One of the most frustrating things I find as a "blogger" is that I tend to ramble, and for what is supposed to be a "tightly focused" blog that is a bad thing. Another bad thing in this medium is the long entry. As I attempted to write up everything I wanted to say in my last entry it was too long and too winding and just plain too. So I am "chunking" the stuff I want to ramble on about in the hopes that y'all out there won't notice.
My last post, Informed Seats and My Favorite Chair, dealt mainly with introducing R0 (Reproduction number) of infectious disease, and specifically, pandemic influenza. How pandemic planners are working with the assumption of a 1.x – 2.x for the R0.
My favorite theory to explain the epidemiology of the influenza pandemic of 1918 has been prior exposure/circulation of H1N1 or a close relative. Now I have to consider heterosubtypic immunity (immunity across subtypes) as at least as likely an explanation, if not more so.
All-cause and P&I monthly mortality rates for all ages (A and B) and all-cause mortality rates by age group (C-H) are calculated per 10,000 population. Observed rates are days-per-month adjusted. Expected model baselines (solid lines) are derived from each series of nonepidemic months. Epidemic thresholds (dashed lines) are the upper 95% confidence limit above each baseline. The major epidemic influenza season months are indicated (shaded). Two 1917/1918 influenza season peaks (arrowheads) show excess mortality primarily confined to the ≥65-years age group in January (C), and to the groups <45 years old in March 1918 (E-H). Other severe mortality events are evident: summer diarrheal disease epidemics were confined to young children (H), the 1916 polio epidemic to all children (G and H), and the summer 1917 heat wave and diarrheal disease epidemic among the youngest and oldest age groups (C and H).
Proc Natl Acad Sci U S A. 2005 August 2; 102(31): 11059–11063.
Published online 2005 July 26. doi: 10.1073/pnas.0408290102.
Graph and legend from Epidemiological evidence of an early wave of the 1918 influenza pandemic in New York City Donald R. Olson, et al.
Of particular interest is section B of the above graphic showing the monthly mortality rates due to P&I (Pneumonia & Influenza) for all ages. The above paper also happens to be one of the major supports for my "prior exposure/circulation" belief.
But what if…
What if we only saw a ~30% CAR (Clinical Attack Rate) and ~2.5% CFR (Case Fatality Ratio) because many people benefited from heterosubtypic immunity from a not too long past bout of seasonal influenza A?
Drawing on A Biological Model for Influenza Transmission: Pandemic Planning Implications of asymptomatic Infection and Immunity John D. Mathews et al.
Reports of past influenza pandemics show marked variation in clinical attack rates between populations. In the 1918–19 H1N1 pandemic, rates of clinical illness were less than 20% in some urbanised communities, but more than 60% in isolated communities such as Western Samoa –. During the 1968 H3N2 pandemic, attack rates in US households were limited to 30–40% , whereas almost the whole population fell ill when the virus reached the isolated island of Tristan da Cunha (TdC) in 1971 . Biologically-based models for pandemic influenza  that incorporate effects of host immunity can help to explain such differences in observed attack rates.
The paper draws a correlation to urban settings and the likelihood of a higher, more consistent rate of seasonal influenza infection than those likely experienced in relatively geographically isolated areas. The island of Tristan Da Cunha is both geographically isolated and remote thus serving as a perfect example.
The population of Tristan da Cunha, a remote island in the South Atlantic, had been free of influenza for 8–9 years when H3N2 was introduced by ship from South Africa in 1971. The resulting epidemic curve over 50 days was based on reports of cases by day of symptom-onset. In two waves, 96% of the population of 284 fell ill; there were 365 recorded attacks, of which 312 could be identified with a precise day of onset. 273/284 islanders experienced a first attack of influenza, and 92/284 experienced a second attack. Most second attacks coincided with the second population wave; a minority of individuals experienced a first (and only) clinical attack during the second wave, possibly following asymptomatic infection during the first wave. Second attacks were generally less severe.
What might this imply for a future influenza pandemic?
This paper's findings suggest someone suffering a bout of influenza A in their recent past may have a degree of immunity, even if the previous influenza is not the same sub-strain (homogeneous). Immunity could range from total, to asymptomatic infection or lessened severity. Conversely, someone who has not suffered a recent bout of influenza A could be as naked and vulnerable to a novel influenza strain as a newborn babe is to the world they arrive into.
Taking this possibility three steps further into supposition territory:
We are currently seeing a frightfully high mortality rate with human infections of H5N1, ~60% cumulative and ~80% in Indonesia. The infections have been in countries and in populations that do not have annual influenza vaccination programs to protect them from the seasonal influenza that arrives yearly. Is it reasonable to postulate that those infected had also suffered a human seasonal A variety sometime within three years previous? I would assume that it is a reasonable assumption that many had. Heterosubtypic immunity did not play a great role here, or if it did, perhaps it allowed for only a severe infection as opposed to a fatal one. A severe infection, that with Tamiflu and medical support ended up being survivable.
In my previous post I made mention that the R0 was not the only staggering gem the recent paper on A Biological Model for Influenza Transmission: Pandemic Planning Implications of asymptomatic Infection and Immunity held.
Unfortunately, heterosubtypic immunity, which can be short-lived, is likely induced more effectively by recent infection with a live influenza virus than by conventional sub-unit vaccines , . This raises the possibility that inter-pandemic sub-unit vaccine, by preventing infection with live inter-pandemic virus, could even make people more susceptible to a novel pandemic virus. The bottom line is that we need much more information about heterosubtypic immunity in humans, and about the potential value of live-attenuated influenza vaccines against H1N1 and H3N2 in protecting populations against H5N1 or any other novel pandemic virus. We await the results of relevant research with great interest.
I will share with you the closing thoughts of the person who pointed out a logical end-point to these findings and assumptions; they say it far better than I could:
"I don't think that it is enough to have had the experience of just not having access to vaccines, and getting seasonal influenza's that would protect a person, else the mortality rate in Indonesia wouldn't be what it is. The problem is not that people do well if not vaccinated yearly, rather that they may do worse if they have been dutifully getting their influenza vaccine." [emphasis added]