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)

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IntroductionGuidelines released June 2008 -1 year of

work by task forceUpdate 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

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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)

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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

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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)

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DefinitionsPopulation 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

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Whom to ScreenAll 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

evidence-based data regarding length of time) -consider provider visit to assess significance of potential exposure

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Whom to ScreenContinuing students – usually a program

rather than an institutional requirementWhen specific activities place them at risk

(study abroad, research, volunteering, etc.)Health professions students -annual

requirement usually monitored by specific program

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Whom to screenMedical Clinic settingAs part of routine evaluation, clinicians should screen for both risk of LTBI and

risk of LTBI progressing to TB disease AND conduct appropriate testing

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When to Screen and TestPrior to arrival on campus, give questionnaireReview with verification of prematricuation

immunization requirementsTest high risk students only

– no sooner than 3 – 6 mos before arrivalComplete by second semester/quarter

registration

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How to Test - TSTTuberculin Skin Test (TST)Mantoux Test – intradermal injection of 0.1

ml PPD (5 tuberculin units)History of BCG doesn’t preclude TSTDelay 4 – 6 weeks after a live virus vaccine

(usually MMR)May give concurrently with live virus vaccine

without compromising results

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How to Test - TSTTwo-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)

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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)

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How to Interpret the TSTRead 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

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How to Interpret the TST>5 mm is positive in the following:Recent contacts of individuals with infectious

TB diseaseChest x-ray with fibrotic changes consistent

with past TB diseaseOrgan transplant recipients and other

immunosuppressed personsPersons with HIV/AIDS

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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

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How to Interpret the TST>15 mm is positive in the following:Persons with no known risk factors for TB

disease

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What to do When the TST or IGRA is PositiveChest 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)

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What to do When the TST or IGRA is PositiveReasons 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 immunity24

What to do When the TST or IGRA is PositiveLTBI Treatment OptionsINH daily for 9 months–preferred, 6 months

minimum Directly Observed Therapy (DOT) – two times

per week at higher doseRifampin in exposures to known INH-

resistant disease

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What to do When the TST or IGRA is Positive Completion of treatment high priorityProvide education in primary language when

possible (refer to translated chart)Insure confidentialityConsider incentivesGain trust by case management with

culturally competent provider

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What to do When the TST or IGRA is PositiveMonitoring of treatmentMonthly symptom checksIf symptoms suggest adverse reactions -

laboratory testingRoutine testing only if increased risk of

complications

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What to do When the TST or IGRA is PositiveConditions requiring routing laboratory

monitoringRegular use of alcoholHistory of liver disorder, risk of hepatic

diseaseHIV/AIDSPregnancy or up to 3 months post-partumMedications with risk of liver toxicity

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What to do When the TST or IGRA is PositivePost-treatment follow upProvide 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

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Student Health Service

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Facts and FiguresPrivate, 280-acre urban campus

24,000 students20,000 full-time (½ undergrad, ½ grad)3,500 international students3000 health professional students

Student Health Service: 45,000 visits/yearPrimary Care, Women’s Health, Sports Medicine, Travel, Immunization/Allergy, Podiatry, Lab, Health Ed, Public Health, Massage/Acupuncture

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Immunization RequirementsRequired:

Hepatitis B: 3 dosesMMR: 2 dosesVaricella: 2 doses or hx of diseaseMeningococcalScreening for TB infection

Web-based data entry and faxed records

Student Immunization compliance: ~97%

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Goals1. Screening2. Documentation3. Testing for TB Infection4. +TTBI follow up5. Compliance

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Screening for TB InfectionMethod: web-based questionnaire

Who gets screened?All 8000 matriculating, full-time students per

year

Who gets tested?Anyone whose answers “yes” to a screening

questionHealth professional students annually

Goal: to find LTBI34

Screening QuestionsHave 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 CountriesAmerican Samoa France New ZealandAndorra Germany NiueAntigua and Barbuda Greece NorwayAustralia Grenada OmanAustria Holland/Netherlands Puerto RicoBarbados Hungary Saint Kitts and NevisBelgium Iceland Saint LuciaBermuda Ireland San MarinoCanada Israel SloveniaCayman Islands Italy SwedenChile Jamaica SwitzerlandCosta Rica Jordan TokelauCuba Libyan Arab Jamahiriya Trinidad and TobagoCyprus Luxembourg Turks and Caicos IslandsCzech Republic Malta United KingdomDenmark Monaco USA

Dominica Montserrat Virgin Islands, British Finland Virgin Islands, US 36

Assessment of Volunteers4 x 4 x 4 Rule

4 hours a day4 days a week4 weeks in a month

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TTBI DocumentationAcceptable proof of +PPD:

Dates of placement AND reading Size in mmOfficial 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 DocumentationAcceptable proof of cxr:

Official US radiologist's report Dated AFTER the positive PPDNegative reading

Not accepted:“Negative cxr” on immunization card is

not sufficientInternational chest xray reportsCxr films

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Prior Treatment Documentation Acceptable proof of treatment

completion:Official letterhead (or signed by the

supervising healthcare provider)Name(s) and dosage(s) of the medicationsInitiation and completions dates

Not accepted:“Treated for TB” on an immunization card

is not sufficient 40

Testing for TB InfectionMethod: PPD

5500 PPDs placed annually3100 incoming international students,

returning travelers2400 Health professional, including 1000

2-steps1200 SON770 SOM430 SDM 41

PPD ReadingWithin 2-3 days Nurse reads PPD

No self-readings If negative, student is compliantIf positive, nurse will:

TB Symptom CheckOrder cxrReview instructions with student Send links to on LTBI, BCG Student is not compliant until cxr is done

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2 Step PPDsRequired for incoming health prof

students

Timing: placed 1-3 weeks apart

Purpose: assess remote TB exposure

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Follow-up of positive results350 positive PPDs (6%)

PHN tracks each +PPD monthly100% compliant with TB Symptom Check97% compliant with required cxr

Follow-up eval for LTBI treatment (~50%)Not required but strongly encouraged12% accept medications for LTBI

Rifampin vs INHMonitored via secure message each monthCompletion of Therapy Letter 44

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ComplianceRegistration hold

Students cannot register for the next semester’s classes if there is an SHS hold on their account

ExceptionHealth professional schools

track/enforce their program-specific requirement of annual PPDs

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STUDENT HEALTH AND DISABILITY SERVICES

IntroductionPrivate, faith-based (Methodist) University on

60 acre urban campus in the lower Midwest3,200 students

3,000 full-time

1,800 undergraduate500 graduate5 doctoral600 law

446 International students – most from China, Taiwan, Korea, West Africa, India, Saudi Arabia. Few from Europe and Canada.

274 Health professional students (Nursing)

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Student Health Services2,300 visits per year

Services:Primary careWomen’s HealthImmunization and AllergyLaboratoryHealth Education

Disability Services is part of program

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StaffingNurse Director – also serves as Disability

Services Coordinator, 12 monthsARNP - full-time, 10 months + 1 day/week in

summer RN – full-time, 10 monthsOffice manager – full-time, 12 monthsReceptionist - full-time, 12 months

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TB Screening

All international students, on matriculationMust be done during first semester

Nursing students’ deadlines vary by program

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Documentation Accepted from AbroadMust be documented on our form, include date

of placement and reading, resulted in mmNotation of “negative” is not acceptedDocumentation less than 12 months oldFor 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.

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ComplianceAccount 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.

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Testing typePPDStudent pays $15 SHIP does not pay

Why not IGRA’s? CostDone free at OCCHD TBCC for positive PPD

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Follow-up of Positive ResultsRN does TB symptoms checkAppt. for IGRA, CXR made at OCCHD TBCCStudent e-mailed date and time of appt. Counseling for LTBI is done by OCCHD TBCC

who provides treatment and monitoring for free.

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IGRABegan looking into IGRA in mid-2007.Not available in Oklahoma until early 2009OCCHD TBCC began offering free QFT in

March, 2009.40 students referred March 1,’09-Mar 1, ‘1020% of positive PPDs (8 students) have been

QFT positive.60% started medication, 40% refused

treatment

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Active TBNo cases of active tuberculosis on our

campus since late 2001. At that time, international student population

was much larger than today.

The End….

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by the Advent of IGRAs

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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.

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Study at ASU: TST & IGRADr 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).

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Study at ASU: TST & IGRAOnly 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.

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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?

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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. ”

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