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Spanish Influenza and Beyond: The Case of Norway
Abstract
This thesis presents the first comprehensive demographic account which consistently uses multivariate techniques of statistical analysis to estimate the demographic effects of Spanish Influenza in one country. The thesis consists of four papers that analyze the immediate as well as the short and long-term impact of Spanish Influenza 1918-19 on mortality and fertility in Norway. The Spanish Influenza was one of the worst epidemics in history, killing perhaps 100 million people in less than a year. The thesis takes advantage of Norwegian micro and macro data that are unique in an international context. Planned censuses and registration of population data, including vital statistics, continued as normal in Norway, undisturbed by the First World War. The fact that Norway was neutral was important in counter-balancing the influence of the 1914-18 war on the demographic indicators studied. A second strength of the thesis compared to earlier demographic accounts which have been descriptive and univariate, is that the independent effect of one variable on mortality net of the effects of other variables could be demonstrated. For example, Paper I demonstrates that there were clear differences in individual survival from Spanish Influenza with respect to social status in the Norwegian capital, net of the effect of age, sex, and marital status. Furthermore, Paper II shows that areas of Norway with a high proportion of Sami (Lapps) in the local population had high mortality, net of such confounding factors as average income and wealth, proportion of the population receiving poverty relief, household crowding, spatial diffusion, and occupational structure. Paper III finds that the Spanish Influenza Pandemic of 1918 created the baby boom in Norway in 1920, because high influenza and pneumonia morbidity and mortality caused a decline in the conception rates in 1918 which consequently led to an increase in 1919. The fourth paper shows that Norwegian male cohorts born 1900-1910 and female cohorts born 1890-1899 experienced significantly higher all-cause mortality in middle and old age relative to “neighbor” cohorts. A large proportion of these cohorts contracted Spanish Influenza, but only a small proportion of them succumbed to the illness in 1918. However, it is argued that many survivors of Spanish Influenza were more susceptible to dying from encephalitis lethargica, Parkinson’s disease, tuberculosis, and coronary heart disease in later life.
... It may be possible, though, that even this very gloomy scenario could turn out to be over-optimistic. The Spanish flu pandemic ran in four different waves during the period 1918 Á20, with the first wave probably affecting the largest total number of previously non-immune people, but the total number of deaths was higher during the second than during the first wave (7,8). During the second wave, it is probable that the population of non-immune and therefore susceptible people was much smaller than it had been at the start of the first wave (7). ...
... Since high mortality affected several ethnically and genetically highly diverse groups (5), it appears unlikely that genetic differences between different populations could have played any major role (7). Differences in the age structure of the population may, however, have played a role, given the curious W shape of the curve describing the average mortality rate of different age groups as a function of age (5,8). But this factor can only account for a minor part of the total geographic variation in excess mortality. ...
The World Health Organization (WHO) no longer regards the Spanish flu pandemic as a worst case scenario as the basis for contingency planning, as to how to meet a possible pandemic with hypervirulent H5N1 influenza. The worldwide fatality rate among confirmed cases has increased from 43% in 2005 to 69% in 2006, while in Indonesia it was 82% in 2006. What the world now needs to be prepared for is a pandemic with something that is equally as transmissible as ordinary influenza virus, but which may have a case fatality rate of 80% or more, if not treated with therapeutic methods much better than those available today (i.e. treatment methods that have not been sufficient to hinder the average case fatality rate from climbing to as much as 82% in Indonesia in 2006). Not only are current treatment methods not efficacious enough, but the situation is also very far from satisfactory as regards vaccine development and production – which means that the world must still be considered to be almost totally unprepared, if a pandemic with hypervirulent H5N1 influenza should start tomorrow. A very detailed description of new experimental work is given to make it possible to understand better some of the main elements of the attack strategy used by the enemy – so that this ‘military intelligence’ information can be used as the basis for a hopefully more rational strategy of defense. The enemy neutralizes a system used for very early detection of invasion with RNA viruses, leading to total or partial immobilization of associated early response defensive weapon systems. The proposed defense strategy comprises two elements: 1) keeping the patient alive until rescue forces (i.e. a good adaptive immune response) can arrive, and 2) making it possible for the rescue forces to arrive as soon as possible. Some tactical principles and weapons that may be used for defense purposes are also proposed, partially on the basis of animal experiments with both lethal influenza and other highly lethal viruses. A main challenge is to reduce pulmonary inflammation causing alveolar edema without simultaneously hindering the development of a good adaptive immune response. Several practical suggestions are given as to how this possibly might be done. However, it is imperative that the suggested new defense strategy (or therapeutic strategy) should be tested as soon as possible both in experimentally infected animals and in spontaneously occurring human cases of hypervirulent H5N1 influenza.
... Basert på en undersøkelse publisert i Social Science and Medicine (1). En tidligere versjon av artikkelen finnes i forfatterens doktoravhandling (2). En populaervitenskapelig artikkel av avhandlingen på norsk er publisert i Samfunnsspeilet (3) ...
Bakgrunn:
I denne artikkelen stilles det spørsmål om hvorfor influensapande-mien i 1918– 19 var forskjellig fra influ-ensaepidemier i nyere tid, som har større sosiale forskjeller i dødelighet enn de fleste andre dødsårsaker.
Materiale og metode:
Multivariat analyse og forløpsdata benyttes for første gang for å analysere variasjon i dødelighet av spanskesyken. Studien omfatter Frogner og Grønland-Wexels bydeler i Kristiania. Historisk-demografiske data for Norge er unike fordi det er mulig å rendyrke spanskesykens effekt på dødeligheten uavhengig av dødelighet som følge av den første verdenskrig ettersom Norge var et nøytralt land.
Resultat:
Dødeligheten i middelklassen og borgerskapet var 19 –25 % lavere enn i arbeiderklassen (ikke signifikant). De som bodde i leiligheter med 4– 6 rom hadde i gjennomsnitt 50 % lavere dødelighet enn de som bodde i ettroms leiligheter (signifikant). Innbyggerne på Grønland-Wexels hadde dessuten 50 % høyere dødelighet enn innbyggerne på Frogner justert for andre forskjeller (signifikant).
Fortolkning:
Funnene utfordrer myten om at spanskesyken tilfeldig plukket sine dødsofre. Studien har internasjonal relevans fordi data som sjelden er tilgjengelig for andre land er benyttet.
For preparation of pandemic plans for the H5N1 bird flu virus, it has been common practice among health authorities in several countries to use crude death figures from the Spanish flu pandemic as a worst case scenario. This has been done without taking into consideration either what is known about the molecular biology of malignant influenza viruses or the detailed statistical information that is available about the Spanish flu pandemic, as regards the variation of death risk as a function of age and also as regards the different behavior of the virus during successive pandemic waves. There is no scientific basis for the assumption that a new pandemic influenza virus cannot be worse than the Spanish flu virus. However, if we hypothetically assume recurrence of a pandemic influenza virus with virulence and transmissibility properties identical to the Spanish flu virus, but belonging to a subtype other than those that have been circulating in human populations since 1918, it will be unrealistic to assume that the older part of the population will be immune against a type of virus that their immune system has never encountered before. Therefore we have attempted to estimate what might have happened by counterfactually assuming that individuals in 1918 had not been immunized earlier against H1 (or H1N1) influenza viruses that were circulating before 1890. An overview is given of age-related changes in immunological factors that may affect the age-specific mortality in different age groups, and also expected consequences for the mortality in different age groups of mitochondrial DNA aging per se. Extrapolations for age-specific death rate have been made for four different scenarios, giving lower and upper boundaries for what might have happened if nobody had been immune when the 1918–1920 pandemic started. For the first (lower boundary) scenario the age-specific death rate is increasing up to the age of 30 and is assumed (very unrealistically) to be constant thereafter. For the second scenario the age-specific death rate is monotonically increasing as a function of age according to an almost cubic functionality. For the third (upper boundary) scenario the age-specific death rate is increasing exponentially with age. For the third scenario the mortality of the world population becomes 0.3. Thus 30% of the world population could have been killed by the Spanish flu virus, had nobody been immune when the pandemic started. For the fourth scenario the mortality by age due to the virus mimics the traditional mortality by age in a population. The fifth scenario is identical with scenario 3, except that it is also counterfactually assumed that the wave 2 virus came first. For this scenario, it is found that as much as 80% of the total world population in 1918 might have been killed by the Spanish flu virus.
The world is now extremely poorly prepared to counter a possible pandemic of hypervirulent H5N1 influenza. Most countries are planning for nothing worse than the Spanish flu pandemic. It may be possible that this can in large measure be explained as a consequence of an epidemic of wishful thinking, which may already have infected the health authorities (and parts of the scientific community as well) in most countries in the world. However, it may also be possible that it can have happened as a consequence of too little contact between medical scientists and more general biologists (natural scientists) from disciplines such as ornithology, ecology and evolutionary biology. This may have led to a lack of proper understanding among medical scientists (and health bureaucrats) of the nature of evolutionary processes affecting influenza viruses, as regards the evolution of host species adaptation, infectivity and virulence properties, and also a lack of appreciation of the ways in which such forms of evolutionary adaptation depend on ecological boundary conditions that have radically changed, comparing the world in 2006 to the world in 1918. While the Spanish flu virus possibly might be compared to a one-headed monster, it may be possible that highly virulent varieties of H5N1 virus might better be compared to a three-headed one – because there is evidence of at least three independent virulence factors connected with three different genes. It is highly unlikely that all of the high-virulence alleles will simultaneously mutate and disappear if and when the haemagglutinin gene changes so as to make the haemagglutinin molecule better adapted for the human-type (alpha-2,6-linked) receptor (which is a necessary prerequisite in order that a pandemic with H5N1 virus may start). It is more probable that evolutionary adaptation of the haemagglutinin of H5N1 viruses to the human-type receptor will happen without any simultaneous change in those other genetic properties that now are important for explaining the exceptionally high virulence of certain strains of avian-adapted H5N1 influenza virus. The change of the haemagglutinin molecule from avian adaptation to human adaptation must be expected to act as an additional virulence factor because it will enhance the total number of cells that can be infected (per host organism), increase the total rate of virus replication and potentiate the effects of the other virulence factors already present. The monster will then have four heads, not three, and case fatality rates must be expected to become even higher than they have been until now, perhaps reaching as high as 98–99% (at least in poor countries with less than optimal nutrition).
The Kermack-McKendrick (KM) (1927) epidemiological equations are used to analyse different pandemic scenarios. The infection rate constant and the withdrawal rate constant of infected individuals for the Spanish influenza pandemic (1918 Á 1920) are found by curve fitting the solution of the KM equations to the historical data for the number of dead and the number of infected individuals during the pandemic. Hypothetically assuming the very same parameters for hypervirulent strains of H5N1 influenza virus (with 50% lethality), our simulations reveal that the latter (without vigorous countermeasures) can infect the total world population during a period of 20 Á30 days, with a mortality of 50% of the total world population. The short time it takes before the pandemic is over precludes the use of new vaccines that are developed only after a pandemic has started. We examine a logistically more feasible method of achieving rapid immunization after a pandemic has started (and if prefabricated vaccines cannot be used either because they are not effective or for logistic reasons): the influence of a counter-pandemic running ahead and immunizing the population before the hypervirulent H5N1 virus attacks. We find that the counter-pandemic can significantly reduce the total death toll during a pandemic with a hypervirulent strain of H5N1 influenza virus, provided that its infectivity at a population level is much larger than for the hypervirulent virus. This can be achieved if everything possible is done to hinder geographic dispersal of the hypervirulent virus (e.g. immediate cessation of all international passenger traffic, immediate cessation of all ordinary road traffic, house quarantine) at the same time as dispersal of the 'vaccine virus' is deliberately facilitated by sending it around in a similar way as for a vaccine, but seeding it only in every local population and not in every person as for ordinary vaccine. From a logistic point of view this might be the only feasible method of achieving immunization of a significant proportion of the population in poor countries with poor infrastructure during the very short time interval available before the superpathogen itself normally would be expected to arrive. However, mortality caused by a counter-pandemic virus will probably be higher than during an ordinary influenza epidemic, especially among elderly and malnourished persons. Vaccination, using vaccines that have been prefabricated and stored before the start of an eventual pandemic, should therefore be the preferred method of achieving immunization whenever logistically feasible.
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