Past and Present Viral Pandemics: Lessons Learnt and Future Recommendations

: Human populations throughout history have been affected by major disease outbreaks such as endemics, epidemics, pandemics etc. However, unlike the others, pandemics have their own distinct natural history which is generally of global and public health importance. An in-depth analysis of past pandemics has the potential of strengthening emergency preparedness and tactical responses that are essential in preventing the incidences of future disease outbreaks. This review aims to identify lapses in preparedness and highlight the lessons learnt from past pandemics such as smallpox, tuberculosis, Black Death, influenza pandemic (Spanish flu), H2N2 virus, H3N2 pandemic, H1N1 pandemic, HIV/AIDS and the present COVID-19 pandemic.

The Molecular Basis for Antigenic Drift of Human A/H2N2 Influenza Viruses

ABSTRACTInfluenza A/H2N2 viruses caused a pandemic in 1957 and continued to circulate in humans until 1968. The antigenic evolution of A/H2N2 viruses over time and the amino acid substitutions responsible for this antigenic evolution are not known. Here, the antigenic diversity of a representative set of human A/H2N2 viruses isolated between 1957 and 1968 was characterized. The antigenic change of influenza A/H2N2 viruses during the 12 years that this virus circulated was modest. Two amino acid substitutions, T128D and N139K, located in the head domain of the H2 hemagglutinin (HA) molecule, were identified as important determinants of antigenic change during A/H2N2 virus evolution. The rate of A/H2N2 virus antigenic evolution during the 12-year period after introduction in humans was half that of A/H3N2 viruses, despite similar rates of genetic change.IMPORTANCEWhile influenza A viruses of subtype H2N2 were at the origin of the Asian influenza pandemic, little is known about the antigenic changes that occurred during the twelve years of circulation in humans, the role of preexisting immunity, and the evolutionary rates of the virus. In this study, the antigenic map derived from hemagglutination inhibition (HI) titers of cell-cultured virus isolates and ferret postinfection sera displayed a directional evolution of viruses away from earlier isolates. Furthermore, individual mutations in close proximity to the receptor-binding site of the HA molecule determined the antigenic reactivity, confirming that individual amino acid substitutions in A/H2N2 viruses can confer major antigenic changes. This study adds to our understanding of virus evolution with respect to antigenic variability, rates of virus evolution, and potential escape mutants of A/H2N2.

Adaptation of Pandemic H2N2 Influenza A Viruses in Humans

The 1957 A/H2N2 influenza virus caused an estimated 2 million fatalities during the pandemic. Since viruses of the H2 subtype continue to infect avian species and pigs, the threat of reintroduction into humans remains. To determine factors involved in the zoonotic origin of the 1957 pandemic, we performed analyses on genetic sequences of 175 newly sequenced human and avian H2N2 virus isolates and all publicly available influenza virus genomes.

A 27-Amino-Acid Deletion in the Neuraminidase Stalk Supports Replication of an Avian H2N2 Influenza A Virus in the Respiratory Tract of Chickens

ABSTRACT The events and mechanisms that lead to interspecies transmission of, and host adaptation to, influenza A virus are unknown; however, both surface and internal proteins have been implicated. Our previous report highlighted the role that Japanese quail play as an intermediate host, expanding the host range of a mallard H2N2 virus, A/mallard/Potsdam/178-4/83 (H2N2), through viral adaptation. This quail-adapted virus supported transmission in quail and increased its host range to replicate and be transmitted efficiently in chickens. Here we report that of the six amino acid changes in the quail-adapted virus, a single change in the hemagglutinin (HA) was crucial for transmission in quail, while the changes in the polymerase genes favored replication at lower temperatures than those for the wild-type mallard virus. Reverse genetic analysis indicated that all adaptive mutations were necessary for transmission in chickens, further implicating quail in extending this virus to terrestrial poultry. Adaptation of the quail-adapted virus in chickens resulted in the alteration of viral tropism from intestinal shedding to shedding and transmission via the respiratory tract. Sequence analysis indicated that this chicken-adapted virus maintained all quail-adaptive mutations, as well as an additional change in the HA and, most notably, a 27-amino-acid deletion in the stalk region of neuraminidase (NA), a genotypic marker of influenza virus adaptation to chickens. This stalk deletion was shown to be responsible for the change in virus tropism from the intestine to the respiratory tract.

The origins of pandemic influenza ? a perspective

Following the isolation of the first human influenza virus in 1933, there have been two Type A influenza pandemics. One was the Asian influenza pandemic in 1957, when an H2N2 virus replaced the H1N1 viruses then circulating, and the other was in 1968 when the Hong Kong H3N2 virus replaced the H2N2 viruses. The H1N1 virus that re-emerged in 1977 did cause a worldwide epidemic (or pandemic) but this virus is not considered by many people to be a true ?pandemic? virus.

E-alert 13 April: Worldwide laboratory distribution of influenza A/H2N2 virus similar to 1957-58 pandemic strain, labs asked to destroy all samples immediately

An influenza A/H2N2 virus, similar to that which caused the 1957-8 influenza pandemic has been inadvertently distributed in proficiency panels for quality control assessment to at least 3686 laboratories