DIVISION OF DISEASE PREVENTION

DIVISION OF DISEASE PREVENTION
TUBERCULOSIS 101 Brenda Mayes, RN December 2008

Epidemiology of TB: World
One third of the world’s population is infected with TB 9 million new cases of TB per year 2 million deaths a year can be attributed to TB disease

Compared to 1960-75, four-fold increase in migration
Have germs, will travel… Migrating populations in the 1990s This map show the travel has increased 4 fold from the 60s and 70s and note the heavist arrows – most frequent paths have US as destination. USING CALIF. AS THE EXAMPLE ~10 million Californians are foreign-born ~400 million crossing US Mexico border each year ~3.5 million visitors to CA ~2 million undocumented enter CA ~250,000 new entrants with perm residence visa ~100,000 new entrants with student visa CA in particular is a major destination , 10 million of 35 million residents are FB. Very large volume of travel and migation for temp and perm residence. Human migration links low and high income, low and high incidence, near and far Air is the vehicle and shared universally There is major flow from Asia to Oceania, SE Asia & the Middle East Europe & the Americas & all points on the globe The even travel to & within Africa has increased In fact the volume of migration has increased 4 times as compared with 20 to 40 years ago Compared to , four-fold increase in migration 4 x increase in volume as compared to 1960 - 75 Source: Population Action International 1994

Estimated TB Incidence Rates, 2001
< 10 No estimate per pop 300 or more The designations employed and the presentation of material on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. White lines on maps represent approximate border lines for which there may not yet be full agreement. © WHO 2003

Epidemiology of TB: National
Decline of TB cases from the 1950s to 1984 Availability and effectiveness of TB medications Increase in TB cases from 1985 to 1993 HIV, increased immigration, decrease in funding, apathy US TB rates have been declining since 1993

TB Case Rates,* United States, 2007
*Cases per 100,000

Population Growth: Virginia Counties 2000-2005

VA TB Cases: Urban vs. Rural, 2002-2005
US born 1 DOT trip = 6 miles, 20 traffic lights Foreign born 1 DOT trip = 75 miles ~1150 VA cases Jan 02-June 05

FOREIGN BORN vs. US BORN

TB Cases by Age: VA,

Reported TB Cases by Race/Ethnicity: VA, 2000-2007
total Virginia cases..230 were foreign born compared to 79 US born…the foreign born were from 42 countries of origin and spoke 18 languages other than English. the top 5 countries of origin were El Salvador with 27 cases, Philippines with 27 cases, India with 21 cases, Bolivia with 18 cases and Mexico with 15 cases

Number of Reported TB Cases By VA Region, 2000-2007

VDH TB Prevention and Control Policies and Procedures
Based on USPHS/CDC, ATS, IDSA and Pediatric “Red Book” guidelines Adapted to address uniquely Virginia issues

Elements of a Tuberculosis Control Program
X-ray Targeted testing/ LTBI treatment Inpatient care Clinical Services Pharmacy Medical evaluation and follow-up Non-TB medical services Social services Laboratory Interpreter/ translator services HIV testing and counseling Patient education Data collection Coordination of medical care Epidemiology and Surveillance DOT Home evaluation Case Management Contact investigation Outbreak Investigation Data analysis Housing Program evaluation & planning Isolation, detention Follow-up/treatment of contacts QA, QI for case management Consultation on difficult cases Data for national surveillance report Training Federal TB Control Program State TB Control Program Guidelines Information for public State statutes, regulations, policies, guidelines Funding National surveillance Training Technical assistance Funding VDH/DDP/TB Apr 2006

THE PUBLIC HEALTH NURSE
CASE MANAGEMENT EDUCATION DESIGNS INVESTIGATIONS IDENTIFIES INEFFECTIVE DRUG THERAPY IDENTIFIES DRUG TOXICITIES RECOGNIZES PATIENT BEHAVIORS DEVELOPS STRATEGIES

M tuberculosis as causative agent for tuberculosis
Robert Koch ~ 1886

M. tuberculosis Complex
The Mycobacteria Human pathogens M. tuberculosis Complex (M. tuberculosis, M. bovis, M. microti, M. africanum, M. canettii) M. leprae

Transmission of TB Spread person to person through the air
In the 1900’s TB was the greatest killer in the US…Today it is still the greatest infectious disease killer in the world and the greatest killer of AIDS patients

Transmission of Tuberculosis
THREE STEP PROCESS transmission of bacteria, establishment of infection, and progression to disease.

TB: Airborne Transmission
TB bacteria airborne Person with active pulmonary TB Person breathing TB bacteria

TB Invades/Infects the Lung
Effective immune response Infection limited to small area of lung Immune response insufficient Active Disease

Probability of TB Transmission
Transmission dependent on three factors Infectiousness of the person with TB Environment in which the transmission occurs Duration of the exposure to TB bacteria

Pathogenesis of TB Infection begins when the inhaled droplets reach the lungs Tubercle bacilli multiply A small number of tubercle bacilli may enter the bloodstream and spread throughout the body (lungs, kidneys, brain, bone) Within 2-10 weeks, the immune system produces a capsule that surround the tubercle bacilli The capsules occur wherever the TB bacteria are in the body

Sites of TB Disease Pulmonary TB (TB of the lungs) 80% of cases
Potential for transmission – infectious until proven otherwise Extrapulmonary TB (outside the lungs) Can occur anywhere in body Portal of entry through lungs Typical sites include larynx, lymph nodes, the pleura, brain, kidneys, bones, or joints Usually not infectious – always rule out pulmonary! Before Anti TB drugs 50 % of all TB patients died...AND OF THE 45% WHO SURVIVED, 25% were chronically ill for a lifetime

Likelihood of Developing TB Disease
Once infected with tubercle bacilli 90% chance of never developing the disease 10% life time chance that TB disease will develop Half the risk within the first 2 years Risk lower after the first 2 years Other personal health factors can influence risk HIV infection - single highest risk for progress to active disease 10% annual risk

Diagnosis of TB Infection and Disease
Signs and Symptoms TST CXR Bacteriology (positive sputa)

Diagnosis of TB Disease: Symptoms
Pulmonary TB Disease Coughing Pain in the chest when breathing or coughing Coughing up sputum or blood General TB Disease Weight loss Fatigue Malaise Fever Night sweats Other symptoms specific to the site of the TB disease

Latent Infection vs. Active Disease
Tubercle bacilli in the body Tuberculin skin test reaction usually positive Chest x-ray usually normal Chest x-ray usually abnormal Sputum smears and cultures negative Sputum smears and cultures may be positive No symptoms Symptoms such as cough, fever, weight loss Not infectious Often infectious before treatment Not a case of TB A case of TB

Classification System for TB
Type Description No TB exposure Not infected No history of exposure Negative reaction to tuberculin skin test TB exposure No evidence of infection History of exposure Negative reaction to tuberculin skin test 1 TB infection No disease Positive reaction to tuberculin skin test Negative bacteriologic studies (if done) No clinical, bacteriological, or radiographic evidence of active TB 2 TB, clinically active M. tuberculosis cultured (if done) Clinical, bacteriological, or radiographic evidence of current disease 3 TB Not clinically active History of episode(s) of TB or Abnormal but stable radiographic findings Positive reaction to the tuberculin skin test Negative bacteriologic studies (if done) and No clinical or radiographic evidence of current disease 4 5 TB suspected Diagnosis pending

Diagnosis of TB Disease vs LTBI
Medical History (Risk Assessment) Exposure to TB Symptoms of TB Previous TB infection or disease Risk factors for TB TB Skin Test Chest X-Ray Bacteriologic Examination Three possible test results from each specimen Smears (+AFB) Culture results Susceptibility results New rapid diagnostic tests DNA based Exposure to TB: Asking the patient about his or her exposure to TB; patients should be asked whether they have spent time with someone who has infectious TB. Some people may have been exposed to TB in the distant past, when they were children. Others may have been exposed more recently.

Identifying Risk Factors That Lead to Development of TB Disease

Persons at Risk for Developing TB Disease
Persons at high risk for developing TB disease fall into 2 categories Those who have been recently infected Those with clinical conditions that increase their risk of progressing from LTBI to TB disease Clinical conditions= all of those medical conditions that we ask about on the risk screen ie high doses of steroids(>15 mg/day for >one month), DM, ca of head / neck, dialysis, TNFa inhibitor drugs

Recent Infection as a Risk Factor
Persons more likely to have been recently infected include Close contacts to person with infectious TB Skin test converters (within past 2 years) Recent immigrants from TB-endemic regions of the world (within 5 years of arrival to the U.S.)

Recent Infection as a Risk Factor (2)
Children  5 years with a positive TST Residents and employees of high-risk congregate settings (e.g., correctional facilities, homeless shelters, health care facilities)

Increased Risk for Progression to TB Disease
Persons more likely to progress from LTBI to TB disease include HIV-infected persons Those with a history of prior, untreated TB or fibrotic lesions on chest radiograph

Increased Risk for Progression to TB Disease (2)
Underweight or malnourished persons Injection drug users Those receiving TNF-α antagonists for treatment of rheumatoid arthritis or Crohn’s disease

Increased Risk for Progression to TB Disease (3)
Persons with certain medical conditions such as Silicosis Diabetes mellitus Chronic renal failure or on hemodialysis Solid organ transplantation (e.g., heart, kidney) Carcinoma of head or neck Gastrectomy or jejunoilial bypass Relative risk of developing active TB for persons with certain clinical conditions: Silicosis times greater Diabetes times greater Chronic renal failure/hemodialysis times greater Gastrectomy times greater Jejunoileal bypass times greater Kidney transplant times greater Heart transplant times greater Cancer of head/neck times greater

Relative Risk of Developing Active TB
Risk Factor Risk Increase AIDS 170 x HIV infection 113 x Recent infection 15 x Certain Medical Conditions 3-16 x

Diagnosis of TB Infection: Mantoux TB Skin Test (TST)
Is the preferred type of skin test Determines if a person has TB infection Is useful in: Screening people for TB infection (contacts and targeted testing) Examining a person who has symptoms of TB disease

Mantoux Tuberculin Skin Test
Multiple puncture test (e.g.Tine Test) are inaccurate and not recommended Emergency Box QuantiFERON Gold QuantiFERON test first out in 2001 QuantiFERON Gold out in Both are blood tests that measure a person’s immune reactivity to MTB. Blood specimens are mixed with antigens and incubated for hours. In a person with LTBI, the blood cells recognize the tuberculin antigen and release interferon-gamma…results are based on the proportion of IFN-y released…….getting a lot of indeterminate test results which they are saying has to do with the type of heparin Used in the blood tubes….expensive test…around $ and most insurances do not cover….blood has to be to lab within 12 hours… 2007 new QuantiFERON TUBE test just released Georgetown University is the only testing site close by Not done on pregnant women, those under the age of 17 or persons with clinical conditions that increase the risk of progression into disease. Quantiferon Spot test released July 2008

Administering and Reading the Mantoux TST
Inject intradermally 0.1 ml of 5 tuberculin units of liquid tuberculin using a 27 gauge needle Use the forearm whenever possible volar surface Produce a wheal 6 to 10 mm in diameter Examine the patient’s arm hours after the tuberculin is injected Assess the injection site for erythema (redness) and induration (swelling that can be felt) Measure across the forearm the diameter of the indurated area only in millimeters Do not measure the erythema A tuberculin unit is a standard strength of tuberculin Most people with TB infection have a positive reaction to the tuberculin

Reading the TST Educate patient and family regarding significance of a positive TST result Positive TST reactions can be measured accurately for up to 7 days Negative reactions can be read accurately for only 72 hours

Persons Positive at > 5 mm
People with HIV infection Close contacts of people with infectious TB Persons with chest x-ray findings suggestive of previous TB disease Persons on TNF-a drugs of high doses of steroids Persons on high doses of steroids TNF-a drugs = Remidaide, Humaria et for Rheumatoid Arthritis or Crohn’s Disease or steroids >15mg/day for a month or longer

Persons born/lived in areas of the world with high TB prevalence Injection drug users Persons who work or reside in high-risk congregate settings People with medical conditions that increase the risk for TB ( those listed on risk screen) Children younger than 4 years old Locally identified groups at higher risk for exposure Code of Virginia requires reporting of +TST of those age 4 and under……CDC guidelines say 5 and under positive at 10 mm but we adjust per State code

Persons who have no risk factors for TB Certain individuals may require TST for employment or school attendance

TST Result: False Positive
Possible causes Nontuberculous mycobacteria BCG vaccination Routinely administered to children in countries where TB is prevalent Not a contraindication for the administration of the TB skin test Wanes over time ; if TST is + likely due to TB infection if risk factors present

TST Result: False-Negative
Causes include Anergy Recent TB infection (within past 10 weeks) Very young age (younger than 6 months old) Incorrect administration and storage of test solution Live-virus vaccination Overwhelming TB Disease Poor TST administration technique Anergy is the inability to react to skin tests because of a weakened immune system. Many conditions, such as HIV infection, cancer, or severe TB disease itself, can weaken the immune system and cause anergy. HIV infection is a main cause of anergy. ANGERY TESTING IS NO LONGER RECOMMENDED EVEN IN HIV + PERSONS Recent TB infection: It takes 2 to 10 weeks after TB infection for the body’s immune system to be able to react to tuberculin. Therefore, after TB has been transmitted, it takes 2 to 10 weeks before TB infection can be detected by the tuberculin skin test. For this reason, close contacts of someone with infectious TB disease who have a negative reaction to the tuberculin skin test should be retested 10 weeks after the last time they were in contact with the person who has TB disease Very Young Age: Because their immune systems are not yet fully developed, children younger than 6 months old may have a false-negative reaction to the tuberculin skin test

Other Issues in Skin Testing
Booster phenomena Ability to react to tuberculin may wane with time Two-step testing to 3 weeks apart Use with groups who will have repeated TSTs as part of infection control programs Use to validate test results Two step Testing ..if first test is neg, repeat test in 1 to 3 weeks If the second test is neg…they are neg If person being tested has had a TST within the past year, you can use that as #1 and just do the #2 test as long as you can get documentation of the #1 TST. If #1 test is – and #2 test is + you have boosted old infection and if the person has not been previously treated, do CXR, R?O TB and TX for LTBI

Diagnosis of Active TB Evaluate all patients with symptoms of TB for TB disease, regardless of the patient’s skin test reaction 1/4 to 1/3 of all active MTB cases have negative TST at onset of treatment

Diagnosis of TB Disease: Chest X-Ray
Check for lung abnormalities suggestive of TB disease Typical findings may include cavities, infiltrates, effusions Does not confirm TB disease May not disprove active TB in immune compromised individuals

Diagnosis of TB Disease: Bacteriologic Examinations
Sputum collection Spontaneous or induced All symptomatic individuals Abnormal CXR M.tb can be cultured from any body fluid or tissue Specimen collected depends on the site of potential disease

Induced sputum (% yield)
Yield of smear and culture from repeated sputum induction for the diagnosis of pulmonary tuberculosis. Induced sputum (% yield) specimen one two three four AFB smear 64 81 91 98 AFB culture 70 99 100 Int J Tuberc Lung Dis Sep;5(90: Al Zahrani K, et al.

Bacteriologic Examination (Cont.)
Microscopy “Smear results” Presence acid-fast bacilli (AFB) AFB are bacteria that remain stained even after they have been washed in an acid solution Tubercle bacilli are only one kind of AFB Results available usually within one day Obtain a smear: Specimen is smeared onto a glass slide, and stained with a dye 4+ smears have 10 times as many AFB as 3+ 3+ smears have 10 times as many AFB as 2+ smears

Bacteriologic Examination: AFB Smear Interpretation
Classify smear according to the number of AFB seen Measure of number of organisms presented ( negative to 4+ ) Helps to determine level of potential infectiousness If no AFB seen, result is negative Does not rule out possibility of TB

Bacteriologic Examination: Culturing the Specimen
Grow the mycobacteria on media Several types of media All specimens should be cultured, regardless of whether the smear is positive or negative Results may take up to 6-8 weeks If M. tuberculosis present, confirms diagnosis of TB disease When the mycobacteria have grown colonies (groups), they can be identified

Bacteriologic Examination: Drug Susceptibility Testing
Critical test for appropriate management of active TB disease Test mandated by VA TB Control laws Determines which drugs will kill the tubercle bacilli that are causing disease in the individual patient Done in initial positive culture for M. tuberculosis May need to be repeated later in treatment course Drug levels Repeat susceptibility testing if patient has positive culture for M. tuberculosis after 2 months of treatment or if a patient does not seem to be getting better Can take 8 to 12 weeks

Antituberculosis Drugs Currently in Use in the US
First-line Drugs Isoniazid Rifampin Rifapentine Rifabutin Ethambutol Pyrazinamide Second-line Drugs Cycloserine Ethionamide Levofloxacin Moxifloxacin Gatifloxacin P-Aminosalicylic acid Streptomycin Amikacin/kanamycin Capreomycin Linezolid

Treatment of MTB Case Initial Phase – Direct Observed Therapy
7 d/wk for 56 doses or 5d/wk for 40 doses INH Rifampin Ethambutol PZA

Treatment of MTB Case CONTINUATION PHASE by DOT Either 4 or 7 months
Daily 126 doses ( INH and RIF ) 5X/wk 90 doses (INH and RIF ) 2X/wk 36 doses (INH and RIF ) 1X/wk 18 doses ( INH and RPT ) The 4 month continuation phase will be used on most clients

Continuation Phase for 7 months
Cavitary pulmonary TB caused by drug- susceptible organisms and whose sputum culture obtained at completion of 2 month initial phase is positive No PZA in initial phase INH and Rifapentine 1X/wk whose sputum culture is + at end of initial phase

Children with MTB CXRs reveal different findings;
see MMWR pg 55 section 8.2 Drug dosages are different Child = less than 40kg by weight or less than 15 years old Not usually given ETH unless drug resistance suspected or adult type cavitation on CXR ( visual acuity ) Younger than 4 start Tx ASAP

DRUG RESISTANCE MONO-RESISTANT resistant to one drug only
POLY-RESISTANT resistant to more than one drug, but not the combination of INH and RIF

DRUG RESISTANCE MDR (Multiple Drug Resistance) INH AND Rifampin
XDR ( Extreme Drug Resistance) INH and Rifampin plus any floroquinolone and at least one of the three injectable second-line drugs (amikacin, kanamycin or capremycin)

Definitions Primary drug resistance:
Infected with TB which is already drug resistant Secondary (acquired) drug resistance: Drug resistance develops during treatment definitions for drug resistance… MDR TB implies resistance to at least isoniazid and rifampin XDR TB is defined as MDR TB and resistance to the 2 most important classes of 2nd-line agents used in MDR TB treatment: fluoroquinolones and 1 of the 3 injectable agents Patients with XDR TB are usually resistant to all four 1st line agents Primary drug resistance means the the patient has drug resistance due to transmission of a drug resistant strain from a drug resistant source. In other words, the patient became infected with a strain that was already drug resistant. Secondary drug resistance means that the resistance was acquired during the course of TB treatment MDR TB Resistance to at least isoniazid and rifampin MDR TB Importance: No short course treatment regimen available and requires use of more toxic drugs XDR TB Importance: Significantly poorer outcome

WHAT CAUSES SECONDARY DRUG RESISTANCE??
TREATMENT FAILURE

WHO IS AT HIGHER RISK OF MDR-TB???
History of previous TB Tx especially if recent Foreign-born patients from countries or ethnicities with high prevalence of MDR Poor response to standard 4 drug regimen Known exposure to MDR-TB case HIV+

XDR TB Cases in the United States (Initial DST), 1993–2007*
8 NYC 16 New Jersey 3 1 2 1 2 11 1 2 * Preliminary data- not for distribution

XDR TB in all regions, more common FSU and Asia (Republic of Korea
Global WHO/IUATLD/CDC Survey Convenience sample (17,690 isolates) submitted to participating international SRL network, 3520 (20%) of isolates MDR TB 347 ( 2%) of isolates XDR TB XDR TB in all regions, more common FSU and Asia (Republic of Korea Denominator information unavailable

2006 Global Distribution of MDR TB Among New Cases
2006 Global Distribution of MDR TB Among New Cases Source: Zignol, Dye et al, JID 2006:194 This 2006 map shows that MDR TB is not evenly distributed in the world. The light green areas indicate the 3-6% of incident cases are MDR. This includes China, the most populous country in the world. The yellow countries have the highest rates of MDR TB of over 6%. This include the Russian Federation and countries of the former Soviet Union. Former Soviet Union and Eastern Block Countries with the highest rates. Some countries record >14% prevalence of MDR TB (eg. Estonia !7.4%, Azerbaijan 14.6%, Kazakhstan 14.6%)

Step 1 PLUS First-line drugs Fluoroquinolones Injectable agents
Use any available Begin with any First line agents to Which the isolate is Susceptible Add a Fluoroquinolone And an injectable Drug based on susceptibilities Fluoroquinolones Levofloxacin Moxifloxacin Injectable agents Amikacin Capreomycin Streptomycin Kanamycin PLUS One of these First-line drugs Pyrazinamide Ethambutol Building a Treatment Regimen Let’s look at this diagrammatic representation of the general approach to designing a treatment regimen for MDR-TB. In Step 1 the first action is to identify any first line drugs which have proven or likely susceptibility. These generally should be used if the organism is susceptible, even if they have been used as part of a failed treatment regimen. Next a fluoroquinolone which will likely be the most important and active drug in the regimen should be added if one is available. When a fluroquinolone is not included in the treatment regimen the likelihood of a good outcome is significantly less. The high mortality of XDR TB is especially related to resistance to fluoroquinolones. Moxifloxacin is regarded by many to be the most active fluroquinolone. Finally an injectable agent should be added. Any of these agents is generally considered equally efficacious but slight differences in toxicity profiles exist. Because the incidence of streptomycin resistance is >10% in many areas of the world, it should only be used if there is documented sensitivity. After incorporation of drugs in step one, the next step is to add one or more of the oral second line drugs to create a regimen of at least four and preferably five to six drugs. When possible consider the medical co-morbidities of your patient. For example you would want to avoid cycloserine in patients with seizures or serious underlying psychiatric diagnoses and ethionamide in those with serious underlying liver disease. The last step is to add a third line drug if an acceptable regimen cannot be built from drugs available in Step 1 and 2. The drug that is most helpful from this group is linezolid. The CDC recommends consulting an expert for the management of all drug resistant cases, but especially those requiring the use of drugs in step 3. BS

Pick one or more of these
Step 1 Use any available Begin with any First line agents to Which the isolate is Susceptible Add a Fluoroquinolone And an injectable Drug based on susceptibilities Fluoroquinolones Levofloxacin Moxifloxacin Injectable agents Amikacin Capreomycin Streptomycin Kanamycin PLUS One of these First-line drugs Pyrazinamide Ethambutol Step 2 Pick one or more of these Oral second line drugs Cycloserine Ethionamide PAS Add 2nd line drugs until you have 4-6 drugs to which isolate is susceptible (which have not been used previously)

Pick one or more of these
Step 1 Use any available Begin with any First line agents to Which the isolate is Susceptible Add a Fluoroquinolone And an injectable Drug based on susceptibilities Fluoroquinolones Levofloxacin Moxifloxacin Injectable agents Amikacin Capreomycin Streptomycin Kanamycin PLUS One of these First-line drugs Pyrazinamide Ethambutol Step 2 Pick one or more of these Oral second line drugs Cycloserine Ethionamide PAS Add 2nd line drugs until you have 4-6 drugs to which isolate is susceptible (which have not been used previously) Building a Treatment Regimen Let’s look at this diagrammatic representation of the general approach to designing a treatment regimen for MDR-TB. In Step 1 the first action is to identify any first line drugs which have proven or likely susceptibility. These generally should be used if the organism is susceptible, even if they have been used as part of a failed treatment regimen. Next a fluoroquinolone which will likely be the most important and active drug in the regimen should be added if one is available. When a fluroquinolone is not included in the treatment regimen the likelihood of a good outcome is significantly less. The high mortality of XDR TB is especially related to resistance to fluoroquinolones. Moxifloxacin is regarded by many to be the most active fluroquinolone. Finally an injectable agent should be added. Any of these agents is generally considered equally efficacious but slight differences in toxicity profiles exist. Because the incidence of streptomycin resistance is >10% in many areas of the world, it should only be used if there is documented sensitivity. After incorporation of drugs in step one, the next step is to add one or more of the oral second line drugs to create a regimen of at least four and preferably five to six drugs. When possible consider the medical co-morbidities of your patient. For example you would want to avoid cycloserine in patients with seizures or serious underlying psychiatric diagnoses and ethionamide in those with serious underlying liver disease. The last step is to add a third line drug if an acceptable regimen cannot be built from drugs available in Step 1 and 2. The drug that is most helpful from this group is linezolid. The CDC recommends consulting an expert for the management of all drug resistant cases, but especially those requiring the use of drugs in step 3. Step 3 Third line drugs Imipenem Linezolid Macrolides Amoxicillin/Clavulanate Consider use of these If there are not 4-6 drugs available consider 3rd line in consult with MDRTB experts BS

Criteria for Reporting TB Cases
All TB cases and suspects are required to be reported in Virginia (EPI 1) Positive smear Positive culture Clinical findings and/or treatment started All children under age 4 found to have latent TB infection are required to be reported (EPI 1) All labs located in or doing business in Virginia are required by code to report any positive smears or cultures and to forward isolates to DCLS

COUNTING CASES Culture confirmed MTB Clinical TB Case
Keep on medicines for two months and if there is clinical and radiographic improvement and meets other CDC guidelines, can be classified as a clinical case Suspects

LTBI Treatment Regimens

Targeted Tuberculin Testing and Treatment of Latent Tuberculosis Infection
As tuberculosis (TB) disease rates in the United States (U.S.) decrease, finding and treating persons at high risk for latent TB infection (LTBI) has become a priority.

Before Initiating Treatment
Rule out TB disease (i.e., wait for culture result if specimen obtained) Determine prior history of treatment for LTBI or TB disease Assess risks and benefits of treatment Determine current and previous drug therapy

Isoniazid Regimens 9-month regimen of isoniazid (INH) is the preferred regimen (270 doses) 6-month regimen is less effective but may be used if unable to complete 9 months May be given daily or intermittently (twice weekly) Use directly observed therapy (DOT) for intermittent regimen

Rifampin Regimens (1) Rifampin (RIF) given daily for 4 months is an acceptable alternative when treatment with INH is not feasible. In situations where RIF cannot be used (e.g., HIV-infected persons receiving protease inhibitors), rifabutin may be substituted.

Rifampin Regimens RIF daily for 4 months (120 doses within 6 months)
RIF and PZA for 2 months should generally not be offered due to risk of severe adverse events 6MMWR August 8, 2003; 52 (31):

Completion of Therapy Completion of therapy is based on the total number of doses administered, not on duration alone.

Number of Reported TB/AIDS Cases: VA, 1993-2007
out of 309 evaluated for HIV were negative

Tuberculosis Mortality VA 1999-2007
16 died during Tx, 11 were Dx post mortum 4 died during TX DX post-mortem

TB in SELECTED RISK FACTORS 2007
HEALTH CARE WORKERS MIGRANT WORKERS LTC CORRECTIONS HOMELESS HIV PEDIATRIC ( 0-14) SUBSTANCE ABUSE

HELP FOR TB CLIENTS DRUG PROGRAM HIP SOUTHWEST DOT PROJECT

QUESTIONS????????? THANK YOU FOR ALL THAT YOU DO!

Who to Call TB PROGRAM YOUR LOCAL HEALTH DEPARTMENT
VDH DIVISION OF DISEASE PREVENTION TB PROGRAM DR. TIPPLE (804) JANE MOORE (804) BRENDA MAYES (804)

DIVISION OF DISEASE PREVENTION

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