ABSTRACT
BACKGROUND: The reasons for the unusual age-specific mortality patterns of the 1918-1919 influenza pandemic remain unknown. Here we characterize pandemic-related mortality by single year of age in a unique statewide Kentucky data set and explore breakpoints in the age curves. METHODS: Individual death certificates from Kentucky during 1911-1919 were abstracted by medically trained personnel. Pandemic-associated excess mortality rates were calculated by subtracting observed rates during pandemic months from rates in previous years, separately for each single year of age and by sex. RESULTS: The age profile of excess mortality risk in fall 1918 was characterized by a maximum among infants, a minimum at ages 9-10 years, a maximum at ages 24-26 years, and a second minimum at ages 56-59 years. The excess mortality risk in young adults had been greatly attenuated by winter 1919. The age breakpoints of mortality risk did not differ between males and females. CONCLUSIONS: The observed mortality breakpoints in male and female cohorts born during 1859-1862, 1892-1894, and 1908-1909 did not coincide with known dates of historical pandemics. The atypical age mortality patterns of the 1918-1919 pandemic cannot be explained by military crowding, war-related factors, or prior immunity alone and likely result from a combination of unknown factors.
Subject(s)
Influenza, Human/mortality , Pandemics , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Kentucky/epidemiology , Male , Middle Aged , Sex Factors , Survival Analysis , Young AdultABSTRACT
The nucleoprotein (NP) gene of the 1918 pandemic influenza A virus has been amplified and sequenced from archival material. The NP gene is known to be involved in many aspects of viral function and to interact with host proteins, thereby playing a role in host specificity. The 1918 NP amino acid sequence differs at only six amino acids from avian consensus sequences, consistent with reassortment from an avian source shortly before 1918. However, the nucleotide sequence of the 1918 NP gene has more than 170 differences from avian strain consensus sequences, suggesting substantial evolutionary distance from known avian strain sequences. Both the gene and protein sequences of the 1918 NP fall within the mammalian clade upon phylogenetic analysis. The evolutionary distance of the 1918 NP sequences from avian and mammalian strain sequences is examined, using several different parameters. The results suggest that the 1918 strain did not retain the previously circulating human NP. Nor is it likely to have obtained its NP by reassortment with an avian strain similar to those now characterized. The results are consistent with the existence of a currently unknown host for influenza, with an NP similar to current avian strain NPs at the amino acid level but with many synonymous nucleotide differences, suggesting evolutionary isolation from the currently characterized avian influenza virus gene pool.
Subject(s)
Nucleoproteins/genetics , RNA-Binding Proteins/genetics , Viral Core Proteins/genetics , Amino Acid Sequence , Animals , Base Sequence , Humans , Influenza, Human/epidemiology , Molecular Sequence Data , Nucleocapsid Proteins , Nucleoproteins/chemistry , Orthomyxoviridae/classification , Phylogeny , RNA-Binding Proteins/chemistry , Regression Analysis , Swine , Time Factors , Viral Core Proteins/chemistrySubject(s)
Disease Outbreaks/history , Influenza, Human/history , Amino Acid Sequence , Base Sequence , DNA, Viral/genetics , Genes, Viral , Genetic Variation , Hemagglutinin Glycoproteins, Influenza Virus/genetics , Hemagglutinin Glycoproteins, Influenza Virus/physiology , History, 20th Century , Humans , Influenza A virus/genetics , Influenza A virus/pathogenicity , Influenza A virus/physiology , Influenza, Human/epidemiology , Influenza, Human/virology , Molecular Sequence Data , North America/epidemiology , Receptors, Virus/physiologyABSTRACT
The coding region of influenza A virus RNA segment 7 from the 1918 pandemic virus, consisting of the open reading frames of the two matrix genes M1 and M2, has been sequenced. While this segment is highly conserved among influenza virus strains, the 1918 sequence does not match any previously sequenced influenza virus strains. The 1918 sequence matches the consensus over the M1 RNA-binding domains and nuclear localization signal and the highly conserved transmembrane domain of M2. Amino acid changes that correlate with high yield and pathogenicity in animal models were not found in the 1918 strain. Phylogenetic analyses suggest that both genes were mammalian adapted and that the 1918 sequence is very similar to the common ancestor of all subsequent human and classical swine matrix segments. The 1918 sequence matches other mammalian strains at 4 amino acids in the extracellular domain of M2 that differ consistently between avian and mammalian strains, suggesting that the matrix segment may have been circulating in human strains for at least several years before 1918.
Subject(s)
Influenza A virus/genetics , Viral Matrix Proteins/genetics , Amantadine/pharmacology , Antiviral Agents/pharmacology , Base Sequence , Drug Resistance, Viral , Genes, Viral , Humans , Influenza A virus/classification , Influenza A virus/drug effects , Influenza A virus/isolation & purification , Molecular Sequence Data , Phylogeny , Sequence Analysis, DNA , SpainABSTRACT
Wild waterfowl captured between 1915 and 1919 were tested for influenza A virus RNA. One bird, captured in 1917, was infected with a virus of the same hemagglutinin (HA) subtype as that of the 1918 pandemic virus. The 1917 HA is more closely related to that of modern avian viruses than it is to that of the pandemic virus, suggesting (i) that there was little drift in avian sequences over the past 85 years and (ii) that the 1918 pandemic virus did not acquire its HA directly from a bird.
