The 100th anniversary of the 1918 Spanish flu pandemic is coming to an end. Reviewing the literature from the last 100 years about this event tells the story of acute disease and suffering; however, some questions still remain unresolved. In 1918, 57 million people (3% of the population), globally, succumbed to the influenza H1N1 virus. The world population is currently 7.6 billion; 3% would amount to 228 million lost lives if the world experiences another influenza pandemic of this magnitude. There have been three pandemics since 1918--Asian flu in 1957, Hong Kong flu in 1968, and swine flu in 2009--but these were all mild in comparison. In light of the accumulated knowledge from the past ten decades, is the world prepared to face another pandemic of this proportion?
One of the most controversial issues surrounding the 1918 pandemic is where it began. Because the influenza virus is endemic throughout the world, it has been difficult to pinpoint the exact location of the first case. John Barry authored an article in the Journal of Translational Medicine outlining his extensive research on the history of the pandemic. Through a literature search of epidemiological evidence, he found that Haskell County, Kansas was likely where it all began, but there were other hypotheses that he considered.
There have been other medical historians and epidemiologists who theorized that the influenza pandemic began in China or that Chinese and Vietnamese workers brought it to the U.S. and France. In 2001, J. S. Oxford published an article supporting his theory that the pandemic began in France. He bases his arguments on two outbreaks of an acute respiratory illness in the winter of 1916 and in March 1917. They occurred on an army base in northern France, which housed 100,000 soldiers at a time with over a million passing through from England to the Western Front. This infection, termed purulent bronchitis, rapidly spread through the base with mortality rates from 25-50%. A characteristic that was seen during both outbreaks was “heliotrope cyanosis,” a bluish tinge to the affected soldier’s skin. Autopsies performed on soldiers who succumbed from the infection appeared to be pathologically consistent with influenza. However, Barry disagrees stating that today, the soldiers would be diagnosed with acute respiratory distress syndrome (ARDS).
ARDS is the most severe form of acute lung injury (ALI). When diagnosing ARDS, the severity of hypoxemia needs to be considered and is determined by the “ratio of the partial pressure of oxygen in the patient’s arterial blood (PaO2) to the fraction of oxygen in the inspired air (FiO2). ARDS was defined by a PaO2/FiO2 ratio of less than 200, and in ALI, less than 300.” A normal PaO2/FiO2 ratio is anything over 500.
In 1927, Dr. Edwin Jordan, editor of The Journal of Infectious Diseases, published his data from an international study of the pandemic sponsored by the American Medical Association. He addressed all the hypotheses, at the time, about the location of the initial case of influenza H1N1. Jordan found no evidence to support the pandemic starting in Asia, and Chinese scientists, who were trained by the Rockefeller Institute, felt the outbreaks in Asia were from endemic strains of the influenza virus. He also looked at fatal respiratory diseases that were claimed to be from influenza, but contemporary researchers had proven these were due to the pneumonic plague. Jordan rejected Oxford’s theory that the “purulent bronchitis” was the beginning of the pandemic because it did not rapidly spread outside the base, and it just seemed to disappear. Barry postulates that there could have been a mutation in an endemic strain causing an epidemic that eventually dissipated.
Since Jordan could not find a starting point for the pandemic overseas, he turned his attention to the U.S. In January and early February 1918, a physician in Haskell County, Kansas, Loring Miner, saw an outbreak of influenza more severe than any he had ever seen. It struck young, healthy adults between ages 20-40 killing them within 48 hours; however, children and older adults did not experience the severity of the infection with most recovering from it. Even though this epidemic disappeared as abruptly as it began, Miner warned national public health officials about its severity and that it was adapting to humans, but no one heeded his warnings. On March 4, 2018, the first soldier at Camp Funston, Kansas reported being sick, and within three weeks thousands of soldiers had to be admitted to the infirmary. The soldiers at this base were transferred to many other locations throughout the U.S. and Europe.
Just as the starting point of the 1918 pandemic has not been completely resolved, it is still unclear about the source of the original animal reservoir. Two strains of the influenza virus can co-infect the same cell facilitating a process called reassortment where a novel influenza virus emerges with a unique genetic code. The 1957 and 1967 pandemics were the result of reassortment of the avian and human flu virus, and the 2009 pandemic from avian, human, and swine flu viruses. In comparison, the 1918 pandemic is thought to have come from a single source, which has not yet been identified because its nucleotide sequence is unique from any other avian and mammalian influenza viruses.
David Fedson addresses an aspect of the infection process of the influenza virus that may help to reduce the mortality rates of seasonal influenza and acute critical illnesses. The differences in mortality rates in children versus young adults during the 1918 pandemic may be due to a higher tolerance of infection rather than resistance related to the host response. His research was directed at the effects on the host response with treatment by generic drugs including statins, ACE inhibitors, angiotensin receptor blockers, and Metformin. His findings suggested that these drugs can change the damaging host response of the adult to match the benign reaction of the child.
Understanding the epidemiology and pathogenesis of the H1N1 virus will facilitate the way we handle another pandemic, especially one of the magnitude of the 1918 pandemic. The speed of transportation today will rapidly spread the infection globally, but further research into Fedson’s hypotheses may elucidate novel and better ways to treat the infection and reduce mortality rates.