1918 flu pandemic

By: lina huang

 

     1918, the most severe pandemic in recent history, known as the “Spanish flu,” spread worldwide. The origin of the 1918 flu pandemic is unclear, the flu was first identified in the United States in the military during spring. 

     Experts estimate that about 500 million, or one-third of the world’s population, contracted the influenza. out of those, at least 50 million died worldwide. 675,000 succumbed to the disease in the United States, and the average life expectancy in the US was lowered by more than 12 years.

The 1918 influenza was unique in that mortality was distributed among different age groups, with high mortality in even those who were healthy; mortality was high in those younger than 5 years old, 20-40 years old, and 65 years or older. At that time, there was no vaccine against the influenza and no antibiotics for bacterial infections that resulted from the lowered abilities of an immune system already working against the influenza. 

 

     The influenza was caused by an H1N1 virus, a subtype of influenza A virus, that causes upper and potentially lower respiratory tract infections. Symptoms included nasal secretions, chills, fever, decreased appetite, and possibly lower respiratory tract disease, which is consistent among most influenza viruses. The H1N1 virus was named so for the types of hemagglutinin (HA), a protein that aids in viral attachment to cells, and neuraminidase (NA), an enzyme that aids release of new viruses, viral surface proteins in the virus; there are 16 different types of hemagglutinin and 9 types of neuraminidase. In 1918, the H1N1 mutated as it passed from a host to us. 

     The H1N1 virus is an orthomyxovirus, a type of RNA virus, with a genome size of approximately 13.5 kb. The genome includes 8 different regions that code for 11 different proteins, including HA and NA, RNA polymerases, and others. HA specifically functions by causing red blood cells to cluster together, and attaching the virus to the cell. NA moves the virus particles through the host cell and assists in viral release from the cell. modern vaccines typically target a virus’ unique HA.

     A 1999 study sequenced the HA gene sequence of the 1918 H1N1 virus. The study authors obtained RNA fragments of the virus and sequenced them. Results suggested that the ancestor of the 1918 virus was transferred to and began infecting humans between 1900 and 1915. The 1918 HA gene seems to also contain a number of mammalian adaptations. The existing strain to which the 1918 virus sequence was most closely related seemed to be “A/sw/Iowa/30,” the oldest classical swine influenza strain. However, contemporary avian influenza virus strains are very different from the 1918 virus, and older strains from around the time of the pandemic are not available for study.

     Also in contrast to modern strains, the 1918 HA contained only four glycosylation sites, a component that is vital for the function of influenza viruses. Modern human HA’s contained up to five additional glycosylation sites due to antigenic drift. Of note, the authors of this study did not find any genetic changes in the 1918 HA that would explain its virulence. A study published june 2000 sequenced the 1918 NA gene. Analysis indicated the source of the NA gene was avian in nature, but could not determine the process by which the virus mutated into its pandemic form. 

     Mutations in the virus may lead to further infections. In 2009, an H1N1 strain caused a pandemic that resulted in fewer than 0.3 million deaths its first year. The virus contained a combination of segments of four different influenza viruses: pig-origin flu North American avian (comprising 34.4%), bird-origin flu of the human influenza strain (comprising 17.5%), North American swine (comprising 30.6%), and Eurasian swine (comprising 17.5%). The viruses interacted, mutated, and formed new strains with variable immunity, thereby allowing it to spread.

Besides the H1N1 pandemic in 2009, the world experienced three additional pandemics post-1918: the 1957 pandemic, caused by an H2N2 strain, caused an estimated 1 million global deaths; the 1968 H3N2 pandemic resulted similarly; and the ongoing COVID-19 pandemic.

 

     Since the virus hit in 1918, worldwide efforts to mitigate its spread and symptoms were limited to non-pharmaceutical interventions such as isolation, quarantine, good personal hygiene, use of disinfectants, and limitations of public gatherings. In addition, the world was still engaged in World War 1 in 1918, and movement and mobilization of troops often placed large crowds in close contact. Health services also were limited, and up to 30% of U.S. physicians were deployed to military service.

     Medical technology also proved to be limited. No diagnostic tests existed at that time for influenza infection - doctors did not know about influenza viruses - and many health experts instead turned to “Pfeiffer’s bacillus,” now known as Haemophilus influenzae, as the source. However, even antibiotics had not been developed yet ( penicillin was not discovered until 1928) and no flu antiviral drugs were available. Health system measures, including intensive care support and mechanical ventilation, were also non-existent. As such, doctors were left with few treatment options.

     No coordinated pandemic plans existed in 1918. A few cities implemented community mitigation measures, such as closing schools, banning public gatherings, and issuing isolation or quarantine orders, but the federal government had no centralized role in helping to plan or initiate these interventions during the 1918 pandemic.

     Similarly, during the 2009 H1N1 pandemic, 26 weeks after a decision to manufacture a monovalent vaccine, the first doses of a pandemic vaccine became available. However, most vaccinations in the US only occured after the illness had peaked.

      Considerable advancements have been made today. Influenza vaccines are produced and updated yearly, and vaccination is recommended for everyone 6 months of age and older. Antiviral drugs to treat influenza exist and antibiotics may treat secondary bacterial infections. Diagnostic tests can identify influenza, and rapid tests, known as RIDTs, can provide results within 15 minutes. 

     The World Health Organization (WHO) developed a Global Influenza Surveillance and Response System (GISRS) to monitor changes in seasonal influenza viruses and the emergence of novel influenza viruses. In accordance with WHO’s International Health Regulations (IHR), countries must notify WHO within 24 hours of any case of human infection caused by a novel influenza A virus subtype. The Strategic National Stockpile stores pre-pandemic vaccines, facemasks, antiviral drugs and other materials. 

     However, severe pandemics likely will overwhelm health care infrastructure today. There would be a significant increase in the manufacture, distribution and supply of medications, products and life-saving medical equipment, such as mechanical ventilators. An influenza vaccine would also prove to be challenging, as it generally takes about 20 weeks to select and manufacture a new vaccine.

     This is particularly relevant in light of the novel coronavirus. As of April 25th, there are 928,619 COVID-19 cases and 52,459 deaths in the US alone. WHO declared the COVID-19 outbreak a global pandemic on March 11. The FDA has granted laboratories approval to test for the COVID-19, and the government has restricted travel and worked on responses to rising unemployment. Many states have implemented “stay-at-home” orders or similar orders, schools have closed or moved to online platforms, and science companies and researchers are working to confront the pandemic. In these times, it is especially important to look back on history and see how it can inform our present.