Objectives • Tuberculosis (TB) background and statistics • Epidemiology of TB in the United States and in Clark County, Nevada • Transmission and pathogenesis of disease • Diagnosis of TB • Treatment modalities of TB • Role of Pharmacies and Pharmacists in the management of TB infected patients
Background • TB is one of the world’s deadliest diseases • One-third of the world’s population is infected with TB • Accounting for approximately 2 billion people • Each year, 8 million people around the world become ill with TB • Worldwide 2-3,000,000 deaths are related to TB each year
Epidemiology • TB cases are reported in every state on an annual basis • Drug-resistant cases are reported in almost every state • Ten to Fifteen million persons in the US are infected with M. tuberculosis • Without intervention approximately 10% of patients will develop disease at some point in there lives
Epidemiology • Southern Nevada 2007 • 92 active cases • 10% were children born in the US • 66% foreign born • 27% born in Mexico • 22% born in Philippines • 9% were homeless • 25% had uncontrolled diabetes • 6%were co-infected with HIV/AIDS
Epidemiology • Southern Nevada 2008 (Clark County had 91 active cases) • 73% were foreign born • 22% were born in Mexico • 26% were from the Philippines • 3% had HIV/AIDS • 8% were homeless • 25% had uncontrolled diabetes • 13% were children born in the US with risk factors
Transmission • Spread by droplet nuclei • Airborne infection • Expelled by TB infected person coughs, speaks, sneezes, or sings • Speaking: 0 to 210 particles • Coughing: 0 to 3,500 particles • Sneezing: 4,500 to 1,000,000 particles
Transmission • Close contacts are at highest risk of becoming infected • Household contact, incarceration, schools ect.. • Transmitted by infectious TB person • NOT latent TB infection
Risk of Transmission • Medical Conditions • HIV infection • Recent infection • Diabetes • Cancer • End stage renal disease • Substance abuse • Rheumatoid Arthritis • HIV is the strongest risk factor for development of TB disease • 7% to 10% per year
Past Medical History • Questions clinician’s should ask: • Any symptoms of TB • Prolonged cough, weight loss, ect.. • History of TB exposure, infection, or chronic disease • Incarceration, household contact to active case • Medical conditions that increase risk of TB disease • Diabetes, HIV/AIDS, Cancer, Rheumatoid Arthritis • Country of Birth • Length of time in the US • If patient is an immigrant
Diagnosis • Symptoms • Systemic • Fever, chills, night sweats, weight loss, fatigue • Pulmonary TB specific • Productive cough, prolonged cough • 3 weeks or longer in duration • Chest pain • Hemoptysis
Diagnosis • TB symptoms and severity can rate from none to overwhelming • Approximately 10% to 20% have none of the “classic symptoms” • Illness can range from indolent to fulminant • Symptoms and findings can be both local and systemic • Local in the case of disseminated TB (CNS, bone, and solid organ – liver and kidney) • TB infection can involve any organ or tissue
Diagnosis • Steps to Diagnosis of TB Disease • Medical evaluation • History and risk of exposure • Mantoux tuberculin skin test • PPD skin test • Blood Assay Test for MTB (BAMT) • Quantiferon (QFT) • Whole blood test • Chest X-Ray • Bacteriologic exam • Smears • Cultures
Mantoux TST • Was the only test available for TB testing in adults and children (established in 1907) • Blood test are now available • As known as PPD skin test • Looking for the presence of antibodies to M. tuberculosis • Redness of the area does NOT constitute a reaction • Patient must have a measureable induration
Blood Assay for M. tuberculosis • QuantiFERON®-TB Gold Test • Approved by the FDA in 2005 • Can be used in young adults and children 18 years and older • Whole blood test used to detect M. tuberculosis infection • Including LTBI and Active disease • Can be used in the same instances a PPD skin test is indicated • Looking for the presence of Interferon-gamma (IFN-gamma) • After blood sample is mixed with antigen • If infected - WBC in the sample will release IFN-gamma • Results are available with in 24hrs • NOT effected by prior BCG (bacille Calmette-Guérin) vaccination
Chest X-Ray • Abnormalities often seen in apical or posterior segments of upper lobeor superior segments of lower lobe • Does NOT confirm the diagnosis of TB • Can be signs of other disease processes • Cancer • Prior lung injury (infectious or non-infectious) • Infection (MAI, bacterial, viral or fungal pneumonia)
Diagnostic Microbiology • Obtain 3 sputum specimens for (Acid Fast Bacilli – AFB) • Smear and Culture • Detection of AFB in stained smears • Provides the firsts bacteriologic clue of TB • Rapid detection of M. tuberculosis • Nucleic acid amplification (NAA) tests • Polymerase chain reaction (PCR) • Cultures are used to confirm the diagnosis of TB and culture identification • Takes 6 to 8 weeks
Guidelines for Preventing the Transmission of Mycobacterium tuberculosisin Health-Care Settings, 2005 “All patients with suspected TB disease should remain under airborne precautions while they are hospitalized until they have had three consecutive negative AFB sputum smear results, each collected in 8--24-hour intervals, with at least one being an early morning specimen; have received standard multidrug antituberculosis treatment (minimum of 2 weeks); and have demonstrated clinical improvement.”
TB Case Studies We are all connected by the air we breathe
CASE STUDY 42 year old Filipina female admitted to a local hospital on 3/7/08 due to the new onset seizures. An MRI showed abnormal lesions in the brain and a spinal tap was done. CSF revealed low glucose and elevated protein. The client then underwent a brain biopsy. The pathology report demonstrated granulomatous cell infiltrate consisting of multinucleated giant cells. Also, there was no evidence of neoplasm. Stains were negative for AFB and fungal. The patient was not discharged on any antimicrobial or antifungal medications. The patient was noted to have decreased cognition and placed on a tapering dose of steroids and seizure medication at discharge on 3/13/08.
CASE STUDY continued.. On 3/27/08 an out of state private lab reported to the pt’s physician that the brain tissue was PCR positive for MTB. This physician called the patient and told her that she had MTB and that she needed to start the 4 TB medications. He called the prescriptions to a local pharmacy for the 4 TB medications. The patient picked up the medicines and begin taking them. On 5/30/08 the patient was readmitted to the same hospital with altered mental status, fever, headache and seizures. The family reported to the physician that the patient stopped taking her TB medications because she felt better. Also, the family reported that the patient’s mother also encouraged her to stop the TB medications because she looked better.
CASE Study continued.. On 6/2/08 the Southern Nevada Health District was notified of the patient by the infection control nurse. The patient was called by TB clinic staff to come to the TB clinic 0n 6/3. The patient was stated she would come and then her mother called back to say that her daughter had her own TB medications at home. The TB clinic nurse had to make many phone calls to the patient to have her come in. When the patient was admitted to the clinic the husband revealed he had schizophrenia and unable to drive. The patient was transported home and the patient gave her TB medications to the TB nurse. The medication bottles were dated 3/31/08 and only 12 days of medications were missing from the bottles. The patient also stated that she would take a red pill one day and a white pill the next day.
Case Study continued.. This patient was placed on DOT by TB clinic staff. This patient has been admitted back to the hospital multiple time and also placed in a skilled nursing home because of her altered mental status. She also has hydrocephalus and a large volume spinal tap was performed that grew MTB on culture. The MTB is pan sensitive . Currently this patient continues on the TB medications DOT and she will need a year of treatment. She is unable to care for herself due to her altered mental status. She is pending disability and she lives with her husband, two children and her parents. She was the family’s primary financial support and made all the family decisions.
Treatment • Overall goal of treatment • Cure individual patient • Minimize transmission of TB to others • Initial drug regimen • Four drug regimen (taken simultaneously) • Isoniazid (INH), Rifampin, Ethambutol (EMB), and Pyrazinamide (PZA) • Therapy is provided by Southern Nevada Health District (SNHD) • Managed by the TB treatment and control clinic • Case management and directly observed therapy (DOT) • Utilized to ensure patient adherence • Utilized not only in active cases but non-compliant LTBI patients as well
Treatment • First line agents (Adult dosing) • Isoniazid (INH) • 5mg/kg daily • 300mg daily (max dose) • Rifampin • 10mg/kg • 600mg daily (max dose) • Ethambutol (EMB) • 15-20mg/kg daily • Pyrazinamide (PZA) • 20-25mg/kg daily
Treatment • Second line agents • Steptomycin*** (Injectable – IV or IM) • 15mg/kg per day ***over 59y/o dose: 10mg/kg per day • Cycloserine (Oral – capsule) • 10-15mg/kg per day • 500-750mg/day given in two divided doses • Ethionamide (Oral – tablet) • 15-20mg/kg per day • 500-750mg/day given in two divided doses • Amikacin and Kanamycin (Injectable – IV or IM) • 15mg/kg per day 5 to 7 days per week
Treatment • Second line agents • p-Aminosalicyylic acid (PAS) (Granules) • 8-12grams/day in 2 to 3 divided doses • Capreomycin (Injectable – IV or IM) • 15-30mg/kg/day as a single daily dose • Fluroquinolones (Oral or injectable-IV) • Levofloxacin 500 to 1000mg per day OR • Moxifloxacin 400mg per day • Linezolid (Zyvox)***** (Oral or Injectable – IV) • 600mg twice daily
Drug Resistance • Multi-Drug Resistant TB (MDR-TB) • Defined as: organism resistant to BOTH INH and RIF • Extensively Drug Resistant TB (XDR-TB) • Defined as: MDR plus resistance to three of the alternative second line agents • (aminoglycosides, cycloserine, PAS, Fluroquinolones, polypetides, and thioamides)
Special Considerations • Adverse Effects • INH: Elevated LFT’s and clinical hepatitis • RIF: Rash (6%) of patients, nausea, anorexia, abdominal pain, hepatotoxicity, thrombocytopenia, organ discoloration of bodily fluids • PZA: Hepatotoxicity, N/V, non-gouty polyarthralgia, acute gouty arthritis, hyperuricemia, rash • EMB: Visual disturbances (decrease in red-green discrimination), peripheral neuritis, skin reactions
Special Considerations • Rifabutin NOT Rifampin • Should be used in HIV co-infected patients • Due to drug-drug interactions • If patient fails to improve after 6 to 8 weeks of therapy drug levels should be obtained • Patients extremely underweight at time of diagnosis • Slow to culture convert • Drug absorption issues • Average duration of therapy 6 to 9 months
TB Drug Resistance - WORLD • Highest rates ever recorded of MDR-TB • Highest rates • China and former Soviet Union • Severely limited laboratory capacity • Means limited data available in highly affected areas such as Africa • Insufficient efforts in many areas of the world to treat and control MDR-TB
TB Drug Resistance - WORLD • Equipment to rapidly diagnose MDR-TB in a week instead of 3 months exist • Most world wide patients affected do not have access to these services • Extraordinary measures are needed in Eastern Europe • Rapid detection, effective care, and access to medications
TB Drug Resistance - WORLD • 490,000 MDR-TB cases emerge every year • 110,000 deaths per year • XDR-TB has been identified in 45 countries • Inversely impacting 10 yrs of progress in TB control and HIV management
The Emergence of XDR TB • XDR-TB (Extensively drug resistant TB) • Cases of TB disease in persons whose Mycobacterium isolates are resistant to INH and Rifampin and at least three of the six main classes of second-line drugs (aminoglycosides,cycloserine,PAS,fluoroquinolones,polypeptides,and thioamides) • XDR-TB case successfully treated in Clark County.
TB Fingerprinting/ DNA genotyping • Restriction fragment length polymorphism(RFLP) is a method of DNA fingerprinting that is used to identify specific strains of TB. • TB outbreaks will be detected earlier and controlled more easily • Unsuspected relationships between cases and new and unusual transmission settings will be discovered • Transmission that occurs between patients in different jurisdictions will be detected more rapidly
Background • On August 6, 2008, CDC notified of 6 pansusceptible TB cases (January 2007–July 2008) • Characteristics of outbreak • Clark County, Las Vegas residents • Mexican origin, some undocumented (illegals) • Methamphetamine dealers and users • Epidemiologically linked to index case • Matching genotype CDC 2008
Health Care Providers • Physicians/Residents/Fellows • Follow isolation protocols • Obtain appropriate testing to ensure accurate diagnosis and treatment • Ensure accurate and adequate dosing (once daily dosing) • Patients should NEVER be under-dosed • Increased risk of resistance • Higher then normal dosing should ONLY be considered in those patients who have been identified as having absorption problems
Health Care Providers • Always report hospitalized active TB cases prior to discharge • Report cases to local health department • There is NO such thing as over-reporting
TB REPORTING • State of Nevada, Confidential Morbidity Report Form Instructions Updated January 2007, Disease Reporting: • The Nevada Administrative Code Chapter 441A requires reports of specified diseases, food borne illness outbreaks and extraordinary occurrences of illness be made to the local Health Authority. The purpose of disease reporting is to recognize trends in diseases of public health importance and to intervene in outbreak or epidemic situations. Physicians, veterinarians, dentists, chiropractors, registered nurses, directors of medical facilities, medical laboratories, blood banks, school authorities, college administrators, directors of child care facilities, nursing homes and correctional institutions are required to report. Failure to report is a misdemeanor and may be subject to an administrative fine of $1,000 for each violation. In December 2006, additional disease reporting requirements were approved by the Southern Nevada District Board of Health, which apply only to Clark County.
TB REPORTING • How to report Tuberculosis†: • † Must be reported when suspect • All cases, and suspect cases, must be reported within 24 hours SNHD TB Clinic fax number is 633-0975
Discharge Planning for TB Patient • The discharge plan should be coordinated with the TB clinic. • Friday, weekend and holiday discharges should be avoided. • The TB clinic will provide the TB medication and every suspect or active case is on DOT (directly observed therapy) • If a suspect case is homeless ensure that a picture is taken and information is obtained about where they go during the day like a park.
Summary • TB infection and disease isn’t ELIMATED • Experts predict a possible resurgence of disease in the 21st century • ALWAYS report active cases • Treatment barriers • Understaffed TB infection and control programs • Reduced TB funding • Under reporting of active cases • Consistency of treatment and reporting across healthcare facilities
Southern Nevada Health District TB Treatment and Control Clinic Located at the North Las Vegas Public Health Center 1820 East Lake Mead Suite HNorth Las Vegas, NV 89030 Call (702) 759-1369 OR Email TBClinic@snhdmail.org Questions
References • American Thoracic Society, CDC, and Infectious Diseases Society of America Treatment of Tuberculosis. MMWR 2003; 52(No. RR-11) • CDC. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care settings, 2005. MMWR 2005; 54(No. RR-17) • Iseman, Michael D. A Clinician’s Guide to Tuberculosis. Philadelphia: Desk. 2000 • Division of Tuberculosis Elimination, Centers for Disease Control and Prevention • http://www.cdc.gov/nchstp/tb • Francis J. Curry National Tuberculosis Center • http://www.nationaltbcenter.edu