Monday, 3 December 2012

Varicella pays a call

Chicken pox arrived this week. Of course P had been playing with her best friend nearly non-stop during the 1-2 days before the spots appeared. She was infectious, but we didn't know it yet. We're still waiting for him to get feverish, but it's only a matter of time: varicella is highly contagious -- approx. 90% of those exposed will get the disease. Which seems a rather amazing statistic given the number of times I've heard about chicken pox parties that apparently didn't work. Hopefully he will only suffer the same mild case she had - about 50 spots that didn't particularly bother her.

Public health policy for chickenpox in the US and the UK is completely different. It seems that the difference lies in consideration of the long term effects on the entire population, and on the adult reactivation of chicken pox virus known as shingles, or Herpes Zoster. Well, there might be some other issues, too. Basically, the UK seems to be waiting and watching the outcomes of the US vaccination program over time.[3] So far it's a success, but the questions were about what happens 30-50 years into the program, so there's some waiting yet to be done.

I'm no expert, but here's what I know of the story: The varicella vaccine was developed in the 1970's and first licensed in Japan in the 1980's. A full vaccine program in the US began 1995, several years after my 4-year-old sister brought the virus home from nursery and shared it with me. I spread it to the local high school. The severity of the disease goes up with age of first exposure, so, while my sister and most of her nursery class got off with a mild fever and a handful of itchy spots, I was pretty miserable for over a week, and one of my friends was out of school for three weeks. Before the US program started, there were an estimated 4 million cases of chicken pox each year. For every 100,000 cases in teenagers, approximately 216 would end up in hospital, and 6 would die.[1]

Since it's beginnings in 1995, the vaccine program has grown so that school systems in 46 states now require vaccination for entry, and some nurseries and day care centers do, too. Current vaccine coverage is estimated at 94%. The program has been touted as a great success for reducing the number of hospitalizations, serious complications, and deaths due to the virus. There were an estimated 100-150 deaths every year before the program was started. The childhood deaths are now nearly eliminated, and the adult deaths are also reduced. The program has also saved a lot of money and hassle for parents who would have otherwise stayed home from work to look after sick children. The estimated savings is on the order of $500 million annually.[1]

So why isn't there a similar program in the UK?

Well, firstly, there do seem to be some hiccups. The vaccine is not as long-lasting as hoped, and there is a 'breakthrough' disease rate, in which children who have been immunized catch the disease anyway. The claim is that these cases are less severe than they might otherwise have been... although it is difficult to know. The rate of hospital visits does seem to be lower. The disease incidence is reported to be reduced by 83%, and the hospitalizations by 88%. Anyway, the original 1-dose vaccine program was changed to a 2-dose program beginning in 2006 to reduce the disease burden in the 7-14 year old age group. The price of the vaccine is also higher than the original cost-benefit analyses estimated. It's currently at about $80/dose. Which seems high, but frankly, it would have been worth $80 for my daughter not to miss a week of school. Maybe even $160. But if you ask if it is worth $160 to have a 60% chance that she will not miss the week of school, well, things start getting complicated, don't they?

And then there's shingles. According to the US CDC:
"Although many people do not remember, approximately 99.5% of people born in the United States who are 40 years of age and older have had varicella. As a result, all older adults in the United States are at risk for herpes zoster."

People like me, who have had full-blown chicken pox, have latent virus in our nerve ganglia. About 90% got it before the age of 10, when the initial infection was not too serious a disease. Our immune systems can fight this virus and keep it dormant. Occasionally, however, we might have a flare-up, which would be called shingles, also known as Herpes zoster, or just plain zoster. If you have heard of shingles, you've probably heard something like 'intensely painful' in the same breath. In older adults, the pain can last for months (as postherpetic neuralgia or HPN), and feels like your nerves are on fire.  I've never had it, and I don't want it. Actually, it's the kind of thing you would only wish on your worst enemy.

It's not entirely clear what causes shingles, but it only happens in people who had chicken pox, and it is more common in people with weakened immune systems, especially over age 50. According to some reports, if people susceptible to shingles are exposed to the live chicken pox virus, the immune system boosts its defenses against the virus, pushing the next bout of shingles into the distant future. On the other hand, someone with an active shingles rash can spread the virus to non-immune people, who then develop chicken pox.

The US CDC estimates there are about 1 million shingles cases each year, with 10 cases/ 1000 adults over 60. Between 1 and 4% of these will be hospitalized. Overall , Americans who live to be 85 years old have a 50% chance of suffering a bout of shingles. The incidence of shingles has been on the rise in the US, but apparently the rise goes back to before 1995, so cannot be entirely due to the vaccination program. The CDC states that there is no evidence the vaccination program has increased the rate of shingles. Nevertheless, the NHS in the UK lists a possible rise in shingles cases as the main argument against a varicella vaccination program.

Great stuff. To model the effects of a vaccine program, we would need to model this complicated viral transmission system, including years of latency in which the virus is inactive. The frequency of re-exposure to the virus plays a part in the dormancy period and reactivation rate of shingles. The cell-mediated immunity seems to be an important factor, and this varies in different life stages. To predict the effects would require a good model for social contact between, say, school children, babies and grandparents. School and nursery settings are the main places where the disease is spread, and there is a marked seasonal variation corresponding with the school year.

What can we predict about introducing a vaccine?

Well, firstly, the number of cases of the disease will decline. The direct societal costs of the disease will go down. (Success!) The number of people exposed to the virus will also decline. Some of those  will develop shingles because their immune systems did not get the boost provided by community exposure to the virus. Shingles goes up. (Failure!) However... time goes by. Eventually, those people who were immunized grow up and are not susceptible to shingles (success!). Only, not according to the CDC, which says that shingles can occur in anyone who has had the chicken pox virus, whether via the illness or through vaccination. (Failure!) But... people who have been vaccinated are 'less likely' to develop shingles. So if you get immunized and live to 85 years old, your chances of suffering a bout of shingles go from 50% for a wild-type case to 22% for immunization... maybe. Are you confused yet? Basically, there isn't a lot of data available to understand this part. A lot depends on how the susceptibility to both 'breakthrough' chicken pox and to shingles changes over time in people who received the vaccine.

Normally, adults who get chicken pox for the first time suffer a 10x greater rate of complications than children. Many more end up in hospital and with more serious complications. Hopefully, the immunity provided by the vaccine will be sufficient to avoid many cases in adults, but it is too early to tell. We would have to know how the immunity provided by the vaccine evolves over time. And since it was only licensed in 1995, we just don't know that yet. As far as anyone knows, the immunity seems to last somewhere between 6 and 20 years in different people, but it's difficult to measure, because exposure to someone who actually has the disease boosts the immunity. For some people at least, booster shots may be needed.

Anyway, varicella virus is making it's way through the local neighborhood. Neighbors are discussing 'pox parties' and the differences between immunity through vaccination vs wild-type disease. I can't turn back the clock on either myself or my kids, and I don't think the arguments for vaccination are entirely clear because the long-term effects are not known. I prefer to believe that my immunity will continue to last through my adult life, and I won't need a booster. Thankfully, no one in my family has suffered significant consequences from the wild-type chicken pox disease. It doesn't seem severe to me, so I am not unhappy about the NHS decision to hold off on a universal vaccine program.

References:
[1]  Zhou F, Ortega-Sanchez IR, Guris D, Shefer A, Lieu T, Seward JF.  An economic analysis of the universal varicella vaccination program in the United States. J Infect Dis. 2008 Mar 1;197 Suppl 2:S156-64.

[2] http://www.cdc.gov/shingles/hcp/clinical-overview.html  Updated: Oct. 23, 2012. Retrieved: Dec. 3, 2012.

[3] P D Welsby, Chickenpox, chickenpox vaccination, and shingles, Postgrad Med J. 2006 May; 82(967): 351–352. doi:  10.1136/pgmj.2005.038984 PMCID: PMC2563790
[4] Lieu TA, Cochi SL, Black SB, Halloran ME, Shinefield HR, Holmes SJ, et al. Cost effectiveness of a routine varicella program for US children. JAMA 1994; 271: 375-81.doi:10.1001/jama.1994.03510290057037Note: This analysis relied on a $35 cost for the vaccine, which is far below the $80 cost for a single shot, much less the $160 for the two shots now required in most areas.
[5] Susan A. Galea, Ann Sweet, Paul Beninger, Sharon P. Steinberg, Philip S. LaRussa, Anne A. Gershon, and Robert G. Sharrar, The Safety Profile of Varicella Vaccine: A 10-Year Review
 J Infect Dis. 197 (Supplement 2): S165-S169. doi: 10.1086/522125