hope simpson seasonal

While people may be aware of the annual flu season, most may not know why. In 1981, R. Edgar Hope-Simpson proposed that a ‘seasonal stimulus ’ intimately associated with solar radiation, explained the remarkable seasonality of epidemic influenza.

Solar radiation triggers robust seasonal vitamin D production in the skin; vitamin D deficiency is common in the winter, and activated vitamin D, 1,25(OH) 2 D, a steroid hormone, has profound effects on human immunity.

1,25(OH) 2 D acts as an immune system modulator, preventing excessive expression of inflammatory cytokines and increasing the ‘oxidative burst ’ potential of macrophages. Perhaps most importantly, it dramatically stimulates the expression of potent anti-microbial peptides, which exist in neutrophils, monocytes, natural killer cells, and in epithelial cells lining the respiratory tract where they play a major role in protecting the lung from infection.

Volunteers inoculated with live attenuated influenza virus are more likely to develop fever and serological evidence of an immune response in the winter.

Vitamin D deficiency predisposes children to respiratory infections.

Ultraviolet radiation (either from artificial sources or from sunlight) reduces the incidence of viral respiratory infections, as does cod liver oil (which contains vitamin D).

An interventional study showed that vitamin D reduces the incidence of respiratory infections in children.

We conclude that vitamin D, or lack of it, may be Hope-Simpson’s ‘seasonal stimulus ’.

How is it that prior strains vanish or disappear so quickly upon the appearance of successor strains?

How is it that successor strains overlap geographically so perfectly with prior strains?

Herd immunity seems to be a superficially attractive hypothesis which can not survive closer scrutiny. Only a vanishingly minority of people are ever infected with influenza in any season. So how can future recipients of the virus actually exercise selective pressure.

He noted old experiments where strains represented solutions to antigens. Infection with Strain A in precense of Strain A antibodies yields Strain B and vice versa.

Virus circulated via 2 phases: initial infection followed by months long asymptomatic low level virus replication in the respiratory tract of recovered patients.

Hardly infectious at all in Phase 1 - iniial infection. Primarily spread when seasonal factors caused the asymptomatic Phase 2 carriers to transmit the virus to others.

The selection for variant strains happens during Phase 2 carrier phase. Over months various mutations emerge as solutions to those antibodies, and most people who got Strain A will incubate Strain B as the most fit successor.

So, Alpha when it emerged would in this view be the most fit solution generated by wild type antibodies.

Alpha replaced prior strains via asymptomatic carriers in phase 2.