Bricks and mortar - a crumbling investment?

Chris Joye talks about the latest housing index for Sydney, despite the incessant beat up by the press the facts are real estate is hardly a stellar investment performer;

In real terms (ie, after accounting for inflation), Sydney house prices have fallen over the past six years. 

Compare housing with Cellestis

The press dont talk about Cellestis because they can't sell them advertising space.


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Feedback from Paris

In the January 2010 newsletter notice was given of the French Satellite IGRA Echo Symposium to be held in Paris on February 26.

So far the feedback is positive

The TST requires a perfect technique to be valid: a strictly placed intradermal injection at the first visit with the doctor and a second visit for reading the result to the skin which is not very easy, because it is evaluated according to the diameter of the cutaneous papule. Moreover, for a subject vaccinated by the BCG (and always immunized) the performance of the diagnosis is even less good.

IGRA is presently seen as an aid to reading the TST! But a consensus is underway to replace the TST, knowing that additionally it is a good candidate for the biological tracking of LTBI and confirmation of the active TB. Thus Cellestis can make it possible to rectify the limits of the TST and to support an effective policy of fighting against tuberculosis.

Live from the coal face

The identity of the posters on the OSHA forum lends more weight to their comments - these are expert opinions!

• Marilie Stuck - Laboratory Coordinator - Children's Mercy Northland

• Nancy Andritsch - employee health - Wisconsin SouthEastern - member of APIC-SEW 

• Vanessa Clendening -  Health Service Coordinator at Providence Healthcare Network Waco, Texas Area

Getting the message

The story is pretty much what you would expect

According to a new study published the February issue of Chest, healthcare workers are nearly five times as likely to decline drug therapy treatment for latent TB, compared to patients in the study.

but the HCWs dont hold back

by Nancy Andritsch on February 24th, 2010 at 11:38 am
This study says nothing about the use of Quantiferon TB-Gold testing which is far more accurate to detect latent TB infection than TB skin testing. I would accept the recommendation for treatment of latent TB infection if the skin test was verified with a positive Quantiferon test, but not based solely on a TB skin test.

By Vanessa Clendening on February 25th, 2010 at 10:36 am
I agree with Nancy. We are currently participating in a Quantiferon TB-Gold pilot program. If an employee or volunteer has a positive skin test, then we send them for QFT testing. Approximately 75% of previously positive skin tests have been verified with negative QFT results, saving lots of unnecessary LTBI treatment.

By Marilie Stuck on March 3rd, 2010 at 12:22 pm
I agree with Nancy. The Quantiferon TB-Gold must be positive and a history of possible exposure present to submit to the INH therapy. We are in the initial start up of the QFT-TB Gold In-Tube test for our Employee Health Testing.

By Dawn Emile on March 17th, 2010 at 3:21 am
Commendable responses from those who are well-informed.

QFT, changing the climate of infectious disease

Forrest links to the Canadian TB Conference and one study in particular is a game changer; it is published in the The Official Journal of the International Society of Chemotherapy and can be found here

Basically it proves the hypothesis that those who are TST+ and QFT- do not need to be treated for LTBI.

-------------------------------------------

Abstracts from the 

26th International Congress of Chemotherapy and Infection
“The Changing Climate of Infectious Diseases”

INCORPORATING THE AMMI CANADA CACMID ANNUAL CONFERENCE 2009
18 21 June 2009
Toronto, Canada • Sheraton Centre Toronto Hotel
International Society of Chemotherapy for Infection and Cancer
www.ischemo.org

The predictive utility of a negative QuantiFERON-TB Gold test in the development of active tuberculosis

W. Chan1 *, E. Der2, G. Tyrrell1, D. Kunimoto1. 

1University of Alberta, Edmonton, Canada, 

2Alberta Health Services, Edmonton Region, Edmonton, Canada
 

Objectives: The QuantiFERON-TB Gold (QFT) test is an assay measuring the amount of interferon-gamma secreted from lymphocytes after stimulation by antigens of M. tuberculosis. Locally, it is used in the setting of patients who are tuberculin-skin test (TST) positive to help decide whether or not to treat these patients for latent tuberculosis infection (LTBI). Our objective was to determine whether patients with a positive TST but negative QFT result developed active tuberculosis if they went untreated for LTBI.

Methods: A retrospective review was conducted of the QFT tests conducted through the Edmonton TB Program from Nov. 1, 2004 to Oct. 31, 2007. Of these, patients that tested positive by TST but negative by the QFT assay were identified, then categorized by whether or not they had received LTBI treatment. This list was then compared to a list of all Alberta patients that developed active tuberculosis from Nov. 1, 2004 to Oct. 31, 2008.

Results: 1853 QFT tests on 1752 patients were reviewed. 1430 were TST positive. 823 of these also had a negative QFT test (57.6%). 97 received LTBI treatment, leaving 726 untreated. 1849 patient years of follow-up were obtained, the minimum follow-up being one year, and the mean and median being 2.5 years. Two cases of active tuberculosis were identified in these 726 patients during this follow up period. Chart review indicated that these two QFT tests were both done in the setting of active pulmonary tuberculosis.

Conclusion: Patients who are TST positive and QFT negative are unlikely to develop active tuberculosis as a result of reactivating LTBI even in the absence of LTBI therapy, at least in the short term.

Happy World TB Day, Kansas City

Back in 2007 the article Tuberculosis screening on a health science campus: use of QuantiFERON-TB Gold Test for students and employees said

Tuberculin skin tests are still the preferred method for detecting present or past infection of TB.

Cellestis' Chief Scientific Officer Dr Jim Rothel then advised that the methodology used by the researchers was not that recommended by the CDC

the use of incorrect CDC guidelines in the Veeser et al1 manuscript... may raise some misconceptions for the reader about when and where QFT-G is recommended for use.

which was accepted by the authors

Dr Rothel is correct that the CDC guidelines quoted in the article were not the guidelines of December 2005.
I have spoken to Dr Rothel regarding these comments and stand corrected with his letter above. Please see the CDC Web site for the most current guidelines for IGRA assays for TB screening [October 2007]. These guidelines are changing as new screening tests emerge.

Kansas City has taken note of guidelines

The plan is to be designed to reduce the risk of tuberculosis transmission and is to be based on the recommendations of the American Thoracic Society, the Centers for Disease Control and Prevention, and the Infectious Diseases Society of America

and passed a bill for funds for a QuantiFERON Lab

AN ACT concerning the department of health and environment; creating the health information exchange — federal fund and the quanteFERON TB laboratory testing fund.

They expressed concern over BCG and false positives

..many students have not had a tuberculosis screening which places all students, staff, and faculty at risk of contracting tuberculosis....Mr. Griffin discussed individuals vaccinated with BCG and false positives generated when the individual undergoes a tuberculosis skin test (TST).

which led to the statement regarding

the requirement for all college students to have a TB test using Quantiferon, the universities want to contract with the KDHE Lab to do these tests and will need a fund to deposit these contractual service payments. The motion was seconded by Senator Kelly. Motion carried on a voice vote.

Thanks to 'doc-gt' and 'equusmedical'

Even educated fleas do it

To borrow a line from Cole Porters song, everybody seems to be doing it - joining a social networking site like Facebook.  Even those overworked underpaid doctors need to socialise and they do it through this site;

More Than 26,000 Medicine faculty students, already graduated Doctors, Young & old Doctors!! from more than 110 different countries, from ANY POINT on the World's map! in one group Why Not?

ONE hundred active discussions, Hundreds of Pictures, more than 100 Medical videos, Free Medical books & many other links!

You can download their toolbar which promises to

Get our freshest content delivered directly to your browser, no matter where you are on the Web.

They also have an offshoot called infectious diseases which gives the latest developments and information and it is a great way to be better informed.

TB and foreign born persons

Whilst forrest and doc-gt have covered the changes to TB detection in migrants to the US it is worth having a look at the overall picture.

Last week the CDC published their annual TB data and, for them, it was a bit of a surprise

The 11.4% decrease in reported TB rate in 2009 is the largest single-year decrease ever recorded. 

and they are trying to establish why this is so

CDC and the National Tuberculosis Controllers Association (NTCA) are investigating whether the decrease represents a reduction in disease rate resulting from improved TB control or population demographic shifts, or might be the result of underdiagnosis or underreporting of disease.

Public health initiatives may be paying off

determining the causes of such a large actual decrease in TB cases will be important, as will understanding which specific public health interventions related to the three U.S. priorities of
1) diagnosing and treating patients with TB disease,
2) conducting contact investigations of TB cases, and
3) targeted testing and treatment of latent TB infection are having the greatest impact, so these interventions can be reinforced and replicated.

Fingers crossed No 3 gets a guernsey

Leaking like the proverbial..

Another peek at the "new" CDC guidelines brought to you by ....the CDC

screening orphans 2-14 years of age with the tuberculin skin test (TST) or interferon-gamma release assay (IGRA) is recommended.

What the...

Referring to the Francis J Curry presentation we see the above slide, accompanied by the voice over which says;

The new guidelines are about to be published, and presentations on this subject by CDC have revealed the following...

...and finally, laboratories are advised to report quantitative results as well as their interpretation.

What is the significance of "quantitative results"?

Another study showed quantitative results to be useful in diagnosing active TB

Higher quantitative IFN-y results were associated with active tuberculosis, and added clinical value to a prediction model incorporating conventional risk factors. 

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The $M question

Dr Kawamura asks and then answers the Big One;

The million-dollar question is: Can IGRAs replace the skin test?

So far, the research indicates that it can. Because of its biological and operational advantages, it is preferred in BCG-vaccinated persons and in screening non-adherent populations. While there is still quite a bit of fine-tuning to do and much to be learned, the rapidly gathering data has been favorable for IGRAs.

I predict that the TB skin test will become a secondary test that is reserved for special situations where IGRAs or blood-based tests cannot be used or are indeterminate.

What to expect when you switch to IGRAs

The Francis J. Curry National Tuberculosis Center has an excellent on line presentation titled Targeted Testing and Treatment Of Latent TB Infection.

Dr Masae Kawamura, from the San Francisco Department of Health, is the presenter.

The title page is here, the presentation can be viewed online here and can also be downloaded here

It is a comprehensive presentation so I will just concentrate on one particular section

Accompanying this particular slide Dr Kawamura makes the following comments;

When you switch to IGRAs you can expect the following: TB programs in San Francisco and New York City using QFT in very high volumes have seen a significant decrease - by about two thirds - in the number of positive results when compared to using the skin test. This has meant a significant decrease in further work up and LTBI treatment. In contrast, we have seen a curiosity that has sometimes led to unnecessary testing and retesting. Our golden rule is, "if the IGRA result is not going to change what you do, please do not order the test!"

When using IGRAs in serial testing, you will again find more negative results compared to the TSTs, but you may also experience a higher rate of "IGRA converters."  This could require further investigation that includes repeating the IGRA and reviewing the quantitative results to look for what some experts call "wobblers." These are individuals who have results that hover around the cut point, sometimes above and sometimes below, and their negative-to-positive result may not be true conversion.

To my mind the presentation is subtly laying down a challenge; IGRAs are only for those who want to change - do you want to change? For those in the TB industry who are happy to continue with the status quo of dubious diagnoses and for those to whom TB testing is just a requirement - the TST will meet those needs. Without an intention to proceed further the diagnosis has little relevance. Therefore it is imperative that guidelines stress that Decision to Test is Decision to Treat!

The requirement to treat throws the responsibility back on to the examiner, which diagnostic is the better?

Transmission of TB

This study into a contact investigation in a UK school gives some interesting data to play with. At the outset of the 765 students and 172 staff tested there were 55 with LTBI and 12 with active TB. So you could say that overall the transmission rate was ~7%.

As no adults were found to be positive it could be assumed that adolescents are more susceptible to TB. The rate of transmission increased with contact, of those tested who were in the same year around 30% were positive.

This appears to indicate that the closer you are to an active TB case the greater the chance that you will get TB.

So general "ball park" rates are not helpful guides to virulence, proximity is the critical factor.

There is no substitite for proper testing

Referring to the case of the nurse with active TB Dr Lawrence Budnick, from UMDNJ said

The outbreak of latent TB infections at a hospital in NYC several years ago resulted from a nurse who answered no to all the questions on 8 symptom surveys over 11 years and then became symptomatic with TB disease

The case was reported in MMWR

Eleven years earlier, nurse A had LTBI diagnosed with a TST result of 15 mm induration during screening for employment at hospital A, after emigrating from the Philippines. She had elected not to take the isoniazid prescribed for treatment. The reason nurse A gave for declining treatment was that most adults from the Philippines, where TB is endemic, have positive TST results and generally do not take treatment for LTBI. She also stated that the positive TST result might have been caused by her bacille Calmette-Guérin (BCG) vaccination for TB disease at birth or potential exposures while she was employed as a nurse in the Philippines. Nurse A had an annual TB symptom screen on eight other occasions and had one other chest radiograph (when she began work in a different area of the hospital) without evidence of TB disease.

Goodness gracious me

Well as they say, any publicity is good publicity;

KANPUR: On the fourth day of the 28th Annual Refresher Course of Indian Medical Association, College of General Practitioners (IMACGP), zonal head of a private pathology Dr Reena Nakra from Delhi spoke on the `Importance and interpretations of commonly used specialised investigations'.

Talking about the recent advancements made in the field of diagnostics, Dr Reena said there are diagnostics tools that can help in quicker and better management of patients, as clinicians can get a clear picture of the status of the disease.

Throwing light on the `Quantiferon Tuberculosis Gold Test', she said: "Generally pathology labs conduct Montoux test for the detection of tuberculosis. But recent advancements includes qunatiferon gold test which works on Polymerase Chain Reaction (PCR) which is a highly sensitive test." It helps in the early detection of extra pulmonary tuberculosis of brain, spine and other parts of the body, she added.

(cont'd)

More on Columbus

Here is a comparison of the competing diagnostics. Whether they are indicative of a maturing trend or a "tipping point" is something that only time will tell, four years may not be sufficient time to draw any conclusion as to the pattern. What is obvious is that the market for the skin test has crashed.

Regardless of the projection the take home message is

The TB program primarily uses the QFT Blood Test to screen for TB exposure.

.

Changing the way we look at TB

Columbus Health Department has supplied data on their TB control plan, when compiled and presented pictorially we can see just how the involvement of QuantiFERON has changed the dynamics of their business.

Actual TB cases have dropped, from 85 in 2006 to 41 in 2009

Thanks to doc-gt

Professor Bill Mitchell takes a look at the ratings agencies..

..like Moodies

Perhaps we can send the bosses at Moody’s some retirement village brochures in places that have nice golf courses so they can just f*** off and leave everybody alone.

and why? Moodies have just issued their “baseline scenario” that

March 15 (Bloomberg) -- The U.S. and the U.K. have moved “substantially” closer to losing their AAA credit ratings as the cost of servicing their debt rose

Prof Billy is frustrated by their basic lack of logic

..the overriding point is that there is no solvency risk in the first place.

..you cannot compare public debt with private debt. Such a comparison is inapplicable

As an investment Moodies has lost their appeal

Warren Buffett’s Berkshire Hathaway Inc. cut its stake in Moody’s Corp. for the sixth time since July after the ratings company was hit by profit declines, lawsuits and criticism from regulators.

Steve Keen takes a walk..

..to Mt Kosciuszko

However, he maintains that the current boom will end in tears..

..

Back to the drawing board

The furore over radiology, especially the more accurate CT scan, is reaching new heights.

The risk of cancer associated with popular CT scans appears to be greater than previously believed, according to two new studies published Monday in the Archives of Internal Medicine.

As for using radiology in mass screening - forget it

Overuse of radiation-based tests is a concern when they are performed to diagnose patients who have a known abnormality. But the concern is even greater when they are performed for screening purposes, said Amy Berrington, an investigator at the National Cancer Institute and an author on both papers. "You're exposing a lot of healthy people" to radiation," she said.

By comparison a simple blood test is positively benign.

Nowhere to run, nowhere to hide

At the time a convincing argument was made by all the theorists and pundits claiming that government's borrowings would send the country spiralling downwards into bankruptcy, hellfire and damnation and even worse..

..but they were wrong and how

"We are going to have a very, very strong budget position relative to what we saw just six months ago," said ANZ chief economist Warren Hogan.

"We haven't done the final numbers yet, but we are thinking the deficit to be announced in this year's budget could be as low as $30 billion. Next year we could be something close to a balanced budget."

... Investment bank Goldman Sachs JBWere has told its clients to expect an economic growth rate as high as 3.75 per cent both this year and the next. "We are looking for unemployment to be 4.9 per cent by the end of this year, but the Treasury are still looking for it to be 6.75 per cent," the note says.

"It looks as if we could see a budget surplus some time in 2012. Investors from offshore who buy Australia right now will be winners. The rest will come in later after the government makes its big upgrades. "

Institute of Irony and their War on Science

This post is more to do with how politics can test science, and vice versa.

The issues of the emails stolen from the Climatic Research Unit of the University of East Anglia, or Climategate, continues to bubble along.  Amongst the evidence submitted to the UK Parliament on the matter was this piece from the Institute of Physics; which points out that

the CRU e-mails as published on the internet provide prima facie evidence of determined and co-ordinated refusals to comply with honourable scientific traditions and freedom of information law.

and that there is

worrying implications for the integrity of scientific research in this field

and

The e-mails reveal doubts as to the reliability of some of the reconstructions

After an embarrassing inquiry

The Guardian has been unable to find a member of the board that supports the submission

the IoP was forced to issue the following statement

IoP’s position on global warming is clear: the basic science is well established and there is no doubt that climate change is happening and that we should be taking action to address it now.

Meterologist and IoP member Dr Andy Russell felt that they didn't go far enough

if the IoP continues to stand by this statement then I will have no other option but to reconsider my membership of your organisation.

Despite a number of inquiries as to the identity of the authors of the IoP statement the IoP maintain anonymity

The IOP added that the submission was approved by three members of its science board, but would not reveal their names. The Guardian contacted several members of the board, including its chairman, Denis Weaire, a physicist at Trinity College Dublin. All said that they had little direct role in the submission.

As reported by the Guardian anonymous sources from the IoP said that

The institute should feel relaxed about the process by which it generated what is, anyway, a statement of the obvious.

..However much we sympathise with the way in which CRU researchers have been confronted with hostile requests for information, we believe the case for openness remains just as strong.

Further digging by The Times forced the IoP to reveal that an "energy consultant" was one of those who had "contributed" to the submission.

MP Evan Harris expressed his concern

that the IOP is not as transparent as those it wishes to criticise

whilst others track the changes made to the IoP statement on the IoP website including this one

Responsibility for the evidence rests with our Science Board, whose members’ names are openly available on our website.

It would appear that the IoP have allowed themselves to be used by a pro energy group and are now trying to absolve themselves of responsibility whilst covering up, which is exactly what they have charged others with.

Assessing his panic

A study of Indian patients with inflammatory rheumatic diseases looked at the performance of 4 diagnostics prior to treatment with a tumor necrosis factor-alpha (TNF-alpha) inhibitor. Those 4 diagnostics were the TB skin test, QuantiFERON, standard chest Xray and a CT scan.

One patient, who had a negative result to all 4 tests, later developed active TB after treatment with the inhibitor.

This result caused a stir in Mexico where rheumatologists observed that

it could be reasonable to receive therapy for latent TB before taking TNF-α inhibitor agents, independent of the TST results

There must be more to this story

Extending the spot

Oh well

Blood samples obtained from 363 sequentially recruited tuberculosis suspects or treated patients were processed immediately (day 0) and at different times after receipt of the sample [∼24-h (day 1) or ∼32-h (day 2)] with and without adding T-Cell Xtend.

..although the use of T-Cell Xtend appeared to reduce the number of conversions/reversions this reduction was not statistically significant.

Watching the grass grow in Nebraska

Back in 2007 the HIV Clinic from the University of Nebraska Medical Center reviewed the clinical utility of IGRA and found that

in summary, the ELISA-IGRA is a new assay based on in vitro detection of IFN-y that may replace PPD as a diagnostic tool for latent and active tuberculosis. The test is more specific and does not require patients to return for a second visit (as TST demands). Cost, technical limitations, and limited data in the most vulnerable groups, such as children and immuno suppressed patients, may prevent the immediate replacement of the TST.

The University of Nebraska did advise that international students were required to have a

PPD (tuberculosis) skin test obtained at the University Health Center TB skin test
Required of all international students - NO EXCEPTIONS

Then in late 2009 it became

International students must have a test for tuberculosis at the UHC

Now they are asking students to fill in the TB QuantIFERON Screening Questionnaire

TB treatment kills patient

A report of the death of an arthritis patient from Dublin

A man who died after he suffered an adverse drug reaction to medication he was prescribed to treat suspected tuberculosis (TB) had no evidence of TB at autopsy.

Whilst he was diagnosed with TB it is not known how that diagnosis was obtained

screening tests for TB (carried out prior to starting a new drug for his arthritis) suggested an active immune reaction to TB. Mr Dowdall had “significant exposure” to TB at the age of 13 when he shared a bedroom with his brother who had TB.

In some countries screening by IGRA before anti TNF medication is recommended

Screening for latent tuberculosis infection is indicated prior to the administration of anti-TNF-a therapy. Due to the better sensitivity and specificity of IGRA tests, their incorporation into current recommendations should serve to detect more cases at risk for reactivation of latent tuberculosis infection and to prevent unnecessary prophylaxis with its potentially adverse effects in patients with false-positive TST.

TB diagnostics outpace new drug development

Writing in the journal of the Asian Pacific Society of Respirology Christoph Lange (Germany) and Toru Mori (Japan) note that

One of the basic indicators of quality in diagnosing tuberculosis is the delay in diagnosis (‘doctor’s delay’, or ‘health system’s delay’), that is, the time from the first visit of a patient until the establishment of tuberculosis diagnosis. 

Developed countries are the ones dragging the chain

It is remarkable that these delays in the low-prevalence settings are always longer than those in the high-prevalence settings.

With regards to IGRA;

Introduction of IGRA into clinical practice is regarded by many as the most important development in the diagnosis of M. tuberculosis infection over the last decade..

..the specificity of IGRA is consistently high and obviously superior to TST

They conclude

tuberculosis control is not possible, if the diagnosis of active cases is delayed as M. tuberculosis continues to be transmitted from cases to contacts. In addition, false positive diagnosis of LTBI has caused unnecessary burden to individuals and healthcare systems.

The urgent need for innovation in diagnostics is obvious.

However, it is good to see that the changes in diagnostics have started towards the end of the last century, assisted by the progress of biotechnology and the late riser’s alertness to the problem. The balance between developments in the diagnosis and in the treatment of tuberculosis has changed. Recent diagnostic advances overweigh the inefficient progress of new drug development against tuberculosis by far.

Saw a private Rheumatoligist today...

From a thread on the Arthritis Foundation;  this person appears to be a veteran with rheumatoid arthritis

Wow what a difference! I always thought VA care was just fine, was I ever wrong. I brought her all my VA medical files which she thought was great called me a dream patient. I have been waiting for over two years for VA to decide what to do about my TB test being positive before starting a biological. She looked at the TB test results and said that it is nothing than order some sort of test I can not recall the name of it Golden something that she said is better than the TB test and will say if it needs to be treated or not. If that turns out good which she said it probably will than I will start Humeria in 2 weeks.

Further down the thread

I googled "TB" and "gold" and found this webpage from the Center for Disease Control and Prevention.

http://www.cdc.gov/TB/publications/factsheets/testing/QFT.htm

The test your RA doc recommended may be the "QuantiFERON®-TB Gold Test."

Seems that whilst Veterans Affairs had dropped the ball the private sector stepped up to the plate

She told I have been suffering way too much over the last four years. I was a damn fool not to do this four years ago. With my insurance it will actually be cheaper than the VA. Well thought this board could use some good news, I know I needed it.

Tipping point in opinion

The furphy that *TB diagnostic guidelines need to be prudent by limiting IGRA testing to an almost unachievable window of ≤ 3 days after the TST has just been tipped on it's head; when French health specialists looked at the Cost-effectiveness of QuantiFERON®-TB test vs. tuberculin skin test in the diagnosis of latent tuberculosis infection they found that

In France, for the diagnosis of LTBI after close contact with TB, the TST is more expensive and less effective than QFT.  Although it is more expensive, QFT is more effective and cost-effective than TST+QFT under a wide range of realistic test performance scenarios.

Given that the TST is less cost effective there is now no logical reason to continue with its usage.

At some point TST camp followers should consider a tactical withdrawal to save further embarrassment.

------

*UK NICE guidelines say

The specificity of interferon-gamma tests seemed better, and there was less potential for false positive results..

Economic modelling was undertaken with various strategies from no action to a two-step strategy with either TST followed by interferon-gamma testing, or serial interferon-gamma tests. Of these options, the model provided most support, on grounds of cost-effectiveness, for a two-step approach with an initial TST, followed by an interferon-gamma test to confirm positivity.

QuantiFERON inspires confidence

You could wonder what possible benefit is obtained from persisting with the antiquated TST; QFT in kiwi haemodialysis units

The Mantoux test is unreliable in renal disease, and appears to have lead to diagnostic nihilism with respect to latent TB infection...

..The IGRA test gives fewer indeterminate and positive results than we expected from overseas reports. Those identified as having LTBI have all been commenced on isoniazid therapy, apart from two patients who are not expected to survive long term. Treatment has been simplified by using directly observed therapy when patients receive dialysis. Those with negative and indeterminate IGRA results will be carefully followed, enabling further clinical validation of the test. Most importantly, the IGRA test has given greater confidence to the renal unit staff and has resulted in active management of LTBI in a high risk group.

Another meta-analysis

this time on the boosting effects of the TST

Despite acknowledging the facts

In general, there is growing evidence that the TST can indeed boost subsequent IGRA results.

the opinion is to

be prudent to assume that IGRAs are dynamic tests that can produce variable results.

and that

guidelines may need to be updated accordingly

This appears to be counter intuitive and it would be more prudent to not use the less precise more problematic TST

The savings of a strategy that uses TST followed by IGRA compared to a strategy that uses IGRA alone are rather small and do not justify the lost in sensitivity which is inherent in such a two step strategy.

Our data suggest that the IGRA is the appropriate test when screening HCW for LTBI

Hepatoxicity of latent TB treatment

From the CDC an analysis of 4 years of data;

Historically the incidence has been estimated at 1 per 1,000 patients who begin treatment but the lack of specific diagnostic criteria and heterogeneous definitions complicate comparisons across studies.

Determining the actual figure was

made difficult by the absence of reliable denominators for the number of persons initiating INH treatment, which has been estimated at 291,000 to 433,000 per year

Over the period

17 patients with events meeting the SAE (severe adverse events) definition had received INH therapy and experienced liver injury. Of the 17 patients, two were children aged <15 years

The effects of hepatoxicity are dire

All patients had received INH therapy and had experienced severe liver injury. Five patients, including one child, underwent liver transplantation. Five adults died, including one liver transplant recipient. 

Reactivation or reinfection - or what?

A large study of 3,483 adults from 837 households from Cape Town, South Africa found that

The prevalence of bacteriologically confirmed TB in our study was high, and the proportion of patients that had >1 previous episode of TB was substantial. 

This means that

persons with previously treated TB are likely to contribute to transmission of Mycobacterium tuberculosis

The reason for the continued presence of TB could be improper treatment however

recent studies using DNA fingerprinting showed that a large proportion of recurrent TB in our study area is caused by exogenous reinfection rather than reactivation 

The presence of HIV may not be a critical factor

we believe that the prevalence rate for HIV in the study area is less than the rate of 12.4% in women attending public antenatal clinics in Cape Town in 2002

and similarly with the presence of drug resistant strains

Drug-resistant TB is probably not the driving force behind the high prevalence of TB in the 2 study communities

The only real conclusion from this is that current treatment strategies are unsuccessful. The WHO have found that treating only active TB is insufficient, you must treat both active and latent TB

and this is supported by other studies, such as this one from Vietnam

the trend in TB notification among young adults reflects increased rates of progression from infection to disease and/or increased transmission within this age group, rather than increased transmission in the population at large.

If IGRAs, by eliminating TST false positives, demonstrate that the prevalence of latent TB is less than previously thought the obvious conclusion is that the rate of progression to an active state is higher than previously thought.

.

Another box ticked

With regards to literature on QuantiFERON we often read informed opinions that are generally positive with the caveat "further studies are needed", in particular regarding clinical accuracy;

additional studies are needed to understand the reproducibility and relative accuracy of the test before its utility in prospective screening programs can be defined.

Well this lot from Finland did just that

Cranking up the PR machine

From tb-usa and elsewhere

1. California

Screening for TB Infection: Embracing IGRAs in Children

You are invited to a dinner symposium on tuberculosis screening using the whole blood interferon gamma release assay QuantiFERON- TB Gold In-Tube (QFT).

IGRA in kids

Writing in the recent Pediatric Infectious Disease Journal Connell et al state;

...the most likely explanation for the high rate of failed PHA mitogen control responses relates to the functionally immature immune system of infants and young children...

In addition to the high proportion of indeterminate assay results, significant discordance between the results of tuberculin skin testing and IGRA in children has been reported. Exploring the immunology underlying this discordance may help in the development of more accurate and reliable immunodiagnostic tests for the diagnosis of TB in children. In addition, long-term follow-up studies are needed to determine the true predictive value of IGRA for the development of active TB disease. We believe that until such data are available, IGRA should not be used as replacement tests for the tuberculin skin testing in children.

This is where I dont quite see the logic. If IGRA has the ability to demonstrate that some immune systems are immature, a feature not present with skin testing, why is skin testing preferred? With an IGRA you know when the immune system is dysfunctional, with the TST it becomes just another false negative.