Utilization of the QuantiFERON-TB Gold Test in a Two-Step Process with the Tuberculin Skin Test To Evaluate Health Care Workers for Latent Tuberculosis

Only available in abstract at this point in time however the question remains unanswered - how can doctors continue to justify prescribing medical treatment for people who are infection free?

A cost analysis of combining a tuberculin skin test (TST) and the QuantiFERON-TB Gold test (QFT-GT) to detect latent tuberculosis in newly hired health care workers was performed. An approximately 50% reduction in the cost of additional care was realized when workers with positive TST results were subsequently screened using the QFT-GT.

Only 22 days, 0 hours, 27 minutes and 12 seconds to go...

After weighing up the policies and taking a look at the candidates

the spin is starting to get to me

Through the looking glass at yesterday and tomorrow

Much angst has been generated by the perceived delays in issuing approvals and guidelines - particularly those of the CDC. CDC director Dr Philip LoBue's presentation on the SNTC website gives an indication as to the process of formulating such guidelines and it is worthwhile giving proper consideration to that process.

Dr LoBue noted that they were constrained in forming decisions based on current studies

because this is limited by a really lack of good, large head-to-head comparison trials.

So this can be very biased by the fact that if you have one study which only looks at T-spot and one study that only looks at QuantiFERON, the populations may be so different that it’s really not fair to compare the sensitivity so I think you need to be very careful with that.

That appears to be entirely reasonable; one would expect locations and populations to differ - such is the way with experiments conducted outside of the laboratory.

And to put it into a purely legal perspective if there isn't evidence the argument cannot be sustained and the claim should be dismissed.

However the CDC had previously changed the TB testing guidelines to only "testing among persons at high risk" involving risk analysis for each location and situation. Populations are assessed into groups and only those groups judged to be at risk, or are "special," are tested.

So what about special situations and populations that we’re interested in? Well, let’s start with contact investigations. So, if you look at the studies done in close contacts of patients with tuberculosis, what you tend to see is that the exposure characteristics associated with increased risk of infection tend to correlate better with IGRAs than they do with the TST.

So it would appear that once populations are segregated into risk groups as per CDC guidelines IGRA are superior to TST. However, these guidelines were not helpful to the CDC review process

It’s not clear to us how they would affect applying this to a hospital which generally deals with low-risk people.

Finding such a hospital may be difficult as hospitals dealing with low risk people, according to other CDC guidelines, would not necessarily test for TB.

Screening of low-risk persons and testing for administrative purposes (e.g., certification of school teachers) should be replaced by targeted testing.

Following CDC guidelines may not always be easy

 "If you test low-risk people, you're going to end up with a lot of false positives," explains Henry Blumberg, MD, hospital epidemiologist at Grady Memorial Hospital in Atlanta. "The idea is not to do repeated tests in low-risk situations."

As advised by the CDC false positives are a latent condition of the TB skin test and using the TST is a risk .

Some persons may react to the TST even though they are not infected with M. tuberculosis.

.

Shorter Portugal - QFT é o melhor!

Link here and here

The health service has selected QFT as the preferred test for latent TB testing.

Results of five-year systematic screening for latent tuberculosis infection in healthcare workers in Portugal

You want longitudinal studies, we got longitudinal studies; link here

Key points;

• Study period = between September 2005 and June 2009
• HCW's = 5,524
• TST = 5,209
• QFT-GIT = 1,686
• QFT indeterminates = 13
• Remaining after 2nd QFT = 4

...Only in a subgroup were IGRA and TST performed simultaneously. This is because IGRA testing was introduced two years after the start of the systematic screening.

...Risk assessment was not confirmed by distribution of TST diameter in our study, e.g. the highest proportion of TST ≥ 15 mm was observed in HCWs assumed to be at low risk of TB exposure.

...estimates of LTBI prevalence vary to a great extent depending on whether prevalence is assessed with TST or IGRA (55% versus 26%).

...Since the implementation of this screening programme, there has been a significant reduction in TB cases. In 2008 only 6 cases of TB were diagnosed and in the first half of 2009 only 1 case. No new measures of infection control were implemented that might explain this effect. We believe that HCWs´ awareness of protective measures increased. They were therefore adhering to the rules more closely.

NYC Bureau of TB Control - Experience with IGRAs

Decision to Use QFT-G
~10% of patients did not return for their TST reading and many needed to be retested

Benefits of Using QFT-G
– Decreased cost for patients because they do not need to return to obtain their result

So there!

Northern delights

In assessing the performance of QuantiFERON these Norwegian researchers explain the reasons for using QuantiFERON (see below). Importantly, this study was

a longitudinal study performed in a regular outpatient TB clinic in a TB low-endemic country. In contrast to a number of studies focusing on particular populations, we investigated the performance of the QFT-TB test in various risk populations referred according to present national guidelines and thus reflecting the clinical situation at a large size Norwegian hospital. We further present data of IFN-γ responses during preventive therapy of latent TB.

and it was found that

The performance of the QFT-TB test was good in this clinical setting.

Loose talk from the CDC

The latest CDC guidelines state that for situations in which a TST is preferred but an IGRA is acceptable

A TST is preferred for testing children aged <5 years.

They also state that

An IGRA is preferred for testing persons from groups that historically have low rates of returning to have TSTs read.

OK, according to an article in the JNMA on children 1-18 years;

We note that the return rate for skin test results in this study was 65%. It is possible that the subjects who failed to return for their results had a higher reactivity rate than those who returned.

However, our return rate for skin test results is comparable to the upper limits reported in the literature for similar communities.

Low rates of return apply to everybody

Aids experts say TST too hard

Denying TB medication until a skin test has been performed is putting HIV+ individuals at high risk of developing active , according to this latest study.

“It’s taking too long for people to get a TST, and among those who have a TST, even for those who have a positive result, it’s taking them a long time to get put onto IPT,” said Dr Jonathan Golub of Johns Hopkins Center for Tuberculosis and the Consortium to Respond Effectively to the AIDS Tuberculosis Epidemic (CREATE).

The skin test is proving to be too difficult to administer - failure to return was the factor in another study from Brazil

Dr Resende stressed that the TST takes two clinic visits; the application of the test and the reading schedule for the skin reaction make it difficult to get patients to come in to have their test results read on the right day.

The solution? skip the TB test entirely

"We could eliminate TST and give IPT to all HIV-infected patients. This would save a lot of money, it would be much more convenient, much easier to conduct at the clinics.”

ARUP to the rescue

University of Utah's lab ARUP has a special page on QuantiFERON, complete with movie - too easy!

The mysterious case of the disappearing debt

Leader of the Opposition, Tony Abbott, in full election mode

"..we’ve got $57 billion worth of deficit and heading towards $90 billion worth of debt"

So where is the rest of the debt?

A look at previous Government debt shows that the Opposition is just playing with numbers

Pressed for facts

Paul Krugman looks at this AP story on Bernanke’s testimony and wonders out loud

How does the AP know that the prospects for deflation are remote (and note the implicit suggestion that worried Fed officials are a bit strange)?

Available data indicates that deflation is a possibility; as Krugman dryly observes

You keep getting things like this in economics reporting; things that are just opinions – and not even consensus opinions, by a long shot — get reported as fact. And strange to say, it’s always one side of the debate that gets this kind of treatment.

The skin test in an HIV infected population

Whilst much of the burden of proof has been lumped onto IGRA in this particular study, Interpreting Tuberculin Skin Tests in a Population With a High Prevalence of HIV, Tuberculosis, and Nonspecific Tuberculin Sensitivity it is the ubiquitous skin test that has had to come up with the goods.

And it failed to deliver and did so in a somewhat spectacular fashion;

Whereas cutoffs in the HIV negative and general populations varied between 9 mm and 24 mm depending on the assumptions about ELISpot performance, in the HIV-positive population, optimal cutoff points were consistently determined as 0 mm, demonstrating the difficulty of interpreting the TST responses in HIV positive populations.

Rifapentine is granted Orphan Drug Status

Rifapentine is granted Orphan Drug Status by European Commission for Treatment of Tuberculosis
 

- Shorter treatment duration with rifapentine expected to bring significant benefits to patients -

Paris, France - July 1, 2010 – Shorter treatment duration with rifapentine expected to bring significant benefits to patients - Sanofi-aventis (EURONEXT: SAN and NYSE: SNY) announced today that the European Commission has granted Orphan Drug status for rifapentine for the treatment of tuberculosis (TB). Rifapentine is an antibiotic member of the rifamycin class, with a higher inhibitory activity against Mycobacterium tuberculosis and a longer half-life than rifampin, the cornerstone of current TB treatment regimen. These combined are expected to improve the drug exposure of patients to the drug and potentially lead to better efficacy.

European Orphan Drug designation is granted to medicines intended for treatment of life-threatening or chronically debilitating pathologies that affect no more than 5 in 10,000 people in the European Community. The European Commission’s decision follows the positive opinion released by the Committee for Orphan Medicinal Products (COMP) of the European Medicines Agency (EMA) that a rifapentine-based combination regimen may be of significant clinical benefit for drug-susceptible TB patients by shortening their tuberculosis treatment.

“Rifapentine is currently one of the most promising drugs for the improvement of patient compliance, which is key to the success of tuberculosis treatment,” said Robert Sebbag, Vice President, Access to Medicines, sanofi-aventis. “To avoid as much as possible the emergence of resistant strains, it is of utmost importance to simplify the treatment of non-resistant TB.”

Sanofi-aventis is revisiting the development of rifapentine to be given daily, in combination with standard daily companion drugs, with the objective of significantly shortening the duration of drug-susceptible TB treatment. This should lead to less premature cessations of treatment, and thus to a reduction ofmtreatment failures, a lesser risk of development of drug-resistance, as well as a reduction of costs, all of which are expected to bring significant benefits to patients and public health systems.

Rifapentine is currently marketed in the United States for the treatment of pulmonary and drug susceptible TB within a standard 6-month course combination regimen.

http://en.sanofi-aventis.com/binaries/20100701_RIFAPENTINE_en_tcm28-28921.pdf

Japan studies - nonsocomial infections

TUBERCULOSIS CONTACT EXAMINATION AND QFT-G TESTING FOR THE PREVENTION OF HOSPITAL ACQUIRED INFECTION

Takashi YOSHIYAMA

Abstract

Hospital acquired infection mainly occurs at hospitals, not clinics.

In Japan, QFT-G is the main tool for the diagnosis of tuberculous infection among health care workers.

Contact examinations are basically done for contacts of sputum smear positive TB cases, but infection may occur at fiberbronchoscopy of sputum smear negative TB cases and at the time of irrigation of TB abscess. Therefore, contact examination requires bigger target group than usual contact examinations.

Mathematical model analysis of cost effectiveness examination showed that contact examinations at the age of 20s to 40s will be cost saving if it is done for the contacts with the risk of infection of 6% and beneficial for the DALY lost due to TB infection if it is done for the contacts with the risk of infection of 3%.

Addition of baseline QFT for the HCWs at the age of 20s requires 100 million yen for the recovery of 1 DALY lost due to hospital acquired TB infection. Also mathematical modeling showed that periodical QFT testing of HCWs at the age of 20s to 40s will be beneficial for the DALY lost due to TB infection if the annual risk of infection will be around 2% and will be cost saving if the annual risk of infection will be around 8%.

Therefore, periodical QFT is recommended for the staff working at the environment with high risk of infection (around 2% per year).

Correspondence to: Takashi Yoshiyama, Fukujuji Hospital,JATA, 3-1-24,


-----------

It is worth reflecting on Recent Trends in Tuberculosis, Japan by Toru Mori

Nosocomial outbreaks of TB are also a problem. Nationwide surveillance data show that during 1987 through 1997, the case rate of all forms of TB among female nurses was 2.3 times higher than that for the general female population. The relative risk among nurses was highest at 3.3 in the 20- to 29-year-old age group; risk declined with age but is still substantially higher for those <60 years of age.

Dead man running

No policies, no party and no direction

Introduction and implementation of QuantiFERON

The Southeastern National Tuberculosis Center (SNTC) Webinar Interferon Gamma Release Assays (IGRAs): Yesterday, Today, and Tomorrow now has a transcript available; the following is a portion of it.

Wikipedia and blind freddy

The current Wikipedia entry for tuberculosis diagnosis has the following entry

The authors concluded that IGRAs are "superior to the TST for detecting confirmed active TB disease..."[citation needed]

What do they mean, citation needed? it is here, in the Chest Journal

The newest commercial IGRAs are superior, in comparison with the TST, for detecting confirmed active TB disease, especially when performed in developed countries.

A tale of unrequited love

Today the Australian Prime Minister, Julia Gillard, announced the date of the next federal election;

“I expect this to be a close, tough, hard fought campaign,” she said. “I do genuinely believe this is a close election.”

The leader of the opposition, Tony Abbott, was quick to respond;

"Why should people trust a Prime Minister who can't guarantee a full term because she can't be sure that the factions would let her?"


"I expect this to be a filthy campaign from the Labor Party,"

Does Mr Abbott have the punter's support? - not yet

Short course therapy with rifampin

Not only is a short course therapy more attractive to users, the side effects are less and Rifampin efficacy can be monitored using QuantiFERON;

Impact of treatment completion, intolerance and adverse events on health system costs in a randomised trial of 4 months rifampin or 9 months isoniazid for latent TB.

....

Conclusions The 4RIF regimen was significantly cheaper per patient completing treatment because of better completion and fewer adverse events.

Previously LoBue and Menzies had said that

Two large scale trials are ongoing; one is comparing efficacy and effectiveness of 9H with 4 months rifampin (both daily and self-administered), while the second, which is nearing completion, compares daily self-administered 9H with 3 months directly observed once weekly INH combined with rifapentine.

The results of these two trials will likely shape future recommendations substantially.

No comment

Lets get physical

The Question;

I am a Pre-Nursing student, but I would appreciate it greatly if practicing nurses, such as yourselves, would give me some information.

17 years ago, I had a positive reaction to the TB test. I then took the INH for 6 months, even though I did not have the actual disease (from chest x-ray). I was informed that I should not be tested again because I will always have a positive reaction, and having it again can cause severe reactions.

I guess my questions are: Were you required by your school to get tested?
If so, at what point in time? Do you know anyone who got kicked out of school because of a positive reaction (with no active TB)?
For the working nurses, what physical tests are required prior and during employment?

I am stressing out because I plan on going to a career college, and am afraid that I will be putting my time, money and effort just to be told that I can't go on. Please help.

The Answers;

I have also had a postive PPD, 9 months of Isoniazid, and a clear xray. My school requires a Quanti- Feron Gold TB test every year for those who have had a + PPD in the past. It requires a blood draw.

------

...I'm a freak of nature who's allergic to phenol (the preservative in the TB test). I was tested for TB repeatedly in my first year of life and developed an allergy.

As a student, I had to get a chest x-ray for nursing school. This is very expensive, especially when compared to the skin test. I believe that the quantiferon gold test is also quite pricey. When you are employed in a health care facility, your employer picks up the charge.

I would see if you employer would accept the chest x-ray and record of taking INH, just to save your pocketbook, before you book the x-ray.

------

...It's nice to hear from someone who's actually tested positive. Did your school require you a doctors note or medical records to prove that you took the Isoniazid? Taking the meds is required by INS (Immigration & Naturalization) before they grant permanent residence status to the US. I took this medication, but cannot remember who prescribed and gave me the clearance, since it's been 17 years ago.

I will google the Quanti-Feron Gold TB test you wrote above. I have no problems with needles.

------

...All I needed was the negative QFG-TB test- no documentation about the meds or anything. Like another poster, I have heard the test is a bit expensive. Luckily, I have fantastic insurance and all my labs and xrays are free.

Good luck!

------

...In my employment physical, they just did a standard assessment with no bloodwork or UA. The drug test part of the physical was separate.

In my job (home health) we have to get a PPD for TB every year. I'm sure they must have an alternative for those who test pos on the skin test so you don't have to have a chest x-ray every year. But your problem is not all that unusual. Best wishes to you!!

 ------

...If it were me, I wouldn't want to be radiated every year. I'd refuse the chest xray but let them do the blood test.

 ------

...The chest x-ray should be good for five years. When I went to school they wanted a TB test every year, or if you had a positive reaction a chest x-ray which you only had to do once as they said it was good for 5 years

------

...If that's the case then I might consent to the xray, but if they will do the blood test in place of the xray, I would still choose that option; there's no sense in extra radiation if it's not necessary. Just my opinion.

Eurosurveillance

More from the EU, on this occasion they estimate the specificity of IGRA in HCW's;

The estimated specificity of in vitro assays was higher than that of TST also among individuals who were not BCG-vaccinated. In conclusion, when used in healthcare workers, in vitro assays may provide a significant increase of specificity for tuberculosis infection compared to TST, even among non vaccinated individuals, at the cost of some sensitivity.

Just how big is the TST non return rate?

It's worth revisiting the Pooran et al. study for the discussion on return rates;

In reality, up to 60% of individuals fail to return for their TST results [27,28])

Such a high failure rate is regarded as commonplace

Within our programmatic setting, only 47% of eligible patients completed repeat TST testing for the purpose of this study. This finding suggests that similar rates of return for follow-up testing during contact studies may be expected in comparable patient populations.

however Pooran et al chose a 90% return rate because

We assumed that there will be a stringent follow up of contacts

At what cost? In the Ugandan trial they had to employ

A team of five experienced home health visitors traced the subjects who did not keep scheduled appointments and encouraged them to return to the clinic.

which must stretch the budget. Pooran acknowledges this by saying

Indeed, for this reason, the Health Protection Agency in the UK [29] recommends IGRA single testing in situations when screening large numbers of individuals makes testing with the TST problematic due to  the large number of people that need to be followed up for TST reading

yet Pooran consistently fails to apply a cost to the follow up procedure.

The failure to return is a latent condition of the TB skin test.

Much has been made of the updated CDC guidelines and the failure to return to have a Mantoux test read is possibly the single biggest factor against the continuation with the skin test. For instance take the study Strategies to Increase Adherence With Tuberculosis Test Reading where various options were canvassed in an attempt to lift the poor rate of return

Before the study the follow-up rate of TB test reading by a trained professional was 45%.

These options were

1) routine verbal and written instructions,
2) reminder phone call,
3) transportation tokens and toy on return,
4) withholding of school forms until time of reading and need to repeat TB test if not timely read,
5) parents taught to read induration with nurse home visit.

The results were

1) 58%,
2) 70%,
3) 67%,
4) 70%, and
5) 72%

Importantly this failure rate was not confined to any particular group

The five groups did not differ with regard to TB risk factor score, maternal education, transportation source, or perceived importance of TB testing.

Just not good enough.

Experts: Too Many People Are Ignorant About TB

QFT as a confirmatory test - FAIL

The Korean study is significant in that it deals with a large number from a relatively homogeneous group ie 7,109 classmates of contacts in which the rate of return was not a significant factor. The rationale to use QFT as a secondary test was because

we thought this would be the most cost-effective strategy. 

The only costs compared were

the reagent costs for QFT per person (US $20 to $30) and those for TST (approximately US $5).

Now consider the real life experience of the County of Los Angeles Department of Public Health where the cost of TST reagent per patient was $1.65/test, cost of labour etc $11.30/test and the amount of retesting required due to failure to return a staggering 50%.

Taking into account the added costs of treating TST false positives the true cost of diagnosing and treating 5,000 persons per year with the TST was calculated at ~$165,000 as compared with $109,000 using QuantiFERON.

The cost of reagent is the TST's only advantage.

Masae Kawamura makes the point that using QFT will not necessarily make TST better

The argument that a dual system is the most cost effective just does not hold water.

Another brick in the wall

From Korea;

The use of QFT resulted in approximately 45% of TST positive students not being given chemoprophylaxis.

The point is fast approaching where the skin test gang will have to choose between their argument and their credibility.

Medical science and Google

When Google co founder Sergey Brin discovered that his parents had Parkinson's and that it was hereditary and that he carried the gene...he immediately swung into action.

Not content with the traditional model he

wanted to collect data first, then hypothesize, and then find the patterns that lead to answers. And he has the money and the algorithms to do it.

Traditional Model

1. Hypothesis: An early study suggests that patients with Gaucher’s disease (caused by a mutation to the GBA gene) might be at increased risk of Parkinson’s.

2. Studies: Researchers conduct further studies, with varying statistical significance.

3. Data aggregation: Sixteen centers pool information on more than 5,500 Parkinson’s patients.

4. Analysis: A statistician crunches the numbers.

5. Writing: A paper is drafted and approved by 64 authors.

6. Submission: The paper is submitted to The New England Journal of Medicine. Peer review ensues.

7. Acceptance: NEJM accepts the paper.

8. Publication: The paper notes that people with Parkinson’s are 5.4 times more likely to carry the GBA mutation.

Total time elapsed: 6 years

Parkinson’s Genetics initiative

1. Tool Construction: Survey designers build the questionnaire that patients will use to report symptoms.

2. Recruitment: The community is announced, with a goal of recruiting 10,000 subjects with Parkinson’s.

3. Data aggregation: Community members get their DNA analyzed. They also fill out surveys.

4. Analysis: Reacting to the NEJM paper, 23andMe researchers run a database query based on 3,200 subjects. The results are returned in 20 minutes.

5. Presentation: The results are reported at a Royal Society of Medicine meeting in London: People with GBA are 5 times more likely to have Parkinson’s, which is squarely in line with the NEJM paper. The finding will possibly be published at a later date.

Total time elapsed: 8 months

Guidelines assessed

Quality of tuberculosis guidelines: urgent need for improvement

Authors: Gallardo, C.R.1; Rigau, D.2; Irfan, A.3; Ferrer, A.2; Caylà, J.A.4; Bonfill, X.5; Alonso-Coelho, P.6

Source: The International Journal of Tuberculosis and Lung Disease, Volume 14, Number 8, August 2010 , pp. 1045-1051(7)

Abstract:
SETTING: Clinical practice guidelines have been developed for many disorders, but their quality varies greatly and does not always reach an acceptable standard. No evaluation of clinical practice guidelines on tuberculosis (TB) has been carried out to date.

OBJECTIVE: To identify and assess the quality of TB guidelines.

DESIGN: We systematically searched documents published from January 1998 to May 2008 in Medline and the Turning Research into Practice (TRIP) database and in clearing houses and on websites of scientific societies. Three appraisers evaluated each guideline using the AGREE (Appraisal of Guidelines, Research and Evaluation) instrument. A standardised score was calculated separately for each of the six domains.

RESULTS: A total of 36 guidelines for TB were identified, and after appraisal good overall agreement was observed among the three evaluators. Results revealed that quality was acceptable in two domains but had serious shortcomings in the other four. A slight improvement in quality was observed in documents published in 2005 or later. After global assessment, 18 documents were considered 'recommended with provisos' and only two documents 'strongly recommended' for use in clinical practice.

CONCLUSION: The methodological quality of TB guidelines was disappointingly low. All guideline developers should adhere to instruments such as AGREE to produce documents of optimal quality.


Table compiled from data in above study

Slowly slowly catchy monkey

Swiss updated guidelines here, they appear to prefer IGRA.

The following is my translation only;

Theoretically three possibilities of monitoring exist: testing alone with Mantoux skin test, testing with IGRA alone and the combination of skin test with IGRA. In the latter case an IGRA is performed only when a prior skin test has a positive result. The monitoring with repetitive skin tests alone contains many disadvantages, one being the booster effect on the skin test and the IGRA, reduced practicability in the implementation and the necessity for the confirmation of a positive test result with a IGRA before a therapy. Therefore this publication no longer describes the concept. Due to the newest study results some foreign institutions, like the German professional association for health service and welfare care (BGW), recommend the monitoring of the exposed personnel with IGRA testing only.

Crises of capitalism

NICE advocates pragmatism

So says Dr Fergus Macbeth, Director of the Centre for Clinical Practice at NICE

"The newer interferon gamma tests for latent TB may offer some advantages over the current internationally recognised standard test - the Mantoux test. However, despite the studies that have been carried out since the original NICE TB guidance was published, important questions remain unanswered about the potential role of these new tests in clinical practice in the UK. The draft guideline therefore adopts a cautious, pragmatic approach by recommending that for many cases the most effective way to diagnose latent TB infection is a Mantoux test followed, depending on the result, by an IGT test."

Despite there being no gold test for latent TB the skin test is now an internationally recognised standard test...

Stakeholders should submit their comments by August 5, 2010

Heavy on the down strokes, light on the up strokes...the pen is mightier than the sword

The latest NICE IGRA guidelines, in draft form, are available here.

It is a very disappointing document; despite acknowledging the failings of the Mantoux skin test

Diagnosis has in the past been reliant on the TST but this has poor specificity if there has been BCG vaccination or environmental mycobacterial exposure, which can lead to false positive results.

and the advantages of IGRA

Interferon-gamma tests showed little evidence of being affected by prior BCG vaccination, and showed stronger correlation with exposure categories than did TST. This was shown in low prevalence groups, in household contacts, and in outbreak situations. The specificity of interferon-gamma tests seemed better, and there was less potential for false positive results.

they are unable to see their way clear

In the absence of a gold-standard reference test, it is not possible to measure directly the sensitivity and specificity of a new test for latent tuberculosis.

In general they advocate "offering" the Mantoux first however

Those with positive results (or in whom Mantoux testing may be less reliable) should then be considered for interferon-gamma immunological testing

By their own definition the Mantoux is always less reliable

Where to now?

Now that the CDC have given QuantiFERON the thumbs up it will be interesting to see how it all pans out - there are some that say that Government austerity could impact on QFT sales. One of the CDC's priorities is on HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (or NCHHSTP) and their goal is to eradicate HIV/AIDS, viral hepatitis, STDs, and TB. One of the tools to be used by the NCHHSTP is the Program Collaboration and Service Integration (PCSI) and CDC director Kevin Fenton talks about the efficiencies of PCSI

Integrated diagnosis implies integrated treatment, to which there has been some success;

“Our findings provide compelling evidence of the benefit of initiating antiretroviral therapy during tuberculosis therapy in patients with HIV co-infection, and also support recommendations by the WHO and others for the integration of tuberculosis and HIV care,”

LabMedica cuts to the chase

A highly accurate blood test for the diagnosis of tuberculosis (TB) is preferable to the Mantoux or tuberculin skin test (TST).

New guidelines published by the [U.S.] Centers for Disease Control and Prevention (CDC; Atlanta, GA, USA) indicate that a one-step blood test is far superior to the archaic TST. Results of the blood test are ready within 24 hours and do not require a return visit from the patient.
 

OK, we get the message - so, who or what is LabMedica?

LabMedica International is mailed free-of-charge to qualified professionals in hospital and clinical laboratories worldwide (outside the USA and Canada). Circulation includes laboratory directors, clinical chemists, other clinical laboratory specialists, and technologists in these laboratories, as well leading distributors and dealers in the field. To qualify, readers in the above categories must request the publication in writing - by mail, fax or through email.

According to the blurb

Total circulation is over 32,000 worldwide

QuantiFERON - highlight of the month

Link

Clear as crystal

Adding to previous notices from Stanford Hospital & Clinics is this one, revised June 2010;

Occupational Health Services uses QuantiFERON Gold instead of the TB skin test for baseline and annual testing of all medical staff unless unavailable or contraindicated

Getting those ducks to line up

The tackletb website gives Quest Diagnostics their own slot as a US distributor

and service provider whilst the link to the Get-QuantiFERON site now lists 142 labs which

have agreed to provide QFT testing services to outside physicians and laboratories.

Quest Diagnostics have put QuantiFERON onto their front page, although they might need to update their information to include the latest CDC guideline.

Under "Healthcare: Pharmacy and Other Services" Fortune magazine listed Quest Diagnostics as number 3 in their World's Most Admired Companies list. From Quest

"Earning our place among the most admired companies for the third consecutive year underscores the commitment of our 43,000 employees to putting our patients first by providing the highest quality service and diagnostics innovation," said Surya N. Mohapatra, Ph.D., Chairman and CEO of Quest Diagnostics. "We are particularly gratified to be the only diagnostic testing company to achieve the important distinction of being ranked among the world's most reputable corporations."



Southeastern National Tuberculosis Center

IGRA Guidelines Now Available
The new Interferon Gamma Release Assays (IGRA) guidelines have been released and are available on the DTBE website.

•TB Guidelines - Testing and Diagnosis section - www.cdc.gov/tb/publications/guidelines/Testing.htm
•PDF version - www.cdc.gov/mmwr/PDF/rr/rr5905.pdf
•HTML version - www.cdc.gov/mmwr/preview/mmwrhtml/rr5905a1.htm?s_cid=rr5905a1_e

CDC has developed several resources that will assist you in learning more about IGRAs.

•Interferon-Gamma Release Assays (fact sheet) - www.cdc.gov/tb/publications/factsheets/testing/IGRA.htm
•Testing and Diagnosis (topic page) -www.cdc.gov/tb/topic/testing/default.htm

QuantiFERON - "worth the cost"

IN the the beginning Dr. Van Voorhees* took the ultra conservative approach to Quantiferon

As with many new studies, the cost of the quantiferon gold test is generally greater than the PPD test. I therefore initially questioned whether this test, which appeared to be less cost-effective, should be more widely used and I first used it only as a second level test, just to verify a positive PPD.

Skin test false positives was one issue

several of my previously PPD- positive patients who had already undergone prophylaxis for latent TB requested the test and felt very vindicated to discover that their quantiferon gold test was indeed negative.

so it was no wonder that

It also has become quite clear that patients prefer this test over the PPD. 

However it was the peer reviewed studies that turned him

More recently however, the quantiferon gold test has been positioned as an alternative first-line approach for the screening of tuberculosis (rather than as a back-up if patients have a positive PPD) in the pulmonary literature.

And now?

The advantages of the quantiferon gold assay have prompted me to switch my patients on immunosuppressive therapies to baseline and annual quantiferon gold screenings. This has been good for both me and my patients. 

His advice to other doctors?

Do consider checking with the labs that you use about whether this test is available to your patients, and if so, I strongly recommend that you consider using it for your patient monitoring.

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*Dr. Van Voorhees is Associate Professor, University of Pennsylvania Health System and Director of its Psoriasis and Phototherapy Treatment Center.

Quantiferon minimises false positives

"Alar's" eagle eyes found this in the updated CDC guidelines;

If persons at low risk for both infection and progression are to be tested, selection of the test with the greatest specificity will minimize false-positive results, reduce unnecessary evaluation and treatment, and minimize the potential for adverse events from unnecessary treatment.

This is what the CDC had to say about specificity

In tested populations of persons unlikely to have M. tuberculosis infection, pooled QFT-GIT specificity was 99% and pooled TST specificity from these cohorts, when available, was 85%. Pooled T-Spot specificity was 88% and pooled TST specificity from these cohorts, when available, was 86%.