On the Epidemiology of Influenza

[Laidback Al]

Virology Journal 2008, 5:29doi:10.1186/1743-422X-5-29

On the Epidemiology of Influenza
John J Cannell<SUP>1</SUP> Michael Zasloff<SUP>2</SUP> , Cedric F Garland<SUP>3</SUP> , Robert Scragg<SUP>4</SUP> and Edward Giovannucci<SUP>5</SUP>
<SUP>1</SUP>Department of Psychiatry, Atascadero State Hospital, 10333 El Camino Real, Atascadero, CA 93423, USA
<SUP>2</SUP>Departments of Surgery and Pediatrics, Georgetown University, Washington, D.C., USA
<SUP>3</SUP>Department of Family and Preventive Medicine, University of California San Diego, La Jolla, CA, USA
<SUP>4</SUP>Department of Epidemiology and Biostatistics, University of Auckland, Auckland, New Zealand
<SUP>5</SUP>Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA, USA


Virology Journal 2008, 5:29doi:10.1186/1743-422X-5-29
The electronic version of this article is the complete one and can be found online at: http://www.virologyj.com/content/5/1/29
<TABLE cellSpacing=0 cellPadding=0><TBODY><TR><TD>Received:</TD><TD>9 February 2008</TD></TR><TR><TD>Accepted:</TD><TD>25 February 2008</TD></TR><TR><TD>Published:</TD><TD>25 February 2008</TD></TR></TBODY></TABLE>
? 2008 Cannell et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The epidemiology of influenza swarms with incongruities, incongruities exhaustively detailed by the late British epidemiologist, Edgar Hope-Simpson. He was the first to propose a parsimonious theory explaining why influenza is, as Gregg said, "seemingly unmindful of traditional infectious disease behavioral patterns." Recent discoveries indicate vitamin D upregulates the endogenous antibiotics of innate immunity and suggest that the incongruities explored by Hope-Simpson may be secondary to the epidemiology of vitamin D deficiency. We identify ? and attempt to explain ? nine influenza conundrums: (1) Why is influenza both seasonal and ubiquitous and where is the virus between epidemics? (2) Why are the epidemics so explosive? (3) Why do they end so abruptly? (4) What explains the frequent coincidental timing of epidemics in countries of similar latitude? (5) Why is the serial interval obscure? (6) Why is the secondary attack rate so low? (7) Why did epidemics in previous ages spread so rapidly, despite the lack of modern transport? (8) Why does experimental inoculation of seronegative humans fail to cause illness in all the volunteers? (9) Why has influenza mortality of the aged not declined as their vaccination rates increased? We review recent discoveries about vitamin D's effects on innate immunity, human studies attempting sick-to-well transmission, naturalistic reports of human transmission, studies of serial interval, secondary attack rates, and relevant animal studies. We hypothesize that two factors explain the nine conundrums: vitamin D's seasonal and population effects on innate immunity, and the presence of a subpopulation of "good infectors." If true, our revision of Edgar Hope-Simpson's theory has profound implications for the prevention of influenza.

Full article at: http://www.virologyj.com/content/5/1/29

Credits to gsgs

 

[mixin]

Re: On the Epidemiology of Influenza

Interesting study; here are some of their thoughts:

To make sense of influenza's epidemiology, we revise Hope-Simpson theory, hypothesizing marked variation in the infectivity of the infected (the good infectors demonstrated in rats by Schulman and Kilbourne in 1963) and that vitamin D deficiency is Hope-Simpson's seasonal stimulus. Adding these two factors to transmissibility, virulence, and adaptive immunity, solves a number of influenza's mysteries.

1. Why is influenza both seasonal and ubiquitous and where is the virus between epidemics?

If influenza were surviving in an endless chain of transmissions from good transmitters to the well ? the good transmitters being generally asymptomatic during times of enhanced innate immunity ? the disease would be widely seeded in the population, explaining its ubiquity. Seasonal impairments in innate immunity would allow seasonal epidemics in temperate latitudes and less predictable epidemics in tropical zones, depending on viral novelty, transmissibility, virulence, and the innate immunity of the population. Non-seasonal isolated outbreaks would usually only appear in nursing homes [85] or prisons [86] where lack of sunlight impaired innate immunity; such isolated outbreaks would seldom lead to community outbreaks. More extensive out-of-season outbreaks, as occurred in 1918, would arise when novel antigenic viruses with significantly greater infectivity and virulence overwhelm innate immunity.

2. Why are influenza epidemics so explosive?

Predictable fall and winter impairments in innate immunity in temperate latitudes ? and less predictable recurrent impairments in subequatorial and equatorial latitudes ? would cause a percentage of the non-immune population to become suddenly susceptible to background influenza virus. The size of that susceptible subpopulation would vary, not only by the size of their impairments in innate immunity, but with the transmissibility and virulence of the virus, and the percentage of the population with competent adaptive immunity. Abrupt deficiencies in innate immunity, especially when large segments of the population also have inadequate adaptive immunity, would allow quiescent influenza to erupt.

3. Why do epidemics end so abruptly?

The rapid depletion of the population with both impaired innate and inadequate adaptive immunity may explain the abrupt disappearance of influenza. Impairments in innate immunity may also increase transmission, in effect, turning more infectors, symptomatic or not, into good transmitters. Furthermore, if only a small population of good transmitters ? and not all the sick ? usually spread the virus, and their transmission period is limited, the epidemic would end shortly after the good transmitters lose their infectivity.

4. What explains the frequent coincidental timing of epidemics in countries of similar latitudes?

Simultaneous impairments of innate immunity at similar latitudes ? due to seasonal sunlight deprivation ? explain the almost simultaneous eruption of influenza at sites of different longitude but similar latitude. If the virus had already imbedded itself in a population and a subgroup of the infected became good transmitters when their innate immunity declines to a critical threshold, such transmitters would coincidentally infect populations at similar latitudes made susceptible by those same impairments in innate immunity.

5. Why is the serial interval obscure?

Good transmitters explain the difficulty identifying influenza's serial interval especially since influenza's incubation period is well known. If only subpopulations of infected persons are good transmitters, and if their infectious period is limited, then the serial interval would remain obscure until we identified the good transmitters. Vitamin D induced variations in natural immunity may also affect influenza's incubation period, further obfuscating the serial interval.

6. Why is the secondary attack rate so low?

The studies we identified found a secondary attack rate of around 20%, impossibly low for a highly infectious virus spread from the sick to the well. If only a subpopulation of the infected, the good transmitters, are infective, this would explain the surprisingly low secondary attack rates. Current estimates of secondary attack rates assume the first case in the family is the index case and is spreading the disease. However, if only a subpopulation of infected persons transmit the disease, the true secondary attack rate could not be accurately determined until we identify the good infectors.

7. Why did epidemics in previous ages spread so rapidly, despite the lack of modern transport?

If influenza were embedded in the population, only to erupt when impairments in innate immunity create a susceptible subpopulation, the disease would only give the appearance of spreading. Instead, it would appear in large segments of the population seasonally, and almost simultaneously, as long as good transmitters were available. Furthermore, as good transmitters traveled, populations with neither adequate innate immunity nor competent adaptive immunity may succumb. That is, the disease would actually spread, as good transmitters traveled and subsequently infected well subpopulations with impaired immunity.

8. Why does experimental inoculation of seronegative humans fail to cause consistent illness?

If influenza is highly infectious, one would expect most, if not all, human volunteers iatrogenically inoculated with a novel virus to fall ill. Although the rate of illness depends on the virus used and the dose of the inoculum, variations in the innate immunity of the volunteers also explain such variable illness response. We propose individual variations in 25(OH)D levels explain some degree of the variations in illness response.

9. Over the last 20 years, why has influenza mortality in the aged not declined with increasing vaccination rates?

Given that influenza vaccines effectively improve adaptive immunity, the most likely explanation is that the innate immunity of the aged declined over the last 20 years due to medical and governmental warnings to avoid the sun. While the young usually ignore such advice, the elderly often follow it [87,88]. We suggest that improvements in adaptive immunity from increased vaccination of the aged are inadequate to compensate for declines in innate immunity the aged suffered over that same time.

 

[mixin]

Re: On the Epidemiology of Influenza

Also in the study is a lengthy discussion regarding vitamin D and they say:

Because humans obtain most vitamin D from sun exposure and not from diet, a varying percentage of the population is vitamin D deficient, at any time, during any season, at any latitude, although the percentage is higher in the winter

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As I was reading the Pandemic Influenza of 1918-1919 and I found this observation by the writer. I wonder if it's possible that by placing the sick outside, it boosted their vitamin D levels enough to aid in their recovery?

"It is difficult to give any opinion as to whether the patients
should be nursed in warm rooms or in cold, or even out of doors ;
at the beginning of the attack warmth, and the production of
perspiration, certainly does seem to tend towards a favourable
course in the disease, so that in the early stages at any rate it
would seem advisable to have the patient in warm, though well
ventilated, rooms or wards.

On the other hand, when one had the opportunity of seeing
the severe " pneumonic " cases verging
upon cyanosis, or with the heliotrope colour actually developed,
sometimes nursed in relatively warm wards and sometimes put
right out of doors with waterproof canopies to keep off the rain,
and warm clothing to keep their bodies warm, though their
faces were exposed to the autumn or winter air, there could be
little doubt that of these two alternative procedures, the outdoor
and apparently more drastic line of treatment gave the better
results.

In some hospitals where there was immense strain
upon the available beds, it became necessary to put the worst,
and apparently hopeless cases, elsewhere, in order to make a
maximum amount of room for ]ess bad cases that seemed
recoverable, and one saw scores of extremely bad cases transferred
from the wards to the quadrangles out of doors, under
waterproof canopies, and whereas at first one felt that this—
though a necessary procedure—would at least not help any of
these dire cases to get better, one found to one's surprise that a
larger number of those very worst cases put out of doors did, as
a matter of fact, recover than would have been the case, one felt
sure, had they remained indoors One is therefore in this
difficulty : one feels that at the beginning of the attack the
patient should be nursed in warmth; that if " pneumonic"
cyanosis has developed he is better out of doors ; but that one
does not know just at what stage the change of conditions of
nursing should be made for the best advantage of a bad case."

http://influenza.sph.unimelb.edu.au/MOH_TOC.php (also linked in a FT post)

 

[gsgs]

Re: On the Epidemiology of Influenza

however, as I wrote on the other thread, now we have the sequencing
data, which seems to show how influenza-A is seeded from
SE-Asia each season and circles the globe.

That doesn't so well fit with the theory that flu survives
silently in some superspreaders and is activated by
immunity-changes.

I was surprised by the 20% 2nd attack rate,
while other diseases have 70%
hadn't seen this before.

they also mention the unsuccessful trials in 1918 to infect "volunteers".
I have seen no explanation yet.
Can some of the experts please comment ???