Introduction to Tuberculosis This isn’t meant to be an exhaustive presentation regarding tuberculosis, but an overview, so that the topic to tuberculosis risk assessment and tuberculin skin testing has a context as it relates to TB disease. We want to welcome you, and hope the next 4 hours will be helpful to you and the facilities where you work. VDH TB Control and Prevention Program 2011

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 These are some of the various guidelines that the Virginia Department of Health TB Program depends on for program standards and guidance. We don’t have separate guidance. We don’t have separate guidance from that provided by the CDC, except in particular clinical situations. Show the “Guidelines for Preventing Transmission of Mycobacterium tuberculosis in Health-Care Settings, 2005.” Every health care setting should be familiar with this document, including the facility risk assessment on page 128.

The Causative Agent

M. Tuberculosis - the causative agent for tuberculosis We have already seen this slide, but take a look at the two pictures to the right. One is a positive AFB stain or smear, with the TB mycobacteria staining red; the dye that is “acid fast”. The other is a TB culture growing on traditional media. Dr. Koch received a microscope for Christmas from his wife, and the rest is history. Robert Koch ~ 1886

Mycobacterium tuberculosis Bacteria A weakly gram positive rod Appears “rough and buff” in standard culture An organism that holds a red stain even in the presence of acid, i.e. “acid fast” Slow growing

The Mycobacteria Human pathogens M. tuberculosis complex includes: M. tb, M. bovis, M. africanum, M. microti, M. canetti M. leprae NTM – non-tuberculous mycobacteria NTM, previously MOTTS (mycobacteria other than TB). We will talk about the various lab work regarding TB later, but all mycobacteria, as well as fungi and some other bacteria can be AFB stain positive.

Transmission and Pathogenesis of Tuberculosis

Transmission of TB Spread person to person through the air A key principle in TB transmission; you must share air with a TB case to develop TB infection. Cough is the major mechanism in transmission, though the droplet nuclei that are spread can also be expelled by shouting or singing. Young children rarely transmit disease, even with cough.

TB: Airborne Transmission TB bacteria airborne Person with active pulmonary TB Person breathing TB bacteria This is just another way to show that for TB infection to occur, a person must share air with the TB case. Those with TB infection alone are not contagious.

TB Invades and Infects the Body Hematogenic spread of bacteria Effective immune response Infection limited Describe two pathways, leading to infection or active disease. Immune response insufficient Or Immune response fails Active Disease

Pathogenesis of TB Infection begins when the inhaled droplets reach the alveoli of lungs Tubercle bacilli multiply A number of tubercle bacilli enter the bloodstream and spread throughout the body (lungs, kidneys, brain, bone) Within 2-10 weeks, the immune system produces an immune response which encapsulates the bacteria, and is detectable with a TST or IGRA blood test In other words, [read the slide]. IGRA stands for interferon gamma release assay. We will talk about IGRAs in a bit. TB disease can occur after infection, wherever the TB bacteria are in the body.

Probability of TB Transmission Transmission dependent on three factors Infectiousness of the person with TB Host factors of the exposed person Environment in which the transmission occurs Not all cases of TB are equally contagious. TB infection depends on: Infectiousness: smear positivity, cavitary vs. non-cavitary disease Host factors: immune competency Environment: ventilation, humidity, duration, proximity

Likelihood of Developing TB Disease Once infected with tubercle bacilli 10% life time chance that TB disease will develop Half the risk within the first 2 years Gradually decreasing risk after the first 2 years 90% chance of never developing the disease Other personal health factors can influence risk HIV infection - single highest risk for progress to active disease, at 10% risk annually Diabetes – 30% risk over lifetime

Sites of TB Disease Pulmonary TB (TB of the lungs) – 80-85% of TB cases Potential for transmission – infectious until proven otherwise Extra-pulmonary TB (outside the lungs) Can occur anywhere in body Typical sites include larynx, lymph nodes, the pleura, brain, kidneys, bones, or joints Usually not infectious – always rule out pulmonary! Laryngeal TB is extremely contagious - hoarseness Extra-pulmonary disease – portal of entry through the lungs at time of infection Put this somewhere else: Before Anti TB drugs 50 % of all TB patients died...AND OF THE 45% WHO SURVIVED, 25% were chronically ill for a lifetime

Diagnosis of TB Disease Symptoms TST or IGRA CXR Bacteriology

Diagnosis of TB Disease: Symptoms Pulmonary symptoms Cough Pain in the chest when breathing or coughing Coughing up sputum or blood Systemic symptoms Fatigue / malaise Decreased appetite Weight loss Fever Night sweats Other symptoms specific to the site of the TB disease The first thing that usually prompts suspicion of TB are symptoms. TB is slow in onset, and will often go unnoticed, even by the patient, for months. Symptoms should be evaluated in the context of the patient’s overall history. For example, a women, aged 50 with night sweats and no other symptoms would not be a concern.

Evaluation for TB Disease Medical History Symptoms of TB Exposure to TB, Hx previous TB infection, or Hx TB disease Risk factors for progression to TB disease TB skin test or IGRA Chest x-ray or CT Bacteriologic Examination of sputa, including: Smears (+AFB) MTD or PCR “direct test (RNA based) Culture results “DNA probes” or traditional culture

Diagnosis of TB Disease 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, opacities A chest x-ray does not confirm TB disease A chest x-ray does not rule out active TB in immune compromised individuals and children

Diagnosis of TB Disease: Bacteriologic Examinations Sputum collection – those symptomatic or with abnormal chest x-rays consistent with TB, for AFB smear and culture: A series of three samples Spontaneous or induced At least 8 hrs. apart, and one in early AM All specimens should be cultured, regardless of smear result Smear/stain results in 1 day, culture results take up to 6-8 weeks M.tb can be cultured from any body fluid or tissue Specimen collected depends on the site of potential disease

Direct Tests for TB MTD – Mycobacterium tuberculosis direct or TB PCR These rapid tests are done directly on raw respiratory samples; culture growth is not needed Very sensitive on samples with higher smear positivity A negative test does not rule out TB, especially with negative smear results Does not provide enough evidence to release from isolation Anyone with a positive culture for M.Tb or a positive rapid test is counted as a case of TB. Clinical cases that don’t have confirming culture results can also be counted under certain circumstances.

Antituberculosis Drugs Currently in Use in the US Second-line Drugs Cycloserine Ethionamide Levofloxacin Moxifloxacin Gatifloxacin P-Aminosalicylic acid Streptomycin Amikacin/kanamycin Capreomycin Linezolid First-line Drugs Isoniazid* Rifampin* Ethambutol* Pyrazinamide* Rifapentine Rifabutin The purpose here is not to make you TB nurses, but recognize some of these medications, especially the 4 most common *, isoniazid, rifampim, ethambutol, and pyrazinamide. TB is usually treated for 6 to 9 months. Drug resistant cases can take years to treat.

Latent Infection vs. Active Disease Latent TB Infection or LTBI Active TB Disease Tubercle bacilli in the body Tuberculin skin test reaction or IGRA usually positive No symptoms Symptoms such as cough, fever, weight loss Chest x-ray usually normal Chest x-ray usually abnormal Sputum smears and cultures, if done, are negative Sputum smears and cultures may be positive Not infectious Often infectious before treatment Not a case of TB, but risk for future disease A current case of TB This chart summarizes the difference between TB infection and TB disease. [read through] After evaluation for TB disease, if the skin test has been positive, there is always the question of what to do for what has been determined to be TB infection. If sputa samples are awaiting culture, NO medication should be started for latent TB infection. However, if TB disease has been ruled out, consideration should be given to treatment for latent TB infection. Treatment of latent TB infection reduces the amount of future TB disease from approximately 1 in 10, to 1 in 100.

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 MMWR August 8, 2003; 52 (31): 735-739

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

Tuberculosis Control and Prevention – it takes a Team!

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 Interpreter/ translator services Laboratory 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 A team effort Review components of slide Mention that DOT is the program standard for treatment of TB disease, meaning a health care worker observes patient taking medication. 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

What is Reportable According to VA Regulation? By medical provider or designee Confirmed or suspected TB disease Positive TST in children under age 4 years By directors of medical laboratories Positive AFB smears or cultures

The Public Health Nurse – TB Case Management Education Assure treatment according to national standards Contact investigation Assure treatment adherence and adequate therapy DOT as international program standard Identify adverse drug reactions Monitor clinical improvement Recognize patient behaviors Develop strategies to problem-solve

Teamwork!! Tuberculosis is suspected, diagnosed, and treated as a team. Treatment of LTBI prevents future TB disease It takes all of us to get the job done! Know your local TB health department staff and ask questions! Only with knowledgeable and trained personnel can tuberculosis be quickly identified and completely managed.