Bacteria and Influenza: The Streptococcus Vaccine Is One Way to Prepare Against the Unknown

There are two excellent papers in the August edition of Emerging Infectious Diseases (open access) about influenza that suggest alternative (or parallel) ways of dealing with an influenza pandemic (note: by "alternative", I don't mean woo). The standard response that is typically discussed is an influenza vaccine--and I've mentioned before how important it is to increase our influenza vaccination surge capacity (not only is it good for dealing with a pandemic, but could serve as a source of vaccine production against the annual epidemic).

There's a problem with this strategy.

We can't be certain what the type of influenza that will lead to an epidemic will be. In other words, we're playing catch-up with a very short clock. After we identify an epidemic strain, it will take at weeks, if not several months, to begin vaccine production. Even if the U.S. were to hoard its vaccine supplies, it would take months to cover a significant fraction of the population.

However, there is something that we do know will happen if there is an epidemic: many, if not most, influenza patients will die, not from the virus itself, but from the secondary bacterial infection--and most of these infections will be caused by Streptococcus pneumoniae for which there is a highly effective vaccine, even against serotypes not included in the vaccine.

So that's the punchline, now to the papers. I'll focus on the Brundage and Shanks paper, which is a historical review of the 1918-1919 pandemic. The authors note:

The findings of sharply different clinical courses and outcomes in subgroups of infected persons of similar ages, sociocultural circumstances, and prior health states belie the importance of host immune intensity and cardiac stroke volume as the definitive determinants of clinical outcomes after infection. Undoubtedly, factors other than the inherent virulence of the virus or the robustness of the host's immune response affected the clinical expressions of influenza infections. In his classic review, E.O. Jordan concluded that "one of the chief reasons for the great variation in case-fatality in different groups is undoubtedly the nature and relative abundance of secondary invaders ... The excessively high mortality in certain army camps, on certain transports and in particular hospitals or barracks seems most readily explicable in this way"

What's interesting (in a kind of horrific way) is the mechanism by which the 1918 strain led to bacterial infection; this is from a review published in 1927 (italics mine):

"(1) The influenza virus weakens the resistant power of the pulmonary tissues so that various bacteria are able to play the role of secondary invaders; (2) the precise nature of the secondary--and tertiary--invaders is largely a matter of accident, dependent on the occurrence of particular bacteria in the respiratory tract of persons at the time of infection, and in the case of group outbreaks, on their occurrence in contacts; (3) the character of the resulting pneumonia, clinical and pathologic, is largely determined by the nature of the secondary invaders, whether Pfeiffer bacillus, streptococcus, pneumococcus, or other organisms; (4) there seems little doubt that the influenza virus, besides depressing the general pulmonary resistance, also acts directly on the pulmonary tissues, causing capillary necrosis, edema, and hemorrhage; (5) it seems to be true, therefore, that the fatal outcome of influenza pneumonia is determined partly by the degree to which the influenza virus depresses local and general pulmonary resistance, and partly by the virulence and nature of the bacteria which invade the tissues in the wake of the specific virus."

In other words, influenza physically damages the lungs (possibly through the "cytokine storm" effect), which makes it much easier for the bacteria that live in and on you to cause disease (think of it as Revenge of the Boogers). The review authors summarize this quite well:

For most patients, infection with the virus was clinically expressed as an "influenza-like illness" that was transiently debilitating but rarely fatal. In addition, however, the virus induced aberrant immune responses, including excessive and prolonged production of interferons, proinflammatory cytokines, and chemokines, particularly among young adults. The pathophysiologic effects included inflammation and destruction of respiratory epithelium; immune cell infiltration of lung tissue with edema and hemorrhage; and ultimately, degradation or destruction of virtually all physical and immune defenses of the lower respiratory tract. Increased susceptibility of the lower respiratory tract enabled invasion by preexisting or newly acquired colonizing strains of bacteria. The synergistic effects of infection with the virus, aberrant immune responses to the virus, and secondary opportunistic bacterial pneumonias were severe and often fatal.

Finally, for brief periods and to varying degrees, affected hosts became "cloud adults" who increased the aerosolization of colonizing strains of bacteria, particularly pneumococci, hemolytic streptococci, H. influenzae, and S. aureus. For several days during local epidemics--particularly in crowded settings such as hospital wards, military camps, troop ships, and mines--some persons were immunologically susceptible to, infected with, or recovering from infections with influenza virus. Persons with active infections were aerosolizing the bacteria that colonized their noses and throats, while others--often, in the same "breathing spaces"--were profoundly susceptible to invasion of and rapid spread through their lungs by their own or others' colonizing bacteria.

I don't mean to downplay the serious of influenza infection by itself--over one percent of the annual non-pandemic influenza cases are fatal, and only one-quarter of those are associated with bacterial infection* (although this is consistent with the virus killing mostly immunologically weakened people, the elderly, and infants). But we can do a lot during a pandemic if a vaccine isn't ready or widely available by vaccinating against S. pneumoniae and other pulmonary pathogens. We also need rapid diagnostics that can identify bacterial infections and which antibiotics will be effective against these infections.

The advantage of these strategies is that we do not have to know what the influenza strain is--stockpiling and preparing these technologies could begin today, if we so choose.

In lieu of an influenza vaccine, these two steps could save many lives. And it wouldn't be a bad idea to have these systems in place all of the time, either....

*These data haven't been published yet, but I've seen compelling evidence that one of the most common bacterial pathogens is routinely missed because clinical labs can't grow it on standard laboratory media. The one-quarter figure should be seen as a lower bound, not a definitive figure.

Cited articles: Brundage JF, Shanks GD. Deaths from bacterial pneumonia during 1918-19 influenza pandemic. Emerg Infect Dis [serial on the Internet]. 2008 Aug [date cited]. Available from DOI: 10.3201/eid1408.071313

Gupta RK, George R, Nguyen-Van-Tam JS. Bacterial pneumonia and pandemic influenza planning. Emerg Infect Dis [serial on the Internet]. 2008 Aug [date cited]. Available from DOI: 10.3201/eid1407.070751

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I am 56-years-old and tried to get a pneumonia shot but was told that it is generally not given to someone under age 65 because its effectiveness wears out and (for some unknown reason) docs don't want to get someone that vaccine twice.

What's the background to that reasoning?

The safety of revaccinating for streptococcus pneumoniae seems to have been questioned in the past but severe adverse reaction seem to quite rare.

L.A. Jackson, P. Benson, V.P. Sneller, J.C. Butler, R.S. Thompson, R.T. Chen et al.,

Safety of revaccination with pneumococcal polysaccharide vaccine.

J. Am. Med. Assoc. 281 (1999)

Paste a search string from the above into Scholar.

Limited to 2008, the search turns up among other things this:

Alternative strategies for adult pneumococcal polysaccharide vaccination: A cost-effectiveness analysis

... vaccination at ages 50 and 65 prevented more IPD than present vaccination policies; four decennial vaccinations were most effective. The present vaccination policy costs $3341/QALY gained, vaccinations at 50/65 cost $23,120/QALY and four vaccinations (50/60/70/80) cost $54,451/QALY; results were sensitive to vaccine uptake assumptions, with current policy no longer favored at present vaccination rates. PPV at ages 50/65 may be clinically and, depending on cost-effectiveness criterion used, economically favored over present vaccination recommendations.....

----end excerpt-----
*QALY -- Quality Adjusted Life Years

My speculation -- the insurance companies don't want to pay that money; after age 65 probably a lot of the cost is borne by Medicare in the US rather than by the private health insurer. I'd guess the refusal to provide the vaccination before age 65 is actually from the insurance company. Try asking your doctor if you can pay for it yourself.

Also ask your doctor if the insurance contract you and she are covered by interferes with her freedom to provide you with medical treatment you pay for yourself. Some contracts do penalize doctors who let you pay yourself for anything disallowed by insurance, my then doctor told me about my then health insurance plan, a few years ago. It's a dirty little secret. Flee that.

By Hank Roberts (not verified) on 31 Aug 2008 #permalink

See also:
Comparison of Pneumococcal Conjugate Polysaccharide and Free Polysaccharide Vaccines in Elderly Adults: Conjugate Vaccine Elicits Improved Antibacterial Immune Responses and Immunological Memory
"... an initial dose of conjugated pneumococcal polysaccharide (PnC) vaccine may be of value in a comprehensive adult immunization strategy."
(better immune response using PnC first than using FPV first)

(the Erratum mentioned is a typo in an author name, not an error in the study itself)

By Hank Roberts (not verified) on 31 Aug 2008 #permalink


Thanks for the links. Like you, I'm guessing that this primarily has to do with cost, and not public health.

my cousin who is 12 yrs.old is in the hospital fighting for her life from what we thought was Strep we found out that she also has the flu type 2.her lungs are not working well they had to give her a lung and heart bypass so they can rest and start to heal. her blood pressure is down to 40 which is not good at all.i just want to know what else can cause her body to start shutting down like this .they also said they found mrsa is her nose.could that have gotten into her system through her strep throat? she is at one of the best hospitals for children.but we are truly lost.If she does make it through this they said that it could take 3 months for her to get back to just being off the machines that shes on.i just need to know if anyone can tell me somthing because they don't know what the secondary infection is that is basicly eating her lungs away is. thanks