Japan - MDR-TB and XDR-TB

This study from Japan examines MDR/XDR TB. 


We are well aware that these resistant strains of TB evolve through the incorrect or incomplete treatment of TB. It would seem then that an obvious approach to reducing the incidence of MDR/XDR TB is to implement better and more complete treatment of "regular" TB. That is clearly true. However, this study postulates and presents data to support the case that more XDR/MDR TB is now being contracted through transmission, rather than by "creation".

In Japan, TB remains a major infectious disease; in 2008, a total of 19.4 cases/100,000 population were reported (6), and Japan is generally classified as a country with intermediate TB incidence. According to the most recent nationwide drug-resistance survey, the prevalence of MDR TB and XDR TB were 1.9% and 0.5%, respectively (7). Approximately one third of MDR and XDR (MDR/XDR) M. tuberculosis strains were isolated from new TB patients, implying ongoing transmission of MDR/XDR TB in Japan.

A high proportion (71%, 12/17) of the XDR strains were involved in clusters ...

... One possible explanation for the high clustering rate of XDR TB is that new cases of XDR TB are more likely to be caused by transmission than by acquisition of multiple drug resistance as a result of treatment failure. Shah et al. reported that patients with XDR TB were more likely than those without XDR TB to be infectious in terms of duration and proportion of sputum smear positivity

The conclusion is inevitable 

Because these findings and our cluster analysis suggest that the current TB control strategy is insufficient to prevent community transmission of MDR/XDR TB, more detailed investigations of MDR/XDR TB transmission based on contact tracing are urgently needed to improve the infection control strategy

Personally, I find this a little alarming. In truth, I accept the possibility of contracting "regular" TB by contact with an infected person and am reasonably relaxed that the treatment is relatively safe and effective. Knowing that I may be infected with MDR/XDR TB just as easily is somewhat worrying. The treatment for these forms of TB is much more severe and (particularly for XDR TB) has a less than perfect success rate, with failure resulting in mortality. 

"Common Wisdom"

One of the topics that has been in my mind to discuss is the many "aphorisms" that are so often quoted in regard to the sharemarket ("no one ever went broke selling at a profit", "buy in May and go away").


Roger Montgomery has beat me to it and has made a bit of a start on discussing this over here. I reckon it's a good read.

Aaaarrrgggghhhhh!!! - Resources Super Profit Tax (RSPT)

A week or so ago I posted about the Resources Super Profit Tax (RSPT). Clearly from the comments received, there are a variety of opinions on this in the community. It's good to discuss these issues.


As part of my post I took the time to very clearly differentiate between the profits made by the mining companies and the salaries paid to the senior employees of these companies. I felt it was an important thing to do because much of the community are not directly involved in business or investing and can easily confuse these two quite different matters. 


Having now seen the "class war" advertisements launched yesterday by the CFMEU (Union), I feel vindicated in carefully make that distinction. These advertisements are using an emotive argument that targets the salaries of the CEOs of the mining companies.


This is totally irrelevant to the discussion of RSPT. It is clearly just an attempt to capitalize on and amplify this misunderstanding that exists in much of our community. The RSPT does nothing, zip, zilch about the salaries paid to mining executives. Those salaries will likely not change one iota under the proposed RSPT regime. It is deceptive and disgusting advertising.


If our Government wanted to target the income of these individuals then they could do so with a "personal super income tax". Personally, I would listen carefully to such a proposal. Of course such a proposal would have to address the incomes of ALL Executives - not just the mining executives.

Thinking about the NBN.

The Australian Government proposes to build a "National Broadband Network" (NBN) providing 100 Mb/s "Fibre to the Home" (FTTH) for something between 90% and 93% of Australians at a cost of $43billion.


I've been thinking about this. Whilst much of the discussion about the NBN has centred around the technology, costs, timing and politics, I think an essential question has been largely overlooked.


Do we need (as opposed to want) the NBN?


Because it would not be palatable to answer this question with the answer that it would enable people to download their pornography faster or play more "World of Warcraft" or live a "Second Life" (I'm too busy with this life to have time for a second one), the answer given is usually:

"Without the NBN, Australian business will be at a competitive disadvantage with the rest of the world"

But, thinking about it, does that statement really stand up to critical scrutiny?


Let's look at it.


I have personally owned and been intimately involved with a number of businesses over the years. Not one of them suffered or is suffering through the lack of an NBN. There are a small number of businesses that probably would benefit (maybe even need) a super fast broadband. One that I can think of is our thriving cartoon industry - they work in conjunction with US studios and need to transfer large volumes of graphic data between Australia and the US on a regular basis. However, they already have super fast broadband. Because it is worth it to them they are quite happy to pay to have fibre optic connections right into their office. The NBN will make no difference to them. 



Ah but I hear you saying (actually I hear the tap tap tap of you typing) "The world is changing. It's an online world and becoming more so day by day. In fact, just today, I heard that Jetstar, in recognition of this, are now allocating 25% of their advertising budget to online advertising. If Australian businesses cannot provide an online presence capable of serving millions of connections a day they will miss out on business. What about all those brave new ideas for online businesses like Facebook, Ebay and the ones that we haven't even thought about yet. Surely they need a high speed internet presence to be able to meet the demands of millions of customers around the world?"

Quite so. However, it simply doesn't work like that. Most companies with such huge reliance upon their online presence simply do not have network servers sitting in the corner of their offices connected to the Internet to meet those demands. What they actually do is rent server space in massive server farms either in Australia, the USA or wherever (often many locations). These server farms have massive bandwidth connections directly into the heart of the Internet. Need more processing power? Rent a bit more. Need more storage? Rent a bit more. Need more bandwidth? Rent a bit more. It makes both technical and commercial sense (that's why they do it that way).

Are there any International businesses that have refused to establish a presence in Australia because they cannot get fast enough Internet? Are there any Overseas companies that refuse to do business with Australian businesses because our Internet is not fast enough? No.



So, business does not need the NBN. Most businesses can operate quite satisfactorily on the currently available 20Mb/s ADSL speeds. For those that need more they can have multiple ADSL connections or if even that does not meet their needs, pay to have a fibre optic or cable connection directly to their business. I am told that there are 1 million premises in Melbourne alone that can have 100Mb/s (ie NBN speed) connections at a cost of around $300 per month. Currently around 200 have taken this up!

Australian business is not suffering and will not suffer because we don't have the NBN.

Now, I'm no luddite. I'm a retired computer geek and I love my Internet (even at the "modest" speed of 3Mb/s that I currently receive). I just think that, in these times, $43bn could be spent on first order needs, rather than something that is nice to have.

A much more modest program of upgrading our backhaul and providing a wider implementation of 20Mb/s ADSL2+ would provide an appreciable increase in Broadband speed for everyone and would not rule out a progression to FTTH at some later time. You may be surprised to discover that of the $43billion that is planned to be spent on NBN, the cost of upgrading the backhaul is only about $4bn. The rest is being spent on running fibre directly into homes. A much more modest program could actually widen the coverage of Broadband - rather than providing faster Broadband to those that already have fast Broadband as the NBN will do.

Over to you.

RSS, email, twitter

You may have noticed that I have added an RSS feed to this blog.


You now have 4 options for being alerted when I make a new blog entry.

• Email alerts (sent at around 5am Aus EST).
• Twitter alerts (sent immediately)
• RSS (sent immediately)
• Just continue to manually check whenever.

Nebraska - Nice Progression.

Rog has previously reported on the gradual implementation of QuantiFERON at the University of Nebraska - Lincoln (UNL).


Now, in their very latest student orientation literature we find this.

No vagueness there!


Congratulations UNL.

Ramsey Correctional TB Outbreak - Legal Outcome.

Many of us have been following the legal fallout from an outbreak of TB at the Ramsey County (USA) Correctional facility in 2008. 


In summary a group of inmates were exposed to an inmate with Active TB and were therefore put at risk of contracting TB. The central claim was that the authorities did not properly test the infected inmate, thus creating the unsafe environment.


Today, we receive news that the case has been settled as a class action with the total cost to the (self insured) County of anything up to $10m.

The settlement would cover inmates who were at the workhouse between April 17, 2008, and June 9, 2008. After the infected inmates came forward, the county sought out people who were there during that time and offered to test them for the disease. About 170 former inmates tested negative, while 93 tested positive for latent infection and seven tested positive for active TB. Nearly 200 more people need to be tested.

Former inmates who have active TB will receive one-time payments of $250,000 and free annual checkups. There's also a process where they could get up to an additional $250,000 if complications arise related to the original diagnosis.
People with latent TB would get one-time cash payments of $54,300 if they show they have completed treatment. Those who don't go through the drug treatment would receive $44,300. Annual checkups would be free. If someone with latent TB develops the active form of the disease, the payment would increase to $200,000.

A further $14m lawsuit by the originally infected inmate remains unresolved, as yet. 


It seems that in the wake of the original outbreak, the authorities were spurred into action.

WHEREAS, The Ramsey County Public Health Department has been doing the testing for both outbreaks for inmates and staff, and it is now necessary to contract with another agency to assist in the testing. Ramsey County Community Corrections intends to contract with an agency to conduct the testing on employees; and

WHEREAS, TB investigations are time sensitive and the next round of testing must take place at the end of June 2009, and there is not enough time to do a formal Request for Proposals process; Now, Therefore, Be It

RESOLVED, The Ramsey County Board of Commissioners approves an Agreement with Multicare Associates, for the period of June 16, 2009 through December 31, 2010, payable at the rate of $16.00 per person per Mantoux test and $82.00 per person per QuantiFERON test with a trip charge of $80.00 per day, in a an amount not to exceed $15,000 per year for 2009 and 2010;

One would have to suspect that many other Counties, Correctional Facilities and, in fact, many other authorities would be paying very close attention to the outcome that has arisen from this situation. The inescapable conclusion is that these facilities have a legal responsibility to screen their employees and inmates for TB in both a timely and effective manner. To not do so opens them up to significant legal outcomes.

A Strong Endorsement for QuantiFERON

With a huge hat tip to "Drrc".

This article by Dr. Abby S. Van Voorhees, Smarter Meds Call for Smarter Screening is well worth reading. Dr. Voorhees is a working practitioner and she makes two points that are of interest to us.

• There are many drug treatments that weaken the immune system, increasing the chances of TB activation. As a matter of course she screens for TB all her patients that are starting most drug courses both before treatment and annually.
• The skin test presents real practical problems and therefore she has moved exclusively to QuantiFERON-TB Gold testing.

It is strong endorsements like these from the very front line that are going to rapidly increase the penetration of QuantiFERON into the TB Screening market.

Trying to Understand the Resources SUPER PROFITS Tax (RSPT).

It seems that everybody (even me) has something to say about the RSPT (Resources Super Profit Tax). However, I'm not sure that many of us (me included) really understand it. So .... I've taken on the task of seeing if I can develop an understanding of the mechanics of it and, more importantly, describe it in simple terms.


In this post I am going to just go to the facts. I'll keep my opinions out of it Furthermore, in this post, I'm not looking at the repercussions of introducing or not introducing this tax.  


I hope that I get it right. I'm sure that if I get something wrong then somebody will let me know in quick order!


Here goes ...

Some Light Relief.

My friend and excellent wordsmith "Arty, aka Pixel" wrote the following and has given me permission to share it with you. I hope you find it as amusing and clever as I did. 


A tip: Read it out loud to somebody, it's even funnier.

"SUPER PROFITS" Tax

Look, I have valiantly tried to keep politics out of this lovely quiet and peaceful little corner of the Internet. However, I now find that I do feel the need to express my opinion about this.


As I have often said. "If you don't have an opinion then you haven't turned your brain on. If you have an opinion and don't express it then you may as well not have had the opinion in the first place - FG 2009"


There are many many issues regarding this matter. I will only address a couple of them here.


Firstly, the name of this tax. Clearly, including the word "SUPER" in the name of the tax is a blatant attempt to somehow implant the idea that this tax in some way relates to SUPERannuation. It doesn't. It's great political spin to create the impression that what this is all about is being "Robin Hood" - taking from those greedy, mean and nasty miners and putting it into your Superannuation Fund. As it happens, only a small fraction of the $10bn or so that the Government hopes to collect from this tax each year will indirectly finance additional superannuation contributions. It's a very tenuous link and is purely a blatant attempt to paint an incorrect picture for political gain only.


As an aside, I personally feel that encouraging people to provide for their future by increasing their superannuation contributions is a good thing. However, doing it as a disguised pay rise is deceptive. Our business economy is fragile and will remain so for some time. Placing the burden of this largely on employers will be counter-productive in the long run. Everybody should be encouraged to provide for their own retirement - however they should not see it as something that somebody else should do for them. We should encourage individual responsibility - we all have to be educated and encouraged to make value decisions about spending our money now or building a nest egg for our future.


Anyway, I digress.


Before I get into the meat, let me make one other observation. The selling of this tax has largely relied upon selling the concept of somebody named "Miner" who is unjustly running away with huge amounts of money for their own benefit. I can say it in no other way than "Codswallop!". I really doubt that "Miner" has accumulated fleets of Ferraris and Luxury Trimarans out there in the desert. (And this is the concept that needs to be understood by everybody), "Miner" does not exist. He/She is not a person. The entities that develop, own and run these mines are Companies. The  vast majority of these companies are listed entities that any of us can own part of, today and thereby share in the wealth (even the Government could do that). I should point out that when thinking about this, it is important not to confuse the mythical person "Miner" with the senior employees of the mining Company - they may well be paid salaries well above what most of us can ever expect to earn. They may even buy Ferraris with their wages. A judgement of their wages has nothing at all to do with this current argument - such a discussion would be much wider and would go well beyond just the mining Companies.


As it happens, I am a small holder of BHP shares. My return (as a dividend) from this investment is about 3% per annum. That is pitiful, of course. I hold the investment because I believe that the profits that are made by the company will be reinvested in the company and ultimately give me increased dividends and perhaps a capital gain. (Ain't looking so great this week!). I am absolutely no different than every other shareholder in BHP - we all get that same return and between us we own every last piece of BHP . None of BHP is owned by the mythical character "Miner". "Miner" gets nothing, zero, zilch.


Okay. So our Government have decided that, as a country, we own the potential wealth that is beneath the dirt and we should therefore charge the mining Companies for exploiting that potential wealth. It is even quite possible to put up a cogent argument for that. Today, I'm not embarking upon that part of the discussion.


My major concern with this whole concept is one that I have not seen expressed elsewhere. It's about what sort of economy and society we the Australian people want.


Allow me to explain.


For all the fiddling around the edges, discussion of exploration rebates etc etc this tax is really a tax based on Return on Equity. Our Government have arbitrarily decided that (for the miners only!) a return on equity of about 6% is reasonable, anything above that is just plain greedy. Others have made the arguments about the quantification and impact of this on investment etc. I am personally concerned about where this takes our wonderful country. This tax based purely on ROE is something totally new. We need to understand exactly what this means. In simple terms it means that the Government is telling us how much profit we are permitted to make on our investment before we are severely penalized. It does not take into account the risk that we take in making the investment and it does not take into account the choices we have made with our hard earned money - whether to buy the latest 3D LCD TV or to invest for the future of our family.


We all know that Governments rarely remove or reduce taxation - if this tax is implemented in this way then it is only a matter of time before it becomes justified by the Government in other investment endeavours.


A society where the Government tells us how well our investments, businesses and endeavours are allowed to reward us? I won't say the word - you know what it is.


Now, you may be happy with this. The majority of Australian people may want us to go along this path - I doubt it but I don't know. All I ask is that we all have the opportunity to understand exactly what this tax means for our society, to express our opinions about it and, most importantly, to vote on it (after all, we are still a democracy last time I checked). I am sick of obfuscation, spin and outright lies. I want the unvarnished truth out there for everybody to understand. I can only hope that in this instance our Parliamentary system will work and the Opposition will take up the challenge of treating the Australian people as thinking adults who can understand what is going on here once it is explained to them.


I owe our Treasurer, Wayne Swann an apology. Last week, when he announced that this taxation change was the biggest change to taxation in living memory, I snorted with derision. Having now thought it through, I realize that he is right - this new taxation method has the potential to totally change our country.


Comments?

Japan Sales Growth.

You probably noticed the following chart in the Cellestis Briefing released today.

You probably also noted that they have not provided us with any y-axis scale. However, it doesn't take too much work to make a pretty good stab at the scale.


We know that total worldwide sales for the Half Year ended December '09 were $18.2m. We were also told that Japan represented 20% of worldwide sales ($3.64m). We can use that number to overlay on the above chart, to turn the current half year figures shown on the chart into $. There is a little difficulty in that the Dec '09 Financial figures that we are working from are sales by Cellestis to the Japan wholesaler whereas these latest figures are end-user sales. However, it's probably not too unreasonable to equate them over an extended period.


It comes out something like this:

Jan 2010 $600,000

Feb 2010 $750,000

Mar 2010 $820,000

Apr 2010 $990,000

That is pretty spectacular growth. Particularly given the special circumstances that we have faced in Japan.


It would be nice to assume a similar growth pattern over subsequent months. However, given that there appears to be a seasonal factor (ref '09 and '08 figures), it is too early to make any real projection. It will be interesting to see how this pans out over the remainder of this Financial Year.


hat-tip to "Tarpot".

The Numbers Are In.

After all the trials, studies and papers, the numbers are in. 


The above results are not from a single trial. They are generated from a meta analysis of all available data. (independently produced by Diel et al, 2010)


For me, after all is said and done, the above table tells the real story about how much more effective the QuantiFERON-TB Gold is for diagnosis of latent TB than any other alternative.


For example, have a look at the first section. Here we are seeing a comparison of the performance of the 3 diagnostics in a population in which 5% of the people actually have TB. That, in truth, is probably the situation in which diagnosis is most commonly used in the developed world. 


The table tells us this for QuantiFERON:

• If you have the QFT test and it comes back as positive, there is an 84.8% probability that you actually do have TB. 
• If you have the QFT test and it comes back as negative, you can be 99.2% sure that you do not have TB.

I would make the comparison with the other diagnostics but I don't want to embarrass them!

Even as you move to higher incidence environments, the QuantiFERON diagnostic has the highest accuracy of all options.

Why are we invested in Cellestis?

Clearly, this is a question that we should ask (regularly) about all of our investments. Cellestis is my largest single share investment and I ask myself this question quite regularly.


I thought, in the interests of encouraging some interactivity here, I would ask if others would like to share their reasons for being invested in Cellestis. You might assume that everybody would give the same answers but I suspect that there may be some variations that will be of interest to all of us. For example, I would think that where each of us is in our jog through life will give us different considerations of how our investment choices should perform over various time frames.


Just to kick the discussion off, here are some of my reasons for being invested in Cellestis. (In no particular order)

1. I can understand the business that Cellestis is in. Essentially they are in the business of exploiting their Intellectual Property (IP) to build a complete business that generates profits. It's easy to understand - they make stuff and then sell it. It may be that the specifics (eg Tuberculosis) require some research but, again, it's not that hard to follow.
2. They have not "sold the farm" in the process of building the company. An awful lot of Australian biotech startups have taken what seems to be a shortcut to success by climbing into bed with big International pharmaceutical companies. In virtually all of these cases, the long time to commercial success has meant that when (if) commercial success is achieved, most of the profits go to the International pharmaceutical company, rather than the shareholders that were attracted to the initial company.
3. They have a financial structure that I can understand. No complex financing arrangements. No part owned subsidiaries. No bonds. No complex derivatives. Their financial statements are as easy to interpret as those of my own little company (was).
4. No borrowings. Borrowings are not necessarily a bad thing (see previous discussion of ROE). However, for a startup biotech, borrowing during the development and early commercialisation phases can be a real weight around the neck. Unlike equity financing, borrowed finance imposes real timewise deadlines. Cellestis has taken much longer to reach the current commercial success than any of us initially thought. Had they had borrowings to service during that time our equity would have been put at severe risk.
5. Trust in Directors. This is probably one of my most important considerations in making and maintaining an investment. Whilst the directors of Cellestis may have made one or two mistakes along the way (in hindsight) they have never, to my knowledge, been dishonest to us, the shareholders. Furthermore, the directors have drawn quite modest salaries through the development phases of the Company. They have been very conservative in their expenditure of our money. This whole Company has been built on around $25m. 
6. A definable market. We know what our market is and we know the potential size of our market. We know who our competition is and we know that the barriers to entry are large (not so much in terms of $ cost but in terms of time to market).

I could continue but I'll leave some for you to add. Hopefully, I can compile and publish a complete list at the end of this exercise.

Over to you.

German Directness.

No messing around here. No playing with skin tests. Just accept that QuantiFERON Gold In-Tube is the Gold Standard.


What is of interest to us here that this is a study to examine the prevalence of LTBI in HCWs, not a study to examine the efficacy of QFT-TB Gold - that is accepted.


Anja SchablonMelanie HarlingRoland DielAlbert Nienhaus


Healthcare workers are still recognised as a high-risk group for latent TB infection (LTBI). Therefore, the screening of people employed in the healthcare sector for active and LTBI is fundamental to infection control programmes in German hospitals.

It was the aim of the study to determine the prevalence and putative risk factors of LTBI.

Methods: We tested 2028 employees in the healthcare sector with the QuantiFERON-Gold In-tube (QFT-IT) test between December 2005 and May 2009, either in the course of contact tracing or in serial testing of TB high-risk groups following German OSH legislation.

Results: A positive IGRA was found in 9.9% of the healthcare workers (HCWs). Nurses and physicians showed similar prevalence rates (9.7% to 9.6%).

Analysed by occupational group, the highest prevalence was found in administration staff and ancillary nursing staff (17.4% and 16.7%). None of the individuals in the trainee group showed a positive IGRA result.

In the different workplaces the observed prevalence was 14.7% in administration, 12.0% in geriatric care, 14.2% in technicians (radiology, laboratory and pathology), 6.5% in admission ward staff and 8.3% in the staff of pulmonary/infectious disease wards. Putative risk factors for LTBI were age (>55 years: OR14.7, 95% CI 5.1-42.1), being foreign-born (OR 1.99, 95% CI 1.4- 2.8), TB in the individual's own history (OR 4.96, 95% CI 1.99-12.3) and previous positive TST results (OR 3.5, 95% CI 2.4-4.98).

We observed no statistically significant association with gender, BCG vaccination, workplace or profession.

Conclusion: The prevalence of LTBI in low-incidence countries depends on age. We found no positive IGRA results among trainees in the healthcare sector.

Incidence studies are needed to assess the infection risk. Pre-employment screening might be helpful in this endeavour.

Author: Anja SchablonMelanie HarlingRoland DielAlbert Nienhaus
Credits/Source: BMC Infectious Diseases 2010, 10:107