Influenza is characterised by fever, myalgia, headache and pharyngitis. In addition there may be cough and in severe cases, prostration. There is usually not coryza (runny nose) which characterises common cold infections.
Infection may be very mild, even asymptomatic, moderate or very severe (see letter from 1918, - attached at end of page).
Consist of:
1. Pneumonia caused by influenza itself; and
3. Other viral superinfection, eg. Adenovirus.
Overall death rates increase in times of influenza epidemics.
A. Viral Isolation:
a) Rapid examination of cells by immunofluorescence.
b) Inoculation of cell cultures (or eggs).
B. Serology
serum antibodies by haemagglutination inhibition
Diagramatic representation of the morphology of an influenza virion.
The other type of envelope spike is
a trimeric protein called the haemagglutinin (HA)
(illustrated on the right)
of which there are 13 major antigenic types. The haemagglutinin functions
during attachment of the virus particle to the cell membrane, and can combine
with specific receptors on a variety of cells including red blood cells.
The lipoprotein envelope makes the virion rather labile - susceptible to
heat, drying, detergents and solvents.
CLICK here to
see Electron
micrographs of the virion
REPLICATION
Receptor-bound viruses are taken into the cell by endocytosis. In
the low pH environment of the endosome, RNP is released from MP1, and the
viral lipoprotein envelope fuses with the lipid-bilayer of the vesicle,
releasing viral RNP into the cell cytoplasm, from where it is transported
into the nucleus. New viral proteins are translated from transcribed messenger
RNA (mRNA). New viral RNA is encased in the capsid protein, and together
with new matrix protein is then transported to sites at the cell surface
where envelope haemagglutinin and neuraminadase components have been incorporated
into the cell membrane. Progeny virions are formed and released by
budding.
The cell does not die (at least not initially).
Flu is one of a rare few viruses that has its genome in separate segments (eight). - This increases the potential for recombinants to form (by interchange of gene segments if two different viruses infect the same cell), and may contribute to the rapid development of new flu strains in nature - can also be duplicated in the laboratory (used for making vaccine strains). Avian and human strains recombining in pigs in the Far East may permit virulent human strains to evolve.
Influenza A -HA undergoes minor and occasional major changes - very
important.
- NA some variation.
Influenza B) Undergoes relatively slow change in HA with time. Known
only in man.
Influenza C) Uncommon strain, known only in man.
| A | SINGAPORE | 6 | 86 | (H1N1) |
|---|---|---|---|---|
| TYPE of influenza |
TOWN where first isolated |
NUMBER of isolates |
YEAR of isolation |
MAJOR TYPE of HA and NA |
EPIDEMIOLOGY
Influenza A virus is essentially an avian virus that has "recently" crossed
into mammals. Birds have the greatest number and range of influenza strains.
Avian haemagglutinins sometimes appear in pig human and horse influenza
strains.
Every now and then (10 - 15 years) a major new pandemic strain appears in
man, with a totally new HA and sometimes a new NA as well (antigenic
shift). This variant causes a major epidemic around the world (pandemic).
Over the subsequent years this strain undergoes minor changes (antigenic
drift) every two to three years, probably driven by selective antibody
pressure in the populations of humans infected.
See chart below indicating main pandemic strains in previous years.
This constant antigenic change down the years means that new vaccines have to be made on a regular basis.
New influenza strains spread rapidly in children in schools and créches and in places where people crowd together. Influenza epidemics may cause economically significant absenteeism.
Antibiotics are often prescribed - have no effect on virus but may prevent or cure bacterial superinfection. The drug Amantadine may prevent influenza if taken continuously by high-risk persons at the time of an epidemic, but is not used widely.
PREVENTION
Vaccines at best give about 70% protection.
They may sometimes not be effective against the most recently evolved strains
because the rate of evolution outpaces the rate at which new vaccines can
be manufactured.
Types of Vaccine
Killed Whole Virus
Rather pyrogenic, not used today.
Live Virus
Attenuated strains were widely used in Russia but not elsewhere.
Virus Subunit
HA extracted from recombinant virus forms the basis of today's vaccines.
For example, the WHO Recommendation for Influenza Vaccine, 1995-1996,
contains two A strains and one B strain:-
Synthetic
Much research is being done to try and find a neutralising epitope that is
more stable, and can therefore be used for a universal vaccine.
PROSPECTS
Because another devastating pandemic strain (cf 1918 pandemic) may appear at any time, the World Health Organisation (WHO) maintains worldwide surveillance of flu strains and makes predictions of suitable strains for vaccine production.
GA Keen
May 1995
UCT
An illustration of what influenza can be like: a copy of a letter by Professor N R Grist (Glasgow) published in the British Medical Journal of 22-29 December 1979:-
Epidemic influenza remains the biggest and unconquered acute threat to
human health, inflicting damage and death far beyond familiar notification
data. The impact of influenza A is particularly severe during periodic pandemics
owing to novel antigenic variants which override immunity from experience
of earlier subtypes. It is salutary to remember that we do not really understand
why the devastating pandemic of 1918-19 was so severe, and that we cannot
therefore be confident that our modern medical measures would succeed against
a similar future challenge.
As a reminder of the grim reality of that pandemic, the following letter
may be of interest. It was found in a trunk in Detroit among other medical
papers handed to the department of epidemiology of the University of Michigan.
A copy was given to me in 1959 by the late Dr T Francis, jun, and it is now
published with the agreement of Dr V Hawthorne, his successor as head of
department.
N R GRIST
Copy of original letter found in Detroit in 1959
Camp Devens, Mass.
Surgical Ward No 16
29 September 1918
(Base Hospital)
My dear Burt-
It is more than likely that you would be interested in the news of this place,
for there is a possibility that you will be assigned here for duty, so having
a minute between rounds I will try to tell you a little about the situation
here as I have seen it in the last week.
As you know I have not seen much Pneumonia in the last few years in Detroit,
so when I came here I was somewhat behind in the niceties of the Army way
of intricate Diagnosis. Also to make it good, I have had for the last week
an exacerbation of my old "Ear Rot" as Artie Ogle calls it, and could not
use a Stethoscope at all, but had to get by on my ability to "spot" ' em
thru my general knowledge of Pneumonias. I did well enough, and finally found
an old Phonendoscope that I pieced together, and from then on was all right.
You know the Army regulations require very close locations etc.
Camp Devens is near Boston, and has about 50,000 men, or did have before
this epidemic broke loose. It also has the Base Hospital for the Div. of
the N. East. This epidemic started about four weeks ago, and has developed
so rapidly that the camp is demoralized and all ordinary work is held up
till it has passed. All assembleges of soldiers taboo.
These men start with what appears to be an ordinary attack of LaGrippe or
Influenza, and when brought to the Hosp. they very rapidly develop the most
viscous type of Pneumonia that has ever been seen. Two hours after admission
they have the Mahogany spots over the cheek bones, and a few hours later
you can begin to see the Cyanosis extending from their ears and spreading
all over the face, until it is hard to distinguish the coloured men from
the white. It is only a matter of a few hours then until death comes, and
it is simply a struggle for air until they suffocate. It is horrible. One
can stand it to see one, two or twenty men die, but to see these poor devils
dropping like flies sort of gets on your nerves. We have been averaging about
100 deaths per day, and still keeping it up. There is no doubt in my mind
that there is a new mixed infection here, but what I dont know. My total
time is taken up hunting Rales, rales dry or moist, sibilant or crepitant
or any other of the hundred things that one may find in the chest, they all
mean but one thing here -Pneumonia-and that means in about all cases death.
The normal number of resident Drs. here is about 25 and that has been increased
to over 250, all of whom (of course excepting me) have temporary orders-"Return
to your proper Station on completion of work". Mine says "Permanent Duty",
but I have been in the Army just long enough to learn that it doesnt always
mean what it says. So I dont know what will happen to me at the end of
this.
We have lost an outrageous number of Nurses and Drs., and the little town
of Ayer is a sight. It takes Special trains to carry away the dead. For several
days there were no coffins and the bodies piled up something fierce, we used
to go down to the morgue (which is just back of my ward) and look at the
boys laid out in long rows. It beats any sight they ever had in France after
a battle. An extra long barracks has been vacated for the use of the Morgue,
and it would make any man sit up and take notice to walk down the long lines
of dead soldiers all dressed and laid out in double rows. We have no relief
here, you get up in the morning at 5 .30 and work steady till about 9.30
P.M., sleep, then go at it again. Some of the men of course have been here
all the time, and they are TIRED.
If this letter seems somewhat disconnected overlook it, for I have been called away from it a dozen times the last time just now by the Officer of the Day, who came in to tell me that they have not as yet found at any of the autopsies any case beyond the Red. Hepatitis. stage. It kills them before they get that far.
I dont wish you any hard luck Old Man but I do wish you were here for a while at least. Its more comfortable when one has a friend about. The men here are all good fellows, but I get so damned sick o Pneumonia that when I go to eat I want to find some fellow who will not "Talk Shop" but there aint none nohow. We eat it live it, sleep it, and dream it, to say nothing of breathing it 16 hours a day. I would be very grateful indeed if you would drop me a line or two once in a while, and I will promise you that if you ever get into a fix like this, I will do the same for you.
Each man here gets a ward with about 150 beds, (Mine has 168) and has an Asst. Chief to boss him, and you can imagine what the paper work alone is - fierce,-- and the Govt. demands all paper work be kept up in good shape. I have only four day nurses and five night nurses (female) a ward-master, and four orderlies. So you can see that we are busy. I write this in piecemeal fashion. It may be a long time before I can get another letter to you, but will try.
This letter will give you an idea of the monthly report which has to be in Monday. I have mine most ready now. My Boss was in just now and gave me a lot more work to do so I will have to close this.
Good By old Pal,
"God be with you till we meet again"
Keep the Bouells open.
(Sgd) Roy.
Illustrations and layout by Linda Stannard, 1995 ©