This review was published in the Nov 18th, 2010 issue of the New England Journal of Medicine. It does a great job detailing the vaccine production and some of the pitfalls in developing newer universal vaccines; influenza vaccines that do not require annual shots. It is a must read.
Lately I have been approached several times about the incidence of fever post vaccination. Data suggests that it is a rare and benign issue at best. In a placebo controlled trials it was no more frequent than in the control group.
Placebo-controlled trials demonstrated that among older persons and healthy young adults, administration of TIV is not associated with higher rates for systemic symptoms
Therefore the presence of low grade fever or the concern for fever should not be a contraindication for vaccination.
Also of interest is the recurring concern for Guillian-barre. In this series there were no cases in over 4 million doses administered.
Just another reason to have the elderly vaccinated every year with Influenza vaccine along with appropriate 23-valent pneumococcal vaccine (when is pneumovax given?).
This prospective study in Hong Kong observed readmission rates among 36,000 elderly patients. The study found statistically significant decrease in the number of deaths, pneumonia, strokes and myocardial infarctions among the studied population.
One may ask “What does a vaccine have to do with prevention of stroke or MI?”. The reasons are that this population is at risk for these stressful infections. The burden of these conditions (sepsis) can further stress a compromised elderly patient and can “push” them into a stroke or and MI. These vaccine may not even completely prevent the illnesses themselves but by reducing the stress of the illness can go a long way in reducing morbidity and mortality from other conditions such as MI and strokes.
Also of note that very few if any “side effects” that are often cited in the lay media were seen. If there were more side effects it should have been seen in the higher hospitalization rate. In fact the vaccinated group had lower death and hospitalization rates.
For more information read the reference:
1. Hung, Ivan F N, Angela Y M Leung, Daniel W S Chu, Doris Leung, Terence Cheung, Chi-Kuen Chan, Cindy L K Lam, et al. 2010. Prevention of acute myocardial infarction and stroke among elderly persons by dual pneumococcal and influenza vaccination: a prospective cohort study. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 51, no. 9 (November): 1007-16. doi:10.1086/656587. http://www.ncbi.nlm.nih.gov/pubmed/20887208.
A lot of confusion about who gets vaccinated with the 23-valent pneumococcal vaccine. I put together this article to help clarify some of the common questions.
Invasive pneumococcal disease is the most common vaccine preventable disease worldwide
- There is no contraindication to give pneumovax at hospital admission.
- Invasive pneumococcal disease is the most common vaccine preventable disease worldwide. 40,000 deaths are attributable to invasive pneumococcal disease in the US annually.
- Current 23-valent polysaccharide vaccine covers 95% of the most common causes of invasive pneumococcal disease.
- Vaccination reduces rates of death from invasive pneumococcal disease. At least half of these deaths are preventable with vaccination.
- Pneumovax reduces duration of hospitalization for CAP. (see reference)
- Pneumovax reduces rates of death from myocardial infarction and strokes as shown in a recent prospective trial (see reference)
- The goal of pneumovax is to reduce death from invasive pneumococcal disease NOT to reduce the number of pneumonia cases.
- The current national average for patients 65 years of age and over is 65% coverage. This is too low.
- To address the issue of why only one dose after the age of 65 please see the attached algorithm that I put together. I hope that it better explains who needs to be vaccinated and how often. The recommendations are that EVERYONE get one dose of pneumovax after the age of 65. Anyone with additional risk factors will get the greater interval of vaccination per the higher risk group.
- Fisman, David N, Elias Abrutyn, Kimberly A Spaude, Alex Kim, Cheryl Kirchner, and Jennifer Daley. 2006. Prior pneumococcal vaccination is associated with reduced death, complications, and length of stay among hospitalized adults with community-acquired pneumonia. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America 42, no. 8 (April): 1093-101. doi:10.1086/501354. http://www.ncbi.nlm.nih.gov/pubmed/16575726.
- Hung, Ivan F N, Angela Y M Leung, Daniel W S Chu, Doris Leung, Terence Cheung, Chi-Kuen Chan, Cindy L K Lam, et al. 2010. Prevention of acute myocardial infarction and stroke among elderly persons by dual pneumococcal and influenza vaccination: a prospective cohort study. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 51, no. 9 (November): 1007-16. doi:10.1086/656587. http://www.ncbi.nlm.nih.gov/pubmed/20887208.
- Dominguez, Angela, Lluis Salleras, David S Fedson, Conchita Izquierdo, Laura Ruiz, Pilar Ciruela, Asuncion Fenoll, and Julio Casal. 2005. Effectiveness of pneumococcal vaccination for elderly people in Catalonia, Spain: a case-control study. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 40, no. 9 (May): 1250-7. doi:10.1086/429236. http://www.ncbi.nlm.nih.gov/pubmed/15825026.
- Vila-Córcoles, Angel, Olga Ochoa-Gondar, Imma Hospital, Xabier Ansa, Angels Vilanova, Teresa Rodríguez, and Carl Llor. 2006. Protective effects of the 23-valent pneumococcal polysaccharide vaccine in the elderly population: the EVAN-65 study. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 43, no. 7 (October): 860-8. doi:10.1086/507340. http://www.ncbi.nlm.nih.gov/pubmed/16941367.
- Johnstone, Jennie, Thomas J Marrie, Dean T Eurich, and Sumit R Majumdar. 2007. Effect of pneumococcal vaccination in hospitalized… [Arch Intern Med. 2007] – PubMed result. Archives of internal medicine 167, no. 18 (October): 1938-43. doi:10.1001/archinte.167.18.1938. http://www.ncbi.nlm.nih.gov/pubmed/17923592.
- Jackson, Lisa a, and Edward N Janoff. 2008. Pneumococcal vaccination of elderly adults: new paradigms for protection. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 47, no. 10 (November): 1328-38. doi:10.1086/592691. http://www.ncbi.nlm.nih.gov/pubmed/18844484.
The preliminary results from the last H1N1 2009 vaccination season are in. So far no excess cases have been reported with the vaccine when compared to previous vaccination years. More people developed Guillain Barre without vaccination than with the vaccine (total numbers). The rate of cases per 100,000 population were slightly greater in those with vaccination than those without vaccination (0.8 per 100,000 persons greater). These results are consistent with the expected safety profile as seen in previous years.
No statistically significant association between GBS and 2009 H1N1 vaccination has been seen
More information on the history of Guillain Barre and vaccinations
The question of vaccination for Influenza (H1N1) in pregnancy is frequently asked. A small study published by NIH does provide some answers around this.
Why all the concern about pregnancy?
To date there have been 100 pregnant women hospitalized with H1N1 in the US this season. 28 deaths have occurred in this group. This is an alarmingly high proportion for this healthy group (28% of admissions!). Though the total numbers seem very small it is the proportion of deaths in this important group that is high. Why is this group more important than other? To say the obvious; too many other lives depend on these women. A pregnant women is likely to have other children at home, those children are not only at risk for illness from mother but if mother is incapacitated or worse dies can changes the social structure of the home and future lives of her young children. Loss of life in other groups of people as traumatic as it may be does not carry as great a social burden as losses in this group can. This group is therefore at highest priority to be vaccinated.
Do pregnant women have adequate response to vaccination?
The study does show that pregnant women do mount an adequate response to a single dose of inactivated injectable vaccine and it is well tolerated. The 15mcgm dose appears to provide adequate response in 92% of recipients and 30mcgm in 96% of recipients. the pool sizes were very small at 25 women in each group.
The H1N1 2009 vaccine is made in an identical process to the existing seasonal influenza vaccine. It is a killed vaccine, therefore cannot cause H1N1. It is also thiomersal free.
If there is one good thing that has come out of this flu season then it is the awareness of vaccination. In years past, on the average we have had 45% vaccine coverage for hospital employees. This has been abysmally low to offer any real herd immunity. This year with an aggressive proactive approach with formal lectures and informal face to face discussions with groups of hospital staff discussing the benefits, myths. We have a record >75% seasonal vaccine coverage. Most of the recipients were taking influenza vaccine for the first time. We may actually run out of seasonal vaccine for the first time.
With regards to H1N1, we did start with live attenuated intranasal last week and had a high acceptance rate among those who qualified. Unfortunately many of the motivated staff did not qualify. This week we did receive inactivated injectable vaccine. The acceptance rate for this has been very good. I did need to go on an education round in the hospital and answer more question. But once a few staff members got motivated more and more followed. I think we will have a good coverage for H1N1 too.
Some factors promoting better acceptance may be the larger numbers of 20-49 year olds that are coming to the hospital with moderate to severe viral pneumonia. A few have required intensive care management. The number of patients coming to the ER with influenza like illness (ILI) has seen a sharp spike in the past week. The proportion of ILI that are influenza A positive has gone up from 3-5% in the weeks of Oct 5th and 12th to 18% in the week of Oct 19th.
So far very few complaints about getting vaccinated aside from the minor injection site aches and pains.
This issue was brought up today. A preprinted consent form at a local hospital has latex allergy listed as a contraindication for vaccination.
The vaccine itself seasonal or H1N1 regardless of live attenuated intranasal or the injectable vaccine does not contain any latex.
It is only the top of the bottle on multi-dose vials of the injectable vaccine that does contain latex. This would therefore not recommended in those with latex allergies.
Persons with latex allergies can take single dose vaccines.
Link to package insert
The New England Journal of Medicine published a study focusing on the safety profile of the H1N1 vaccine.
It was conducted in China where 2200 subjects received a dose of H1N1. 2103 (95.6%) received the second dose. They ranged in age from 3y to 77y the subjects were randomized to either vaccine or placebo. Patients were removed from the study once they achieved an increase in antibody titer of 4x baseline. Which is considered adequate protective levels. Those that did not achieve this level of antibody received a second dose at day 21.
The results did show good efficacy of the vaccine in adults with just a single dose. Children and the elderly did need the second vaccine dose to get the needed antibody level.
One adverse result was seen in the study, it was development of atrial fibrillation in a man who was receiving placebo. There were no serious adverse results in any of the vaccine recipients. Local pain at the injection site was the main complaint.
This is the New England Journal article: A Novel Influenza A (H1N1) Vaccine in Various Age Groups
In this day of rising health care costs it is reasonable to ask the question if mass immunization costs are worth it? It may be worth it if it only decreases the number of deaths and hospitalizations from influenza related illnesses. Some benefit appears to be from vaccinating on a community level to create herd immunity.
So what is herd immunity? Think of a group of persons in a large room. If a virus is introduced into the room it can infect the first person, multiply, infect say 3 more, multiply these 3 will infect 9 more, and so on. However if some of the persons in the room are immune to the virus then it cannot multiply in that immune individual. If more and more persons are immune in that room then it becomes very difficult for viruses to spread as it runs out of susceptible persons. If enough persons in a group are immune then the few persons with less immunity like the elderly really start to benefit from the immunity of the herd.
An estimate of this was made by Weycker et al they estimated that a 20% vaccination rate among children would decrease the number of influenza cases by 46% and an 80% coverage would be needed to decrease the disease by 91%. This is a significant finding. This can be done, as has been proven in the case of small pox where high levels of vaccination literally cornered the virus until it had no one to infect. As of december 1979 there are no human cases of small pox.
In Ontario Canada Jeffery Kwong et al did show improvement in hospitalization, emergency room visits for pneumonia and influenza like illnesses. This study was undertaken after Ontario decided to provide free influenza vaccination to all of its citizens in 2000. The study was conducted on data collected from all hospitalizations and ER visit for pneumonia and influenza like illnesses between the years 1997 and 2004. Vaccination rates increased to 38% of population from the pre 2000 rates of about 18% coverage. The data was compared to other Canadian provinces with similar population sized in the same year which had 24% vaccination coverage rates. During this time hospitalizations and deaths from influenza related illnesses decreased throughout Canada but the decrease was more pronounced in Ontario. Ontario saw 74% reduction in influenza related deaths compared with a 57% reduction in other provinces. In this study the rate of hospitalizations and ER visits was 40% less in Ontario than in other provinces. The group that saw the greatest benefit from vaccination with reference to ER visits, hospitalization and physician ER visits were the 50-64 yr age group they saw up to 80% less healthcare visits. The difference becomes much less obvious as we look at older groups that probably have other medical problems and respond less favorably to vaccination. Notably no significant increase in side effects or Guillian barre were seen in Ontario.
The societal cost savings can also be measured in terms of days lost at work, child care etc. This was shown in a study done by Bridges et al. That showed that even in years where there is a poor match between circulating virus and vaccine a net societal cost of $65.59 per person was seen in terms of lost wages compared with no vaccination. Whereas in years that a close match is seen a net societal cost of $11.17 per person is seen. These are very small prices to pay for improvement in healthcare cost.
In conclusion, there are reductions in healthcare costs with adequate vaccination though this is not seen at the individual level especially when community vaccination rates are low.