Primary Care Corner with Geoffrey Modest MD: USPSTF LTBI Screening Recommendations

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By Dr. Geoffrey Modest

The USPSTF just came out with their recommendations for screening for LTBI (latent TB infection) in populations at increased risk, giving it a “B” Grade (a recommended service, with “high certainty that the net benefit is moderate, or there is moderate certainty that the net benefit is moderate to substantial”  (see http://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/latent-tuberculosis-infection-screening ).

Details:

Background:

  • The Natl Health and Nutrition Examination Survey in 2011-12 found a national prevalence of LTBI of7% of the US population and 20.5% in those foreign-born
  • 5-10% of those with LTBI progress to active TB during their lifetime

Results:

  • Benefits of screening
    • No eligible studies were identified showing that targeted screening for LTBI in primary care settings in asymptomatic adults improves quality of life or reduces active TB/transmission/mortality
    • Accuracy of tests:
      • Pooled estimates for sensitivity/specificity of TST (tuberculin skin testing)depends on degree of induration
        • 5 mm: sensitivity 0.79, specificity 0.30-0.97
        • 10 mm: sensitivity 0.79, specificity 0.97
        • 15 mm: sensitivity 0.52, specificity 0.99
      • Pooled estimates for sensitivity/specificity of IGRAs (interferon-γ release assays), for different tests
        • T-SPOT: sensitivity 0.90, specificity 0.95
        • QuantiFERON-Gold: sensitivity 0.77, specificity 0.98
        • QuantiFERON-Gold In-Tube: sensitivity 0.80, specificity 0.97
      • No studies were identified that evaluated sequential screeningstrategies of using both TST and IGRAs in asymptomatic patients
    • Benefits of treatment: does CDC-recommended regimes improve quality of life/reduce progression or transmission of TB?
      • INH for 6 months va placebo leads to a relative risk reduction of 0.35 (1.4% in placebo group over 5 yrs, vs 0.5% with INH)
      • Rifampin for 4 months is equivalent to INH for 9 months
      • Once-weekly rifapentine plus INHx3 months (directly-observed therapy) vs INH for 9 months were also statistically equivalent
    • Harms of screening: no eligible studies
    • Harms of treatment:
      • INH hepatitis
        • Hepatitis incidence rate vs placebo: INH had RR=4.59 for 24 weeks (Number-Needed-To-Harm, NNH=279) and RR=6.21 for 52 weeks
        • Mortality rate vs placebo: INH had RR=2.35 (NNH= 6947, 0.14/1000 persons treated)
      • INH discontinuance rate from adverse events: 1.8% vs 1.2% on placebo (mostly GI distress)
      • Rifampin (in 3 studies comparing Rifampin to INH): for INH in the 3 studies, hepatotoxicity in 5.2%, 3.7% and 11.4%; for Rifampin: 0%, 0.7%, and 4.4%: ie, pooled INH RR of 3.29 vs Rifampin
      • Also <1/2 the rate of discontinuations with Rifampin vs INH

Commentary:

  • The USPSTF recommendation does appropriately highlight the important issue of checking TB status. There are increasing numbers of high risk people in this country, especially in foreign-born. And I have seen several untreated people develop active TB late in life, after being here for decades.
  • I do have concerns about the reliability and stability of the IGRAs, as noted in prior blogs (see https://stg-blogs.bmj.com/bmjebmspotlight/2016/03/15/primary-care-corner-with-geoffrey-modest-md-latent-tb-infections-screening-and-treatment-and-probs-with-igras/, which also goes into more detail on identifying who are high-risk of LTBI. But most importantly, it reviews a couple of studies finding quite remarkable inconsistency of IGRAs: many people who were initially positive but subsequently negative on repeat testing within a couple of months and without treatment, i.e. high and unexplained “reversion” rates
  • In terms of treatment regimens, the CDC-recommended ones overall are the INH for either 6 or 9 months (though the 9 month is preferred given somewhat better results) or the rifampin for 4 months (reviewed in http://www.cdc.gov/tb/publications/ltbi/default.htm). Over the past several years, I have been prescribing only the rifampin one (unless there are difficult drug-drug interactions), without a problem. easier/shorter regimen and better tolerated
  • Though I realize the issues of anecdotal medicine, I will still bring up one of my long-term patients who reinforced 2 of the above points to me: he is a 60 yo Haitian man I have known for several decades with really bad uncontrolled diabetes, hypertension, HIV, and now on dialysis (of those, his HIV has been consistently well controlled, with CD4 in the 250-300 range and viral load consistently suppressed). He worked for decades as a health aide in a nursing home and had repeatedly negative annual PPDs (about as good as one can get for accuracy of PPD screening). He was being evaluated by a transplant physician who insisted that he go to ID/HIV clinic to be cleared for surgery. They did a QuantiFERON-Gold test which came back positive for TB. He was started on INH, but within 2 months developed a nearly fatal case of INH hepatitis leading to a many week stay in an ICU. He recovered, but I decided to check the QuantiFERON-Gold again, which turned out to be negative……
  • So, my bottom line: I still rely on TST screening for TB, based on that prior blog and reinforced by my anecdotal case, though I understand the appeal of the  IGRAs (I had had assumed I would be using IGRAs in my patient population, which is largely foreign-born and has had a high rate of prior BCG vaccination, since it made sense mechanistically that it would be more accurate than PPDs and there is no need to come back in 48-72 hours for a reading, no need for booster PPDs in those who had not had one for a long time, etc.) And, I do find the rifampin based treatment of LTBI to be easy and well-tolerated, though with forewarning about red urine….

For the CDC recommendations on PPD screening, see http://www.cdc.gov/tb/publications/factsheets/testing/skintesting.htm )

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