Choosing substance over conjecture.

University of Miami Health Lab tells it as it is, not how it might be;

Tuberculosis / QuantiFERONGold

This test due to its accuracy has become the best alternative to test your patients, employees and the health professionals. The QuantiFERON ® Gold test doesn't require double testing, x rays or medical visits to diagnose a sick person. In South Florida the percentage of false positives is so high because the influence of immigrants from countries where the tuberculosis vaccination is a common practice. The QuantiFERON ® test's results are not affected by people that have been vaccinated who usually show positive results under other tests.

The Miami lab is not exactly a backyard operation;

The Immune Monitoring Laboratory is one of the most advanced laboratories in the USA. The IML was created to support the transplant program and other specialized patient population, employing over 100 highly-qualified employees that use more than 40 computerized laboratory instruments and apply the most sophisticated analysis techniques to perform well above a million analyses annually.

This meta no better than the latter.

Another study, this one titled The Utility of an Interferon Gamma Release Assay for Diagnosis of Latent Tuberculosis Infection and Disease in Children: A Systematic Review and Meta-analysis. concludes

Sensitivity of the IGRA for TB disease was no different from TST, and a significantly reduced IGRA sensitivity was found in high-burden TB settings compared with low-burden TB settings. Further studies are needed to determine the value of IGRAs in LTBI and TB disease diagnosis in children.

Dearie me, these characters have concluded that there is evidence that IGRA and TST are comparable with active TB whilst there is no evidence to suggest that IGRA is better than the TST in latent TB. For some reason they felt that IGRA should be used for disease when it's described function is that it accurately identifies people infected with Mycobacterium tuberculosis.

Is it worth reading the whole study? Probably not as they seek refuge behind the old caveat there is no gold standard for latent TB

Healthcare in China - anti corruption efforts intensify.

Lawyers Sidley Austin LLP warn

In 2010,we witnessed an increasing number of enforcement actions taken by the local Administrations for Industry and Commerce ("AIC") in China against sales and promotional activities undertaken by healthcare companies, alleging commercial bribery. The enforcement actions were taken by AICs in many cities across China, and many targeted multinational companies.

These recent AIC initiatives have focused on companies' interactions with healthcare professionals, especially on speaking engagements, sponsorships for participation in scientific and educational activities, and direct or indirect donations to healthcare institutions. Although these activities may have genuine scientific or educational purposes and were approved internally according to companies' compliance policies and the local industry code of conduct, the AICs in some cases view them quite differently. Thus, Foreign Corrupt Practices Act ("FCPA") policies alone will not exempt companies from local enforcement exposure.

In 2011, there is no sign that the AICs will decrease these enforcement efforts. On the contrary, enforcement actions may become increasingly intensive and aggressive because the AICs are obtaining more knowledge about the business models adopted by the multinational companies for the Chinese market.

The Chinese Government is amending the Law for Anti-Unfair Competition, the legal basis for the AIC enforcement against commercial bribery. If the amended law does not provide sufficient clarification on key substantive and procedural issues,AICs may have even greater power and discretion in the future.

In response to this situation, companies should carefully review their sales and promotional activities in light of China standards. Employees should be trained on AIC standards. More importantly, industry should continue to help the AICs and the Chinese legislative bodies to understand legitimate scientific and business activities which are otherwise being disrupted by AIC enforcement efforts.

QuantiFERON in Georgia - it's on my mind.

QFT use in a Georgia setting...March 2011

They ask the right question and get all the right answers.

 

Lawn in Lancet - the gold standard diagnostic for latent TB is IGRA

Link

For the past century, the tuberculin skin test has been the only screen available for the diagnosis of latent infection with tuberculosis. Its major failing is its inability to reliably distinguish individuals infected with M tuberculosis from individuals sensitised to other mycobacteria, including BCG. A decade ago the interferon-γ release assays (IGRAs) were developed whereby interferon-γ titres were measured after in-vitro stimulation of peripheral blood mono - nuclear cells with antigens such as ESAT-6 and CFP-10 (immunodominant antigens expressed by members of the M tuberculosis complex).  These have now become the gold standard for identifying individuals whose immune system has previously encountered M tuberculosis.

It would appear that the authors are well qualified, Stephen D. Lawn's profile is here and Alimuddin I Zumla's profile here.

How miners mined what was once mine.

One year too late - how big companies can and do bend democratically elected governments to their corporate will.

Tony Abbott: The government had clobbered Australia's most successful industry with a proposal for the world's highest taxes. And even before Labor's mining tax has been implemented, it's already done massive damage. In just one year, Australia has plunged 13 places in the world rankings as a safe place to do business in mining.

We now rank, this is Australia, we now rank behind Argentina, Tanzania, Zambia, Ghana, Namibia and Botswana as a safe place to invest in mining, thanks to the actions of this government, and this from a government which claims to be a good economic manager.

Stan Correy: The Opposition leader was quoting a survey of the safest places for mining companies to invest globally. Incidentally, that survey is conducted by a Canadian think tank that is funded heavily by the Canadian mining industry.

Tony Abbott used the same information several times during media interviews in the election week last year...

.

Tuberculosis cases drop to record low in San Francisco

Link

IGRA has been of assistance;

Many public health offices are now using blood tests, which are much faster at diagnosing tuberculosis and often more accurate than traditional skin tests.

Santa Clara County advise on IGRA and the BCG vaccinated

People who have had the BCG vaccine should get this test.

Link

More on NTM false positives

Full study here

data suggest that most infections with non-tuberculous mycobacteria are acquired in childhood and are not likely to be influenced by adult employment in a health care institution..

..The present dual skin test data show that MAC and other NTM infections are responsible not only for most 5-9 mm PPD reactions but also for a substantial proportion of 10-14 mm PPD reactions in our subjects.

False positives due to nontuberculous mycobacteria (NTM)

Virginia's 2011 World TB Day agenda includes a presentation by Dr Thomas Dobbs from the Mississippi Department of Health. Included was this slide;

World TB Day - QuantiFERON news

Link here

A Tale of Two Cities #II

In the UK they recommend that you consider an IGRA (do they still drink lots of tea in the UK?) whereas in Wake County they have embraced technology by utilising GIS (Geographical Information System), geoprocessing, non traditional testing sites and QuantiFERON.

Why?

It's like opening a door and walking into a new time zone....the 21st Century.

.

For those who lose their way - a BCG Atlas

Link

"Let's say I'm looking at somebody who has come from the Philippines, Ukraine or Japan, and they don't remember how many shots of BCG they got, or when they got the BCG. I can easily look up the country policy and say 'OK, in all likelihood this person got the vaccine too many times.' Therefore I probably shouldn't rely too much on the skin test and I could ask for a blood test, which is unaffected by BCG," Pai said.

So says Dr. Madhukar Pai, a co-author of the BCG World Atlas. They produced a study paper on their work and they have a website where you can check out your BCG status.

Looking at the map..apart from the USA it appears that everybody has been BCG vaccinated. To test the veracity of their claims I clicked on Australia

Which year was vaccination introduced?    1950s
Year BCG stopped?    mid 1980s

That didnt make sense as that was the period during which I was growing up and I had never heard of BCG. So I did some digging around and guess what..

In Australia, the broad-based BCG vaccination program originated at a time when the epidemiological circumstances of tuberculosis (TB) were quite different. Initially in 1948, vaccination targeted health workers, Aboriginal people and close contacts of active cases, especially children. In the 1950s the program was expanded to include all Australian school children except those from New South Wales and the Australian Capital Territory . This policy was discontinued in the mid-1980s (1991 in the Northern Territory) in favour of a more selective approach. The change occurred because of the low prevalence of TB in our community and concerns about the balance between the benefits and the risks.

So even in Australia there is a large group who have been BCG vaccinated...probably forgot about it..come to think of it we were always getting jabs for this and that.

We should all be using IGRA.

Updated NICE guidlines for the diagnosis and management of TB

Link

Moving at a snail's pace;

2006:

To diagnose latent TB:
those with positive results (or in whom Mantoux testing may be less reliable) should then be considered for interferon-gamma immunological testing, if available.

2011:

To diagnose latent TB:
Consider interferon-gamma testing for people whose Mantoux testing shows positive results, or in people for whom Mantoux testing may be less reliable, for example BCG-vaccinated people.

TB control in the UK - mostly uncooperative and generally non compliant.

Darent Valley Hospital, Dartford sent out a survey Investigation of Latent TB to 156 departments - and 39% responded. Of those that responded 75% said that they had full access to IGRA yet only 58% used to IGRA to confirm a positive TST - as recommended by NICE.

They really are falling behind with their TB control.

A survey carried out in the UK explored the use of IGRAs for the diagnosis of LTBI in HIV-positive patients [19]; they were not systematically performed in all departments, not being performed in 22% of the participating clinical departments and only sometimes being performed in 8% of them. The majority of the surveyed centers (63%) use these novel diagnostic techniques, although their application in this cohort of immunocompromised individuals is not totally supported in the present national NICE guidelines. Contrary to expectations and to NICE guidance, when Patel et al. analyzed their overall use in the general population, it was found that the majority of the clinical settings do not (42%) or do with limitation (12%) utilize IGRAs in TST-positive subjects.

Link

Europe should commemorate World TB Day in NYC

When it comes to the proper application of IGRA NYC TB Control and UMDNJ can demonstrate that wisdom comes from experience.

Australian Central Bank looks ahead.

Link

Looking ahead, our job is to try to manage the terms of trade and investment booms. Historically, Australia has often not managed periods of prosperity conferred on us by global trends terribly well. On this occasion, we have to do better. We have to take the opportunity to capitalise effectively on some very powerful trends in the global economy to which we are, almost uniquely, positively exposed. 

A few things are working in our favour. One is that the exchange rate is playing a role of helping the economy to adjust to the change in the terms of trade in a way that it was prevented from doing on numerous previous occasions. Another is that, at least so far, households are behaving with a degree of caution, insofar as spending and borrowing are concerned, that we have not seen for a long time. Having taken on quite a degree of debt over the preceding 15 years or so, households have thought better of taking on too much more. They are saving more than at any time for 20 years or more. So are households in many other countries, of course, but our good fortune is to be making that adjustment against a backdrop of rising income.
 
We are now engaged in a national discussion about how to stretch the benefits of the resources boom over a long period, and how to manage the risks that it will bring. These are complex matters that involve a wide range of policy areas – macroeconomic, microeconomic, taxation, industrial and so on. But if that discussion can be conducted in a mature fashion, and followed up with sensible policies, then we have a good chance of leaving to the next generation a wealthier, more secure and more stable Australian economy.

Cellestis' state their commitment to TB Control.

From the Cellestis 2010 AGM presentation

Commitment to the treatment of Latent TB as a means to control tuberculosis worldwide

– That effective vaccines remain elusive
– That despite the best intentions, all current TB control practices in high burden areas are proving insufficient
– That QFT identifies infected persons at risk of developing active TB
– That the mindset of current TB control contains falsehoods and needs to alter

“Cellestis is committed to promoting detection and treatment of latent TB –wherever in the world it occurs -to reduce active TB rates more effectively, more immediately, and more practically than any other means”

TB control - a tale of two cities.

TB control can be roughly divided into two camps - those that only diagnose and treat active TB and those that diagnose and treat both active and latent TB. For instance, the UK Action Plan incorporates the following aims

- reduce the risk of people being newly infected with TB
- provide high quality treatment and care for all people with TB
- maintain low levels of drug resistance, particularly MDR-TB.

Indeed, the UK toolkit primarily concerns itself with the threat to the public once the infection becomes active. Nothing much was said about reducing the pool of infection, latent TB. Compare this policy with that of the USA

An estimated 9.6--14.9 million persons residing in the United States have LTBI (39). This pool of persons with latent infection is continually supplemented by immigration from areas of the world with a high incidence of TB and by ongoing person-to-person transmission among certain populations at high risk. For TB disease to be prevented among persons with LTBI, those at highest risk must be identified and receive curative treatment (4). Progress toward the elimination of TB in the United States requires the development of new cost-effective strategies for targeted testing and treatment of persons with LTBI

Consider two similar cities, NYC and London. Whilst the TB rate in NYC is 9.1 per 100,000 people they say they can do better

“New York City has long been a model for the rest of the world in TB control,” he said. “But there is more to be done, and we can’t do it alone. We must continue to work with our partners to prevent the spread of disease and to ensure that TB patients receive proper care.”

On the other hand Lancet has cited London as being at the centre of the resurgence of the "white plague"

In the UK there were over 14.6 cases of TB reported per 100,000 population in 2009; it is the only European country in which incidence rates continue to rise.  In London TB has returned ‘in force’ with 3450 cases diagnosed in 2009 (almost 40% of all UK cases), compared to 2309 in 1999.  This is likely to be an underestimate as sputum microscopy and culture only detects up to 70% of active cases.  Drug-resistant TB is also becoming a problem in the capital, with 172 isoniazid-resistant cases and a further 58 multi-drug resistant cases reported in 2009.

Risk and the consumer's response.

The global financial crisis, extreme weather and geological events, political instability and now a nuclear failure - catastrophic events are having an impact on the Australian consumer's appetite for risk;

HT Christopher Joye

Let's party like its...whenever.

When it comes to radiation conservative commentators are spinning like tops on steroids. As soon as Ann Coulter gives the word

radiation is good for you.

our Andrew (screw loose) Bolt slavishly recycles the tosh saying

the low levels of radiation emitted by the Fukushima reactor may even be good for the Japanese

Please Andrew, do everyone a favour and hop on a plane and go to Fukushima, it may even be good for everybody.

Europe - ad hoc TB control

Upon reflection the ECDC guidelines for IGRA raise more questions than it answers. As a backgrounder, the European Centre for Disease Prevention and Control (ECDC) is an organisation that was set up in response to the SARS outbreak in 2003

ECDC was set up in record time for an EU agency: the European Commission presented draft legislation in July 2003, by the spring of 2004 ECDC’s Founding Regulation had been passed and by the spring of 2005 the Centre started operating.

So by any measure it is a fairly new outfit. This newness is reflected in the statement that

ECDC originally developed the document as an FAQ list (frequently asked questions) and then presented to an ad hoc scientific panel of experts.

Ad hoc? My understanding of ad hoc is improvised or impromptu and the specific usage in this document indicates that the panel was created specifically to deal with this issue. In other words, this is their very first time on the job.

In forming an opinion this ad hoc panel relied on

The bulk of the evidence presented in this guidance document is based on two systematic reviews and metaanalyses assessing the role of IGRAs in the diagnosis of active TB and LTBI, conducted by the TB Network European trials group (TBNET) for and under the supervision of ECDC1-2.

The 1 refers to the Sester meta analysis Interferon-γ release assays in the diagnosis of active tuberculosis and the 2 is the Diel meta analysis Interferon-γ release assays in thediagnosis of latent M. tuberculosis infection.

The summary of the Sester meta analysis, which was confined specifically to active TB, concludes

Although the diagnostic sensitivities of both IGRAs were higher than that of TST, it was still not high enough to use as a rule out tests for tuberculosis.

The summary of Diel meta analysis summary, which was confined specifically to latent TB, concludes

IGRAs may have a relative advantage over the TST in detecting LTBI and allow the exclusion of M. tuberculosis infection with higher reliability.

Whilst in both instances IGRA were found to be superior to the TST the panel felt that the evidence supplied was not sufficient or compelling to warrant recommending IGRA over TST. However, when it came to BCG they were on safer ground

IGRAs have a clear advantage in diagnosing LTBI in BCG-vaccinated populations, as they are not influenced by BCG vaccination in terms of false-positive reactions. In a BCG-vaccinated population, IGRAs have an added value as part of an overall risk assessment, identifying individuals for whom preventive treatment should be considered.

As TB control in Europe is conducted on an ad hoc basis there should be plenty of scope for IGRA

In 2005, all 25 EU countries, as well as Andorra, Bulgaria, Norway, Romania and Switzerland, participated in a survey on BCG vaccination in children. BCG was recommended nationally for children under 12 months in 12 countries, in older children in five countries and in children at risk (from origin, contact or travel) in 10 countries. Seven countries did not use BCG systematically. Revaccination was practised in four countries. In countries with universal vaccination, BCG coverage was high (83.0% to 99.8%).

Europe CDC guidelines on the use of interferon-gamma release assays.

Link here

Summary This guidance document presents the evidence-based expert opinion of an ad hoc scientific panel on the use of the interferon-gamma release assays (IGRAs) for the diagnosis of latent tuberculosis (TB) infection and active TB. The panel expressed that IGRAs should not replace the existing standard diagnostic methods for the diagnosis of active TB and that a negative IGRA result does not exclude active TB disease. As to the diagnosis of LTBI, the panel expressed that IGRAs may be used in conjunction with an overall risk assessment in order to identify individuals for whom preventive treatment should be considered.

Expert opinion IGRAs have a clear advantage in diagnosing LTBI in BCG-vaccinated populations, as they are not influenced by BCG vaccination in terms of false-positive reactions. In a BCG-vaccinated population, IGRAs have an added value as part of an overall risk assessment, identifying individuals for whom preventive treatment should be considered.

A screw loose

Controversial conservative commentator Andrew Bolt let loose on the media’s nuclear meltdown…

Via our friend Professor Barry Brook, comes this marvellously sane and cool explanation of the emergency at Japan’s the Fukushima nuclear reactor..

Marvelously sane and cool Barry, a devout nuclear advocate, has just had his own meltdown

Newborn babies targetted in TB contact investigation

Not what you want to read about; babies in IC units are just so defenceless;

NEARLY 200 families may have been infected with tuberculosis after a Sydney hospital health worker was diagnosed with the disease.

Liverpool Hospital, in Sydney's southwest, has contacted parents of babies born in its maternity unit or cared for in the Neonatal Intensive Care Unit between December last year and March 6.

Up to 187 children passed through the NICU and nine babies were cared for in the birthing unit in that time, the state health department said yesterday...

TB, risk and HCWs - BMJ guidelines confuse the issue further.

Guidelines here.

UK guidelines currently recommend a two step screening strategy for latent infection in asymptomatic healthcare workers..

Lets just confine ourselves to the NICE costing report;

Tuberculin skin tests = £13.89
Interferon gamma test = £25.67

A two step screening strategy uses 2 x TST (£27.78) plus an IGRA to confirm. In the unlikely event that all TST were negative the two step screening strategy is more expensive that an IGRA only strategy. For every 1% increase to the TST positive rate and additional cost of £0.2567 would be incurred. A study by Pai and Menzies of TB in HCWs in low and middle-income countries found that

the prevalence of LTBI in all HCWs ranged from 33% to 79% in various studies, with a pooled prevalence estimate of 54%

Even a 20% TST positive rate would add another £5.13 bringing the cost of a two-step strategy up to £32.91, £7.24 more than an IGRA only strategy.

The other aspect to consider is the direction

..TST taken to be positive ..if TST is likely to be unreliable...

By stating in guidelines that a positive TST should be confirmed by an IGRA NICE have challenged the reliablity of all TST. In fact from this you could say that all positive TSTs are unreliable.

HCW confusion over TB testing.

Discussion amongst health & occupational safety managers turned to TB; Betty writes

I attended a TB Certification conference yesterday.  American Lung informed the occupational health nurses that every new-hired employees must have a 2-step TB Skin Test, (I agree with this),but you cannot use a  TB Skin Test that was given within the past 12 months for step #1 and then administer a TB Skin Test at post-offer physical (Step #2).  We must have 2 - TB skin tests within the 4 week time frame or we must have their original 2-Step plus all of their TB skin test results since the date of their original 2-step test.    If all of the appropriate documentation is obtained then only 1 TB Skin Test is required.

I am doing more research with American Lung and CDC on this topic and would like the opinions and practice of others on this topic.

Kathleen responds

That's not our practice..

..Our State Dept of Health has stated that "Employees who provide documentation of negative results of a single Mantoux skin test performed within the 12 months preceding the start of employment shall receive only one Mantoux skin test upon hire."  The State also allows a person with a 2 step TST within 12 months of the start of employment to be hired without a TST, and then to have a TST within 12 months of the latest TST, but we did not include that in our policy.

Bruce jumps in

Wow Betty

Not sure who your instructor was,  but it looks like they must really be living in another world (or planet).  This fly's in the face of a lot of scientific information on the booster effect and also the current CDC guidelines. It also does not appear to include the current trend to move to IGRA testing (Quantiferon Gold,  in our case).   Not saying the IGRA does not have it's own issues,  but it is a move in the right direction.  Your class, and the American Lung Association would appear to want to move us backwards.

We do IGRA on all new hires.  We follow up with a medical review (for risk issues) and a chest x-ray for positive IGRA's.  This is then followed by a repeat IGRA in 3 months.

While we still have a number of positive IGRA's;  according to our statistics,  our positives have decreased by about 30 percent.   A large number of our IRGA positive employees have no risk factors and come back negative in follow up testing.  We are also getting our lab to report the results.  Most of the positive IRGA's fall right around the low cut off.

I do need to clarify that we only have 1 to 2 active cases of TB in patients throughout our 50 Clinics around our state, so our risk factor is very low.

Betty then asked

Bruce, What is the cost of a single IGRA test (Quantiferon Gold)

to which Bruce responded

Our lab charges $75 for the test.  When we added in the amount of time it takes to do the PPD and then get the employees back to read it, including time off from patient care for providers, it was less expensive than the Skin test.

If you add in that our positives are down by 30%, and that also relates to that many employees are now not taking medications that would have been put on under the old Skin Testing, the cost is worth it.

Cindy then asks Bruce

In your post you replied that you test all new hires with Quantiferon Gold.   Do you do the same for your annual employee population TB screening as well?  We have been looking at IGRAs too but our Health Department (who we follow their guidelines as a TB contract hospital) really hasn't taken a stand on how they wish to handle/treat employees referred to them with the added information.  We still perform TB skin screening but if there is any inkling of suspicion of a positive test with the skin screening or in discussion wtih the employee we draw a Quantiferon for clarification.  If it is positive we proceed (depending upon their history) per our protocol,  chest xray and referral to Health Department for evaluation.  Unfortunately, the health department has said "it (skin testing) has done well as a screening tool for us for many years, what reason do we have to change and support added cost".   

I am tossing the idea around of performing a Quantiferon on ALL new hires eliminating 2 step testing.

to which Bruce responds

Because of our very low risk status (following the CDC guidelines), none of our facilities require annual testing.  Your state may have stricter rules for Health Care, but ours allows us to follow the CDC guidelines.  Most hospitals/Clinics in the State of WI fall into low or very low risk and really do not need to do annual testing under the CDC guidelines.

Right now, the only employees we do annually are lab personnel who may be working with TB cultures or personnel that have privileges at hospitals that still require annual testing.

We found that in reducing our annual testing to only those employees who have a documented risk, we are able to keep our testing costs down and focus more effort on really following up on the few exposures we have.

There is still some issues with the IGRA as to doing follow up on positives.  In our case, we do a chest x-ray and if the person has not risk factors and a negative CXR, we repeat the IGRA in 3 months.  If this comes back positive, our providers normally will put the person on INH and treat as a latent TB.

............

One of the primary reasons I would respond on the use of the IGRA is that we do have a lower positive rate.  This seems to be a debated issue, depending on the amount of TB,  but in the US,  it does appear to be holding up that IGRA has less positive tests.   For a health department,  this would result in less persons being put on medications for latent TB.  That would equate in a lot less risk for the people taking the medications AND a lot less work for the public health personnel.  If you add in the cost of the time spent following up with TST and the follow up needed if you do put a person on medications, the cost is really less.

Betty then said that

We test every employee that has patient contact in one way or another. This includes Nursing,  Food and Nutrition,  Environmental Services,  Radiology Services,  Laboratory Services,  Cardiology,  Surgical Services,  Ambulatory Care Centers,  Urgent Care Centers and,  Volunteers,  Social Work,  Infection Prevention,  Security,  Medical Staff,  Admitting,  Rehabilitation,  Pharmacy Services,  Plant Operations, and Spiritual Care to name a few.

re conversions and progression the question was asked

Just curious, but of those that do annual testing.  Has annual testing found cases of active TB or any significant amount of conversions?

"Yes" and "yes" were the answers from California and from New Jersey came this response

We see about 6-10 employees per year with newly diagnosed LTBI.  In the last 2 years, we had 1 resident physician and 1 medical student with active TB disease working in our hospital.  The resident was TST pos, QFT-G pos, h/o BCG, had a negative symptom survey and refused Rx when dx LTBI about 1/2 year before hospitalization and diagnosis with TB disease.  If taxes get lower in Wisconsin than NJ, perhaps some of our employees with LTBI who refuse Rx may want to transfer.  Good luck.

For want of a halfpenny of tar, the ship was lost.

Those engaged in what some have called a nuclear renaissance should understand the risks attendant to nuclear power generation; the known knowns, the known unknowns and the unknown unknowns;

"Reactor analysts like to categorize potential reactor accidents into groups," said Bergeron, who did research on nuclear reactor accident simulation at Sandia National Laboratories in New Mexico. "And the type of accident that is occurring in Japan is known as a station blackout. It means loss of off-site AC power—power lines are down—and then a subsequent failure of emergency power on-site—the diesel generators. It is considered to be extremely unlikely, but the station blackout has been one of the great concerns for decades.

"The probability of this occurring is hard to calculate, primarily because of the possibility of what are called common-cause accidents, where the loss of off-site power and of on-site power are caused by the same thing. In this case it was the earthquake and tsunami. So we're in uncharted territory, we're in a land where probability says we shouldn't be. And we're hoping that all of the barriers to release of radioactivity will not fail."

Northwestern Uni demands a QuantiFERON for foreign students.

Northwestern University make their entry requirements quite clear

A QuantiFERON-TB GOLD blood test will be required upon your arrival to Northwestern University.  You may not participate in clinical activities until this has been completed.  Results of the test are usually received within 72 hours but may take longer.  This test is free of charge only if you have purchased the NU insurance AND the test is performed at NU. If further testing is required, you are responsible for all other health care costs. Insurance will not cover these costs.

Earthquake aftershock.

From Reuters;

Shaken by the prospect of nuclear meltdown after a devastating earthquake and tsunami, Japanese investors will dump overseas assets on Monday and bring their money home to help finance reconstruction.

Positioning for this could send the dollar plummeting versus the yen on Monday and lead to a sharp slide in Treasuries since U.S. government bonds are a favorite asset of Japanese investors, market analysts said.

Stocks also are likely to come under pressure.

Japanese insurers will probably sell some of their most liquid foreign assets such as U.S. Treasuries so they can respond to the worst disaster since World War Two.

The crisis could lead to insured losses of nearly $35 billion, risk modeling company AIR Worldwide said, making it one of the most expensive disasters in history and nearly as much as the entire worldwide catastrophe loss for the global insurance industry.

Traders braced for just such an outcome on Friday, when the yen surged and Treasuries fell. The Bank of Japan probably will add money to the system to limit the liquidation of assets. But the big question remains of how much follow-through selling is yet to come.

Dan Fuss, the vice chairman of $150 billion Loomis Sayles, told Reuters on Sunday that his best guess is that Treasuries will continue to see losses.

Because Japan is the second-biggest holder of U.S. government debt and they have nearly $900 billion in dollar reserves, Fuss said Japan will likely use reserves for rebuilding.

"A big buyer of bonds is taken out of the market," Fuss said, adding that Japan "will be less able to add to their reserves and less able to buy Treasuries.".....

This medicine is making me sick.

More chat about taking isoniazid for 6 months...roll on the short course therapy...and QFT..

I have latent TB and decided to take the meds as I have niece with leukemia and has recently had a transplant. I did not want to inadvertently infect her so I have been taking this for almost 6 months. After experiencing fatigue and itching when taking every night, my doc had me take it every other night. That helped the fatigue and the itching went away after a few weeks. The one thing that I found out from my pharmacist is to avoid pineapple and raisins. they contain a certain ingredient that counter-acts the meds. Also to avoid ibuprofens and tylenol to reduce the risk of liver problems..

..my doctor told me i had to take this medicine for 6 months..i took it for one month, every nite right before bedtime i'd take one pill, about 2/3hrs. later i'm up with severe stomach cramps..i also noticed at times when reading or watching t.v. my eyes would get watery and couldn't see very clear..after 30days, i asked my doctor to see if there was any way he could lower the dosage or an alternative other than this pill/medicine, he told me no. great! i told him then i have no choice but to stop this medicine 30days of severe stomach cramps every night like clock work was enough for me! it was killing me slowly! i don't like the idea that i have this tb/inactive..but there has to be another form of medicine, i've read up on this recently and i can't believe all the side effects it has, i also recently had blood work done and my doctor tells me that my white blood count is 13 when it should be 10..hello...from what i read this medicine can do that i'm so confused, i felt so much better before getting on this medicine and now other things can be happening to my body, who knows if my doctor knows what he's doing! i just want to know if there is another form of medicine with much much less side effects than this one.

..after taking this medication for 9 mos. i've developed an allergy or sensitivity to sun! I immediately breakout in sun-blisters after 5 minutes of exposure to the sunlight.

..I have been taking Isoniazid for two weeks now. My joints are painful and I am worried about lupus, it is one of the side effects of this drug. My sister has lupus now that she got from one of her heart medications. I am going to press my Dr for a QuantiFERON-TB Gold blood test before I will continue with this treatment. My sister has undergone two hip replacements and is always off of work because of the lupus. I had the BCG vaccine as a child and am wondering if that is the cause of my positive skin test. My chest xray is clear.

..I am having some of these side effects and will call my doctor today. Thanks for your info. I thought I was going crazy.

..It makes me feel like crap after I take it. I get blured vision that come with headaches.

..I have been on meds for 7 months complained from month one about numbness in hands and was told that unless they are numb all the time it's something else....huh? I don't want to wait that long. I also feel tired all the time but since I have two children I was told that I'm just overworked. Really was not given option on meds. I hate having to check in at the dept of health like a criminal monthly. This whole thing sucks.

..so i have been on this drug for a week and i was told to look out for nerve related problems. After two days i felt a wierd pain in my foot by my toes. I thought nothing of it, and thought i stepped on it wrong. Now on the seventh day the pain has increases and is severe. I have read the reviews and no one has commented on the nerve damage possibility, which if it occurs, i was told it could be permanent.

US Air Force Academy, Colorado.

As of March 2011 this appears to be their admissions criteria

An untreated positive tuberculosis skin test with a positive Quantiferon-Gold test is disqualifying.

More on the military bureaucracy.

This from Army in Europe, Heidelberg, regarding CYSS employees (child, youth and school services). It would appear that the current standard Army procedure is TST followed by QFT if the TST is positive. However, for outside employees a QFT is acceptable in lieu of the TST as from 20 January 2011*

*This regulation supersedes AE Regulation 608-10-1, 15 May 2009.

Update 1: It appears that for the redeployment of US Army personnel QFT only is required

• Requirements

– Completed in theater at RAA
– DD Form 2796
– Blood Sample x 2

• HIV/Post-deployment
• QuantiFERON-TB

 but there is every possibility that a countermanding ruling or order or direction has been made.

Update 11: as previously forecast, a ruling from the DoD serves to further muddy the water;

April 28, 2010

Subject: Medical Standards for Appointment, Enlistment, or Induction in the Military Services

Current or history of untreated latent tuberculosis (positive Purified Protein Derivative with negative chest X-ray) (795.5). Individuals with a tuberculin reaction in accordance with ATS and United States Public Health Service (USPHS) guidelines are eligible for enlistment, induction, and appointment, provided they have received chemoprophylaxis in accordance with ATS and USPHS guidelines. A negative QuantiFERON®-TB Gold (QFT®-G) with a positive tuberculin skin test DOES meet the standard.

So what does the United States Public Health Service have to say on the matter? This is an extract from their Standards For The Basic Level Of Readiness

Two negative tuberculin skin test (TST) results no greater than 12 months apart or a single negative interferon-gamma release assay (IGRA) test (e.g., QuantiFERON – TB Gold Test) result is sufficient evidence of the absence of infection with Mycobacterium tuberculosis (TB) and no additional annual TB screening is required.

In the absence of two negative TSTs within 12 months, the officer must continue annual TST screening until this requirement is met or obtain a single IGRA result.

These standards were altered to comply with an Order of the Assistant Secretary for Health which (in part) said that;

An IGRA test is a blood test method now available as an optional screening test and may be used in place of the TST.

So snap to it!

US military switches to QuantiFERON

From Bamberg, a notice that BMEDDAC has adopted CDC recommendations and will be using QuantiFERON. BMEDDAC covers the US Army installations in Bavaria.

BMEDDAC provides the command and control for an ambulatory network of seven primary care health clinics throughout Bavaria that, combined, support over 40,000 Soldiers and Family Members in the Bamberg, Grafenwoehr, Hohenfels, Illesheim, Katterbach, Schweinfurt, and Vilseck communities.

TB skin test, like seriously way too much hard work

San Jose State University School of Nursing has the following immunisation requirements;

A The quantiferon test is done annually to detect exposure to TB.

OR Most agencies still accept the PPD:

B. 1. Initially, a two-step PPD must be done on entry to The Valley Foundation School of Nursing (see clinical documentation form information sheet).

2. Then, if negative, done every year.

3. Those with BCG vaccine or positive Mantoux test, need chest X-ray, one time only, and annual TB symptom review; follow-up as warranted by Dr.

And then, just to make it that little bit harder

TB skin tests are no longer done at Student Health as the Quantiferon blood test is supposedly more accurate. Some agencies still require the 2 step PPD but not many…

Difficulties in understanding let alone implementing TB law.

According to the following article, whilst having amended their existing laws in 2010 Dubai Health authorities are still requiring a TB Xray for visa applicants.

Dr Hassan Shurie, consultant and head of technical services at the DHA's medical fitness department, said: "We have effectively implemented the new law since November 2010.

"As per Law No 28 of 2010, TB testing is a part of the medical fitness requirement for those people who are getting their work permit or residency visa for the first time. This no longer applies for renewal of visas," he said.

It would appear that the law is open to interpretation and negotiation

Dr Mariam al Mulla, the regional officer for communicable diseases at Haad, said all new residents in Abu Dhabi, as well as those renewing their visas, must follow the emirate's visa screening standards, as set down by Haad (Health Authority-Abu Dhabi), to receive their medical fitness certificate.

Apparently other parts of the country have abandoned such tests, in accordance with the same law. After spending some time looking at UAE websites I can see why the situation remains unclear.

Fortunately a private site, Dubai FAQ was more helpful about health requirements for foreign workers to Dubai;

Tuberculosis (TB): New resident expatriates will be tested for tuberculosis (TB), and denied a residence visa and deported if results are positive. TB sufferers are treated first before deportation at the Muhaisnah Medical Center in Dubai. If treatment takes longer than 2 months, they are transferred to Rashid Hospital infectious diseases ward. Expats renewing resident visas are not tested for TB. Khaleej Times reported 09 October 2010 that those with HIV and tuberculosis are deported and can come back to the country only after six months and if completely cured. Doesn't make sense for HIV as that is not curable as far as we know.

After the new 2010 law Dubai FAQ advise

Tuberculosis chest X-ray. If tested positive, person is held in isolation in a detention center for treatment then deported. Deportation still applies for pulmonary TB, but not for extra-pulmonary TB or pneumonia. Apparently. Only new visa applicants tested as of 19 August 2010 news. Visa renewal applicants no longer tested.

Dubai FAQ note confusion had spread to the press

Khaleej Times (KT) reports 12 August 2010 that the Dubai Health Authority (DHA) website no longer includes Tuberculosis and Hepatitis B or C as deportable conditions for foreigners under the medical fitness rules, except for some worker categories.

• KT report says: As per the details published on the website, testing for Hepatitis B and C, highly infectious diseases of the liver and tuberculosis, are no longer part of the medical fitness testing rules that have been compulsory before obtaining a work permit or residency in the country until now. 

• Except when we checked, the DHA website said that a Chest X-ray is still part of the screening process, which we thought was for the test for TB.

and

Updated report in the Gulf News 19 August 2010 (GN quotes in italics):

• Ministry of Health has announced changes in the medical tests for UAE resident expatriates.
• Tubercolosis (TB) only for new visa applications, not renewals, and only for pulmonary TB. Not clear what happens if found positive, previously was deportation after treatment. Presumably that is still the case?

Probably. Possibly. Elsewhere the situation was similarly muddled

The rules governing tuberculosis will also be relaxed under the new amendment. Only patients with “new, old or active pulmonary tuberculosis (TB)” will be refused residency, the law says.

A bit later another report said

A national tuberculosis guideline is being prepared by the UAE health ministry for all government, semi-government and private sectors to become a national reference when dealing with tuberculosis disease, Gulf News has reported.

A good idea!

A can of worms.

An interesting bit of chat on one of those mothering forums - I had not fully understood the fears that some mothers hold regarding vaccinations and in some respects the TST can be regarded as a "vaccination" - it requires an injection of foreign material into the body. When the "body" is only 5 years old and is required to undergo a contact investigation requiring two TST placements Mum becomes a little concerned. Canada TB control are unhelpful but with the internet more information is forthcoming - QuantiFERON. The contact investigation raises more questions, why are kindergarten teachers whose TB results have not been returned still in close contact with young children? Why are teachers who test positive for latent TB allowed to be in close contact with young children?

How infectious is drug resistant TB?

According to this study

Drug-resistant tuberculosis (DR-TB) in adults is either acquired due to poor treatment management or transmitted from infectious DR-TB cases, while children mainly have transmitted disease.

The rates of transmission was confirmed by this study onto the epidemiology of DR-TB in China

The prevalence of MDR-TB was 16.61%, which was significantly different between new cases (7.63%) and those with previous treatment history (33.07%).

which was consistent with other studies

MDR‐TB patients were more likely to have received previous treatment in 22 studies, with a pooled risk estimate 10 times higher for treated than for new patients

As Shao et al note, drug resistance is a public health dilemma presenting challenges of an alarming scale. Studies in China and Russia indicate that the scale of the epidemic to be greater than previously estimated.

Reverse engineering the CDC guidelines on TB testing

I was somewhat amused by this

The results obtained in our study support the view that IGRAs could be a valid alternative to the TST in the study of TB contacts, and while the timing of QFT conversion remains to be established, the test should be carried out 2 months after exposure, either for the first time or as a confirmatory analysis in cases with a positive TST. Some countries have already included these recommendations in their national guidelines (ref CDC)

CDC had included this study in their guidelines - maybe a translation error?

It is worth reading the CDC on the subject

If IGRAs are to be used in contact investigations, negative results obtained prior to 8 weeks after the end of exposure typically should be confirmed by repeat testing 8–10 weeks after the end of exposure. This recommendation is similar to one used for TST, because data on the timing of IGRA conversion after a new infection are not currently available.

The only interesting bit was how the Spanish extended the storage time of QFT samples

Peripheral blood was processed for the IGRA using the QuantiFERON-TB Gold In-Tube assay (QFT) according to the manufacturer’s instructions (Cellestis Ltd, Carnegie, Australia). Samples were frozen and stored at -70°C until analysis, 3 – 4 weeks later.

The Use of Interferon-γ Release Assays for Tuberculosis Screening in International Tr

Clinicians from Belgium have compiled this lengthy analysis on IGRA which bears further study. For instance

More than 500 studies have been published to describe the characteristics of IGRAs as compared to the classical TST. On the one hand, the plethora of studies illustrates the dire need for an alternative diagnostic method for LTBI; on the other hand, it is a sign of the many questions remaining unanswered. This situation is reflected in policy guidelines of reference research bodies that are not in complete agreement and are still evolving

The authors note the quantity of studies and suggest that this illustrates the desire to move on from the TST. This is probably quite true as invariably each study commences with a brief description of the TST including it's known shortcomings. Lets face it, they have over 100 years of data to support the dire need for an alternative diagnostic method for LTBI.

However, they conclude that a lack of certainty with IGRA is influencing guidelines. Lets look briefly at the two major guidelines, the CDC and NICE. The CDC clearly state that their guidelines are based on expert review of the scientific evidence and whilst there existed variations within the data

no major deficiencies have been reported in studies involving various populations

The CDC then advised that IGRA can be used in place of the TST and in certain situations IGRA they are the preferred test. They did look at costs but found that

cost-effectiveness studies are limited by the lack of critical data

In their original guideline NICE said that

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.

and in their update

The Mantoux test has been the preferred test in clinical practice for several years but it is not an ideal reference standard.

So there appears to be agreement between the guidelines. At this point it is worth pointing out that NICE guidelines are primarily concerned with health economics and that their decisions are formed

on the best available evidence of both clinical and cost effectiveness

It is the uncertainty of costs that influences NICE guidelines and it is costs in which there is disagreement. NICE have made assumptions as to costs of testing immigrants, however the evidence from those who actually test migrants suggests that NICE are neither clinically or economically relevant

For immigrants from high risk countries QFT blood testing followed by CXR is feasible for TB screening, cheaper than screening using the NICE guideline and identifies more cases of LTBI. 

Maryland need only look to Kansas TB Control.

Link

View presentation of QFT experience in Kansas.

Maryland looks at implementing QuantiFERON.

The State Public Health Laboratory System of Maryland DHMH looks forward

Fiscal Year 2011-12 Goals

● Implement a pilot program of quantiferon testing to detect latent tuberculosis infections in certain target populations as a lead-in to State-wide testing

Cellestis management not managing their image very well.

Top level management company Egon Zehnder International takes a look at the role of women in Corporate Australia

Some pessimists (or are they realists?) say Australia's corporate culture is currently too toxic for many leading women to speak out. Some argue that gender discrimination is now so deeply embedded in organisational life here that it is virtually indiscernible. Even some women who feel the impact are hard pressed to know what has hit them. Many toxic bosses claim to like women. But they don't really like them as power players. Toxic bosses are often not overtly, outrageously sexist, and they are not even impossible to work for. But they do poison the atmosphere and environment by creating alienating and macho cultures that really aren't much fun for women. Perhaps the most pervasive problem is that a lifetime of social conditioning has trained many men to think of women as wives, daughters, secretaries, and not as equal colleagues. It's hard to completely resocialise people. Hard, but not impossible.

Claire Braund found a good example of a toxic boss in Cellestis

This finding is not surprising given the attitude on display at the 2010 AGM of bio tech company Cellestis, when a male shareholder asked the all male board whether it would be complying with the new guidelines on gender diversity for ASX companies. The Chairman Ronald Pitcher responded along these lines: That they would only appoint women on merit and that women were harder to find because they needed to take time off for biological functions like having children.

So far so good, MVA85A TB vaccine passes the first hurdle.

The MVA85A vaccine, which is designed to be used with BCG

is safe in adolescents and children, and induces polyfunctional CD4+ T cells.

Note that they have yet to test the vaccine in TB infected people.

Twenty six adolescents and 56 children were screened between November 2006 and January 2008. Twelve adolescents and 24 children, none infected with M.tb, were found eligible for vaccination.