Articles

Varicella Vaccination Program Success

One of the basic human “needs” is the desire for simplicity. We have limited cognitive resources, and when we feel overwhelmed by complexity one adaptive strategy is to simplify things in our mind. This can be useful as long as we know we are oversimplifying. Problems arise when we mistake our schematic version for reality.

In this same vein we also like our narratives to be morally simple, so there is a tendency to replace the complex shades of gray with black and white. This is perhaps related to cognitive dissonance theory. We have a hard time reconciling how someone can be both good and bad, or how a good person can do bad things. So there is also a tendency to see people as all good or all bad. We can transcend these tendencies with maturity and wisdom, but that takes work.

A good example of the desire for simple moral clarity is the anti-vaccine movement. Their world is comprised of white hats and black hats (guess which one they perceive themselves as wearing), as evidenced by the blog posts and comments over at Age of Autism. There is a certain demand for purity of thought and message that seems to be getting worse over time in a self-reinforcing subculture. Many now see their struggle in apocalyptic terms.

The desire for simplicity even extends to factual claims. They oppose vaccination, and so they tend to make every argument against vaccines possible – even arguing, against all the evidence, that vaccines do not work. If vaccines were effective but carried significant risks, that would cause a genuine dilemma (cognitive dissonance). But if vaccines are both ineffective and risky, there is no dilemma, the cognitive dissonance is resolved, and the brain is given a nice dose of dopamine as a reward.

This means that defenders of science-based medicine have to counter anti-vaccine propaganda stating that vaccines do not work. For example, the data on measles is overwhelmingly clear, but this has not stopped vaccine deniers from distorting the data to argue that measles just happened to decline all on its own. It’s a massive exercise in not seeing the forest for the trees. Deniers look for anomalies in the data (usually artifacts of data collection) and then use that to call the big picture into question. Or they confuse death rates with incidence rates (death rates can decline just by improvements in medical care – this does not mean that the spread of the disease was decreasing). Meanwhile the big picture is dramatically clear – vaccine introduction lines up nicely with plummeting disease incidence.

So forgive us if we take the time to point out when further evidence comes to light that vaccines are effective public health measures. A recent study published in Pediatrics reviews the evidence for the effect of the varicella (chicken pox) vaccine on varicella-related deaths. They found:

During the 12 years of the mostly 1-dose US varicella vaccination program, the annual average mortality rate for varicella listed as the underlying cause declined 88%, from 0.41 per million population in 1990–1994 to 0.05 per million population in 2005–2007. The decline occurred in all age groups, and there was an extremely high reduction among children and adolescents younger than 20 years (97%) and among subjects younger than 50 years overall (96%). In the last 6 years analyzed (2002–2007), a total of 3 deaths per age range were reported among children aged 1 to 4 and 5 to 9 years, compared with an annual average of 13 and 16 deaths, respectively, during the prevaccine years.

That’s an impressive decline, if the absolute numbers are low. But when you are talking about childhood deaths, any reduction is welcome. Although it was not covered in this study, other studies also have looked at varicella incidence and hospitalizations, also finding a dramatic decrease. For example:

The vaccination program reduced disease incidence by 57% to 90%, hospitalizations by 75% to 88%, deaths by >74%, and direct inpatient and outpatient medical expenditures by 74%.

All of this data is also with the single doses vaccine, which was found not to produce adequate antibody levels in some children. The current recommendation is for a second follow up dose to boost immunity levels. It is probable that the two-dose vaccine will produce even more impressive results.

And so as not to oversimplify the picture – the varicella vaccine did come with a possible unintended consequence. Previous generations were often exposed to chicken pox in children throughout their life, resulting in a natural immunity booster. With the near elimination of chicken pox due to the vaccine, older adults have waning immunity and this has possibly led to an increase in herpes zoster. Once infected with varicella the virus is never completely eliminated from the body. It goes dormant in the dorsal root ganglia (packets of sensory nerve cells just outside the spinal cord) and can be reactivated later in life. It’s possible that decreasing antibody levels in older adults who are no longer getting exposed to cases in children are allowing more cases of zoster to occur.

The data on this is currently mixed. Models predict an increase, but actual surveillance has produced unclear results. The worst case scenario is that the older generation will experience an increase in herpes zoster, but this will be a temporary effect as the next generation will never have had chicken pox due to the vaccine. There is also available a varicella zoster vaccine to reduce the risk of zoster in the at risk generation.

Conclusion

There is a large and growing body of scientific data from which we can draw a few very reliable conclusions. Vaccines work. The general concept is sound, and specific vaccines have clearly been effective in significantly reducing (and in two cases eliminating) infectious disease. They are not risk free, but the incidence of adverse events is orders of magnitude lower than the benefits of the available vaccines.

We need to continue active surveillance of vaccine safety and effectiveness, as well as tight regulation of vaccine manufacturing. Vaccines are an important public health intervention, and we need to watch the vaccine program closely.

Despite this, vaccine opponents have continued to argue that vaccines are not safe or effective. Thankfully the data is so clear that the public is largely ignoring them.

Posted in: Vaccines

Leave a Comment (47) ↓

47 thoughts on “Varicella Vaccination Program Success

  1. windriven says:

    “It’s possible that decreasing antibody levels in older adults who are no longer getting exposed to cases in children are allowing more cases of zoster to occur.”

    Is the herpes zoster vaccine that is advocated for those 60 and over effective in preventing outbreaks? How contagious is herpes zoster?

  2. TsuDhoNimh says:

    Is the herpes zoster vaccine that is advocated for those 60 and over effective in preventing outbreaks? Effective in preventing those who have had chickenpox from having shingles show up later? Yes.

    How contagious is herpes zoster?Less than chickenpox, because it’s not aerosol spread. it takes direct contact with the blisters, or objects recently contaminated by fluid from the blisters such as hands, towels or bedsheets.

  3. windriven says:

    @TsuDhoNimh

    Domo arigato.

  4. Harriet Hall says:

    I have a further question about the herpes zoster vaccine. Those over 60 have been encouraged to take it even if they have already had shingles. Is that advice based on any evidence that the vaccine reduces the incidence of repeat episodes in those people, or is it based on the idea that the episode of shingles might have been a mis-diagnosis so it’s safer to just vaccinate everyone?

  5. SloFox says:

    @Harriet,

    I haven’t seen the justification for the CDC recommendations but the original efficacy studies and the first retrospective evaluation of ‘real-world’ use included anyone over 60 who consented. Exclusion criteria did not include prior episodes of zoster.

    My question is why doesn’t reactivation of VZV in vivo confer a protective effect similar to inoculation with the vaccine?

    Disclaimer: immunology was one of my weaker subjects in med school. I apologize in advance if it’s a stupid question.

  6. margaretrc says:

    “My question is why doesn’t reactivation of VZV in vivo confer a protective effect similar to inoculation with the vaccine?” I have the same question. Last year, when I was getting inoculated for a trip abroad, I asked the doctor about getting the varicella zoster vaccine (not for the trip–just because I thought I might like to avoid getting it–again. He asked if I had ever had shingles. When I said I did have a diagnosed case a year or so back, he said that, in that case, getting the vaccine was pointless–that I shouldn’t get shingles again. Is he right? I hope, hope… Or should I pursue getting the vaccine?

  7. nybgrus says:

    From a not super in depth look, it seems the literature is a bit lacking on the topic, specifically. However, it would seem that some data show that reactivation of zoster does provide an immunity boost. The data also demonstrates some evidence for sub-clinical reactivation leading to boosts in immunity as well.

    This seems to jive with what we do know about the virus and how it spreads and replicates. I skimmed a chapter from a virology text, and it seems that animal models are hard to do with VZV (as opposed to HSV-1) and so specifics on reactivation immunity boosts are not quite solid. A couple of pertinent quotes:

    “A more controversial issue is whether CMI is boosted by internal but sub-clinical reactivation events… evidence for sub-clinical reactivation has been mounting… A recent 1 year longitudinal study of adult patients with little chance of exposure to exogenous varicella found unexplained peaks [of VZV CD4+ and CD8+ cells] that suggested subclinical reactivation events…” – SK Weller, Alphaherpesviruses: Molecular Virology, January 2011, pg 356

    So it seems that there is a bit of evidence that sub-clinical reactivation can happen, and that it can confer an immunity boost. This is far from robust though it is supported by another finding:

    “The finding of subclinical viral shedding in saliva in high stress individuals (astronauts) has established the potential for subclinical reactivation and Hope Simpson’s proposed ‘internal boosting by contained reversions’ (Mehta et al., 2004, 2008; Cohrs et al., 2008). This issue remains controversial and is in need of further assessment” – page 356

    So there seem to be some converging lines of evidence to say that sub-clinical zoster occurs and it does seem to confer that immunity boost, but the author notes limitations:

    “The fact that we cannot yet efficiently experimentally induce reactivation of VZV from human ganglionic tissues or from small immune competent animal models make VZV reactivation somewhat a mysterious black box. If such an animal model were to become available, it may open the gateway to assess its interaction with adaptive immunity.” – page 365

    In skimming the rest of the chapter it seems that the immune evasion is very complex for VZV and that a reactivation of zoster should confer an immunity boost even without exogenous varicella (thus, the vaccine after having an outbreak of shingles would seem to be superfluous) but the data is not complete and there still seems to be a subset of people for whom the reactivation would not be sufficient to provide that immunity boost (my sister’s FIL has had recurrent shingles bouts over the past few years). But whether this is a function of the zoster itself, a continued decline in the body’s cell mediated immunity (CMI), or some combination thereof is unclear. My guess would be that in the vast majority of cases, zoster would confer the immunity boost and the vaccine would be uncalled for. For those in which is failed to provide the boost, I think that the majority of them would be due to some sort of defect in CMI an as such I am unsure of whether the vaccine would be helpful to induce an appropriate response. However, since vaccines tend to have adjuvants and are more potent at inducing an immune response it could work. But to address that I’d have to read the nitty gritty details on the VZV vaccine specifically and then it would still be a guess since the data on the CMI side of things is incomplete.

    I think from a clinical standpoint (and any practicing clinicians please let me know if I am wrong on this one) if a patient presented to me with a singl episode of zoster I would say the vaccine likely won’t be useful, but if they had a second or third episode, I would consider giving it a try (unless they were immune compromised or some other such issue) simply in the hopes that it may give relief.

  8. lilady says:

    I checked out the current 2011 recommendations from ACIP and it states:

    ACIP Recommends routine vaccination of all persons =/> 60 years who have no contraindications including persons reporting a previous episode of zoster.

    These recommendations for zoster vaccine have not changed since those published in the MMWR:

    Prevention of Herpes Zoster: Recommendations of the Advisory Committee on Immunization Practices (ACIP) June, 2008

    The June 2008 ACIP Recommendations does delve into any research about zoster that applies to the vaccine as well as the double blind studies conducted prior to and post licensing. Unfortunately, just as Nybgrus found, some studies have found a weak association for second and third cases of zoster in a small subset of people.

    ACIP points out that blood titers are not indicated for zoster which is a clinical diagnosis and that zoster cases are not “reportable”…which has an impact on the study of the efficacy of this rather new vaccine.

  9. belarm says:

    I developed VZV, due to immunodeficiency, before I was thirty years old. I opted for the vaccine as soon as I was safely able to take it, as the treatment for my disorder will make me somewhat immunocompromised until they’ve got a good gene therapy for it. The risks of the vaccine seem very small – especially since you can plan when you’re exposed to the virus, choosing a time when you’re best able to respond to it, and the prevention rates are impressive – 50% reduction in VZV occurrence, 66% reduction in postherpetic neuralgia. That seems like a pretty straight-forward choice to me, so long as it’s not contraindicated.

    Having had VZV, I cannot recommend the vaccine strongly enough. It’s great that we’ll have this disease knocked out in the relatively near future, but in the mean time, any safe prophylactic against shingles is worth it – having a virus destroy your nervous system is actually slightly more painful than it sounds!

  10. wales says:

    Given that the “impressive” decline in mortality (risk of varicella mortality has decreased from 0.00000041% to 0.00000005%) is attributable to the one-dose varicella program, it begs the question why a two-dose program? Perhaps we should be looking at “economic-based medicine” in these interesting economic times.

  11. wales says:

    In the vein of “moral clarity” mentioned in this article, how many families in the US have lost their jobs and homes, and don’t have enough food? The cost of vaccinating every US child with that second dose might be put to better use.

    “Compared with the 1-dose program, the incremental second dose was not cost saving (societal incremental BCR, 0.56).”

    http://www.ncbi.nlm.nih.gov/pubmed/18419391

  12. Chris says:

    Given that the “impressive” decline in mortality (risk of varicella mortality has decreased from 0.00000041% to 0.00000005%)

    Isn’t wasn’t the mortality but the incidence that prompted the change. And does societal cost include lost wages for a parent who must stay home for about two weeks with a sick child (and more weeks if there are multiple children)?

  13. wales says:

    Yes…”With regard to indirect costs, our model estimated the economic value of life lost prematurely, indirect costs associated with permanent disability, and indirect costs associated with work time missed by parents who stayed at home to care for sick children.”

  14. wales says:

    Here’s a very conservative estimate for possible cost savings related to varicella vaccination.

    The cost to vaccinate 4 million (birth cohort) US children each year with a second dose of Varicella is about $280 million. That’s at the CDC’s discounted rate of $70 per dose, so the actual cost is higher given that the private sector cost of the vaccine is $84. This is conservative as the paper previously cited estimates that 66% of vaccines were administered by private sector providers. (I have not included societal costs of vaccination, which the paper previously cited estimates as roughly the same amount as the cost of the vaccine itself, so in effect the vaccine cost is doubled.)

    There are about 113 million households in the US, according to the Census Bureau, each averaging 2.9 individuals. The $280 million saved by foregoing a second varicella dose could be distributed to the 113 million households at over $2 million per household….more than enough to pay for any varicella-related medical bills and unpaid parental sick leave. As a bonus, this would leave ample spare change for each citizen to pay off their $47,000 share of the US National Debt, solving that problem as well and sparing us the ongoing antics of politicians during the “debt crisis”.

    Food for thought.

  15. Scott says:

    By my math, $280 million a year distributed among 113 million households (more natural to do it per person, but we’ll use the method you had) is about $2.50 per household. Which won’t make much of a dent in medical bills, sick leave, OR debt.

  16. Scott says:

    Sorry, hit post too soon.

    Your point is not unreasonable, in that it’s definitely important to make sure our health care system provides maximum bang for the buck. But when you make such a gross and egregious error in the benefits claimed, it can’t help but make your position look bad.

  17. wales says:

    Just making sure you are paying attention. Glad someone is reading.

  18. wales says:

    In a rather Swiftian mood today, hence my modest proposal.

  19. WilliamLawrenceUtridge says:

    Defunding the NCCAM would provide sufficient funds several times over.

    I’m just sayin’…

  20. Scott says:

    Defunding the NCCAM would provide sufficient funds several times over.
    I’m just sayin’…

    I gather that this was meant to be a bit tongue-in-cheek, but it’s not a good argument anyway. Defunding the NCCAM is a good thing and would save money too, but not really linked to varicella vaccination.

    IOW the options are just not NCCAM+no second dose vs. no NCCAM+second dose. We could also do no NCCAM+no second dose and hence the possibility of defunding NCCAM isn’t good support for the second dose.

  21. nybgrus says:

    Scott, that was defiinitely tongue in cheek. We just kinda wanna see the NCCAM defunded. :-)

    As for your points, very valid indeed. In light of the US budget deficit $280mil is a pittance, but I agree that even then, the cost effectiveness should really be evaluated. Even at the spread out cost of $2.50 per household, I am not sure that a second dose is warranted for everyone. The thing that sucks is we need to make such decisions for everything otherwise saving the $280m is really not doing much of anything.

  22. Okay, I’m really not qualified to talk about this AND I’m bad enough at number’s that I didn’t even notice Wales “mistake” until Scott pointed it out, but…

    My main concern with the chicken pox vaccine was the partial immunity that the one shot system gave. Word on the street was that this gave the child an increased risk of catching chicken pox as a teenager or young adult, which usually results in a more miserable case of chicken pox with more scarring and possible complications. The two teenagers I knew who had chicken pox were much sicker and missed much more school than the young school age children I knew who had chicken pox.

    The thing that convinced me to have my daughter vaccinated was the addition of the booster which, I was told by my doctor, gave better immunity throughout the vaccinated person’s life.

    So was I wrong? Isn’t there a concern with teenagers/young adults getting full fledged chicken pox without the second shot?

  23. Chris says:

    And I thought my six month old breast fed daughter had a bad time with chicken pox. What she experienced was nothing compared to this video of Adam.

    Wales, do you think the cost of the second vaccine worth what that young man has to go through for the rest of his life?

    Oh, and while I am at it: some hospitals do provide daycare for sick kids, and they include a chicken pox room. They are very expensive by more than several times $2.50 per day! Last I looked, in my city very few employers offered it as benefit.

    I spent a full month dealing with chicken pox a year before the vaccine was available. I did not have a job to go to, primarily because I have a disabled child who required more of my time than my former employer. I still had issues with two boys in speech and/or language therapy as I juggled their appointments, a very sick baby and not sleeping due to both the very sick baby and continually washing sheets due to older child being so sick he wet his bed.

    I say take those “societal costs” and shove them where Nicholas Gonzalez thinks you should take your coffee!

  24. nybgrus says:

    @chris:

    I want to take a second to make it clear that I wasn’t necessarily agreeing that the second shot should be removed to save costs. I was merely agreeing with the concept that such metrics should be taken into consideration across the board. I haven’t looked into it nor done the metrics, so I shouldn’t comment, even though I did lean that way in my previous comment. That was ill informed and poorly worded. I can say though, that I’d reckon vaccines to be cost effective enough that unless no change was shown it would pretty much always be a good way to go.

  25. belarm says:

    @wales:

    The second dose may not be cost-saving right now, but as has been pointed out, the later in life you contract varicella, the more pronounced the infection. As more children are vaccinated, sub-clinical reactivations will continue to become less common. This has already lead to an increase in VZV incidence, and it’s a fair bet that, until varicella is eliminated, we’ll be in a type of limbo – where there’s not enough of the virus around to keep antibody production up, but there’s still enough to get teenagers and adults very ill.

    People made the same argument against the smallpox vaccine when the incidence of smallpox had become incredibly low, but you must take the societal benefit into consideration.

  26. lilady says:

    Wales: I think you misread the cost of 1 dose of varicella vaccine to the government and to the private provider. I checked the VFC/CDC price list and the costs you quoted are for varicella vaccine 10 packs, not single doses.

    Costs are available (update July 18, 2011) on their website:

    VFC/CDC Vaccine Price List

    According to this website Varivax single dose vial cost to the VFC is $6.97 and to private doctors $8.38.

    I would love to continue this discussion, but I have to leave for a weekend getaway.

    Just one suggestion however, check out the ACIP Recommendations website for their reasoning behind recommending a second dose. All their updated recommendations for all vaccines are there.

  27. wales says:

    lilady: According to this site, the vaccine is sold in 10-dose packages, but the per dose cost is $69.73

    http://www.cdc.gov/vaccines/programs/vfc/cdc-vac-price-list.htm

  28. WilliamLawrenceUtridge says:

    MIM:

    So was I wrong? Isn’t there a concern with teenagers/young adults getting full fledged chicken pox without the second shot?

    I believe the concern would be for things like herd immunity and those that don’t “take” the first time. You get one shot, you get a herd immunity of (random number) say 90%. You get two and the herd is now 95-99% immune. A booster would also goose the immunity of people already immune, possibly giving longer or even permanent immunity. I believe there would be a societal benefit to a second round of vaccination in addition to the potential benfit to individuals. While you could probably test individuals to see if the original shot “took”, ultimately you’re probably just better off to give a booster (in terms of resources required).

    I could be wrong, natch.

  29. Chris says:

    In a way the one dose of varicella vaccine was useful, even when kids actually caught chicken pox.

    In first few years as my daughter was in kindergarten and first grade some of her classmates came down with chicken pox. They were the first group to get the vaccine less than a year after she had the actual disease. They all had milder forms that lasted closer to a week and not two weeks.

    Though even less than a week of painful itching can be too much for some kids.

  30. Chris
    “In a way the one dose of varicella vaccine was useful, even when kids actually caught chicken pox.”

    Yes, We think that my daughter contracted atypical chicken pox when we were in China adopting our son. She had had her first vaccine. She had a fever and was out of sorts a couple of days before we left China and then a couple of days after we arrived home she was itching at about ten funny bumps. We took her to the doctor because the Embassy/Immigration had warned us to watch out for chicken pox symptoms since a child in our hotel (non-vaccinated, recently adopted) had it.

    Long story (sorry) but the doctor couldn’t be certain it was chicken pox, but thought it was. I got the impression that a titer blood test isn’t available.

    Anyway, I was relieved that she had been vaccinated, because it’s possible that we may have been quarantined in China without it. Not a fun thought.

    I’ve always felt kinda bad though, because she was probably contagious (pre-spots) on our 24 hour flight home, through the airports, etc.

  31. Th1Th2 says:

    Previous generations were often exposed to chicken pox in children throughout their life, resulting in a natural immunity booster. With the near elimination of chicken pox due to the vaccine, older adults have waning immunity and this has possibly led to an increase in herpes zoster.[...]It’s possible that decreasing antibody levels in older adults who are no longer getting exposed to cases in children are allowing more cases of zoster to occur.

    Hey Steven stop barking up the wrong tree! It’s time to let go of your superstitious belief. I don’t want to break up the party but you are terribly and deliberately giving false information. Not good.

  32. nybgrus says:

    Nobody mind the Thing Troll. Pay it no never mind. Don’t feed it, don’t get it wet. Especially after midnight.

  33. Th1Th2 says:

    nygbrus,

    In skimming the rest of the chapter it seems that the immune evasion is very complex for VZV and that a reactivation of zoster should confer an immunity boost even without exogenous varicella (thus, the vaccine after having an outbreak of shingles would seem to be superfluous) but the data is not complete and there still seems to be a subset of people for whom the reactivation would not be sufficient to provide that immunity boost (my sister’s FIL has had recurrent shingles bouts over the past few years).

    No, you’re understanding is incomplete.

  34. Harriet Hall says:

    Ignore the troll.

  35. Chris says:

    Thing1Thing2 lives in another reality.

  36. Th1Th2 says:

    SloFox,

    My question is why doesn’t reactivation of VZV in vivo confer a protective effect similar to inoculation with the vaccine?

    Where is Steven when someone needs him? Isn’t embarrassing to ignore your herd? But let me give you a clue SloFox. You’re asking a question like you’ve never done your homework.

  37. Harriet Hall says:

    Again, ignore the troll.

  38. Th1Th2 says:

    Harriet,

    Nice attempt to evade utter humiliation eh especially with what I did to RI. They are still in a state of shock and disbelief after their long-held superstitious belief about VZV and the vaccine crumbled into pieces.
    But I want your Masters like Gorski and Steven N. to pick up the pieces. Are they still in latency?

  39. Harriet Hall says:

    Not responding to the troll.

  40. David Gorski says:

    An excellent idea. Boring troll is boring—and wrong, as usual.

  41. Nescio says:

    Is there a killfile that works here?

  42. WilliamLawrenceUtridge says:

    Mmmm, extinction burst

  43. Th1Th2 says:

    Gorski,

    An excellent idea. Boring troll is boring—and wrong, as usual.

    And like what happened to your RI, this thread is done. And I bet you will not post another stupid article regarding VZV and and the vaccine. Yes, this thread is done. Although I can still see some occasional and transient fibrillating motion artifacts, however, those are not to be confused as having viable reperfusion rhythm. It’s all over Gorski. Not only you’ve become a master infection promoter, you’re also the leading source of their myths and superstitious beliefs. What a shame.

  44. Harriet Hall says:

    Continue to ignore troll.

  45. nybgrus says:

    @Chris:

    In first few years as my daughter was in kindergarten and first grade some of her classmates came down with chicken pox. They were the first group to get the vaccine less than a year after she had the actual disease. They all had milder forms that lasted closer to a week and not two weeks.

    Doing a bit more reading, and based on some of the stories being told here jiving with that reading, I think that advocating a second shot might not be a bad idea. I agree that even a milder, shorter bout of chicken pox is not as good as no bout at all and at such a low cost I see no reason not to try and eradicate the disease with the booster.

    It also seems clear that if a person >55 came in with a a 2nd bout of zoster that a vaccination would be reasonable to offer, but I am not sure about after just 1 bout. But considering the cost and safety profile, I don’t think I would be terribly reticent about administering the shot in either case. Perhaps some sort of middle ground where the patient can choose the shot on their own dime after only 1 bout but be offered it covered after the second? Either way, careful documention so we could actually get some epidimiological data on it would be requisite, I reckon.

  46. lilady says:

    @ Wales: Thanks for the correction…I did misinterpret the cost.

    While I have been out of town, I see many more interesting posters…with one exception.

    Ignoring boring delusional troll.

Comments are closed.