1. 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

2. 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.

3. The Causative Agent

4. 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

5. 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

6. 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.

7. Transmission and Pathogenesis
of Tuberculosis

8. 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.

9. 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.

10. 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

11. 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.

12. 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

13. 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

14. 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

15. Diagnosis of TB Disease
Symptoms
TST or IGRA
CXR
Bacteriology

16. 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.

17. 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

18. 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

19. 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

20. 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

21. 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.

22. 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.

23. 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.

24. LTBI Treatment Regimens

25. 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.

26. 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

27. 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

28. 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.

29. 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):

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

31. Tuberculosis Control and Prevention – it takes a Team!

32. 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

33. 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

34. 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

35. 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.