Targeted testing and treatment for latent TB infection

> Introduction
> Definitions
> Indications for testing
> Contacts
> BCG
> Two-step testing
> Evaluation for TB disease
> Prioritizing Treatment
> Treatment Regimens
> Pregnancy
> Monitoring for Toxicity
> Completion of Therapy
> References

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Introduction

The Centers for Disease Control and Prevention and the American Thoracic Society published new guidelines for targeted testing and treatment for latent TB infection (LTBI) in the spring of 2000. The Advisory Council for the Elimination of TB and the Institute of Medicine of the National Academy of Sciences also published reports in 1999 and 2000 that advise major expansion of targeted testing and treatment efforts as one of the crucial means of progressing toward TB elimination. This statement summarizes the current approach of the TB control program of Public Health, Seattle and King County to these guidelines and directives. This approach is based on an interpretation of the available scientific literature, local epidemiology, previous screening guidelines, program experience, and an acknowledgement of limited resources. It also encourages a current trend to increase targeted testing and treatment for latent TB infection in primary care settings.

Definitions

Targeted testing
"Targeted tuberculin testing for LTBI is a strategic component of tuberculosis (TB) control that identifies persons at high risk for developing TB who would benefit by treatment of LTBI, if detected. Persons with increased risk for developing TB include those who have had recent infection with Mycobacterium tuberculosis and those who have clinical conditions that are associated with an increased risk for progression of LTBI to active TB." (ATS/CDC 2000) In some settings in King County, persons are also tested as an initial screening measure to trigger further evaluation for TB disease, to comply with state and federal requirements for employment or for change of immigration status.
ATS Classification of TB diagnoses
0: no TB exposure, not infected
1: TB exposure, no evidence of infection
2: latent TB infection, no disease (LTBI)
3: tuberculosis, clinically active
4: tuberculosis, not clinically active
5: tuberculosis suspect (diagnosis pending)
MOTT: Mycobacteria other than TB
Latent TB infection
Persons with LTBI have evidence of TB infection based on a tuberculin skin test reaction that has been professionally interpreted to be positive and have no clinical, bacteriological or radiographic evidence of active TB. Persons with HIV infection or other severe immunosuppression may be diagnosed to have LTBI even though a tuberculin skin test is negative if they are contacts of an infectious case of TB and have no evidence of active TB. Persons with LTBI have a 5% to 10% lifetime risk of developing active TB, half of which is in the first year after becoming infected. Persons with HIV infection and LTBI have up to a 7% per year chance of developing active TB. Neither the state of Washington nor Seattle and King County require reporting of persons with LTBI, although reporting of TB infection is required in Pierce County. LTBI is a chronic medical condition that belongs on a patient's primary care problem list, even if it has been treated.
Treatment for latent TB infection
Treatment regimens have been shown to have 60% to 90% effectiveness at reducing the chance of developing active TB. Roughly speaking, if a person with LTBI has a 10 % lifetime risk of developing TB without treatment, after completion of treatment for latent TB infection this risk drops to approximately 1%. Although it may be strongly advised, treatment of LTBI is not legally required in Washington State.

Tuberculin skin test interpretation
Tuberculin skin tests, Mantoux method only, are interpreted based on the professionally measured size of induration at 48 to 72 hours. The size of induration considered to indicate TB infection depends on the nature and extent of the risk of future disease, those at highest risk being read as positive at the lowest cutting point. Sometimes the cut-off size for which a chest x-ray is legally required is different from the size that is determined clinically to indicate infection.

Skin test read as positive at 5mm:

1.	contact of an infectious case
2.	known or suspected HIV infection
3.	abnormal chest x-ray with fibrotic lesions suggestive of inactive pulmonary tuberculosis (not including isolated calcifications or minimal pleural thickening)
4.	organ transplantation and other heavily immunosuppressed patients

Note: Civil surgeons and the county jail are required by their own guidelines to get chest x-ray evaluation on all persons they serve who are found to have reactions of 5 mm or more, even though they may be determined not to have TB infection.

Skin test read as positive at 10mm:

1.	persons with immunosuppressive medical conditions other than HIV infection, including diabetes, renal insufficiency, gastrectomy, corticosteroid therapy (> 15 mg/day of prednisone for 2 weeks), and other immunosuppressive therapy and conditions
2.	Persons who develop a new positive skin test and an increase of 10 mm or more in size of the skin test reaction within a 2 year period ("recent converter").
3.	Persons who within the past 5 years have lived in or traveled extensively in areas of the world where TB is endemic including most of Asia, Africa and Latin America. Asian countries of the former Soviet Union, Albania, Bulgaria, Moldova and Romania are considered to be endemic areas with a 10 mm cutoff for diagnosing TB infection. (Countries of former Yugoslavia are not considered by the King County Public Health TB Program to be in this category, although they were during and shortly after the wars in that region.)
4.	homeless persons, if recent transmission of TB has been demonstrated in their setting
5.	persons who live in some congregate settings, or have done so in the last 2 years, voluntarily, such as in assisted living or drug treatment programs, or involuntarily, such as in jails, prisons or refugee camps
6.	persons in substance abuse treatment programs, if recent transmission of TB has been demonstrated.
7.	persons in certain occupations, including health care workers and others who work with large numbers of persons at risk of tuberculosis

Note: Persons starting certain jobs, such as day care and nursing home work are required to get chest x-ray evaluation if they are found to have reactions of 10 mm or more, even though they may be determined not to have TB infection.

Skin test read as positive at 15mm:

Persons who are not in the above high-risk categories. In general persons without high risk are advised not to undergo tuberculin skin testing because of the high false-positivity rate in groups with low prevalence of TB infection. Persons from countries with established market economies and persons from countries of the former European socialist economies are considered to have TB infection if their skin test reactions are larger than 15 mm.

Other persons who receive screening services at the TB clinic and are found to have LTBI but are not in these highest priority groups are advised to discuss treatment for LTBI with their private medical provider or to seek further care at one of a list of medical clinics that have agreed to treat persons for latent TB infection regardless of their ability to pay.

Indications for testing

Persons in the high-risk groups listed above should receive tuberculin skin testing. Those who are found to have negative skin tests but who remain in high-risk settings, such as health care workers, should have periodic follow-up skin testing, in order to achieve early detection of new TB infection.

Contacts

Contacts of persons with infectious TB are the most important persons to test for TB infection. A contact who is determined to be at risk for new infection is generally determined to have TB infection if the skin test shows > 5 mm induration. Degree of risk is usually determined in the context of the details and findings of the TB control program's contact investigation. Household contacts of infectious cases are usually offered a CXR in addition to the skin test. Treatment is usually recommended for contacts with TB infection in whom TB disease has been ruled out. Treatment is also recommended for the highest risk persons - HIV infected and those younger than 5 years old - even though a skin test is negative, once TB disease has been ruled out. Persons with an initial negative skin test are also offered a repeat skin test about 3 months after the contact has been "broken," which may mean the day the source case starts treatment. 3 months is after the end of the 10-day to 10-week incubation period for developing a positive skin test. Small children who have negative skin tests at 3 months can be taken off TLTBI at that time. HIV-infected contacts are usually advised to complete a course of TLTBI regardless of the 3-month skin test result.

BCG

Targeted testing and treatment for LTBI should be performed regardless of a patient's history of BCG vaccination. Please also see our webpage on BCG Vaccination.