USPSTF LTBI screening recommendations

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 tb LTBI recs uspstf2016 in dropbox, or go to 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 of 4.7% 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 screening strategies 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 http://gmodestmedblogs.blogspot.com/2016/03/the-uspstf-just-circulated-draft.html 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, ie 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​ )