fever, night sweats, cough, and weight loss) 8
Who Should be Tested for TB Infection? Targeted Testing for TB Infection Contacts of persons with active TB HIV positive individuals Recent immigrants (<5 yrs) from high prevalence countries Injection Drug Users Residents and Employees of high risk congregate settings: Correctional facilities and Homeless Shelters Hospitals, Clinics, Nursing Homes, Substance Abuse Facilities Newest Category: Patients considering treatment with TNF α Antagonists Children exposed to high risk adults or environments Contacts of Active TB Case Among close contacts to a TB Case: 30% have TB Infection 1 3% have active TB disease Without TB Infection treatment: 10% with TB Infection with develop Active TB Approximately 5% of contacts with newly acquired TB Infection progress to TB disease within 2 years The other 5% activate > 2 years after acquisition Examination of contacts is one of the most effective strategies for TB Infection diagnosis and TB control! MMWR December 16, 2005 / Vol. 54 / No. RR 15 9
Reported Tuberculosis (TB) Cases United States, 1982 2015* No. of cases *As of June 9, 2016. Year Number of TB Cases Among U.S. Born versus Foreign Born Persons, United States, 1993 2015* No. of cases *As of June 9, 2016. 10
Trends in TB Cases Among Foreign Born Persons, United States, 1993 2015* No. of cases Percentage *As of June 9, 2016. Who Should be Tested for TB Infection? Targeted Testing for TB Infection Contacts of persons with active TB HIV positive individuals Recent immigrants (<5 yrs) from high prevalence countries Injection Drug Users Residents and Employees of high risk congregate settings: Correctional facilities and Homeless Shelters Hospitals, Clinics, Nursing Homes, Substance Abuse Facilities Newest Category: Patients considering treatment with TNF α Antagonists Children exposed to high risk adults or environments 11
Percentage of Foreign Born Persons with TB, by Time of Residence in U.S. Before Diagnosis, 2015* Percentage *As of June 9, 2016. Foreign born TB patients for whom information on length of residence in the United States before diagnosis is unknown or missing. TB Cases Among Persons Aged 15 Years Residing in Correctional Facilities, United States, 1993 2015* No. of cases Percentage *As of June 9, 2016. Note: Resident of correctional facility at time of TB diagnosis. 12
TB Cases Reported Among Homeless Persons During the 12 Months Before Diagnosis, Ages 15 Years, United States, 1993 2015* No. of cases Percentage *As of June 9, 2016. Note: Homeless during the 12 months before TB diagnosis. Percent Risk of Disease by Age Age at Infection Risk of Active TB Birth 1 year* 43% 1 5 years* 24% 6 10 years* 2% 11 15 years* 16% Healthy Adults HIV Infected Adults + 5 10% lifetime risk 30 50% lifetime *Miller, Tuberculosis in Children Little Brown, Boston, 1963 + WHO, 2004 13
Getting Started I need to pick a test. TST Versus In vitro Assays Andersen et al. Lancet 2000;356:1099 14
Original QuantiFERON TB (QFT) versus TST QFT TST 1 patient visit 2 patient visits Measurement of IFN by machine (more objective) Induration measured by human (more subjective) Antigen: PPD Antigen: PPD Antigens for Newer Generation IGRAs Negative control or nil (e.g., saline, heparin) Positive control or mitogen: non specific immune response stimulator (e.g., phytohemagglutinin) M. tuberculosis specific antigens Unlike PPD used in TST, do not cross react with BCG or NTM (some exceptions) ESAT 6, CFP 10, TB 7.7 (actually simulated using overlapping peptides) 15
(New) ATS/CDC/IDSA Guidelines Will be covered in detail in the talk on IGRAs First! The single most important thing prior to starting treatment for TB Infection is to RULE OUT ACTIVE DISEASE!! 16
Standard Components of TB disease/tb Infection Evaluation If the TST/IGRA or symptom screen is Positive Patient History Physical examination Radiologic evaluation?collect sputum or other specimens Who should be treated for TB Infection? A decision to test is a decision to treat (think)! Tests should only be placed on persons who would benefit from treatment Occasional tests placed for administrative reasons and these individuals should be evaluated on a case by case basis regarding initiation of treatment 17
TB Infection Treatment Options CDC Recommended Treatment regimens: INH/Rifapentine x 3 months (3HP) Once weekly DOT x 12 weeks Rifampin x 4 months Daily (10 mg/kg: 600 mg max) INH x 9 months Daily (5 mg/kg: 300 mg max) or BIW (15 mg/kg: 900 mg max) INH x 6 months (only if.) Daily or BIW CDC. November 2011. Duration of Therapy INH 9 Rifampin INH +RPT 9 months (270 doses) 4 months (120 doses) 12 weeks (12 doses) The longer the duration/more doses, the less likely your patient is to complete Rx! Fewer than 60% complete 9 months of INH! 18
INH/Rifapentine TB Infection Treatment 3HP Must be administered by DOT Approved for individuals >12 y/o Published data shows safety down to age 2 Dosing: INH: 15 mg/kg rounded up to the nearest 50 or 100 mg; 900 mg maximum RPT: 10.0 14.0 kg 300 mg 14.1 25.0 kg 450 mg 25.1 32.0 kg 600 mg 32.1 49.9 kg 750 mg 50.0 kg 900 mg maximum 19
INH/Rifapentine TB Infection Therapy It is another effective regimen option for otherwise healthy patients aged 2 years who have a predictive factor for greater likelihood of TB developing including: Recent TB contacts TST/IGRA Converters Radiographic findings of healed pulmonary TB INH 900 mg + rifapentine 900 mg once weekly for 12 weeks Note: INH tablets are 300 mg, Rifapentine tablets are 150 mg Total pill burden: 9 pills (plus vitamin B 6 ) CDC. November 2011. INH + RPT is NOT recommended for: Children under 2 y/o HIV infected persons on Antiretroviral Therapy Presumed INH or Rifampin Resistance in the source case Pregnant women 20
Rifampin TB Infection Therapy 4 Months Rifampin vs 9 Months INH for Treatment of TB Infection Menzies et al AJRCCM 2004, 170; 445 Completion of therapy significantly better with rifampin with fewer side effects than INH Lardizabal et al Chest 2006, 130; 1712 Patients receiving rifampin were significantly more likely to complete therapy than those receiving INH Menzies et al Ann Int Med 2008, 149; 689 Significantly higher rate of treatment completion with fewer serious adverse events 21
Rifampin Treatment of TB Infection Pros: Higher Completion Rates Fewer Side Effects Less Hepatotoxicity Cons: Drug Interactions Hormone Contraceptives Warfarin Prednisone HIV Antiretrovirals And many more must look up all drugs for interactions!!!!! Orange Body Fluids Other Potential Side Effects: Rash Thrombocytopenia Anemia Leukopenia Allergic Interstitial Nephritis Rifampin Drug Interactions It is imperative to be aware of all medications a patient is taking when that patient is placed on rifampin. 22
Rifabutin A substitute for rifampin for patients who are receiving drugs, especially antiretroviral drugs, that have unacceptable interactions with rifampin. Adverse effects: Less severe induction of hepatic microsomal enzymes, therefore, less effect on the metabolism of other drugs INH TB Infection Therapy 23
Potential INH Side Effects Hepatotoxicity Migraine Headaches Gastrointestinal Nausea, Diarrhea, Constipation Rash Peripheral Neuropathy Pyridoxine 50mg daily can help prevent this INH Hepatotoxicity Asymptomatic elevation of aminotransferases: 20% of patients Clinical hepatitis: 0.6% of patients Fulminant hepatitis (hepatic failure) Approximately 4/100,000 persons completing therapy (continued INH with symptoms of hepatitis, prior INH hepatotoxicity, malnutrition). 24
Severe INH Liver Injuries Among Persons Being Treated for LTBI, U.S., 2004 2008 MMWR 3/5/10/ 59(08); 224 229 Medical providers should emphasize to patients that INH treatment should be stopped immediately upon the earliest onset of symptoms (e.g. excess fatigue, nausea, vomiting, abdominal pain, or jaundice), even before a clinical evaluation has been conducted, and that initial symptoms might be subtle and might not include jaundice. MDR Contacts And travel to MDR endemic countries.. Knowing the susceptibilities of the source case is very important Call for help (Heartland) and we will walk you through it 25
Barriers to TB Infection Testing and Treatment Why do I have to do this again..? We don t do this where I come from. Take a pill every day.every single.day Pearls of Wisdom for Treating TB Infection How are you presenting/offering treatment? Consider the shortest regimen possible to increase the odds of completion Young folks like technology. Text! Be vigilant.and suspicious Be supportive..and forgiving 26
Questions? Lisa.Armitige@dshs.texas.gov 1 800 TEX LUNG 27