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)
1
Introduction
 Guidelines released June 2008 -1 year of work by
task force
 Update needed to strengthen public health
measures on campuses to prevent TB and to
include IGRAs
 TB Subcommittee - part of Coalition of Emerging
Public Health Threats and Emergencies
 Request -present program to illustrate application
of guidelines
2
Presentation Goals
• Review guidelines
• Describe implementation at a large private university in
east (University of Pennsylvania)
• Describe implementation at a small, private university in
southern midwest (Oklahoma City University)
• Q & A (providing input for a FAQ document for ACHA)
3
4
Purpose
 Highlight screening and testing as key strategy for
controlling and preventing infection on campuses
 Target population – incoming students who are at
increased risk for TB
 Review appropriate follow up care for students
diagnosed with latent tuberculosis infection (LTBI) or
TB disease
5
Definitions
 Screening – identification of high risk students who
need testing, commonly by a questionnaire
 Testing – procedure for diagnosing LTBI; using
Mantoux tuberculin skin test (TST) or blood tests
using interferon gamma release assay (IGRA)
6
Definitions
 Population risks vs Medical risks
Definitions
 Population risks – epidemiological and population-
based risk factors of incoming students that increase
their likelihood having LTBI, therefore targeting these
for testing
 Medical risks – factors placing an individual who is
already infected with TB (LTBI) at high risk for
progressing to active disease
8
Whom to Screen
All incoming students using screening questionnaire
• Highest risk group – international students from countries
with increased incidence of TB
• High- incidence – countries with annual TB disease greater
or equal to 20 cases per 100,000
• Close contacts to known or suspected TB disease
• Workers in high risk congregate settings (healthcare
facilities, nursing homes, homeless shelters, corrections
institutions, etc)
• Persons who inject illicit drugs, etc
• Travelers to areas of high incidence of TB (no evidencebased data regarding length of time) -consider provider
visit to assess significance of potential exposure
12
Whom to Screen
Continuing students – usually a program rather
than an institutional requirement
 When specific activities place them at risk (study
abroad, research, volunteering, etc.)
 Health professions students -annual requirement
usually monitored by specific program
13
Whom to screen
Medical Clinic setting
As part of routine evaluation, clinicians should
 screen for both risk of LTBI and
risk of LTBI progressing to TB disease
AND
 conduct appropriate testing
14
When to Screen and Test
 Prior to arrival on campus, give questionnaire
 Review with verification of prematricuation
immunization requirements
 Test high risk students only
– no sooner than 3 – 6 mos before arrival
 Complete by second semester/quarter registration
15
How to Test - TST
 Tuberculin Skin Test (TST)
 Mantoux Test – intradermal injection of 0.1 ml PPD (5
tuberculin units)
 History of BCG doesn’t preclude TST
 Delay 4 – 6 weeks after a live virus vaccine (usually
MMR)
 May give concurrently with live virus vaccine without
compromising results
16
How to Test - TST
Two-step testing:
 Initial testing for persons retested periodically (health
professions students, volunteers)
 TST #2 is performed 1 to 3 weeks after TST #1 is
negative
 If TST #2 is positive, LTBI is diagnosed (identifying a
childhood infection)
17
Interferon Gamma Release
Assays (IGRAs)
• May be used in all circumstances where TST is used
• Use with caution in immunocompromised individuals
• Has greater specificity than TST – no reaction to BCG
or most non-tuberculous mycobacteria
• Usually single test is adequate making compliance
easier
• Cost and availability are limitations
• CDC does not support use of IGRA as a confirmatory
test after positive TST however, this practice is
prevalent in the US (following international use)
18
How to Interpret the TST
 Read 48-72 hours after injection; measure induration
in transverse diameter; record in mm of induration (0
mm if no indiration)
 Interpretation – based on induration and risk factors
19
How to Interpret the TST
>5 mm is positive in the following:
 Recent contacts of individuals with infectious TB
disease
 Chest x-ray with fibrotic changes consistent with past
TB disease
 Organ transplant recipients and other
immunosuppressed persons
 Persons with HIV/AIDS
20
How to Interpret the TST
>10 mm is positive in the following:
• Persons born or residing in high prevalence country
• History of illicit drug use
• Mycobacteriology lab personnel
• Workers, volunteers of high risk congregate settings,
including health care facilities
• Persons with clinical conditions including diabetes,
silicosis, chronic renal disease, leukemia, lymphoma,
cancers of head, neck or lungs, body weight >10% below
ideal, gastrointestional conditions such as gastrectomy,
intestinal bypass, malabsorption syndromes
21
How to Interpret the TST
>15 mm is positive in the following:
 Persons with no known risk factors for TB disease
22
What to do When the TST or
IGRA is Positive
Chest x-ray and medical evaluation (review signs and
symptoms)
If abnormal x-ray OR any signs and symptoms of TB
• Must exclude active TB disease
• Sputum smears and cultures, chest CT, bronchoscopy
If normal x-ray and medical evaluation
• Diagnose LTBI
• Recommend treatment for LTBI
• Contact with public health officials (reportable in some
states)
23
What to do When the TST or
IGRA is Positive
Reasons to treat LTBI
• Reduce risk for progression to TB disease (90%)
• Reduce burden of TB in US
Highest risk of progression from LTBI to TB disease
• TST or IGRA conversion within 2 year
• HIV/AIDS or other clinical conditions with increased
risk due to impaired immunity
24
What to do When the TST or
IGRA is Positive
 LTBI Treatment Options
 INH daily for 9 months–preferred, 6 months
minimum
 Directly Observed Therapy (DOT) – two times per
week at higher dose
 Rifampin in exposures to known INH-resistant
disease
25
What to do When the TST or
IGRA is Positive
Completion of treatment high priority
 Provide education in primary language when possible
(refer to translated chart)
 Insure confidentiality
 Consider incentives
 Gain trust by case management with culturally
competent provider
26
What to do When the TST or
IGRA is Positive
Monitoring of treatment
 Monthly symptom checks
 If symptoms suggest adverse reactions - laboratory
testing
 Routine testing only if increased risk of complications
27
What to do When the TST or
IGRA is Positive
Conditions requiring routing laboratory monitoring
 Regular use of alcohol
 History of liver disorder, risk of hepatic disease
 HIV/AIDS
 Pregnancy or up to 3 months post-partum
 Medications with risk of liver toxicity
28
What to do When the TST or
IGRA is Positive
Post-treatment follow up
 Provide documentation of TST or IGRA results, chest
x-ray results, dosage and duration of medication
treatment
 Reinforce signs and symptoms of TB disease with
instructions to seek medical attention upon
developing any
29
Student Health Service
30
Facts and Figures
Private, 280-acre urban campus
24,000 students
20,000 full-time (½ undergrad, ½ grad)
3,500 international students
3000 health professional students
Student Health Service: 45,000 visits/year
Primary Care, Women’s Health, Sports Medicine,
Travel, Immunization/Allergy, Podiatry, Lab,
Health Ed, Public Health, Massage/Acupuncture
31
Immunization Requirements
 Required:
 Hepatitis B: 3 doses
 MMR: 2 doses
 Varicella: 2 doses or hx of disease
 Meningococcal
 Screening for TB infection
 Web-based data entry and faxed records
 Student Immunization compliance: ~97%
32
Goals
1. Screening
2. Documentation
3. Testing for TB Infection
4. +TTBI follow up
5. Compliance
33
Screening for TB Infection
Method: web-based questionnaire
Who gets screened?
All 8000 matriculating, full-time students per year
Who gets tested?
Anyone whose answers “yes” to a screening question
Health professional students annually
Goal:
to find LTBI
34
Screening Questions
Have you ever :
1. been in close contact with anyone with active TB?
2: worked/volunteered with people in prisons?
3: worked/volunteered with the homeless?
4: worked/volunteered with refugees?
5: worked/volunteered with people in hospitals?
6: been diagnosed with diabetes?
7: been diagnosed with cancer?
8: Do you have a history of prolonged use of corticosteroids
and/or immunosuppressive treatment?
9: Are you HIV positive?
10: Country of Origin:
35
Non-TB Endemic Countries
American Samoa
Andorra
Antigua and Barbuda
Australia
Austria
Barbados
Belgium
Bermuda
Canada
Cayman Islands
Chile
Costa Rica
Cuba
Cyprus
Czech Republic
Denmark
France
Germany
Greece
Grenada
Holland/Netherlands
Hungary
Iceland
Ireland
Israel
Italy
Jamaica
Jordan
Libyan Arab Jamahiriya
Luxembourg
Malta
Monaco
New Zealand
Niue
Norway
Oman
Puerto Rico
Saint Kitts and Nevis
Saint Lucia
San Marino
Slovenia
Sweden
Switzerland
Tokelau
Trinidad and Tobago
Turks and Caicos Islands
United Kingdom
USA
Dominica
Finland
Montserrat
Virgin Islands, British
Virgin Islands, US 36
Assessment of Volunteers
 4 x 4 x 4 Rule
 4 hours a day
 4 days a week
 4 weeks in a month
37
TTBI Documentation
 Acceptable proof of +PPD:
 Dates of placement AND reading
 Size in mm
 Official letterhead or signature of provider
 “Positive" on an imm. card is not sufficient
 Acceptable proof of a negative IGRA:
 Official lab report with reference ranges noted
 < 12 months old
 Not accepted:
 proof of negative PPD
38
Chest XRay Documentation
 Acceptable proof of cxr:
 Official US radiologist's report
 Dated AFTER the positive PPD
 Negative reading
 Not accepted:
 “Negative cxr” on immunization card is not
sufficient
 International chest xray reports
 Cxr films
39
Prior Treatment Documentation
 Acceptable proof of treatment completion:
 Official letterhead (or signed by the supervising
healthcare provider)
 Name(s) and dosage(s) of the medications
 Initiation and completions dates
 Not accepted:
 “Treated for TB” on an immunization card is not
sufficient
40
Testing for TB Infection
 Method: PPD
 5500 PPDs placed annually
 3100 incoming international students, returning
travelers
 2400 Health professional, including 1000 2-steps
 1200 SON
 770 SOM
 430 SDM
41
PPD Reading
 Within 2-3 days
 Nurse reads PPD
 No self-readings
 If negative, student is compliant
 If positive, nurse will:





TB Symptom Check
Order cxr
Review instructions with student
Send links to on LTBI, BCG
Student is not compliant until cxr is done
42
2 Step PPDs
 Required for incoming health prof students
 Timing: placed 1-3
weeks apart
 Purpose: assess
remote TB exposure
43
Follow-up of positive results
 350 positive PPDs (6%)
 PHN tracks each +PPD monthly


100% compliant with TB Symptom Check
97% compliant with required cxr
 Follow-up eval for LTBI treatment (~50%)
 Not required but strongly encouraged
 12% accept medications for LTBI



Rifampin vs INH
Monitored via secure message each month
Completion of Therapy Letter
44
45
Compliance
 Registration hold
 Students cannot register for the next semester’s
classes if there is an SHS hold on their account
 Exception
 Health professional schools track/enforce their
program-specific requirement of annual PPDs
46
STUDENT HEALTH AND DISABILITY SERVICES
47
Introduction
 Private, faith-based (Methodist) University on 60 acre
urban campus in the lower Midwest
 3,200 students
3,000 full-time
1,800 undergraduate
500 graduate
5 doctoral
600 law
 446 International students – most from China, Taiwan, Korea, West
Africa, India, Saudi Arabia. Few from Europe and Canada.
 274 Health professional students (Nursing)
48
Student Health Services
 2,300 visits per year
Services:
 Primary care
 Women’s Health
 Immunization and Allergy
 Laboratory
 Health Education
 Disability Services is part of program
49
Staffing
 Nurse Director – also serves as Disability Services
Coordinator, 12 months
 ARNP - full-time, 10 months + 1 day/week in summer
 RN – full-time, 10 months
 Office manager – full-time, 12 months
 Receptionist - full-time, 12 months
50
TB Screening
 All international students, on matriculation
 Must be done during first semester
 Nursing students’ deadlines vary by program
51
Documentation Accepted from
Abroad
 Must be documented on our form, include date of
placement and reading, resulted in mm
 Notation of “negative” is not accepted
 Documentation less than 12 months old
 For positive results when CXR films sent with patient –
send to Oklahoma City/County Health Dept. TB
Control Center (OCCHD TBCC) for evaluation.
 Borderline results (between 5 and 9 mm), we re-test.
52
Compliance
 Account and registration holds for non-compliance.
Holds go on mid-way during first semester.
Student reminded by e-mail and via advisors.
Those with positive PPD are not off hold until
CXR and IGRA are resulted.
 Nursing students cannot attend clinical if non-
compliant.
53
Testing type
 PPD
 Student pays $15
 SHIP does not pay
 Why not IGRA’s? Cost
Done free at OCCHD TBCC for positive PPD
54
Follow-up of Positive Results
 RN does TB symptoms check
 Appt. for IGRA, CXR made at OCCHD TBCC
 Student e-mailed date and time of appt.
 Counseling for LTBI is done by OCCHD TBCC who
provides treatment and monitoring for free.
55
IGRA
 Began looking into IGRA in mid-2007.
 Not available in Oklahoma until early 2009
 OCCHD TBCC began offering free QFT in March,
2009.
 40 students referred March 1,’09-Mar 1, ‘10
 20% of positive PPDs (8 students) have been QFT
positive.
 60% started medication, 40% refused treatment
56
Active TB
 No cases of active tuberculosis on our campus since
late 2001.
 At that time, international student population was
much larger than today.
 The End….
57
by the Advent of IGRAs
58
Question to SHS Listserv
 In March 2010, I queried the SHS Listserv about the
difference in our international students in the
incidence of + TST versus + IGRA.
 Anecdotally, we have noted dramatically fewer
+ IGRA’s than + TST among our international
students.
59
Study at ASU: TST & IGRA
 Dr Sanford Ho at Arizona State University described a
study at their health center.
 The Quantiferon Gold Test was used as a confirmatory
test for 40 international students with + ppd’s.
 The number of females and males were equal, and the
majority of the patients were between 20-29 years of
age (55%), while less than 8% were 40 years or older.
 A total of 24 (60%) had a history of BCG vaccination,
12 (30%) were not sure (but were more likely to have
received BCG due to country of birth).
60
Study at ASU: TST & IGRA
 Only 12 (30%) patients had a positive QFT-G, resulting
in a positive predictive value of 0.3 of a positive PPD
for diagnosing latent tuberculosis infection (LTBI).
 Of those patients who have received BCG vaccination,
8 (33%) tested positive on the QFT-G assay while 3
(25%) tested positive from the group with an unclear
BCG history.
 Therefore, it can be inferred that 16 (67%) of the
patients reviewed who had previous BCG vaccination
as well as 9 (75%) of those with unclear BCG history
had a false positive PPD skin test.
61
This raises the possibility:
 Would screening international students w/ IGRA
rather than TST identify fewer positives?
 Could this save costs in terms of unnecessary CXR’s
and prophylactic INH?
 Might we lower costs and improve patient care?
62
Another SHS Response
“If the only worldwide test easily available for years has
been the tuberculin skin test (TST), then are all data
on the incidence of latent TB infection (LTBI) based
on this test? Now that we can do IGRA tests which
show many fewer positives than TST, does this mean
that the incidence of LTBI is really much lower??? I
feel like I need an TB expert AND an epidemiologist to
help us wrap our minds around this question. ”
63