Onwards and upwards

Morgan Stanley wrap up 2009 and forecast 2010

This year was all about the exit from the Great Recession. Next year will be all about the exit from super-expansionary monetary policy - we expect the major central banks to start exiting around mid-2010. The prospect and process of withdrawal may have unintended consequences: we think government bond markets will be the first victim.  

A tale of two worlds. We forecast 4% global GDP growth in 2010, but this masks two very different stories. One is a still fairly tepid recovery for the advanced economies. The other is a much more positive outlook for emerging markets, where we forecast output to grow by 6.5% in 2010. In short, we think that the themes of global rebalancing and EM growth outperformance have staying power and have even been bolstered by the crisis.

More here

.

There's no place on earth like Hawaii

That's what the tourist brochure says.

Following release of the procurement notice for QuantiFERON a second version has been issued;

After circling the word "unique" the writer adds

"It is the only FDA approved blood test for latent TB infection in the market that does not require microscopy (labor intensive) and is automated"

Drug resistant TB - a diabolical twist

There is now evidence pointing to a strain of DR-TB thriving in the presence of some antibiotics;

We report a case of rifampicin (RMP) dependent/enhanced multidrug-resistant (MDR-TB) from a patient who had been treated with the World Health Organization optional thrice-weekly treatment and document the clinical and bacteriological features. RMP-enhanced tubercle bacilli that grew poorly without RMP but grew better in its presence were isolated from the patient with treatment failure.

Said senior author John Hopkins Professor Ying Zhang

“Rifampin-dependent tuberculosis is an unrecognized and potentially serious treatment issue,”

Detection is an issue

rifampin-dependent tuberculosis is difficult to detect and may be a bigger problem than we currently realize, since the bacteria do not grow well in the culture medium unless rifampin is added.

TB tipping point - drug resistance in the US

Following a six month investigation into medical drug resistance by the Associated Press the recent case of extremely drug-resistant tuberculosis - being referred to as XXDR-TB - has caught the media's attention.

Oswaldo Juarez, a 19-year-old Peruvian studying English in the US, was diagnosed and treated by Dr. David Ashkin, who heads the Southeastern National Tuberculosis Center (SNTC) and is also from A G Holley State Hospital

According to Dr Ashkin Juarez's strain of extremely drug-resistant TB has never before been seen in the United States and is so rare that only a handful of other people in the world are thought to have had it.

2010 - the tipping point?

On December 16 2005 the CDC released it's long awaited guidelines for the use of QuantiFERON TB Gold.

These guidelines, whilst welcomed, listed areas of performance that remained uncertain viz

Medicare update

Without too much fuss the trend - in Quantiferon's favour - appears to be established in Australia

Stop the stimulus!

Opposition members renew their cry to stop the stimulus now!

Now we again call on the Government to pull back on its massive spending program, otherwise interest rates are going to go up much higher than they need to be.

It is an interesting point of reference, than they need to be.

National TB Center - Diabetes and QFT

From National TB Center and Drs Dean Schillinger and Gisela Schecter (University of California San Francisco and CA Department of Public Health), a course on Diabetes and TB

Why treat latent TB in people with diabetes?

• People with DM have 3 fold greater risk of reactivation of latent TB
• Attributable risk is significant given growing prevalence of DM globally
• Derive significant public health benefit (prevention of spread in population)
• Promote individual well being (prevention of disease in patient)
• Novel methods: QuantiFERON® testing may make even more feasible

Diabetes is said to be in epidemic proportions

In 2000, according to the World Health Organization, at least 171 million people worldwide suffer from diabetes, or 2.8% of the population.[4] Its incidence is increasing rapidly, and it is estimated that by the year 2030, this number will almost double.[4]

According to the CDC

Approximately 800,000 new cases of diabetes are diagnosed each year. It is the seventh leading cause of death in this country and a major contributor to serious health problems such as heart disease, stroke, blindness, high blood pressure, kidney disease, and amputations.

Roland Diel - a meta analysis

Whilst it is acknowledged that the skin test is not very good at detecting TB disease (active TB) when it comes down to it doctors dont have that many other tools at hand. Sputum smear is problematic and inaccurate and culture can take many weeks, if not months before a result.

To the extent that the TB skin test is by default the standby test, the evidence is that IGRA outperforms the TST;

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

Indeterminates - a conceptual conundrum

This study compared the performance of TST and QuantiFERON-TB Gold In-Tube (QFT-IT) on immunocompromised patients in South Korea. Due to the prevalence of QFT-GIT indeterminates they opted to use both QFT-GIT and TST in immunocompromised patients.

In immunocompromised patients, the QFT-IT may be more sensitive than the TST for detection of LTBI, but it resulted in a considerable proportion of indeterminate results. Therefore, both tests may maximise the efficacy of screening for LTBI in immunocompromised patients.

The problem here is understanding anergy, or lack of reaction. A state of anergy is indicative of an immune system that is unable to mount a normal immune response against a specific antigen.

Immunocomprised patients are, by definition, in a state of anergy. Traditionally the recommended test for anergy was by the skin test and this was how the CDC once saw it

persons with HIV infection should be evaluated for DTH anergy in conjunction with PPD testing..
..Companion testing with two DTH skin-test antigens (i.e., Candida, mumps, or tetanus toxoid), to which most healthy persons in the population would be sensitized, is recommended.

Subsequent data, like this, convinced the CDC to revisit anergy testing and conclude

the use of anergy testing in conjunction with PPD testing is no longer recommended routinely for screening programs for M. tuberculosis infection conducted among HIV-infected persons in the United States.

It doesnt take to much imagination to see that the TB skin test must also be inappropriate for testing immune compromised individuals. By including a "no antigen" tube in the assay QuantiFERON allows the examiner to find a low response result as being indeterminate. A large number of indeterminates could indicate a procedural fault

We implemented the QuantiFERON-TB Gold (QFT-G) In-Tube test to identify latent tuberculosis infection among potential employees prior to employment. The rates of indeterminate QFT-G In-Tube test results were higher than expected and prompted an investigation that led to successful interventions (eg, manual vortexing before incubation and the use of a modified in-tube method). The tracking of indeterminate results is suggested as an important quality control measure.

If the lab procedure is correct the only conclusion left is that the indeterminate was due to the anergy of the patient.

A low response result with TST could mean no TB or a lowered immune system. Without any way of testing anergy TST is of little use in an immune compromised population however, the appearance of indeterminate QuantiFERON results seems to have rattled examiners sufficiently for them to hang on to the TST.

More on costs

Roland Diel looks at the costs of using Quantiferon or TST or Quantiferon as a confirmatory test for TST results and includes treatment over a 2 year period;

IPT on the basis of using the QFT assay alone produces less cost and reduces more TB cases than other strategies in a low-incidence setting

Columbia - predictive value of CFP-10

A study into 2060 household contacts (HHCs) in Colombia using TST, IGRA and culture;

The main goal of our study was to establish the value of IFNy responses to CFP-10 as prognostic marker of tuberculosis disease development...

Herein we present evidence that levels of IFNy response to CFP-10 assessed shortly after exposure to an infectious source may be predictive of tuberculosis development in a population of HHCs at high risk of infection...

Turkey - Quantiferon in Rheumatoid Arthritis patients

The study can be viewed here and here (or over the fold) and is in this months Journal of Rheumatology; when comparing QFT with TST among patients with rheumatoid arthritis and ankylosing spondylitis researchers concluded that

QTF-G is less susceptible to external factors than TST

Quest Diagnostics ramp up QuantiFERON

This presentation is very new, December 2009 and gets straight to the point;

Tuberculosis in the U.S.

• 10 to 15 million people infected with latent TB
• 12,898 new cases of active TB in 2008
• Targeted screening and treatment
• 18-20 million skin tests/year
• 50% performed in hospitals 
  

TB migrant study - UK

From Leeds; the title says it all;

Cost effectiveness of the NICE guidelines for screening for latent tuberculosis infection: the Quantiferon-TB gold IGRA alone is more cost effective for immigrants from high burden countries.

QuantiFeron and congenital toxoplasmosis

Is there a role for IGRA in determining congenital toxoplasmosis? According to this study there is

...We present a simple test based on IFN-gamma secretion to assess cell-mediated immunity in toxoplasmosis.

...In a cohort of 124 congenitally infected patients aged between 1 and 30 years, the sensitivity of the test was 100%.

So is congenital toxoplasmosis an issue? Apparently so, its one of those nasty infections that rear it's head once you not 100%

Up to one third of the world's human population is estimated to carry a Toxoplasma infection.[3] The Centers for Disease Control and Prevention notes that overall seroprevalence in the United States as determined with specimens collected by the National Health and Nutritional Examination Survey (NHANES) between 1999 and 2004 was found to be 10.8%, with seroprevalence among women of childbearing age (15 to 44 years) of 11%.[4]

During the first few weeks, the infection typically causes a mild flu-like illness or no illness. After the first few weeks of infection have passed, the parasite rarely causes any symptoms in otherwise healthy adults. However, people with a weakened immune system, such as those infected with advanced HIV disease or those who are pregnant, may become seriously ill, and it can occasionally be fatal. The parasite can cause encephalitis (inflammation of the brain) and neurologic diseases and can affect the heart, liver, and eyes (chorioretinitis).

Peer to peer marketing

The Berkshire study is now showing up on Medscape. And so it should, it presents such a ringing endorsement of QuantiFERON.

our results suggest that QFT-GIT has a superior specificity over TST and can be the test of choice

Deloitte - Technology Fast 50 - Australia 2009

For a fifth year Cellestis gets a guernsey from Deloitte ;

Soar to new heights

IGRA study - UK

It would seem that the peak medical body in England and Wales, the Health Protection Agency (HPA), are getting serious about IGRA

We are looking for a Scientific Co-ordinator to manage a large study on Interferon Gamma Release Assays in the UK. You work closely with principal investigators at study sites, study nurses, laboratory staff and the trial coordinating committee.

French HCW study

Same study as here but now online here (and below)

Interesting that the use of QuantiFERON showed up a fault in the national guidelines

our data suggest that the French guidelines for the interpretation of TST in exposed HCWs should be reconsidered.

and that QuantiFERON in France was cost effective

our analysis corroborates the findings of other cost-benefit analyses.

Parallel universes collide

In a presentation made at the 2nd Global Symposium on IGRAs  Professor Tony Catanzaro said that

 The science tells us QFT should be more predictive

and then supplied the evidence supporting the science. After reviewing the evidence he then asks the audience to

tell me in what area are there solid data, information supportable by facts (as distinct by tradition) to support the preferential use of the TST application?

In his closing remarks Dr Lee Reichman referenced comments made on the traditional skin test*

“ I am constantly astounded by the faith that clinicians have in this procedure…
…Under the best of circumstances these tests are worthless, and under the worst of circumstances they’re delusional.”

RE Chaisson, Clinical Infectious Diseases, 1996; 22:668

Parallels can be made with the current debate on climate change; whilst the evidence from scientific bodies such as NASA, CSIRO, Bureau of Meterology and the American Academy of Scientists (amongst many others) is compelling and irrefutable there are those that continue to deny both the science and the evidence.

Senator Nick Minchin is on record denying that there is any link between the activities of man and climate change. After reading Senator Minchin's letter on the subject former CSIRO climate scientist, and now head of a new sustainability institute at Monash University, Graeme Pearman said

"I am worried that a federal minister would believe this crap."

Senator Minchin is also on record as denying the science linking tobacco smoke with addiction and cancer;

Senator Minchin wishes to record his dissent from the Committee’s statements that it believes cigarettes are addictive (1.25) and that passive smoking causes a number of adverse health effects for non-smokers

Senator Minchin was unable to provide any credible evidence and his points were dismissed.

It is of concern when politicians are peddle junk science as truth for political gain.

*Update: this remark was made for anergy testing using the skin test

HCW study - Portugal

Therefore IGRA should be introduced into TB screening programmes

HCW study - France

Clear and to the point - dump the skin test

Our data show that the increase criteria (increase >10 mm) for TST interpretation lead to a low sensitivity of the TST without reducing the specificity problems of the TST in a meaningful way.

Therefore the use of the increase criteria should be reconsidered.

Furthermore it could be shown that a two-step strategy – IGRA if TST ≥10 mm – might also lead to a low sensitivity of a TB screening. Therefore our data suggest that IGRA should replace TST when screening HCWs for tuberculosis.

Full study here