thimerosal

US marketing approval precursor to final FDA approval:

CSL has approval to begin marketing its US seasonal flu vaccine ?this step is regarded as a precursor to final FDA approval. CSL has previously indicated that it will only attempt to sell c.2m doses in the USA in the current season. We understand that all 2m doses - both bulk dose and thimerosal free pre-filled syringe have been shipped to the USA in anticipation of final FDA approval within weeks.

US Flu season is well underway - no interest in CSL vaccine so far?

We expect c.132m doses to be made available to the US market in the current season - the actual market may be c.100m. The key is to ship early ?for the current season the 'window of opportunity' will close soon. Notably GSK has only recently shipped, though the product had not arrived at key distributors as at last week. With no guarantee of final FDA approval, there appears no firm commitment to buy CSL flu vaccine at this point - this may change if approval comes in Oct-07.


Current season pricing is solid $10-12 per dose to manufacturers:

On current pricing gross margins should be >70%; but given �ll or nothing?risk we apply c.50%. Whilst FY08 is not a material sales level, the season will be important to future marketing; a successful FY09 could prompt market upgrades.


Valuation: PT $108.70ps; Buy Rating (unchanged)

Price target is based on FY09 NAV estimate and a DCF analysis of future growth. We note 3 for 1 proposed stock split, if supported will have effect from 24 Oct 07.





Global airline cycle likely to continue, with 5%pa capacity growth:

Our global Aerospace and Airlines teams have reaffirmed our view that the current strong global airline cycle is likely to continue due to global demand matching our 5%pa capacity growth prediction and external cost pressures continuing to force capital discipline. Demand is where we now see downside risk, given recent heightened concerns about the US and global economies.

We expect 8-10%pa capacity growth on Qantas?key trunk routes:

For Qantas, we expect capacity growth of 8%pa over the next three years, which materially exceeds the global average. We also conclude in this report that the combination of Virgin� entry on the US route and our analysis of the likely capacity intentions of its major foreign competitors (Singapore, Cathay, Emirates, etc) means that Qantas is likely to be subjected to 8-10%pa growth over the next three years on at least 70% of its international network.

We feel Qantas is well positioned to cope with this growth:

We believe Qantas?investment in product, two-brand strategy, and absorption of next generation aircraft into its fleet place it in good stead for this growth. We also expect at least one-half of Qantas?growth to go into new point to point routes for Jetstar, which will stimulate demand. Further, our international forecasts already imply flat unit revenue beyond FY09, versus the 2-3%pa long run average growth.

Sept. 17, 2007 issue - Columbia, S.C.: I recently put my kids in day care and they have had constant cold symptoms and mild diarrhea. I realize day care is an adjustment and exposes them to all sorts of new bacteria and viruses, but it's been more than a month and I am having symptoms as well. How long should this be expected to last?
Dr. Claire McCarthy: There are all sorts of studies to show that children who attend day care get sick more often than those who don't. The number of illnesses each year varies a lot from child to child, from about three times a year to as much as six or seven―which could feel like almost constant illness to a parent, especially if the parent is catching the illnesses, too!

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As much as this may make you want to pull your kids out of day care, it isn't necessarily a bad thing. It turns out that getting exposed to plenty of bacteria and viruses when you are young may be a really good thing―because it helps promote the healthy development of the immune system. In fact, research has shown that early exposure to germs can decrease a child's risk of getting asthma and other allergic diseases. It may even decrease their risk of certain cancers such as Hodgkin's disease.

It would be a good idea, though, to talk to your day-care provider about its procedures for preventing the spread of infection. Hand washing alone can make a huge difference. Toys should be wiped down at least once a day. And clearly infectious children (such as those with fevers, diarrhea or bad coughs) should be excluded from day care until they are better.

Selmer, Tenn.: With all the publicity about autism and immunizations, I've chosen not to immunize my kids. What are your thoughts?
There is a lot of publicity about autism and immunizations. What there isn't a lot of, though, is scientific data to link them. Children get lots of immunizations in the first two years of life―and that's when the signs of autism emerge. So it's entirely possible, if not probable, that families or doctors will begin to notice autistic behaviors within a month or two of a child's getting a vaccine―but that doesn't mean the vaccine caused the autism.

It's not that the concern hasn't been taken seriously. On the contrary, scientists have studied it very closely. There is a lot of talk about mercury in vaccines (in thimerosal, a preservative) causing autism. However, while exposure to large amounts of mercury (way more than is in thimerosal) can cause brain damage, it is not a known cause of autism. Thimerosal was removed from all routine vaccines given to children preschool age and younger. The only vaccine currently given to young children that contains thimerosal is the influenza vaccine, and that is also available in a preservative-free form.

Thiomersal is harmful by inhalation and ingestion, lethal between 50 and 1000 times[citation needed][1] the usual intake (hazard symbol T+).[2] It is a neoplastigen and a teratogen. Thiomersal is also dangerous for the environment (hazard symbol N).

For more safety information on how to handle thiomersal, consult its MSDS (material safety data sheet). Thiomersal causes susceptible bacteria to autolyze (break down their own cells with self-produced enzymes) via an unknown mechanism.[citation needed] In the body, it is metabolized to ethylmercury (C2H5Hg+) and thiosalicylic acid.[3]


[edit] Risk Assessment
There are hardly any studies on the toxicity of thiomersal in humans. However, many animal studies have been conducted which demonstrate the various toxicities of thiomersal. Many of these studies demonstrate that thiomersal has abortifacient properties in animals. For example, a 1975 study by Gassett et al. showed a dramatic increase in fetal death following intraocular and intraperitoneal application of thiomersal in rabbits and rats.[4] Itoi et al. showed a similar increase in fetal death in rabbits given thiomersal intraocularly in a 1972 study.[5] These findings of fetal death were matched in a 1987 study by Digar et al. involving chicken embryoes.[6] Similarly, a 1990 study by Batts et al. showed that thiomersal damages cilia function when applied topically to the trachea of sheep. This finding may indicate a potential mechanism for reproductive toxicity in women in regard to fallopian tube ciliary function.[7][8]

Official reports indicate that children can receive ethylmercury at levels higher than the US Evironmental Protection Agency's guidelines for methylmercury (MeHg) exposure. Burbacher et al (2005) made a "Comparison of Blood and Brain Mercury Levels in Infant Monkeys Exposed to Methylmercury or Vaccines Containing Thimerosal" and found considerable differences. They write in the conclusion of their study: "The key findings of the present study are the differences in the disposition kinetics and demethylation rates of thimerosal and MeHg. Consequently, MeHg is not a suitable reference for risk assessment from exposure to thimerosal-derived Hg. Knowledge of the biotransformation of thimerosal, the chemical identity of the Hg-containing species in the blood and brain, and the neurotoxic potential of intact thimerosal and its various biotransformation products, including ethylmercury, is urgently needed to afford a meaningful interpretation of the potential developmental effects of immunization with thimerosal-containing vaccines in newborns and infants. This information is critical if we are to respond to public concerns regarding the safety of childhood immunizations."[9]


[edit] History
Thiomersal was developed by Dr. Morris S. Kharasch, a chemist and Eli Lilly and Company fellow at the University of Maryland and then at the University of Chicago.[citation needed]

A patent for the alkyl mercuric sulfur compound, which was felt to have possibilities as an antiseptic and antibacterial product, was filed in the 1920s.[citation needed] Eli Lilly and Company registered the compound under the trade name Merthiolate in 1929. It was used to kill bacteria and prevent contamination in antiseptic ointments, creams, jellies, and sprays used by consumers and in hospitals. Thiomersal was used in many such products (e.g. nasal sprays, eye drops, contact lens solutions, immunoglobulins, and vaccines).

Thiomersal was first put in vaccines in 1931 by Eli Lilly Corporation and used as a preservative (bactericide) so multi-dose vials of vaccines could be used instead of single dose vials, which were more expensive.[10]

Products that may contain thiomersal include blood plasma components such as Rho(D) Immune Globulin, pit viper, coral snake and black widow spider antivenom[11] and vaccines in which it is not used as a preservative[12] may contain a trace of thiomersal from steps in manufacture.[1].


[edit] Timeline
Early-1930s- first added to vaccines as a bactericide.[10]
Mid-1980s- used as a preservative in virtually all whole-cell DPT vaccines, which were routinely administered four times each to children before eighteen months of age, starting at two months.
Late 1980s- Hib vaccines are recommended for administration to children at eighteen months. They contain thiomersal.
Early 1990s- In the USA three doses of Hepatititis B vaccine (at that time containing Thiomersal) are recommended for infants under six months of age, beginning on the day of birth; four doses of Hib are recommended within an eighteen month period, beginning at age two.
Late 1990s- three of the vaccines included in Vaccination schedules for children between six and eighteen months of age contain thiomersal.
1999- The American Academy of Pediatrics requests removal of thiomersal from all pediatric vaccines.
2001- The Institute of Medicine, citing insufficient evidence, is unable to prove or disprove any link between thiomersal and autism. However, they conclude that a causal connection between thiomersal and autism is "biologically plausible".[1]
2002- The USA Centers for Disease Control (CDC) and the USA Food and Drug Administration (FDA) state that: although thiomersal was to be discontinued in some paediatric vaccines, they would not be recalling any unused stocks, as there is no proof that low doses of thiomersal is dangerous, and that the change was purely cautionary.
2004- The Institute of Medicine, based on new information from epidemiological studies undertaken since its 2001 report, rejects the hypothetical causative link between thiomersal and autism.[1]
2006- Some vaccines provided by the World Health Organization for children in developing countries contain the same amounts of thiomersal as vaccines used previously for American children. Current vaccination schedules[citation needed] give these in a shorter time period.[citation needed]
2006- In the latest review by the WHO committee (at its meeting of 6-7 June 2006) the conclusion previously reached was reaffirmed that there is no evidence of toxicity in infants, children or adults exposed to thiomersal in vaccines.[13]
2007 - Theresa and Michael Cedillo, the parents of 12-year-old Michelle Cedillo asked a federal court Monday June 11th, to find that their child's autism was caused by common childhood vaccines.

[edit] Thiomersal and allergies
Thiomersal is used commonly in patch testing[citation needed] people who have dermatitis, conjunctivitis and other potentially allergic reaction. The substances implicated ethyl mercury, phenyl mercury, and other mercurious compounds. Allergies to mercury compounds are reported to be quite common especially among young people and women.[citation needed]


[edit] Thiomersal and autism
Thiomersal, as a preservative ingredient in common childhood vaccines, is blamed for the development of autism in a current federal lawsuit in the United States. Since 1999, over 4800 American families have alleged a link between vaccines and autism, most implicating thiomersal.[14]

When thiomersal was phased out as a preservative, autism levels were completely unaffected.[15]

In July, 2007, President Bush threatened to veto an appropriations bill that would ban the use of childhood flu vaccines that