Practical Considerations of Latent Tuberculosis Infection

1
Practical Considerations of Latent Tuberculosis
Infection

• Susan Even, MD
• University of Missouri
• Sharon McMullen, RN, BSN
• University of Pennsylvania
• Brenda Johnston, RN, MSN
• Oklahoma City University
• Tim Crump, RN, MSN, FNP
• University of Portland

2
Disclaimer

• The presenters have NO actual or potential
  conflict of interest in relation to this
  educational activity or presentation

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
3
Campus Case

•  
• 22 yo Vietnamese female graduate student
• Tested during fall orientation
• Risk factor country with high TB incidence
• Symptom review negative
• QFT-GIT positive

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
4
Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
5
Case management
Partnered with local health department Smears
negative Culture positive for M. tuberculosis,
pan-sensitive Contact investigation - roommates
negative initially and 8 weeks Completed 9
month treatment (3 drugs) May 2011  
Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
6
Tuberculosis is a very Ancient Disease

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
7

• Evidence of tubercular decay has been found in
  Egyptian Mummies.
• 3000-2400 BCE

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
8
Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
9

• Recently, discoveries in the submerged village of
  Atlit-Yam suggest Tuberculosis was present 7000
  BCE

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
10

• Atlit-Yam was a village that now is submerged
  just off the coast of Israel.
• The village dates from the very dawn of Neolithic
  times, earliest agricultural settlements.
• Both skeletal and DNA evidence demonstrate TB in
  a woman and an infant buried together.

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
11
Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
12

• TB already established at dawn of agricultural
  settlements.
• DNA supports that human TB was not from Bovine TB.

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
13
Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
14

• In the 17th and 18th Centuries, Tuberculosis
  caused up to 25 of all Deaths in Europe

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
15

• In 1854, Herman Brehmer proposed TB was a curable
  disease.
• Established the Sanitorium movement.

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
16
Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
17
TB Established as Infectious Disease

• In 1882, Robert Koch discovered the bacteria that
  caused TB
• In 1900, he isolated tuberculin from tubercle
  bacilli, which became the basis of the ppd.

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
18
Robert Koch

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
19
BCG

• In 1921, the BCG Vaccine was first used in
  humans, though widespread use did not occur till
  after WWII.

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
20
BCG

• Most effective against TB Meningitis and Miliary
  TB.
• Most useful in pediatric age group.
• Efficacy Varies. Studies in UK consistently have
  shown protective effect of 60-80.
• Closer to equator, benefit appears less.
• Causes false positive TST results.

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
21
BCG Method of Administration

• TST administered prior to BCG positive TST
  contraindicates BCG administration.
• Positive TST does not imply immunity, only that
  there is high probability of severe local
  reaction.
• Intradermal administration.
• BCG Leaves a Characteristic Scar, often used as
  proof of prior immunization.

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
22
Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
23
Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
24
Effect of BCG on TST

• The effect on TST of BCG received in infancy is
  minimal, especially gt 10 years after vaccination
• BCG received after infancy produces more
  frequent, more persistent and larger TST
  reactions.

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
25
Medications to Treat Tuberculosis

• In 1946, Streptomycin was introduced as the first
  antibiotic to be effective against TB.
• In 1952, Isoniazid (INH) was introduced.
  Originally an antidepressant.
• While initial results were dramatic, resistance
  was soon noted to develop.
• As other TB antibiotics were discovered, it was
  noted that combination therapy prevented or
  slowed the development of resistance.

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
26
Selman Waksman

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
27
Burden of Tuberculosis

• In 2008, WHO estimated that 1/3 of the global
  population is infected with TB.
• In 2005, 1.6 million people died of TB.
• The emergence of drug-resistant organisms
  threatens to make TB once again an incurable
  disease.

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
28
Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
29
High Incidence Countries are defined as areas
with reported or estimated incidence of 20
cases per 100,000 population
Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
30
Afghanistan, Algeria, Angola, Argentina, Armenia,
Azerbaijan, Bahrain, Bangladesh, Belarus, Belize,
Benin, Bhutan, Bolivia (Plurinational State of),
Bosnia and Herzegovina, Botswana, Brazil, Brunei
Darussalam, Bulgaria, Burkina Faso, Burundi,
Cambodia, Cameroon, Cape Verde, Central African
Republic, Chad, China, Colombia, Comoros, Congo,
Cook Islands, Côte d'Ivoire, Croatia, Democratic
People's Republic of Korea, Democratic Republic
of the Congo, Djibouti, Dominican Republic,
Ecuador, El Salvador, Equatorial Guinea, Eritrea,
Estonia, Ethiopia, French Polynesia, Gabon,
Gambia, Georgia, Ghana, Guam, Guatemala, Guinea,
Guinea-Bissau, Guyana, Haiti, Honduras, India,
Indonesia, Iraq, Japan, Kazakhstan, Kenya,
Kiribati, Kuwait, Kyrgyzstan, Lao People's
Democratic Republic, Latvia, Lesotho, Liberia,
Libyan Arab Jamahiriya, Lithuania, Madagascar,
Malawi, Malaysia, Maldives, Mali, Marshall
Islands, Mauritania, Mauritius, Micronesia
(Federated States of), Mongolia, Montenegro,
Morocco, Mozambique, Myanmar, Namibia, Nepal,
Nicaragua, Niger, Nigeria, Pakistan, Palau,
Panama, Papua New Guinea, Paraguay, Peru,
Philippines, Poland, Portugal, Qatar, Republic of
Korea, Republic of Moldova, Romania, Russian
Federation, Rwanda, Saint Vincent and the
Grenadines, Sao Tome and Principe, Senegal,
Serbia, Seychelles, Sierra Leone, Singapore,
Solomon Islands, Somalia, South Africa, Sri
Lanka, Sudan, Suriname, Swaziland, Syrian Arab
Republic, Tajikistan, Thailand, The former
Yugoslav Republic of Macedonia, Timor-Leste,
Togo, Tonga, Trinidad and Tobago, Tunisia,
Turkey, Turkmenistan, Tuvalu, Uganda, Ukraine,
United Republic of Tanzania, Uruguay, Uzbekistan,
Vanuatu, Venezuela (Bolivarian Republic of), Viet
Nam, Yemen, Zambia, Zimbabwe
Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
31
Low Incidence Countries are defined as areas
with reported or estimated incidence of lt20
cases per 100,000 population
Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
32
Albania, Andorra, Antigua and Barbuda, Australia,
Austria, Bahamas, Barbados, Belgium, British
Virgin Islands, Canada, Chile, Costa Rica, Cuba,
Cyprus, Czech Republic, Denmark, Dominica, Egypt,
Fiji, Finland, France, Germany, Greece, Grenada,
Hungary, Iceland, Iran (Islamic Republic of),
Ireland, Israel, Italy, Jamaica, Jordan, Lebanon,
Luxembourg, Malta, Mexico, Nauru, Netherlands,
New Zealand, Norway, Oman, Puerto Rico, Saint
Kitts and Nevis, Saint Lucia, Samoa, Saudi
Arabia, Slovakia, Slovenia, Spain, Sweden,
Switzerland, United Arab Emirates, United
Kingdom, United States of America, West Bank and
Gaza Strip
Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
33
Screening our Students

• ACHA Recommendations
• Screening vs. Testing

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
34

• Increased Risk For Tuberculosis Infection
  (Population risks)
• Foreign-born persons who have immigrated within
  the last 5 years from countries with high
  incidence of TB disease
• Persons with a history of travel to/in areas
  with a high incidence of TB disease
• Persons with signs and symptoms of active TB
  disease
• Close contacts of a person known or suspected to
  have TB disease
• Employees, residents, and volunteers of
  high-risk congregate settings (e.g., correctional
  facilities, nursing homes, homeless shelters,
  hospitals, and other health care facilities)
• Some medically underserved, low income
  populations as defined locally
• High-risk racial or ethnic minority populations
  defined locally as having an increased prevalence
  of TB disease
• Persons who inject illicit drugs or other groups
  of high-risk substance users (e.g., crack cocaine)

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
35
What are Schools Doing?

• Informal study via SHS
• Some schools following ACHA Guidelines and
  screening all students and testing appropriately.
• Some schools are testing certain higher risk
  populations who are easily mandated for testing
  (International, health-care, education students).
• Some schools do not require asymptomatic testing.

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
36
Why should we care about Tuberculosis Screening?
Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
37
Identify, Treat, and Minimize Transmission of
Active TB
Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
38
Also Important Identify and Treat Latent TB

• 10 of persons with Latent TB will develop Active
  TB at some point in their life.
• 80 of Active TB in the US is from reactivation
  of previous disease.
• Nearly all of those cases could have been
  prevented by prior administration of prophylactic
  treatment of latent infection.

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
39
Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
40
TUBERCULIN SKIN TEST

• Also known as PPD (Purified Protein Derivative)
• Or
• Mantoux Test

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
41
Im Preaching to the Choir
Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
42
Purpose of the TST

• PPD (Mantoux) is indicated for the detection of a
  delayed hypersensitivity reaction to tuberculin
  as an aid in the detection of infection with
  Mycobacterium tuberculosis

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
43
History of the TB Skin Test

• Test created in 1907 by Charles Mantoux in
  France, modified in 1939 in USSR
• Used worldwide, largely replacing Tine test
• Tuberculin is a glycerol extract of the tubercle
  bacillus
• PPD is precipitate of molecules obtained from
  filtrates of sterilized concentrated cultures

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
44
Indications for use

• Immigrants from countries where prevalence of TB
  is high
• Risk of reactivation due to impaired immunity
• Healthcare workers
• Travelers at risk from travel in high-endemic
  countries
• Staff members in correctional facilities

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
45
Methodology of TST

• 0.1 ml (5 TU)
• Injected intradermally with ¼ to ½ needle,
  usually anterior surface of forearm
• Requires producing wheal of 6 to 10 mm
• Read at 48-72 hours

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
46
Why and how does this test work?

• After initial exposure with M. Tuberculosis,
  sensitization occurs primarily in regional lymph
  nodes
• T lymphyocytes proliferate in response to the
  antigenic stimulus
• Subsequent re-stimulation by PPD evokes a local
  reaction mediated by these cells
• Incubation of 2 to 12 weeks usually necessary
  after exposure to TB in order for result to be
  positive.

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
47
Two-Step Testing

• Not a test of dance skills!
• 2-step used to detect individuals with past TB
  infection who now have diminished skin test
  reactivity
• Reduces the likelihood that a boosted reaction is
  later interpreted as a new infection
• 2-step testing is indicated as initial test for
  persons who will be retested periodically, such
  has health profession workers. (not indicated if
  IGRA available)
• Method A second TST is placed 7 days after first
  
• Abbreviated method first test read 7 days after
  placing it and 2nd test administered during same
  visit.

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
48
Interpretation

• Read at 48-72 hours
• Induration is produced through vasodilatation,
  edema, fibrin deposition and other inflammatory
  cells
• Measure induration transversely across the
  forearm
• Result is positive if
• gt5mm in immunocompromised persons or those who
  have had recent close contact with active TB
• gt10 mm if born in countries in Asia, Africa,
  Caribbean, Latin America or high-risk
  communities. Also healthcare workers
• gt15 mm if general population with no other risk
  factors

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
49
False Negatives

• Can be caused by
• Viral infections such as MMR, chickenpox and HIV
• Live virus vaccinations given within 1 month
• Active TB
• Immunosuppressive agents
• Malignancy

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
50
Documentation

• Document
• Date, brand, lot number, expiration date, result
  in mm
• Provide patient with documentation of date and
  result in mm
• Do not accept documentation stating positive or
  negative
• Most Universities do not accept testing beyond 1
  year

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
51
Variables

• A history of BCG vaccine may cause a positive
  result persisting for years.
• Clinical Infectious Disease 2000 Sept 31 Suppl
  3S71-4
• Those who were vaccinated with BCG after the
  first year of life or had more than 1 dose of
  vaccine have the greatest likelihood of
  persistent positive results vs. those who were
  vaccinated as infants.
• Readings beyond 72 hours may underestimate the
  size of response.

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
52
Risks and Limitations

• Sensitive test, but poor at predicting
  reactivation TB
• Very slight risk of severe reaction including
  redness, swelling, blistering
• Live bacteria is NOT used, so no chance of
  getting disease from TST.
• Untrained and even trained persons providing
  results may read incorrectly.
• Serum not stored properly may not provide
  accurate results.
• Specificity of TST in BCG-vaccinated populations
  is low and highly variable

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
53
Advantages to TST

• Inexpensive
• Experienced persons can provide and read
  accurately
• Colleges have a captive audience that must
  return for readings due to option to place
  holds on accounts
• Still a valid screening tool for latent TB
• Specificity in non-BCG vaccinated populations
  high 97

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
54
A little TB Art lesson
Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
55
About the history of the poster

• The Federal Art Project (FAP) was the visual arts
  arm of the Great Depression-era New Deal Works
  Progress Administration (WPA) program in the U.S.
• FAP operated from August 1935, until June 1943.
• Artists created more than 200,000 separate
  posters, murals and paintings
• The City of Chicago Sanitarium was one of the
  largest TB hospitals in the nation and the world.
  

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
56
Interferon Gamma Release Assay (IGRA)

• Blood test for TB infection (TTBI)
• 1 visit
• 2-step not required
• Less reader bias and error
• More specific, with less cross-reaction with most
  non-TB mycobacteria and BCG than TST

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
57
Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
58
Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
59

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
60
Why targeted testing is important

• A low probability of infection increases the
  likelihood of a false-positive result

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
61
? Risk for Progression to Active TB

• HIV infection
• Children under 5 years
• Therapeutically immunosuppressed
• Recently infected with M. tb
• Untreated or inadequately treated active TB
• Silicosis, diabetes, chronic renal failure,
  leukemia, lymphoma, or cancer of the head, neck,
  or lung Gastrectomy or jejunoileal bypass
• lt90 of ideal body weight
• Smokers and persons who abuse drugs or alcohol
• Populations defined locally ?incidence of active
  TB

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
62
Which test?
Despite the indication of a preference, the use
of an alternative test (IGRA or TST) is
acceptable medical and public health practice.
Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
63
What about using both?

• An IGRA may be used in place of
• (but not in addition to)
• a TST in all situations
• where testing for TB infection is indicated.
• HOWEVER

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
64
3 Situations when Testing with both may be
Considered

• If the initial test is indeterminate, borderline,
  or invalid AND a reason for testing persists
• If the initial test is negative
• If the initial test is positive
• under certain circumstances

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
65
When the initial test (TST or IGRA) is negative
and

• 1) the risk for infection, progression, and poor
  outcome are increased
• OR
• 2) clinical suspicion exists for active TB and
  confirmation of infection is desired.

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
66
When the initial test (TST or IGRA) is positive

• 1) In healthy persons with LOW risk for
  infection/progression
• OR
• 2) To encourage compliance (BCG)

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
67
False Positive TST?

• If TST lt15mm
• AND history of BCG
• AND no increased risk for poor outcome if
  infected
• AND IGRA,
• THEN false positive

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
68
Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
69

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
70
Neither IGRA nor TST can distinguish LTBI from
active TB

• The Point?
• Treating active TB (often 4 antibiotics)
• with an LTBI regimen (1 antibiotic)
• can lead to drug-resistant TB

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
71
Medical Management after TTBI (test for TB
infection)

• Diagnoses are not based on test results alone and
  should include
• epidemiologic context
• medical history
• clinical information

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
72

• Required after TTBI
• TB Symptom Check
• Chest x-ray
• Both negative? ? patient cleared
• Either positive? ? follow-up required
• Treatment for LTBI is encouraged, not required

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
73
Treatment of Latent TB

• Why careful treatment decisions are essential
• Drug resistance
• Treatment failure
•   

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
74
Always rule out active TB!
Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
75
LTBI -To treat or not to treat?
Risk of developing active TB
vs. Risks of treatment
Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
76
 Risk for progression to active TB

• Advanced, untreated HIV infection (RR10)
• Close contact infectious TB (RR6)
• X-ray old, fibrotic untreated TB (RR5)
• NEJM Latent Tuberculosis Infection in the US,
  Horsburgh and Rubin, April 14, 2011

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
77
More risks for progression

• Conditions with suppressed immunity -
• Prednisone over 15 mg per day (RR2.8)
• Chronic renal failure, treatment with TNF-alpha
  inhibitor (RR2.4)
• Poorly controlled diabetes (RR1.7)
• Underweight gt10 below normal (RR1.6)
• Smoking (RR1.5)
• NEJM Latent Tuberculosis Infection in the US,
  Horsburgh and Rubin, April 14, 2011

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
78
LTBI Treatment Options

• Endorsed by ATS, CDC, IDSA
• INH -daily 9 months (preferred)
• -daily 6 months
• Rifampin daily 4 months

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
79
INH 9 months

• Daily for 9 months or 270 doses
• 90 effectiveness
• Recommended in HIV infection and old fibrotic
  changes on x-ray
• Dosing
• Daily - 5 mg per kg (max 300 mg)
• Twice weekly-15 mg per kg (max 900 mg)

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
80
INH 6 months

• Daily for 6 months or 180 doses
• 60 to 80 protection
• Consider
• Unable or unwilling to do 9 months
• Nonadherent, cant take rifampin

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
81
Rifampin 4 months

• Treatment trial underway to evaluate
• May offer less hepatotoxicity and greater
  treatment completion rate
• Consider
• when INH resistance is known or suspected
• when unable to tolerate INH

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
82
Rifampin

• 10 mg per kg (600 mg) daily for 4 months in
  adults
• Not recommended as monotherapy in HIV infection
• increased rates of resistance
• drug interactions with many antiretrovirals

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
83
Any other options?

• INH and Rifampin for 3 months (UK)
• not first-line
• may be option in selected cases 
• Rifampin and PZA for 2 months eliminated due to
  significant hepatotoxicity

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
84
Risks of treatment Hepatotoxicity

• Serious potential
• side effect of
• both
• INH and
• Rifampin

•  

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
85
To minimize risks

• Proper drug selection and dose
• Education
• Appropriate clinical monitoring

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
86
Hepatotoxicity with INH

• 0.1 to 1.0 risk of hepatotoxicity
• Increases with chronic liver disease (alcoholism,
  viral hepatitis and older age)
• Clinical symptoms of hepatitis
• Can be severe, even fatal
•  

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
87
INH-induced Neuropathy

• Use Pyridoxine (Vit B6) with INH to reduce risk
• Alcoholism, preexisting neuropathy
• Diabetes, pregnancy,
• Uremia, malnutrition
• HIV
• Underlying seizure disorder
• Daily dose - 25-50 mg

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
88
INH other adverse effects(Low incidence)

• Rheumatologic lupus like syndrome
• Dermatologic hives, rash
• GI abdominal pain, nausea, vomiting
• Seizures, optic neuritis
• Bone marrow suppression
• Toxic psychosis
• Idiosyncratic drug-induced reactions

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
89
INH Monoamine toxicity

• Flushing may occur
• Avoid foods with high levels of monoamines
  (tyramines)
• Aged cheeses
• Cured sausages
• Wines, beer

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
90
Risks of Rifampin

• Hepatotoxicity
• Interference with metabolism of many drugs -oral
  contraceptives
• -anti-retroviral drugs used in HIV disease
• -methadone

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
91
Other adverse effects of Rifampin

• Bone marrow suppression
• Immune reactions
• Pruritis
• Orange discoloration of body fluids 

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
92
Monitoring adverse effects

• No data from prospective studies available
• Baseline testing check liver enzymes
• Underlying liver disease
• HIV infection
• Substantial alcohol consumption
• During pregnancy through 3 months after delivery
• Medications with hepatotoxic potential

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
93
Monitoring guidelines

• Monthly testing of liver enzymes
• only in those whose baseline levels are elevated
• Monthly monitoring for clinical signs and
  symptoms of hepatitis or adverse reactions
• Particularly if pre-existing liver disease and
  higher risk for hepatoxicity

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
94
Discontinue Treatment

• No symptoms - when LFTs exceed 5 times upper
  normal limit
• WITH symptoms - when LFTs exceed 3 times upper
  normal limit

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
95
Adherence to regimen

• Important determinant of effectiveness of
  treatment
• Side effects - small percent of low completion
  rates
• Shorter regimens increase completion rates 45
  - 60 completion in 9 month INH 55 - 57 with 6
  month INH
• 69 - 78 with 4 month daily rifampin

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
96
Challenges of Treatment Adherence

• Access to care
• Interpretation of wellness
• Financial burden
• Attitude, knowledge and beliefs about treatment
• Laws and immigration status
• Patient characteristics
• Family, community, household influences

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
97
Document Completion of Treatment

• Provide relevant details of treatment
• LTBI diagnosis with specific test method
• Medication
• Number of treatments
• Time interval of therapy
• Contact information
• Appropriate signatures

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
98
Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
99
Declining therapy

• Consider documenting that treatment for LTBI was
  recommended
• Identify students reason
• Another educational opportunity
• -review signs and symptoms of active TB
• Leave the door open to future treatment

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
100
Treatment for Latent Tuberculosis Infection Declination Form I have been identified as having latent tuberculosis infection (LTBI). My healthcare provider has recommended a course of treatment with Isoniazid (INH). Treatment with this drug will prevent active TB disease in most persons. Without treatment, approximately 10 of persons with normal immune systems who have LTBI will develop active TB disease during their lifetime. Some medical and other conditions increase the risk of LTBI progressing to active TB disease, such as HIV infection, certain chronic medical conditions i.e. diabetes and end-stage kidney disease, becoming infected with TB within the past two years, and injecting illicit drugs. I understand the tuberculin skin and/ or tuberculin blood test should not be repeated, as they will always likely remain positive. I also understand routine chest x-rays are not recommended for persons with LTBI unless signs or symptoms of active TB disease occur. I confirm I do not have any signs or symptoms of active TB disease. I understand I am to seek immediate medical attention and inform my provider I have LTBI if I develop any of the following signs or symptoms of active TB disease Treatment for Latent Tuberculosis Infection Declination Form I have been identified as having latent tuberculosis infection (LTBI). My healthcare provider has recommended a course of treatment with Isoniazid (INH). Treatment with this drug will prevent active TB disease in most persons. Without treatment, approximately 10 of persons with normal immune systems who have LTBI will develop active TB disease during their lifetime. Some medical and other conditions increase the risk of LTBI progressing to active TB disease, such as HIV infection, certain chronic medical conditions i.e. diabetes and end-stage kidney disease, becoming infected with TB within the past two years, and injecting illicit drugs. I understand the tuberculin skin and/ or tuberculin blood test should not be repeated, as they will always likely remain positive. I also understand routine chest x-rays are not recommended for persons with LTBI unless signs or symptoms of active TB disease occur. I confirm I do not have any signs or symptoms of active TB disease. I understand I am to seek immediate medical attention and inform my provider I have LTBI if I develop any of the following signs or symptoms of active TB disease Treatment for Latent Tuberculosis Infection Declination Form I have been identified as having latent tuberculosis infection (LTBI). My healthcare provider has recommended a course of treatment with Isoniazid (INH). Treatment with this drug will prevent active TB disease in most persons. Without treatment, approximately 10 of persons with normal immune systems who have LTBI will develop active TB disease during their lifetime. Some medical and other conditions increase the risk of LTBI progressing to active TB disease, such as HIV infection, certain chronic medical conditions i.e. diabetes and end-stage kidney disease, becoming infected with TB within the past two years, and injecting illicit drugs. I understand the tuberculin skin and/ or tuberculin blood test should not be repeated, as they will always likely remain positive. I also understand routine chest x-rays are not recommended for persons with LTBI unless signs or symptoms of active TB disease occur. I confirm I do not have any signs or symptoms of active TB disease. I understand I am to seek immediate medical attention and inform my provider I have LTBI if I develop any of the following signs or symptoms of active TB disease
? Fatigue ? Cough lasting three (3) weeks or longer Night sweats Coughing up blood or sputum Chills Weakness Loss of appetite Unexplained fever Unexplained weight loss Chest pain Respiratory Difficulty Loss of appetite Unexplained fever Unexplained weight loss Chest pain Respiratory Difficulty
I have read the information given to me about LTBI and treatment of LTBI. I believe I understand the benefits and risks of taking the recommended treatment. I have had the opportunity to have my questions regarding LTBI and LTBI treatment answered to my satisfaction. I have chosen not to take the recommended treatment for LTBI at this time. The MU Student Health Center has offered to provide me with the medication and nursing supervision at no cost. I understand if, in the future, I decide to take the medication, the TB Nurse at the Student Health Center will be available to advise me on this matter (phone [phone]). I have read the information given to me about LTBI and treatment of LTBI. I believe I understand the benefits and risks of taking the recommended treatment. I have had the opportunity to have my questions regarding LTBI and LTBI treatment answered to my satisfaction. I have chosen not to take the recommended treatment for LTBI at this time. The MU Student Health Center has offered to provide me with the medication and nursing supervision at no cost. I understand if, in the future, I decide to take the medication, the TB Nurse at the Student Health Center will be available to advise me on this matter (phone [phone]). I have read the information given to me about LTBI and treatment of LTBI. I believe I understand the benefits and risks of taking the recommended treatment. I have had the opportunity to have my questions regarding LTBI and LTBI treatment answered to my satisfaction. I have chosen not to take the recommended treatment for LTBI at this time. The MU Student Health Center has offered to provide me with the medication and nursing supervision at no cost. I understand if, in the future, I decide to take the medication, the TB Nurse at the Student Health Center will be available to advise me on this matter (phone [phone]).
Reason For Declining Treatment Reason For Declining Treatment Reason For Declining Treatment
Signature Signature Date
Provider/Nurse Signature Provider/Nurse Signature Date
Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
101
CDC/ACHA Survey Immunization and TB

• How do US colleges and universities handle
  immunization requirements and TB Screening with
  their international student population?
• Do they use ACHAs Prematriculation Immunization
  and TB Screening and Testing Guidelines?
• Help by completing the survey this Fall!

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
102
Questions?
Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
103
References

• ACHA Guidelines Tuberculosis Screening and
  Targeted Testing of College and University
  students http//www.acha.org/Publications/docs/AC
  HA_Tuberculosis_Screening_Apr2011.pdf
• CDC Fact Sheet BCG Vaccination
  http//www.cdc.gov/tb/publications/factsheets/prev
  ention/BCG.htm
• CDC. Core Curriculum on Tuberculosis. Third
  Edition. 1994
• CDC.gov/tb
• Dyer, Carol. Tuberculosis (Biographies of
  Disease). Santa Barbara, CA Greenwood Press.
• Farhat, Greenaway, Pai, and Menzies,
  False-positive tuberculin skin tests what is
  the absolute effect of BCG and non-tuberculous
  mycobacteria, Int J Tuberc Lung Dis 2006 10
  1192-1204.
• Horsburgh, C., Rubin, E. (2011). Latent
  tuberculosis infection in the United States. The
  New England Journal of Medicine, 3674(15),
  1441-1448.
• Inge and Wilson, Update on Treatment of
  Tuberculosis, American Family Physician, August
  15, 2008
• Kik SV, Franken WP, Mensen M., et al. Predictive
  value for progression to tuberculosis by IGRA and
  TST in immigrant contacts. Eur Respir J 2010 35
  1346-53
• Madhukar P, Zwerling A, Menzies D. Annals of
  Internal Medicine 2008 149 177-184
• Mazurek, G. H., Jereb, J. A., Vernon, A., LoBue,
  P., Goldberg, S., Castro, K. G., . . . Centers
  for Disease Control and Prevention (US). (2010).
  Updated guidelines for using interferon gamma
  release assays to detect mycobacterium
  tuberculosis infection, united states, 2010 Dept.
  of Health and Human Services, Centers for Disease
  Control and Prevention
• Menzies. What Does Tuberculin Reactivity after
  Bacille Calmette-Guerin Vaccination Tell Us?
  Clinical Infectious Diseases 201031 (Suppl 3)
  S71-4
• Munro et al., Patient Adherence to Tuberculosis
  Treatment a Systematic Review of Qualitative
  Research PLoSMed. 2007, 4 (7)e238
• TB an Overview http//www.emedicinehealth.com/tu
  berculosis/article_em.htm
• World Health Organization Incidence of
  Tuberculosis by Country http//apps.who.int/ghoda
  ta/?vid510

Even-McMullen-Johnston-Crump, ACHA, 6.2.2011