Infectious Diseases Society of America Emerging Infections Network. Comments for Query: Diagnostic Testing for Mycobacterium tuberculosis

Transcription

1 Infectious Diseases Society of America Emerging Infections Network Comments for Query: Diagnostic Testing for Mycobacterium tuberculosis [Pediatric comments provided in blue] Susceptibility Testing of Initial M. tuberculosis Isolates Rapid assessment of resistance (e.g., NAAT) to first line drugs would be helpful occasionally [TX] We continue to be plagued by slow turn around time in sensitivity testing. I worry that this issue is a driving force behind the emergence of drug resistant strains - we don't get the news until much time has passed and the situation is even worse. [NJ] We need better rapid diagnostics (and second line drug susceptibility test results) for drug resistant TB. Fortunately, the prevalence of MDR-TB in our area is low but this is an enormous public health problem in many areas around the world. When someone actually has MDR-TB, it takes very long (months) to get full susceptibility test results back (i.e., second line DST). Advances need to be made in second line DST and rapid diagnostics and implementation of new methods focused on these needs. [GA] We have a lot of drug resistant and MDR TB. Fortunately, our state TB lab offers molecular beacon testing for rapid identification of INH and RIF on request. The greatest difficulty is timeliness for susceptibility testing for second line drugs. [CA] T-cell-Based Testing for Latent M. tuberculosis Infection Availability of QuantiFERON (physical distance to lab, the 12 hour interval for processing): Need better/local access to QFT [2 from CA, GA, NH, NY, Puerto Rico, VT, WA] QFT is about to become available in our area [MA, SC, TX and WV] QFT when I checked >1yr ago was available in a lab in St. Louis or someplace & specimen had to get there in 12 hrs. I would like to know more about the modified QFT or IGRA. What are the requirements? Are state labs offering these tests? [MD] The QFT test is available across town/some distance away/100 miles away [MN, NJ, NJ, SC] We have low incidence of TB. Quantiferon has not been readily available in the area. [NJ] Lack of local availability of QFT precluding reg use, esp would like for employee screening [CA] We are limited by the 12-h window of processing and therefore cannot use interferon-based tests [IN, MA, NC, OK, OR] I am currently in private practice & I've had serious difficulties ordering quantiferon. a) Labcorp and Quest don't do it. b) People didn't even know what I was talking about. I would like to get some help in this regard. [FL] I have had to send patients by plane to Houston, Tx to get a Quantiferon Gold test, since it is not available in Oklahoma. Most patients can't afford to do this. The labs just won't bend on this. Perhaps QFT(TM) assay will help. [OK] We have tried to get QFT. The lab issue has been the breaker. I will my lab that there is a test where the blood can be held 3 days. I assume the sendout company will do the test now. [MA] Page 1

2 Increasing the time to 3 days will allow us to use Quantiferon TB Gold [LA] QFT is available in the region, but not available in the city of Seattle, as far as I know. As a result, it is cumbersome to accomplish testing because of timing issues around specimen collection and processing. We have been interested in bringing the test into our lab for occupational health screening, but have not considered for pediatric use because of relative lack of data and FDA approval for peds. I realize there is more data in pediatrics now. We would like to see labeling change to include pediatrics before using the test in systematically in our patients. [WA] I can think of at least 20 instances in the past 18 months in which availability of the QFT test would have been optimal management. Despite the limitations of the test, applied as a tool to a clinical scenario, it may be a very helpful adjunct in the provision of optimal care. It was difficult coming from a location where it was readily available to a location where it is not. [GA] Limitations of QuantiFERON: We still argue about the role of T cell based testing for latent infection [IN] More data are needed on use of Quantiferon and similar tests. Despite the limitations of the TST, I have not advocated to have Quantiferon in the TB Clinic where I am the Medical Director [MA] Gold (Quantiferon) is not the last word. Hopefully better and more reliable tests will be available [NY] Seeing indeterminate QFTs both with high background IFN gamma and with lack of stimulation due to anergy [OR] I converted to PPD+ in 1994, confirmed with a second PPD, read by 2 trained readers. I took 6 months of INH. I had to have a Quantiferon done in 2006 when I joined the county hospital (per policy despite my history; PPDs not done there, all Quantiferon for employees/staff) and the result was negative. I have not found a satisfactory explanation for it. [AZ] Most of the patients I see here for?tb are immunosuppressed and likely to have an indeterminate or unreliable Quantiferon result [AZ] More discussion is needed for what is known and not known of the use of INF gamma release assays for serial monitoring for new TB infections in populations at risk- eg HCWs [FL] We had problems with the quantiferon test in our jurisdiction and are not currently using it [CA] We see lots of discordant TST+ and QFT -, and in people with no known history of BCG [OR] Lack of gold standard for decisions re LTBI still a problem [MA] There is a need for extensive additional data on children with LTBI before either of the interferongamma release assays should replace PPD skin testing [OH, OR] Have avoided use of Quantiferon Gold since it has not been validated in children (including foreign born children) or in immunocompromised patients [3 members from CA, NE] We rarely have children with active TB. I don't think the IGRA is effective for diagnosing latent TB so have not used it [VT] We need better QFT studies looking at latent TBI and risk for developing disease over long term followup [WI] We have had TB meningitis with negative TST and positive quantiferon and positive AFB PCR. We do not use QF test routinely. [NE] Our division does not recommend using QFT in pediatric population [NY] Cost and labor/lab issues: I would like to use QFT more often, but our lab director refuses, saying the initial steps are too labor intensive. We are eagerly awaiting the promised automation, as well as more data. [CA] Our local lab declines to perform the QFT because of the cost. [DC] They are deaf the fact that there would be system wide savings, especially to Occ Health/Employee Health. [NY, VA] Cost-effectiveness analyses of using the IFN-gamma assays in various situations Page 2

3 Our laboratory has not adopted this test because of cost. The laboratory budget is distinct from the clinical budget and as such, PPD testing has no impact on the laboratory budget. Moving to the QFT would increase costs in the laboratory and not materially reduce clinical costs. We are not convinced the GFRA at present is reliable and worth the cost. We document about 7 patients per year admitted without our realizing that they have active TB. Once in awhile the positive culture comes back AFTER the patient has been discharged. Most of these patients are at moderate risk of having TB. Other comments about PPDs, QuantiFERON, and LTBI: Quantiferon challenged significantly the management of LTBI. Questions: 1- Should qf be used as a confirmatory test or should it replace TST? 2- What do we do with ppd(+) qf (ind)? 3- What happens with qf after tx? We saw a patient with meningoencephalitis who was being treated as CNS vasculitis with steroids; ppd was (-) but qf was (+) and the CSF ended up growing Mtb. [FL] Since so few PPDs are ordered on inpatients now, we are having problems w/ maintaining competence in staff placing the test. We are considering using quantiferon for inpatient testing but cost certainly is an issue. [IL] We hope to have our hospital develop the capacity for quantiferon gold in tube within the year [NC] Most QFT testing is for employee health [CO, NY] I do not see active TB pts. Have only wanted to order QFT Gold (+PPD pts w/ history of BCG) but it is not available at our institution and the lab does not have mechanism for sending it out. [MA] It is difficult to ignore TST results over 15 mm so I rarely get IGRA tests in that patient cohort. I find the IGRA most helpful for those patients with TST results between 5 and 15 mm. [WI] Quantiferon is done by our Public Health lab, but is not available within our staff-model HMO. We occasionally see patients who demand this test because they are sure their PPD is a false-positive due to BCG received 40 years ago, but otherwise there has been little need. [CA] Though rare, there have been questions about PPD testing- most of the time it related to inappropriate interpretation/reading. We have not had to do T- cell based test so far; we have identified a lab in out area to approach if we needed. [TN] In case of indeterminate Quantiferon-Gold, we call the lab to ask if it is a noisy background or anergy as cause of indeterminate. If it is anergy, repeat it might not be helpful. [MN] Positive PPD in young children emigrating from TB endemic areas [NY] Parents are asking for this test by name for their children adopted from a TB-endemic country (and who've received BCG at birth) especially if the child now has a positive TST. [OR] We are considering setting up the quantiferon test [AR] It is very difficult to get the interferon testing because it has to be sent to another hospital and there are reimbursement issues. It can only be done with excellent justification that is reviewed and accepted by our hospital pathologist. [FL] I primarily care for pediatric patients but also oversee the infection control program for a large pediatric healthcare system. I await further validation of IGRAs in the pediatric age group. The local county public health dept is using QTF GIT to screen all refugees on a study basis, and will do individuals as special request. One of the larger systems that provides Occ Health services is doing QTF testing for HCW screening. It is much more expensive, but we will be implementing this for our employees next year in hopes of better compliance with TB screening. [MN] Rapid Nucleic Acid Assays for M. tuberculosis Availability of NAAT and which specimens are used: We use Gen-Probe for in-house NAAT - on culture only [MI] Page 3

4 NAAT on smear negative specimens or non-respiratory specimens is available by request but not routinely done [3 from CA, MD, 3 from NY, OH, WI] Lab will perform test if requested, with all the caveats about non-fda approved uses of the test in smear negative samples [OR] Uncertain if our lab offers NAAT but I think not. We have used PCR but no more sensitive than smears in our hands. [WA] Can't WAIT for NAAT testing to be more available! [NH] Our state public health lab now has NAA up and going so our hospital lab is just now gearing up to send isolates to the state lab, but we have to order and send 2 separate specimens [NC] NAAT performed at public health/state lab [CA, OR, WI] re NAAT: they perform Mtb PCR - is that what you are talking about and give numbc on + cx [CA] We send our specimens to a VA reference lab. They will only do smear pos sputums. The local Quest send out company will do pcrs on anything that is sent to them. [MA] NAAT tests are send-out only - not locally available [MO, WY] We use a local PCR for MTB and MOTT on resp and non-resp specimens [AR] Our labs send specimens to city DH TB lab, which is about 500 miles away from our rural hospital. This way, they do perform NAAT-based testing directly on smear + or - specimens by special request. [IL] NAAT's can be ordered but not without several phones calls asking for specimen to be sent to a reference lab [KY] Such testing is performed only on isolates that have grown on culture media [MI] Most cases are handled by our county's public health department. They can perform NAAT tests on positive respiratory samples. [CA] Limitations of NAAT: We recently had a pt with 6 intracranial lesions, CSF 700 WBC, PCR neg; brain biopsy PCR neg with 6 organisms seen on two smears and ultimately grew out 50 colonies on plate. Lab told me this is the fourth case they have seen with discordant PCR vs smear/culture. Makes me lose a little confidence in the PCR. [WA] Several instances of discordant results between NAAT and culture on non-respiratory samples (NAAT may be significantly less sensitive on such specimens) [GA] My experience with PCR on CSF for MTb has been that it is not reliable [TX] PCR testing should probably be discouraged on CSF (smear neg) as there are false pos and neg [CA] I had a case of TB meningitis. The rapid test came back negative in the CSF. But CSF culture was +. I have seen discordant results with NAAT and culture results [NC] The NAAT-based testing on clinical samples other than sputum has rarely been helpful [WI] NAAT directly to initial specimens limited, in my opinion, by poor sensitivity in smear negative cases. The smear neg patients with a high pre-test probability for TB are the most challenging cases. [PA] Scant pediatric data and limited usefulness of NAATs for gastric aspirates (most common specimen for pediatric pulmonary) [OR] Advantages/positive performance of NAAT: NAAT can be used to differentiate between active TB & possibly colonization by MAC in smear+ pulmonary specimen, so that pt can be d/c home faster [NY] We use NAAT to speciate [SC] We have seen excellent performance of the MTD test on smear-positive sputa, which is very important because we see a lot of non-tuberculous mycobacterial disease (mainly MAC, of course) [CA] I run a mycobacterial clinic and our local diagnostics would be improved if we they did NAAT on smears (and not isolates), as well as if we had pcr or other technique to speciate NTM quickly [OR] I like the NAAT testing and can get it as a sendout to Mayo. Sometimes useful in CSF as well. [CA] Page 4

5 Other comments about NAAT or PCR: PCR on tissue specimens at University of Washington has been helpful. [OR] Note that the lab for NAAT only reports results officially on smear positive samples. Smear negative sample results are reported to infection control or the provider but not officially. [MA] I have used NAAT testing on non-respiratory samples to assist with diagnosis, due to the low sensitivity of AFB stains and cultures; however, I have not found it to add much to the diagnosis in respiratory specimens. [PA] I haven't been using this test and am not aware of how it is being used locally. PCR testing of all kinds in our institution is sent out to a reference lab. [NC] Mayo is developing home-grown PCR tests for tuberculosis that is currently being tested on stools [MN] I primarily care for pediatric patients. There is no utility for NAAT in young children [DC, MN] Comments about Challenges in the Diagnosis of tuberculosis General mycobacterial testing issues: It is hard to stay current with the many new drugs, tests and changing recommendations [TX] Rapid testing is extraordinarily helpful in our center [FL] Newer tests more expensive and with limited budgets and micro being at the bottom of the priority list most hospitals don't offer many of the newer tests. Would be nice to get help from experts to give to administrators the cost benefit of using these newer tests. [NJ] Our local/academic lab is ARUP, which is also a national reference lab for micro. We have the advantage of multiple technologies for diagnosis and detection. PCR can be done on any specimen with arrangements with the lab, but generally we discourage smear neg sputum. For MDR strains however, we consider re-running sensitivities at National Jewish. [UT] The time delay in obtaining culture results to separate M-tb from atypical mycobacteria remains a problem. New tests may be useful for the separation of M-tb from atypicals. [MA] Lack of funding. Most of our TB patients are uninsured. [NJ] Lab capability for TB diagnostics locally has been greatly reduced since Katrina - specimens from public hospitals still go out of state [LA] Still need faster cheaper tests/ quick turnaround time and reliable test for M tb. [FL, GA] I don't know about Quantiferon or NNT testing in my area (metro or state). My hospital uses PPD skin testing. Cultures performed by state lab. [MN] Turn around time is long with our send out for AFB smear [WA] I keep pestering the lab folks to get access to these tests [TX] Insurance will not pay for these tests in patients under 18 years of age [DE] Interpretation of TST results in the setting of mycobacteria other than TB and history of recent BCG is quite challenging [IL] Diagnosis is affected by the availability of the different tests to the clinician and the lack of ease of ordering them [AZ] General tuberculosis issues: Increase in cases of TB meningitis in past year [CA] I have seen 2 cases where the surgeon took a biopsy and placed it in formalin thinking that it was cancer without sending a sample for Micro with subsequent path showing granulomas and/or AFB orgs requiring second biopsy or difficult treatment decisions [CT] Increasing recovering isolates of NTM compared to M. Tbc in the last 5 years [Puerto Rico] County TB control is not consistent with their recommendation on patients - different MDs in the dept want you to do different things [CA] Major thing is still to think TB [MO] Page 5

6 The main issue arises in cases with low clinical suspicion - where in the absence of good diagnostic tests, we are forced to err on the side of caution and treat empirically [UT] Recently, we are seeing more cases diagnosed after thoracotomies with no or minimal prior clinical suspicion of MTB. Such cases increased the # of exposures we have to follow; we are currently evaluating such cases. [NY] A few recent studies have indicated that induced sputum for AFB performs at least as well as bronchoscopy for most patients who are coughing up gobs of AFB. However, without exception, every hospital I've ever worked it has systematic barriers to getting these done in a timely fashion. IF IDSA/CDC agrees that induced sputum is a viable option for diagnosis, perhaps there should be a national level discussion with resp therapist societies and hospitals to make this testing more standard. It would lead to shorter hospitalizations and fewer bronchoscopies, and perhaps more timely diagnoses. [PA] Recently had case of TB meningitis in 11yo w -PPD, -CXR, -US citizen, not immunocompromised, pulm symptoms; =MTB PCR on CSF. Most challenging case I've seen in 30 years. [GA] 1. Problematic when trying to diagnose in a low prevalence area with few symptoms. Testing more selectively based on risk factors is problematic as can potentially miss more. 2. As money for the public health providers becomes tighter, being able to do contact investigations adequately becomes more problematic (labor intensive). Inadequate contact investigations means more spread, especially if latent. 3. It would be nice to have more accurate testing available, especially for our higher risk population (mainly immigrants). Getting them tested is another barrier. [NC] General pediatric tuberculosis issues: Do care for children with TB but no experience yet with these tests [AL] This survey doesn't seem especially relevant to pediatrics, as the quantiferon assay hasn't been evaluated (to my knowledge) in that population. I've never ordered an IGRA assay or a nucleic acid test for TB on a patient; I'm sure we could get these if we really needed them, but they're outside my area of knowledge. For children in Memphis, we continue to rely on TSTs to diagnose LTBI, and we confirm active pulmonary TB with AFB smears and cultures of sputum or gastric aspirate specimens. I believe that TB isolates are tested for susceptibility at our State lab, but I have no idea how soon we see those results (we diagnose few cases in children, and susceptibility results are rarely relevant to our management). [TN] As usual, survey has little application to pediatrics. Not really licensed for peds although I forget the details. Have used tests in a few special cases, not enough numbers to justify answers. [IL] Gastric aspirates in young children are always a challenge. Many young children need bronchoscopic studies to help with diagnosis. [IN] As a pediatric ID consultant I am only the local expert for pediatric cases but most cases are handled by our county's public health department [CA] This is not done in-house. However, the actual number of patients with suspect disease each year is minimal (fewer than 10)... and the number of culture confirmed cases is <1 per year [OH] Page 6