QFT, Progressing Along Nicely

Following on from the events in March 2010 was the Chicago Symposium. Dr. Paul Terpeluk from the Cleveland Clinic gives a thorough and detailed account of “Implementing QFT-GIT in a Large Integrated Health System”, Phil Griffin and Thorton Elliott from the Kansas State Department of Public Health describe "IGRA Implementation Against All Odds, Even in Kansas" and David Marder MD, MPH, University of Illinois at Chicago told of “TB Surveillance Using QFT”

These are "warts and all" accounts by early adopters of QuantiFERON and, after detailing all the trials and tribulations, represent a positive endorsement of QuantiFERON.

Caught silly mid on.

The recent survey into latent TB practices in Australia and New Zealand shows just how ineffectual the current guidelines are

This survey has shown that current practice is highly variable in key areas, and the development, implementation, and regular updating of guidelines specifically for the Australian and New Zealander context are important. Such guidelines must be developed with input from a variety of stakeholders to assist with ensuring broad acceptability but are likely to be most beneficial if approached uniformly across the region.

The NTAC have released their advice on IGRA, which seems to have been ignored. This could be due to the fact that health is a State not Federal matter.  It could also be due to their failure to properly review their position with the available data and to be less reliant on opinions of others, like Canada.

Whatever the reason, the NTAC have had little effect on the uptake of IGRA in Australia.

QuantiFERON and HIV

Hot off the presses, from Japan;

Our data suggested that QFT-G had high sensitivity and specificity in HIV-infected populations with CD4+ greater than 50/μL. However, QFT-G did not perform well in HIV-positive patients with CD4+ less than 50/μL.

The comparison was made between QFT and TST

QFT-G appeared to have at least as good sensitivity as the TST and significantly better specificity, but the number of subjects was insufficient to make definitive conclusions.

As always, the devil is in the detail

We used the liquid antigen version of the QFT-G test, which has been replaced by the In-Tube version of the test (QFT-GIT) in most countries worldwide. This makes comparisons of our results with those from other studies difficult as most other studies have used QFT-GIT. Since Harada et al. have shown that QFT-GIT has higher sensitivity than QFT-G with the same high specificity [21], it could be expected that the better performance would be obtained than that obtained in this study.

Praying for a miracle.

Only 15,286 out of 48,000 TB cases are reported in hospitals in Ghana in 2009, a World Health Organisation (WHO) report on Tuberculosis in Ghana has said.
   
This is due to the stigma associated with contraction of the disease and the preference of prayer camps by TB patients to hospitals.

Link

Can't bowl, bat or field - just what are we good for?

Overall, clinicians were more likely to use an IGRA than TST for the diagnosis of LTBI.

All is forgiven.

Several questions offered a choice between the two tests in a variety of situations, with respondents opting for IGRA more frequently. Most clinicians would use an IGRA for diagnosis of LTBI in patients known to have had BCG vaccination, and while clinicians frequently reported using an IGRA after a positive TST, no respondent performed TST following a positive IGRA. Following an indeterminate IGRA, clinicians were more likely to perform TST than to repeat IGRA. Additionally, a small number of respondents indicated that they would use IGRA becoming negative as a guide to successful therapy.

Are you game enough?

Recent studies show that performance based remuneration and stock based remunration may not be performing as envisaged. In one study they found that

it is very difficult to devise performance-based compensation contracts that reward portfolio managers who generate excess returns while screening out managers who cannot generate such returns.

whilst in another study they found that stock based remuneration did not necessarily equate to increased performance

stock-based compensation not only induces managers to exert costly effort, but also induces them to conceal bad news about future growth options and to choose suboptimal investment policies to support the pretense. This leads to a severe overvaluation and a subsequent crash in the stock price.

Maybe it just seemed like a good idea.

Climate change, a gamble worth taking?

Regarding climate change popular commentator Andrew Bolt says

Time’s up for this absurd scaremongering. The fears are being contradicted by the facts, and more so by the week.

On the very same subject Australia's CSIRO (Commonwealth Scientific and Industrial Research Organisation) says

Globally, observed CO2 emissions, temperature and sea levels are rising faster than expected.

and

Our present scientific understanding of climate change, although incomplete, is sufficiently robust to inform decision-making and action.

Deutscher Bank became aware of similar differences of opinion

For most of this year, the volume of this debate has turned way up as the ‘skeptics’ launched a determined assault on the  climate findings accepted by the overwhelming majority of the scientific community. Unfortunately, the increased noise has only made it harder for people to untangle the arguments and form their own opinions. This is problematic because the way the public’s views are shaped is critical to future political action on climate change.

So they looked at the facts, in fact they referred to one of the sources that Andrew Bolt recommends ie US National Oceanic and Atmospheric Administration (NOAA). They published their results in a paper titled Climate Change: Addressing the Major Skeptic Arguments

The paper’s clear conclusion is that the primary claims of the skeptics do not undermine the assertion that human-made climate change is already happening and is a serious long term threat..

..To us, the most persuasive argument in support of climate change is that the basic laws of physics dictate that increasing carbon dioxide levels in the earth’s atmosphere produce warming..

..Simply put, the science shows us that climate change due to emissions of greenhouse gases is a serious problem. Furthermore, due to the persistence of carbon dioxide in the atmosphere and the lag in response of the climate system, there is a very high probability that we are already heading towards a future where warming will persist for thousands of years. Failing to insure against that high probability does not seem a gamble worth taking.

For people like Andrew Bolt it would appear that some things are just too simple to understand.

Look what Santa brought me

Not one but two pressies

2010 - it's a wrap.

Paul Krugman looks back in wonder

When historians look back at 2008-10, what will puzzle them most, I believe, is the strange triumph of failed ideas. Free-market fundamentalists have been wrong about everything — yet they now dominate the political scene more thoroughly than ever..

...politics is the art of the possible. We all understand the need to deal with one’s political enemies. But it’s one thing to make deals to advance your goals; it’s another to open the door to zombie ideas. When you do that, the zombies end up eating your brain — and quite possibly your economy too

.

QuantiFERON - CMV

A couple of promising studies recently published. In this one CMV was predicted after kidney transplantation

we observed the Quantiferon-CMV assay to be a sensitive specific test to detect a virus-specific T-cell response. We propose that this assay in combination with viral DNA load estimates may prove to be useful to stratify patients at risk of CMV disease.

and this one from Switzerland

Measurement of cell-mediated immunity against CMV appears to be a promising strategy to identify patients at highest risk for the development of CMV disease and, therefore, to individualize preventive strategies for CMV in transplant recipients.

As the Swiss study notes, CMV is one of those diseases that has always been a problem

Cytomegalovirus (CMV) infection has historically been a major complication among immunocompromised patients, such as solid-organ and stem-cell transplant recipients and patients with advanced HIV infection.

The bear facts.

Commentator "grizzly1", who claims to be a HCW handling refugees on Christmas Island, has been discussing the relative merits of some TB tests and makes the following comment;

QFT requires overnight incubation then on the next flight to a central testing lab for analysis, for us that means a weeks wait, at least, for a result that just tells us that at some time this person has been exposed to TB

This statement is not correct; by only utilising effector T-cells QFT differentiates between existing and past infection. It is the skin test that reacts to both effector and memory T-cells making it less accurate.

QFT is significantly more precise than TST in identifying people who will progress to active TB disease

These relatively simple misunderstandings all help to keep TB the #2 fatal infectious disease in the world.

UK TB trend confirmed

According to the HPA the increase in TB has been steady;

The trend of a gradual rise in the number of tuberculosis cases observed over the last 20 years continued in 2009, with a 4.2% rise giving an overall rate of 15 cases per 100,000 population in the UK.

A total of 9,040 cases of tuberculosis were reported in 2009 with the majority of disease concentrated in urban centres. All 19 primary care organisations with a rate of 40 per 100,000 or more were in major urban areas. London accounts for 38% of cases, with a rate of 44.4 per 100,000

Changing the way the world looks at TB

An analysis by Shelley E. Haydel, Arizona University identifies major issues;

• worldwide TB is the second leading cause of death from a single infectious agent
• worldwide the number of new cases has increased (9.4m p/a)
• worldwide the number of deaths is stable (1.8m p/a)
• relative to population increase these numbers have reduced slightly
• worldwide the number of HIV+ and TB+ has increased (525,000 p/a)
• worldwide TB accounts for 25% of HIV deaths
• in 4 years the number of MDR-TB rose by 64% (424,000 in 2004)
• WHO estimates 30,000 cases of XDR-TB p/a

The development of new drugs may not be the answer

ensuring TB drug compliance and susceptibility testing is critical, since the introduction of new antibiotics could, ironically and unfortunately, generate additional antibiotic resistance and further intensify the existing problem.

Perhaps they need to change the way they look at TB

aggressive strategies and innovative approaches are desperately needed to fight XDR-TB or we are likely to lose our grip on TB control and witness the emergence of completely drug-resistant TB.

Certainly there is evidence that we are losing our grip on TB control

"Of the estimated half a million people who develop multidrug-resistant tuberculosis each year, less than 7% are diagnosed and only one in five of these have access to effective treatment,"

All these new cases of MDR-TB infect others, in particular their family

"Our findings suggest a worrisome hypothesis: household members face a common and persistent exposure to MDR tuberculosis in the community,"...These findings lend support to international guidelines that recommend prompt assessment of close contacts of all patients with MDR tuberculosis, and to suspect a close contact presenting with active tuberculosis as having MDR tuberculosis until proven otherwise,"

The extra drug resistant strains are more aggressive

the frequency of active tuberculosis was nearly two times higher in contacts of patients with XDR tuberculosis than it was in contacts of patients with MDR tuberculosis

and more contagious

In the 359 contacts with active tuberculosis, 142..had had isolates tested for resistance against first-line drugs, of whom..90·9%...had MDR tuberculosis.

To tackle drug resistant TB they need to tackle latent drug resistant TB, before it becomes active and infectious.

BCG vaccination, the facts of the matter

Researchers recently studied the effects of BCG vaccination on 5,662 newborn and infants - and found no evidence of its usefulness.

Although BCG induced complex patterns of intracellular cytokine expression, there were no differences between protected and unprotected infants....Critical components of immunity against Mycobacterium tuberculosis, such as CD4 T cell IFN-γ production, may not necessarily translate into immune correlates of protection against TB disease.

Vaccination with BCG is not seen as an effective method of dealing with TB in the US

TB in the UK - basket case or perfect storm, take your pick.

Whilst nice committees engage in gentle discussion as to "uncertainties" the headlines are shouting

Massive increase in TB in London to be revealed

..the assumption that TB is being spread by recently arrived immigrants in London is erroneous, according to one frontline medical practitioner in the East End I spoke to. “Most of the cases occur in people who have been here at least three years,” he said..

..one experienced doctor I spoke to said, “We need an urgent and radical rethink about how we go about this.”

Achieving targets

The new test for active TB should be of assistance to WHO in achieving their target and  then allowing them to move to the next stage, tackling global latent TB

quicker and more accurate diagnoses produced by Alland’s test will allow healthcare providers to begin tuberculosis treatment far sooner, sharply reducing the risk that infected individuals will spread the disease to others

More on QuantiFERON conversions

It's not that QFT throws false negatives that convert at a later date, more that the time interval for contacts has to be more properly established

20/20 Vision

Link

The response by the WHO and the Stop TB Partnership was ...setting out a strategy and a plan for halving prevalence and death rates by 2015

..Beyond 2015, the internationally agreed goal is to eliminate TB by 2050, that is, to cut the annual incidence of new cases to less than 1 per million population

..we argue that the goal of eliminating TB by the mid-century is most likely to be achieved if current treatment programmes can be coupled with new approaches to reduce the vast reservoir of latent human infection.

Eliminating human tuberculosis in the twenty-first century

Christopher Dye* and Brian G Williams

*Christopher Dye is Director of Health Information in the Office of HIV/AIDS, Tuberculosis, Malaria and Neglected Tropical Diseases at the World Health Organization

The eyes have it

For those who find it hard to comprehend that treating latent TB is as important as treating active TB; from the StopTB department of WHO, TB epidemic and progress towards the Millennium Development Goals

It’s time to “cut the cord” with TSTs.

Dr Daz has found this gem

Ratio of the odds - NICE

In their (draft) updated guidelines NICE refer to

ratio of odds ratios (ROR). In this guideline ROR is mathematically defined as (odds of positive IGT in a high-risk area divided by the odds of a positive test in a low-risk area).

Whilst ROR was generally good they found that the evidence, that is the peer reviewed studies, to be not so good eg

The GDG was presented with evidence showing the meta-analysis of ROR for comparing IGTs with Mantoux tests. This was stratified by percentage BCG vaccination. When adjusted for BCG vaccination, IGTs showed a better ROR  than Mantoux tests. The GDG felt that although IGTs seemed better from ROR, the evidence was of poor quality..

See what I mean?

If public health, like that of Canada, don't treat latent TB with the respect it deserves their TB program is doomed to fail;

Now, the pernicious disease written so indelibly upon Inuit history and psychology is making an unwelcome return to the North. This week, Nunavut recorded its 98th case of tuberculosis in 2010, the most logged in the territory’s 11-year history...Nunavut’s infection rate is now 62 times the national average, adding to the territory’s standing as one of the world’s worst places for respiratory health...TB is a bit of a forgotten sheep in the medical field here.”...“This prevalence of latent infection is the tinder for the forest fire, and the social conditions provide the spark... For a long time now, I’ve thought that TB does not get the recognition it should be getting.”

Opinion pieces - Australia and TB

Link.

How should Australia respond internally to this persisting TB problem? Limiting migration and ostracising migrants is not indicated, acceptable or practicable in the “global village” of the 21st century. We require migrants and temporary visitors for our economy, for plugging skill gaps in our workforce, and for nation building. Moreover, molecular epidemiological studies in Australia and overseas have demonstrated that there is negligible transmission of TB from migrant communities to the general population.13,14 The appropriate interventions are to optimise pre- and post-migration detection of active TB disease, to familiarise migrants with the TB clinical services that are freely available if they develop disease, and to detect and treat latent TB infections among subgroups of migrants who would benefit from this intervention (eg, children under 15 years old).

The 2006 annual report of the National Tuberculosis Advisory Committee does highlight one migrant subgroup requiring particular attention by documenting that the number of TB cases among health care workers (HCWs) has risen from 34 in 2001 to 65 in 2006.7 This rise is attributable to the increasing recruitment of HCWs from high-incidence TB countries. There were no reports of TB transmission from HCWs to patients in 2006.7 Nonetheless, public and private health institutions, particularly those recruiting HCWs from high-incidence TB countries, must ensure that adequate TB screening is undertaken before and during employment.

And this one

A quarter of the refugees who were screened with a Mantoux or QuantiFERON-TB Gold test had a positive result, although this rate was much lower than the 50% reported in a Minnesota study of sub-Saharan African refugees.5 Possible explanations for this difference include variations in patient age, previous exposure to vaccination, and country of origin or transit. The significant number of refugees with apparent latent TB emphasises the importance of testing in this population, as it is considered that about 10% may go on to develop active TB.15 Prophylactic treatment with isoniazid will reduce the chance of active disease by 2.5 times,16 and treatment is recommended in Victoria17 and overseas18 for those under 35 years of age with a positive screening test result.

Missing the boat, people.

The Liberal Party is currently led by people whose conviction on climate change is that it is "crap" and you don't need to do anything about it.

The policy of the Abbott led coalition opposition, to block every policy of the government, has put us at the back of the pack

Australia’s failure to impose a higher cost on carbon emissions has discouraged investment in renewable energy, according to a report prepared for the institute by London-based Vivid Economics and published today. Investment in cleaner energy in Australia was less than $1 billion last year, compared with $11 billion in the U.K, $18 billion in the U.S. and $35 billion in China, it said...

..“The myth is that Australia risks moving ahead of other countries in making businesses responsible for the pollution they cause,” the Climate Institute’s Deputy Chief Executive Officer Erwin Jackson said in a phone interview. “The reality is that countries in Europe and China are moving to position themselves to gain the first mover advantages.”

Changes in latitude

The WHO have produced their Stop TB plan - their goal by 2015 is to

Reduce prevalence and death rates by 50%

Once they have reduced TB

the Plan represents a step towards the elimination of TB as a global public health problem by 2050

The UK also has a plan, called an Action Plan which shares the same aspirations as WHO

to reverse the rise in TB

The is Action Plan is somewhat enthralled by TB control in the US

It used the successful control of TB in the USA as the underlying philosophy of how success can be achieved.

but this is about as far as it goes - latent TB receives scant attention in this Action Plan. Contrast the UK approach to that of the US where the emphasis is on both Control and Elimination and latent TB is included in the government policy to eliminate TB

Identification of other persons with latent TB infection at risk for progression to TB disease and treatment of those persons with an effective drug regimen

It is fair to say that the model used by the UK and other is a failed model

Cases of tuberculosis in the UK have reached 9,040 in 2009 - the highest number in the UK for nearly 30 years while the number of new drug resistant TB has nearly doubled in the past 10 years, from 206 cases in 2000 to 389 cases in 2009.

To reduce or stop TB you must eliminate the source of future infection, latent TB.

A decision to test for latent TB is a decision to treat latent TB.

That is the message from the American Thoracic Society, the CDC and Marshfield Clinic

Since only persons who would benefit from treatment should be tested, a decision to test presupposes a decision to treat if the test result is positive

Marshfield Clinic only use QuantiFERON

NICE TB guidelines (draft)

Link

Note that 

this is still draft guidance and has not been sent out to the NHS....pre-publication check of factual errors

I guess that there will be more testing of "hard to reach populations" than previous.

Changes to the existing guidelines that involve IGRA are as follows;

Losing the plot

Responding to questions on the Wikileak issue the Australian Prime Minister Julia Gillard made the following claims;

the foundation stone of this WikiLeaks issue is an illegal act...there's also the issue of a warrant relating to an alleged sexual assault in Sweden...we've got the common sense test about the gross irresponsibility of this conduct.

Australian law does not extend to acts committed overseas by US citizens, the leaking of classified material was made by a US citizen in the US. How the issue of an alleged sexual assault has become co-joined with issues of national security is bizarre and defies common sense. For the Prime Minister to make statements and issue judgments on law before taking legal advice is irresponsible.

If the only tool you have is a hammer, you tend to see every problem as a nail

Seems like we are no further ahead on coming to grips with the basics of TB and what QuantiFERON is all about.  Forrest is battling to deliver some degree of understanding, and good luck to him. Frankly I don't think that the market wants or is able to understand. For instance, comments like these coming from Cellestis shareholders

I don't believe you can catch TB from a latent carrier or can you ???  

It's back to school for some

Pathology. (of an infectious agent or disease) remaining in an inactive or hidden phase; dormant.

Regarding latent TB

This huge repository may not even exist!...Latent TB could go just continue to be latent and never harm anyone !

There is no medical evidence to support this hypothesis. In fact, the evidence against this theory is comprehensive and overwhelming. However evidence is not what concerns Mr Market, it is the shareprice. If Mr Market sets the shareprice then we have a trade in degrees of stupidity not value.

More TB labs for India

"At present, India has 60,0000 MDR TB detectable cases across 10 states. By March 2011, we'll be able to detect MDR TB in all states," Dr Chauhan said.

India estimates that around 3% of all new cases are MDR TB while 12%-17% among retreatment cases are MDR. Meanwhile, the nation is also increasing its lab count to better diagnose TB among those suffering from HIV/AIDS. Christian Medical College, Vellore, is presently testing and evaluating a new technology called Xpert. This rapid molecular detection of TB and rifampin resistance test not only detects the presence of TB, but also identifies whether it is resistant to rifampin, a critical first-line drug, in only eight hours. "We desperately need a test like Xpert. We are therefore accessing its performance in the Indian scenario," Dr Chauhan said

Link

Contacts of drug resistant TB

With the welcome news that the new diagnostic for active TB also tests for some drug resistant TB comes evidence of the pressing need to test for contacts of drug resistant TB

Of the estimated half a million people who develop multidrug-resistant tuberculosis each year, less than 7% are diagnosed and only one in five of these have access to effective treatment," wrote Helen Cox, PhD, of the Centre for Population Health in Melbourne, Australia, and Gilles van Cutsem, MD, of Médecins Sans Frontières in Cape Town.

"These results support recommendations for active screening of household contacts of people with MDR tuberculosis and provide valuable lessons for other programs striving to improve case detection and to reduce community transmission of MDR tuberculosis," the editorialists observed.

University of Medicine and Dentistry, New Jersey

The prestigious UMDNJ is running the Omerod story TB Blood Tests Call for All East Lancashire Immigrants (United Kingdom)

The study proposes that high-risk groups be given blood tests before being vaccinated, if there is no evidence of latent infection. If the tests are positive, then the patient should be referred for the more expensive chest X-ray. Omerod stated that it is important to find people who have been infected, but do not have active disease, and treat them to prevent disease from developing later. He advises that costly X-rays should not be given to everybody, but should be reserved for those with positive blood test results.

More on the new TB test

According to the press

The Geneva-based WHO said in a statement it was endorsing the test because it could "revolutionize" TB care and control by accurately diagnosing patients in about 100 minutes, compared to current tests that can take up to three months to give results.

This might well invigorate TB treatment, which for so long has been an almost hopeless proposition for developing countries.

New TB test to hit the market

LONDON (AP) Health officials say a new test to diagnose tuberculosis will be available to poor countries for a fraction of its original price.

The Swiss-based Foundation for Innovative and New Diagnostics said Wednesday a test to detect tuberculosis in less than two hours will be sold to more than 100 developing countries at a 75 percent discount for about $17 instead of $67.

The World Health Organization said the test could revolutionize tuberculosis treatment and is a dramatic improvement on the standard test, which takes up to three months to confirm a diagnosis. The test was announced in September.

The test is the Xpert® MTB/RIF test and it should be a good thing for TB diagnosis and treatment - the sooner they get active TB under control the sooner they can tackle latent TB.

We need the law to protect us from these lawless politicians.

Whilst blowhard media personality and unremitting blabbermouth Andrew Bolt gaily swings from one extreme to another; Assange is the neocons friend and Assange arrested, the Leftist tribe protects its own sharper minds have been at work.

The reason the government hasn’t acted to take down WikiLeaks is it knows, as does every First Amendment scholar, that would run afoul of the Supreme Court’s decision in the Pentagon Papers case,” said Kevin Bankston of the Electronic Frontier Foundation. He was referring to the landmark 1971 Supreme Court ruling that rejected the Nixon administration’s attempt to stop The New York Times from printing leaked, high-level military reports on the Vietnam War.

Negligent litigation, a lawyers' picnic.

A case of negligence in which, on appeal, the original finding was dismissed

The Court held that the trial judge could not therefore conclude that Dr Tompsett had breached her duty of care.

However, when it came to damages the original verdict was upheld

The Court did not alter the trial judge's findings on quantum and held that when the matter proceeded to a retrial, the issue of damages should not be re-litigated.

 Damages were $345,690 plus costs, ouch!

In addition the plaintiff had to pay the hospital's costs

His Honour ordered Ms Chaker to pay the hospital's costs for the period 11 March 2008 to 20 October 2008

Footnote: as commenter "puzzled' pointed out, the appeals court can only decide if a retrial is allowable.

A spell at the Oz

Graham Lloyd, Environment editor for The Australian, defends his paper's editorial position in a piece entitled Climate debate no place for hotheads.

You could summarise it thus

"I now regret not suing Clive Hamilton over Scorcher and various other writers who have completely misrepresented my position and, much more importantly, that of the paper," 

Next week will be The Australian's policy on defamation law reform.

Is sputum the "gold test?"

Maybe for pulmonary TB but for non pulmonary TB it is inappropriate and of little use. And according to the evidence non pulmonary TB is rife in some communities;

Another point we would like to emphasize is the high prevalence of extrapulmonary TB among dialysis patients that generally makes it difficult to diagnose TB. Although Lai's ELISPOT study revealed that extrapulmonary TB was found in only 25% (3 of 12), over half of the previous studies reported that extrapulmonary TB accounted for 50% or more of the total TB cases in end-stage renal disease (ESRD). The high rate of ∼80% was also noted in two recent studies. Those findings raise the possibility that a number of extrapulmonary TB cases could have been overlooked in Lai's study, which might have been detected if QuantiFERON had been applied.

The enemy of my enemy is my friend

Some of the best argument for IGRA appear to be as a consequence of recommendations for the TST. Whilst written and published years ago, in Nephrology Dialysis Transplantion, the case for the discontinuance of the TST is still just as valid.

Despite the low overall incidence of symptomatic tuberculosis infection in low-prevalence countries, the potential lethality and morbidity mandate constant vigilance to identify patients at risk for reactivation.

Therefore, current guidelines, aimed at preventing tuberculosis infection in immunocompromised individuals, recommend a generalized screening for evidence of latent infection prior to and after transplantation to target appropriate preventative prophylaxis. At present, tuberculosis control programmes exclusively rely on the tuberculin skin-test to identify a latent infection in asymptomatic individuals. Among others, a major drawback of the tuberculin skin-test is its impaired sensitivity in immunocompromised patients. As a consequence, the threshold defining a positive skin-test reaction has been reduced to an induration of >5mm in this patient group.

Nevertheless, depending on the degree of immunosuppression, the actual number of latently infected individuals may be considerably underestimated due to false-negative diagnoses. Moreover, the skin-test is logistically demanding as it requires at least two visits by the patient for placing and reading of the test. This may not only affect overall compliance, but may significantly decrease the adherence to recommended routine screening programmes in out-patient settings. In addition, the widespread application in transplant recipients may further be precluded by test-related exclusion criteria, as several of those criteria such as skin disorders or intercurrent pyrexiel illness are most frequently observed in transplant patients.

Finally, cross-reactivity of purified protein derivative (PPD)-specific T-cell immunity towards the Mycobacterium bovis bacillus Calmette–Guerin (BCG) vaccine strain may contribute to a decreased specificity in BCG-vaccinated individuals.

Thus, based on the low specificity, sensitivity and practicability, the skin-test is of limited use for widespread screening programmes and identification of latently infected individuals among transplant recipients.

Down the yellow brick road

The editor of The Australian (or more properly the Oz) has now gone from the sublime to the ridiculous. Let Jonathan Holmes explain

But as to Blake Dawson's letter, and Chris Mitchell's demand for an apology from Julie Posetti, and his offer to her to come into The Australian "to observe how the news conference and editing process works to satisfy yourself that they are open and accountable", well, to my mind it is all quite simply bizarre.

Julie Posetti, arguably, made one small error in her reporting of what Asa Wahlquist said - as I explained at length in my previous column. Instead of tweeting: "Wahlquist: 'In the lead up to the election the Ed in Chief was increasingly telling me what to write.' It was prescriptive", she could have tweeted: "Wahlquist: 'In the lead up to the election the Ed in Chief and editors becoming more prescriptive. You were being told what to write'". 135 characters. And totally accurate.

That's easy for me to say in hindsight, and with the benefit of a recording. But live-tweeting with perfect accuracy is hard, which is why it's a dangerous exercise. In the circumstances, and in layman's as opposed to legal terms, Posetti's tweets were a pretty fair reflection of what Asa Wahlquist said, as even Caroline Overington has conceded.

So why on Earth should Julie Posetti apologise? Why should she need to "satisfy herself" that The Australian's editing process is open and accountable? It's not she who made allegations about The Australian's, and Chris Mitchell's, prescriptive attitude to the climate change story. It was his former rural affairs reporter Asa Wahlquist.

Whatever amount Murdoch pays his minions, even if they work for free, they are being overpaid.

TB in renal transplants

Link

Despite obvious limitations of TST and the potential that IGRAs hold

The evidence requires further clarification

QFT-CMV gets a guernsey

Link

...we observed the Quantiferon-CMV assay to be a sensitive specific test to detect a virus-specific T-cell response. We propose that this assay in combination with viral DNA load estimates may prove to be useful to stratify patients at risk of CMV disease.

Canada - cautious endorsement of IGRA.

The Canadian Pediatric Society

The interferon-gamma-release assays were developed to overcome  the pitfalls and logistic difficulties of the tuberculin skin test (TST) for the diagnosis of latent tuberculosis infection (LTBI). These blood tests measure the in vitro production of interferon-gamma by sensitized lymphocytes in response to Mycobacterium tuberculosis-specific antigens. Two interferon-gamma-release assays are registered for use in Canada: the QuantiFERON-TB Gold In-Tube assay (Cellestis Inc, Australia) and the T.SPOT–TB test (Oxford Immunotec, United Kingdom). Evaluation of these tests has been hampered by the lack of a gold standard for LTBI, and limited paediatric data on their use. It appears that they are more specific than the TST, and may be useful for evaluating TST-positive patients at low risk of true LTBI.  Moreover, they may add sensitivity if used in addition to the TST in immunocompromised patients, very young children and close contacts of infectious adults. A summary of these tests, their limitations and their application to clinical paediatric practice are described.

Forecasters get burned

Back in 2008 Keenlyside, Latif et al said

we make the following forecast: over the next decade, the current Atlantic meridional overturning circulation will weaken to its long-term mean; moreover, North Atlantic SST and European and North American surface temperatures will cool slightly, whereas tropical Pacific SST will remain almost unchanged.

The message is getting out there..

..it is latent TB that is critical to TB control.

majority of active disease cases in low or low-intermediate incidence countries in immigrants/expatriates originating from TB endemic countries occur as a result of reactivation of previously acquired infection..

..Identification and treatment of latently infected individuals has greatly helped in control of TB in rich, advanced countries and similar approaches hold great promise for other countries with low intermediate rates of TB incidence.

This from Professor Suhail Ahmad, Kuwait University.

CDC guidelines pay dividends.

This is a presentation by Doctor Veerasuthen, who I believe to be Senior Registrar of the National Hospital of Sri Lanka.

The presentation is about IGRA and TB and contain no real surprises. However, what is noteworthy is that for the presentation he has adopted the US CDC guidelines and makes no mention of the UK NICE guideline.

Don't worry, be happy man.

Following a recent out break of TB Professor Hugh Pennington, microbiologist and public health expert, said the parents should not worry.

"It is quite rare to catch TB in the UK.

"Parents shouldn't worry, even if a skin test shows positive for the infection in their children, it doesn't mean they are going to get TB.

"The odds of it developing into TB are low because kids are so well fed these days, they can fight the bug off, unlike 40-50 years ago."

Limited News Inc.

In a recent speech head of NewsCorp Rupert Murdoch said

“A free society requires an independent press: turbulent, inquiring, bustling, and free. That's why our journalism is hard-driving and questioning of authority. And so are our journalists

This seems at odds with the behaviour of his national paper The Australian. One of its editors, Chris Mitchell, threatened legal action in what was later proved to be a correct rendition of events by a journalist. Mitchell has since admitted that the reportage was factual but has yet to withdraw his threat of legal action over defamation.

Regardless of the finer details of the matter, it is ironic to find that Rupert Murdoch is apparently in a position to define what constitutes a "free society" whilst his business acts to restrict free speech.