Pathogenic Responses among Young Adults during the 1918 Influenza Pandemic

[tetano]

EID Journal
Past Issues
February 2012

Volume 18, Number 2?February 2012
Perspective
Pathogenic Responses among Young Adults during the 1918 Influenza Pandemic
Article Contents

Unique and Unexplained Characteristics of the 1918 Pandemic
Hypotheses
References
Figure
Suggested Citation

G. Dennis ShanksComments to Author and John F. Brundage
Author affiliations: Australian Army Malaria Research Institute, Enoggera, Queensland, Australia (G.D. Shanks); Armed Forces Health Surveillance Center, Silver Spring, Maryland, USA (J.F. Brundage)

Suggested citation for this article
Abstract

Of the unexplained characteristics of the 1918?19 influenza pandemic, the extreme mortality rate among young adults (W-shaped mortality curve) is the foremost. Lack of a coherent explanation of this and other epidemiologic and clinical manifestations of the pandemic contributes to uncertainty in preparing for future pandemics. Contemporaneous records suggest that immunopathologic responses were a critical determinant of the high mortality rate among young adults and other high-risk subgroups. Historical records and findings from laboratory animal studies suggest that persons who were exposed to influenza once before 1918 (e.g., A/H3Nx 1890 pandemic strain) were likely to have dysregulated, pathologic cellular immune responses to infections with the A/H1N1 1918 pandemic strain. The immunopathologic effects transiently increased susceptibility to ultimately lethal secondary bacterial pneumonia. The extreme mortality rate associated with the 1918?19 pandemic is unlikely to recur naturally. However, T-cell?mediated immunopathologic effects should be carefully monitored in developing and using universal influenza vaccines.

http://wwwnc.cdc.gov/eid/article/18/2/10-2042_article.htm

[tetano]

Re: Pathogenic Responses among Young Adults during the 1918 Influenza Pandemic

1918 Influenza, a Puzzle with Missing Pieces


EID Journal
Past Issues
February 2012

Volume 18, Number 2?February 2012
Commentary
1918 Influenza, a Puzzle with Missing Pieces
Article Contents



David M. MorensComments to Author and Jeffery K. Taubenberger
Author affiliations: National Institutes of Health, Bethesda, Maryland, USA

Suggested citation for this article

Shanks and Brundage offer thought-provoking hypotheses about influenza pathogenesis during the catastrophic 1918?1919 pandemic (1). Although we neither agree nor disagree with their views, its central hypothesis of T-cell?mediated immunopathogenesis begs examination of past events in light of modern immunologic and virologic understanding. We also emphasize that effects of the pandemic virus should not be measured only by illness and death in 1918?1919, but should also take into account disease caused by its descendent seasonal and pandemic influenza viruses up to the present (2). Thus, for human influenza history to be better understood, it must be continually reevaluated.

Figure
Thumbnail of Combined influenza plus pneumonia (P&I) age-specific incidence, mortality, and case-fatality rates, per 1,000 persons/age group, US Public Health Service house-to-house surveys, 8 states, 1918, and US Public Health Service surveys during 1928?1929. A) P&I incidence for 1918; B) mortality rate for 1918 (ill and well persons combined); C) P&I case-fatality rates for 1918 (solid line) compared with a more typical curve of age-specific influenza case-fatality rates (dotted l

Figure. Combined influenza plus pneumonia (P&I) age-specific incidence, mortality, and case-fatality rates, per 1,000 persons/age group, US Public Health Service house-to-house surveys, 8 states, 1918, and US Public Health Service surveys during...

Specifically, Shanks and Brundage hypothesize that high mortality rates in 1918 resulted from immunopathogenic effects of cell-mediated immune responses elicited by previously circulating influenza viruses. They also suggest that clues to immunopathogenic mechanisms are found in the unique, but well-documented, W-shaped age-specific mortality curve of the 1918 pandemic (3) (Figure) in which the typical (U-shaped) curve of pandemic influenza, featuring mortality rate peaks in young and old persons, was augmented by an unprecedented third mortality rate peak in persons 20?40 years of age.

A complicating fact about ≈1918?1919 mortality patterns and pathogenesis hypotheses is that for ≈98% of infected persons, influenza was clinically unremarkable in its traditional signs and symptoms (fever, cough, myalgia) and severity (4). Clinical and epidemiologic differences were confined to 2 aspects: higher frequency of its long-appreciated post-illness complication (bacterial pneumonia) (5) and an unusual peak in fatal or nonfatal pneumonia cases in persons 20?40 years of age. In 1918, a higher percentage of persons of all ages, and especially those 20?40 years old, experienced influenza that led to cases of secondary bacterial pneumonia, which were caused by highly prevalent pneumopathogenic bacteria (especially pneumococci, streptococci, and staphylococci). These bacteria had been continuously causing primary pneumonia and pneumonia after influenza and other respiratory illnesses, and had long been exacting a substantial death toll.

..

http://wwwnc.cdc.gov/eid/article/18/2/11-1409_article.htm

[Emily]

Re: Pathogenic Responses among Young Adults during the 1918 Influenza Pandemic

From the first CDC article that covers need for caution in designing a universal flu vaccine:

Studies in pigs suggest that the NP of most swine influenza strains contains a strongly immunogenic CD8+ T-cell epitope. For example, pigs that were primed with a DNA vaccine that expresses NP, and subsequently challenged with an influenza A strain with the same NP, had dysregulated, pathogenic immune responses (35). Also, pigs that were primed with an inactivated swine influenza A vaccine (A/swine/Iowa/15/1930 H1N1) and subsequently challenged with a later generation swine influenza A strain with markedly different surface proteins (A/swine/Minnesota/00194/2003 H1N2) showed development of enhanced (immunologically potentiated) pneumonia that were not observed after challenge with the homologous strain (36). The findings have been reproduced by using pandemic (H1N1) 2009 virus as the challenge strain and adding a recombinant matrix 2 protein to the vaccine construct (37).

Post from 2009:

http://www.flutrackers.com/forum/sho...65&postcount=3

Study below in swine showing dramatically enhanced disease in pigs vaccinated with mistmatched swine flu strain. (This effect, called a 'train wreck' is seen in the field at times. Pigs are less genetically diverse that humans, so this effect would be more scattered and harder to detect in humans.)

http://www.ars.usda.gov/research/pub..._no_115=204405

http://www.newscientist.com/article/...on.html?page=1

Flu outbreak: The pig connection

16:18 05 May 2009 by Peter Aldhous
[snip]
Do these vaccines work?

Yes and no. "When stars aligned and we picked the right virus there was great success," says Baker. But when his pigs were infected with a different virus by the time they were injected with a bespoke vaccine, the result was sometimes a "train wreck".

It sounds like the US pork industry has been having a nightmare.

You could say that. Under some circumstances, vaccination may even have made the disease worse. While at Premium Standard Farms, Baker ran one experiment in which 20,000 pigs were given a mass-produced vaccine, and 20,000 were left unvaccinated. Alarmingly, there were twice as many deaths in the vaccinated group.

This paradoxical result is thought to be due to a phenomenon called "original antigenic sin", in which antibodies produced against a virus that is subtly different from a previously encountered vaccine don't eliminate the virus, but instead shield it from other components of the immune system.

The 'bespoke' vaccines are quickly formulated in response to an urgent situation on one farm. Since they aren't formulated for mass distribution, the testing requirements are not as rigorous.