3-dose 7-Valent pneumococcal vaccine use associated with increased nasopharyngeal acquisition of pneumococcal Serotype 19A Strain
A recent study published in the Journal of the American Medical Association (JAMA) has found an association between the 7-valent pneumococcal vaccine (PCV-7) and an increase in nasopharyngeal (in the nose and throat) acquisition of pneumococcal serotype 19A strain, which is not one of the 7 strains the PCV-7 protects from. According to the authors of the study, a possible association had been observed between the use of PCV-7 vaccine and a rapid increase in serotype 19A strain acquisition, but studies had never been done to confirm this association, and the current study is the first one to address that concern. Let us look at it:
Elske J. M. van Gils, MD; Reinier H. Veenhoven, MD, PhD; Eelko Hak, PhD; Gerwin D. Rodenburg, MD; Wendy C. M. Keijzers; Debby Bogaert, MD, PhD; Krzysztof Trzcinski, DVM, PhD; Jacob P. Bruin; Loek van Alphen, PhD; Arie van der Ende, PhD; Elisabeth A. M. Sanders, MD, PhD
JAMA. 2010;304(10):1099-1106. doi:10.1001/jama.2010.1290
Study Summary – The study was conducted in the Netherlands. 948 healthy infants, from 6 weeks up to 24 months of age, were enrolled, and followed between July 7, 2005, and February 14, 2008. Infants were randomly assigned to receive 2 doses of PCV-7 at 2 and 4 months; 2 + 1 doses of PCV-7 at 2, 4, and 11 months; or no dosage (unvaccinated control group). Nasopharyngeal swabs were obtained at the age of 6 weeks and at 6, 12, 18, and 24 months to test for the presence of the 19A strain of the pneumococcal bacteria. Rates of bacterial presence were compared between the different groups.
Results – 54 nasopharyngeal serotype 19A carriage isolates from 318 in the 2-dose group, 66 isolates from 327 in the 2 + 1-dose group, and 33 isolates from 303 in the unvaccinated were collected from 6 weeks through 24 months. The cumulative proportion who tested positive for new nasopharyngeal serotype 19A acquisition from 6 through 24 months of age was significantly higher in those having received the 2 + 1-dose PCV-7 schedule (16.2%; 95% confidence interval [CI], 12.6%-20.6%) vs those who were unvaccinated (9.2%; 95% CI, 6.5%-13.0%; relative risk [RR], 1.75; 95% CI, 1.14-2.70) but not after a 2-dose schedule (13.2%; 95% CI, 9.9%-17.4%; RR, 1.43; 95% CI, 0.91-2.25).
Conclusion – This study is methodologically sound. The sample size was fairly large, subjects were randomly assigned, and there was a proper control group. If the results of this study hold, and can be replicated, it would strongly suggest that a 3-dose of the PCV-7 pneumococcal vaccine might lead to higher rates of acquisition of the 19A strain in infants between 6 weeks and 24 months of age. It is very interesting that there were no statistically significant differences between the non-vaccinated children and the ones that had not received the 3rd dose yet. From the information that can be gleamed by the abstract of the study, the authors don’t seem to speculate on why it appears that the 3rd dose makes the difference. They conclude simply as such:
A 2 + 1-dose PCV-7 schedule was associated with an increase in serotype 19A nasopharyngeal acquisition compared with unvaccinated controls.
How should we interpret this study? By the author’s own admission, this is the first study to look at the association between PCV-7 and increased serotype 19A acquisition rates. As such, it is imperative that its results be replicated, to rule out mistakes, or other things that could have affected the results. On the other hand, the study looks to have been conducted well, and appears to have been designed properly. It provides intriguing evidence that 3 doses of the PCV-7 vaccine might be causally related to an increase in nasopharyngeal acquisition of pneumococcal serotype 19A Strain. More studies are needed to verify these results.
Until then, the best course of action is to speak to your pediatrician, and talk to her about using the 13, or the 23, valent version of the pneumococcal vaccine which also covers serotype 19A strains of the pneumococcal bacteria. You should not unilaterally decide to skip the pneumococcal vaccination completely based solely on this one study.
The number of children admitted to English hospitals with bacterial pneumonia decreased by a fifth in the two years following the introduction of a vaccine to combat the disease, according to a new study published in the journal Thorax.
Bacterial pneumonia is a serious illness caused by Streptococcus pneumoniae bacteria that mostly affects babies, young children and elderly people. In Europe, around one in ten deaths in the under-fives is caused by the disease.
Bacterial pneumonia usually develops as a complication following a respiratory tract infection such as influenza. Symptoms include difficulty breathing, wheezing, fever and loss of appetite.
In September 2006, a vaccine known as PCV7 was introduced into the childhood primary immunisation programme across the UK, to protect against seven different strains of Streptococcus pneumoniae bacteria.
Today’s study, led by researchers from Imperial College London, shows that in the first two years following the introduction of this vaccine, hospital admissions for bacterial pneumonia decreased by 19 per cent amongst children aged under 15 years. Admissions for empyema, a rare and serious complication of bacterial pneumonia, decreased by 22 per cent.
The pneumococcal vaccine is administered at two, three and 13 months of age. When it was first introduced there was a catch-up campaign for children up to two years. Take-up of the vaccine over the study period was high. It was administered to an average of 84 per cent of eligible children in England in the first year following its introduction and 91 per cent the following year.
“Pneumonia vaccine ineffective against repeat infections: study” screams the headline. The article goes on to clarify that a study just published seems to suggest that the pneumococcal vaccines in use in Canada do not seem to perform any better than no vaccine. How is that possible? Well, so far as I can tell, it isn’t, and this seems to be another case of dubious reporting by the journalists, and careless conclusions by paper authors.
I could not get my hands on a copy of the full published study the article refers to, although I will probably be able to in the near future. In the mean time, all I can go on is the abstract which can be found at PubMed or at Chicago Journals. Let us examine exactly what this study seems to suggest, based on the publicly available abstract.
Background.There is debate surrounding the effectiveness of the 23‐valent pneumococcal polysaccharide vaccine (PPV). We determined whether PPV was associated with reduced mortality or additional hospitalization for vaccine‐preventable infections in patients previously hospitalized for community‐acquired pneumonia (CAP).
Ok, so first thing to keep in mind: they only studied people who got pneumonia. This is not a study comparing vaccinated vs. unvaccinated, and seeing if there is any protection offered by the vaccine in the form of reduced infection rates. This is a study consisted of only people who got sick, breaking those down into two groups and seeing how each group fared.
Now, it is an accepted fact that no vaccine is 100% effective, meaning that no vaccine will prevent the disease on all people who receive it. For one reason or another, some people get no benefit from any given vaccine. Those people will get sick from the disease, regardless of their vaccination status. By definition, if you are gathering together people who are sick in the hospital, you are already limiting yourself to only that subset of the vaccinated population for whom the vaccine has already failed. So from that point alone, this is like saying “Well let me find all the people for whom the vaccine failed & let me measure how effective the vaccine was for them“. Just to make a comparison, this sounds kind of like saying “let me find out which team lost, and see how likely they are to have won!“.
Results.A total of 2950 patients were followed up for a median of 3.8 years. The mean patient age was 68 years; 52% were male. One‐third (n=956) received PPV: 667 (70%) before and 289 (30%) during hospitalization. After discharge, 1404 patients (48%) died, 504 (17%) were admitted with vaccine‐preventable infections, and 1626 (55%) reached the composite outcome of death or infection. PPV was not associated with reduced risk of the composite outcome (589 [62%] vs 1037 [52%] for those unvaccinated; adjusted hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.79–1.04). Results were not altered in sensitivity analyses using propensity scores (adjusted HR, 0.91; 95% CI, 0.79–1.04), restricting the sample to patients 65 years or older (adjusted HR, 0.90; 95% CI, 0.77–1.04), or considering only those who received PPV at discharge (adjusted HR, 0.84; 95% CI, 0.71–1.00).
Second point to keep in mind; the mean patient age was 68 years. The study is itself limited to only “adults at high risk for pneumonia”. So at best, the results of this study might hold for adults, average 68 years old, for whom the vaccine has already failed to offer immune protection. That is quite a small subset of all people who get the vaccine. The question to ask ourselves is: how reliable are such results and how can they be applied to the total vaccinated population?
Conclusions.One‐half of patients discharged from the hospital after pneumonia die or are subsequently hospitalized with a vaccine‐preventable infection within 5 years. PPV was not associated with a reduced risk of death or hospitalization. Better pneumococcal vaccination strategies are urgently needed.
And this is the careless conclusions that I was referring to: “Better pneumococcal vaccination strategies are urgently needed.” Better than what? That is the confusing part. If you choose to only look at the people for whom the vaccine has already failed, what really do you expect the results to be? If the person got sick, the vaccine failed to protect them. If the vaccine failed, wouldn’t we expect both failed-vaccinated and unvaccinated groups to show the same pattern? What insight can one gain by looking at the failed vaccine group? Confirmation that a vaccine that failed to prevent the disease in the person, also fails to reduce mortality rates from the disease? So this study possibly tells us that in people over 68, when the pneumococcal vaccine fails, it fails completely. Hmm, ok, isn’t that kind of to be expected anyway?
How can these results support the conclusion that better pneumococcal vaccination strategies are urgently needed though? The study did not examine pneumococcal vaccine efficacy, like this one properly did, by comparing vaccinated vs. placebo shots and checking out infection and morbidity rates. The only question this study aimed to answer is this: When the vaccine fails to build immunity, does it also fail to protect from death? And the answer, unsurprisingly, is coming back to be yes.
Maybe some vaccines reduce death rates from the disease even if they fail to build immunity against the disease. I guess that is plausible; I don’t know enough to say. However, it appears to me that, the way this study was designed, the way the groups were chosen, leaves a lot to be desired and seems to be set up so as to provide only one possible answer. This study seems better equipped to figure out the mortality rate from pneumococcal than the efficacy of the pneumococcal vaccine. The authors should be more careful with their conclusions and keep in mind the limits of their design; they should be the first ones to acknowledge that their study cannot be generalized to the whole vaccinated population. Yet, somehow they fail to do that and instead make unwarranted conclusions about improving vaccination strategies. That coupled with journalists looking for sensational headlines unfortunately has the effect of sending a message to the public that is not supported by the science. And that is sad; sad and dangerous.
REMINDER: These comments should be held as temporary until I get my hands on the full PDF. That will either verify that my interpretation of the abstract is correct, or I will have to come back and modify my interpretation.
Are vaccines effective? That is another question that worried parents often ask. Do we know for sure that these vaccines do what they are supposed to do? Well, as I’ve said before, that question is very broad, so we will try to break it down into manageable bits. This entry will look and see if we can find any evidence for the efficacy of the pneumococcal vaccine in preventing pneumonia and pneumonia deaths. As usual, PubMed makes for an excellent start. A quick search there brings up this interesting study.
Efficacy of 23-valent pneumococcal vaccine in preventing pneumonia and improving survival in nursing home residents: double blind, randomised and placebo controlled trial. Maruyama T, Taguchi O, Niederman MS, Morser J, Kobayashi H, Kobayashi T, D’Alessandro-Gabazza C, Nakayama S, Nishikubo K, Noguchi T, Takei Y, Gabazza EC. Department of Pulmonary and Critical Care Medicine, Mie University Graduate School of Medicine, Tsu City, Mie Prefecture, Japan. BMJ. 2010 Mar 8;340:c1004. doi: 10.1136/bmj.c1004.
Study Summary – The study was set up to examine the efficacy of the pneumococcal vaccine in preventing pneumonia and/or reducing pneumonia-related deaths. There were a total of 1006 participants from nursing homes in Japan. They were randomly split into two virtually equal groups (in size); one group received the vaccine, the other a placebo. The study was double-blind, meaning that non only did the participants not know if they were on the vaccine or placebo, but those administering the doses did not know either. The results showed a 39.32% decrease in all-cause pneumonia infections between the placebo and the vaccinated group (form 20.6% in the placebo group to 12.5% in the vaccine group). As far as pneumococcal pneumonia rates were concerned, it also showed a decrease, this time of 61.64%. Furthermore, no deaths occurred amongst those in the vaccinated group that developed pneumococcal pneumonia, whereas the placebo group had a death rate of 35.1%. However, death rate from ALL CAUSE pneumonia did not differ between the two groups. The study’s conclusion was as such:
CONCLUSION: The 23-valent pneumococcal polysaccharide vaccine prevented pneumococcal pneumonia and reduced mortality from pneumococcal pneumonia in nursing home residents
So how should we interpret this study? I interpret it like this: the pneumococcal vaccine was significantly effective (as compared to placebo) in preventing both infections and deaths by pneumococcal pneumonia. The vaccine appears to be highly effective for the age group the study investigated. It also significantly decreases all-cause pneumonia infections, but appears to have no effect in death rates for all-cause pneumonia.