Influenza Virus
Influenza was the cause of probably the world’s most serious epidemic of the 20th century though it may have been going on since the 6th century B.C.
A severe epidemic of influenza occurred in 1802 and again in 1806-1807. Pneumonia also started appearing in 1814 and had a particularly severe episode around Harrisonburg between 1851 and 1852.
Although Louis Pasteur and others in the 19th century thought that bacteria were responsible for all disease, it became clear that there were other agents. Initially this was indicated by their ability to pass through filters that bacteria would not. This included the development of a “graded” filter by W.J. Elsford.
A second major advance was the ability to grow viruses in the tissues of developing chick embryo, largely by Ernest W. Goodpasture, MD. With the development of the electron microscope, viruses could actually be seen. These were frequently spherical but occasionally filamentary in form (this was particularly true of influenza viruses). These viral particles could enter a cell, take over host cell’s metabolism, and reproduce themselves.
Figure 1: Spanish Influenza in American Army hospitals. Masks and cubicles were used at Fort Porter, where patients’ beds are reversed, so breath of one will not be directed toward another. Nov. 19, 1918.
Three major pandemics of influenza occurred in 1918, 1957 and 1968. The 1918 influenza pandemic, also known as the Spanish flu, claimed the lives of around 40 million people in just one year. The subsequent pandemics of influenza were far less deadly probably due to changes in the virus genome but also due to mitigation efforts to minimize spread. This was a nice example of how RNA viruses are particularly susceptible to genetic instability and thus sponsor mutations with new manifestations. The virus causing influenza was first recognized by virologist Richard E. Shope, MD. He also recognized that following the infection there were new proteins found in the blood that seemed to be protective.
Paul A. Lewis, MD, played a major role during the 1918 influenza pandemic. He trained first as a scientist before being brought into the Navy in 1918 as a lieutenant commander. Although he was trained as a physician, he had never taken care of patients. But he had other credentials as the founding head of the Henry Phillips Research Institute at the University of Pennsylvania. As a young investigator in 1908, he proved polio was caused by a virus and devised a vaccine that was 100% effective in protecting monkeys.
Between 1918 and 1920, the Spanish flu infected a half a billion people around the world. Interestingly, what was impressive about this variant of influenza was that it had an unusually high mortality rate in young adults, instead of targeting the very young and very old. This disease ended up killing more people than World War I. Shortly after Pasteur’s observations, Lister added antiseptics to operative surgical procedures.
Thus, when in July of 1918 physicians and scientists were faced with a new challenge as the wards filled up with bloody and dying young men, they might have been more prepared. Some scientists were prepared since the development of the Rockefeller Institute in New York City where a decade earlier it had been proven by Dr. Shope that polio was caused by a virus.
Ranking by Death Toll
Since statistics have never been kept in detail, some of the following is conjecture. In terms of total number of deaths, the influenza pandemic of 1918-20 may well have killed the most. But if we look at the death rate as a percentage of the population the bubonic plague would win hands down. It not only killed a sizeable portion of the population of Europe (30%-50%) but interrupted social development.
Smallpox (now eradicated) may have killed more than 80% of the indigenous population of the Western Hemisphere as well as a sizable portion of the indigenous population of Australia, New Zealand and the Pacific Islands.
The Great Influenza Pandemic
The first cases of influenza in 1918 probably appeared in Haskell County, Kan., which has a large avian community. The virus spread east to a military base (Fort Riley) and then to Funston. The deployment of troops from Funston to other military bases caused a rapid spread. This form of influenza infected young men and caused problems with epistaxis and hemoptysis. There was substantial darkening of their skin. There were no recognized ophthalmic complications.
This influenza spread to Camp Forest in Greenlift, Ga., where 10% of the forces of both camps were reported sick. The epidemic erupted at the Naval Facility in Boston, where the sailors complained of abdominal, muscle and rib cartilage pain as well having headaches.
Dr. Lewis knew he had to find the pathogen. He was the first to suggest that this new disease was a variant of influenza. This was likely related to influenza’s use of RNA which was much more likely to mutate. Although this epidemic was to last two years, many deaths occurred in a period of just 24 weeks. It killed more people in 24 weeks than AIDS later killed in 24 years.
The first influenza outbreaks in Europe occurred in early April in Brest, where American troops disembarked. In Brest the French Naval Command was suddenly crippled. From Brest the disease spread quickly to adjacent cities.
The French army developed cases starting in April 1918. These first outbreaks were relatively mild with few complications and the recovery of many troops. Interestingly the Germans also suffered outbreaks starting in April 1918. These events did have an effect on abating the fighting.
Although Spain had only a few cases by May, the government did not censor the press and, unlike the French, German, American, and British newspapers, the Spanish papers were filled with reports of the disease, especially when King Alfonso XII fell seriously ill. Misled about its origin, influenza began being called the “Spanish” influenza. In June, Germany suffered initial sporadic outbreaks, and then a full-fledged epidemic swept across all of the country. Portugal, Greece, Demark, and Norway began suffering in July, Holland, and Sweden in August. Influenza reached India via a May 29 transport and Shanghai towards the end of May. It jumped to New Zealand and then Australia in September.
Initially, mortality was not all that high, only one of 613 Americans admitted to the hospital in France died. In the French army, fewer than 100 deaths resulted from 40,000 hospital admissions. In England, 10,313 sailors in the British fleet fell ill, crippling naval operations, but only four sailors died.
Figure 2: Soldiers gargle with salt and water to prevent influenza. Sept. 24, 1918. Camp Dix, New Jersey, during the 1918-19 ‘Spanish’ Influenza pandemic.
In Louisville, Ky., 40% of those who died were age 20 to 35. Between June 1 and August 1 - 200,825 out of 2 million British soldiers in France were hit hard enough that they could not report for duty.
The second wave started in August 1918 with an increasing prevalence of pneumonia associated with influenza.
When William Welch, MD, performed an autopsy of a young person, it led him to conclude that this was a new infection or even plague. He walked out of the autopsy room and made phone calls to Boston, New York and Washington, D.C., where he then provided a detailed description of the clinical and pathological features of this new disease. He urged that provisions be made in every military camp for the rapid expansion of hospital space. He emphasized the use of quarantine and as such he impressed the White House chief of staff about the lethality of the disease.
While Dr. Lewis worked in the labs at Penn and the Navy hospital, the virus infected more than 600 sailors and Marines, requiring hospitalization. The Naval hospital ran out of beds. Besides affecting Puget Sound in Washington, the Great Lakes Naval Training Station 32 miles outside Chicago was affected. It contained 45,000 sailors. At this base, influenza ripped through the barracks. On Sept. 21, 1917, the Board of Health made influenza a reportable disease requiring physicians to notify health officials of any case they treated.
Lt. Cmdr. R. W. Plummer, the chief health officer called in by Dr. Lewis, arranged for a quarantine of military personnel. By the end of September 1,400 sailors were hospitalized in the Navy yard. Joseph A. Capps, MD, wrote an article in the August 10, 1918, issue of JAMA where he reported masks were so successful that after less than three weeks, he had abandoned testing and simply started using them as a routine measure.
Three thousand troops were sent from Camp Hancock in Pennsylvania to a camp outside Augusta, Ga. By the time the train arrived, over 700 men were taken directly to a base hospital. Not only did members of the military die, but also the health care workers and nurses. In 10 days, the epidemic had exploded from a few hundred to hundreds of thousands ill and hundreds of deaths each day. They had no place to put bodies. Gravediggers were either sick or refused to bury influenza victims. The director of the city jail offered to have prisoners dig graves, but then rescinded the offer because he had no healthy guards to watch them.
In the western world the virus demonstrated extreme virulence which led to pneumonia in 10 to 20 percent of all cases. This translated to 2 million to 3 million cases in the United States. There were other unusual manifestations, including subcutaneous emphysema, episodes of extreme earaches with discharge of pus from the external canal. The ability to smell was affected, sometimes for weeks.
Epistaxis was common with 15% of those affected suffering. In spite of the fact that it started in military camps, in the United States it killed 15 times as many civilians as military. The pathology affecting the lungs seemed to resemble that seen in pneumonic plague and also those that had been exposed to poisonous gas.
Tremendous efforts were made to produce a vaccine but unsuccessfully. The first commercial vaccines for influenza were not available until the 1940s. This new pathology obviously was a form of acute respiratory distress syndrome (ARDS). Although the role of cytokines was not really recognized until the 1970s, it is likely that cytokines produced by the immune system contributed to the lethality of this form of influenza (as is also seen in our current epidemic of COVID-19).
Dr. Welch was himself probably infected with influenza. Johns Hopkins staff were affected so hard that the university closed its hospital to all but its own staff and students. Three medical students, three nurses and three doctors died at Johns Hopkins.
Congress finally appropriated $1 million for the public health service, which allowed Blue to hire 5,000 doctors for emergency duty. This added 72,219 physicians. Unfortunately, nurses were harder to find than doctors. The Red Cross played a major role in recruiting nurses. By early September, the virus had killed 5% of all Philadelphian naval personnel. The Archbishop released nuns for service in hospitals and released priests to help with burials. Student nurses were recruited from Vassar.
Investigators around the world became interested in influenza, in particular the Rockefeller. Others included Dr. Welch at Johns Hopkins; the University of Michigan’s Victor C. Vaughan, MD; Harvard’s Charles Elliot; University of Pennsylvania’s William Pepper, MD; and a handful of colleagues. Probably the most important was Oswald T. Avery Jr., MD, at Rockefeller.
At the same time, Dr. Lewis, who had spent time under Dr. Welch was also looking for an answer. During the war, Dr. Lewis was given a commission in the U.S. Navy. He continued cooperating with Dr. Avery on the development of pneumonia serum. Experiments in Philadelphia used both whole blood and serum.
Preparations were geared up for the industrial production of serum. Avery could not find bacteria in influenza cases, and neither could Dr. Park. Avery ended up adding blood to his petri dishes and therefore invented chocolate agar. By October 1918 Austria and Germany separately sent peace inquires to the allies.
Figure 3: U.S. 39th regiment in Seattle, wear masks to prevent influenza. Dec. 1918. The soldiers were on their way to France during the 1918-19 ‘Spanish’ Influenza pandemic.
Provost Marshal Penoch Crowder canceled the next draft in fall 1918 because of the influenza pandemic. The severity of the diffuse illness could be measured by the fact that absentee records ran around 50% in shipyards. When the war ended with armistice on Nov. 11, 1918, the disease did not end. Some of the attempted cures were fantastical and made no sense. Camphor balls and garlic hung around people’s necks. Others gargled with disinfectants. Interesting was the internal injection of hydrogen peroxide (which killed 50%). The more things change, the more they remain the same.
In October 1918, vaccines began to appear in New York City from the health department, based on Dr. Lewis’ work. Unfortunately, the public health service made no effort to produce or distribute a vaccine or treat civilians. The Armed Forces Institute of Pathology would mount a massive effort to make a vaccine, but in spite of this, the death rate at Walter Reed Hospital in Washington, D.C., reached 52%. These early vaccines seemed only to protect against secondary pneumonias. In spite of all of this, the mortality rate remained extremely high, probably highest following the epidemic at Camp Sherman Ohio. Isolation was insufficient to prevent spread.
Indigenous people were hit particularly hard with mortality in Eskimo villages, sometimes exceeding 50%. Similar statistics were reported from eastern Canada. Labrador lost at least one-third of its population. In South America, Rio de Janeiro suffered an attack rate of 33.5%, and in Buenos Aries the virus attacked nearly 55% of the population. The virus would go on to kill 7% of the entire population in much of Russia and Iran. In the Pacific, 14% of the population of the Fiji Islands would die in 16 days. In Western Samoa, 22% of the population died. Statistics were hard to get in China, but in Chunking one-half of the population was ill.
Similar to what we are seeing in our current pandemic, the most terrifying numbers would come from India. This affected not just the native population, but British troops stationed in India who had a mortality rate of 9.6%. The lethality peaked in Army Cantonments, in the first five bases attacked 20% of its soldiers’ caught influenza and 37.3% of the soldiers who developed pneumonia died. Quarantine and isolation remained the only effective measures against influenza. Older patients had a much lower mortality rate.
A third wave of the virus occurred in December 1918. Although much less than the second wave, it was still a lethal epidemic. The response to quarantine and isolation varied from city to city, with San Francisco probably doing the best job after public health director Dr. William Hassler quarantined all naval instillations. One of the last countries to be affected was Australia. A troop ship carrying 90 ill soldiers arrived, but fortunately by then the strain had lost most of this lethality and the death rate from influenza was far less than any other westernized country.
Unfortunately, in some cases the disease left a coda with an infection of the brain and the nervous system causing delirium, psychosis, with occasional agitation and mental depression. It was possible that Sir William Osler, one of four founding Johns Hopkins professors, also suffered from influenza which led to his secondary bacterial empyema which killed him.
Even then it was not over. In February 1920, influenza returned with ferocity. Only over the next few years would the mortal disease finally fade away. New York City was left with 21,000 orphans.
The first real attempt to quantify the death toll came in 1927 when the American Medical Association sponsored a study estimating that 21 million died. Every revision since then has increased the numbers. Most epidemiologists settled on a number of 675,000 who died out of a population of 105 million in the United States.
Considering the world’s population at that time, influenza killed probably in excess of 5% of the people in the world. Young adults had died at an extraordinary, and frightening, rate. The elderly, normally the group most susceptible to influenza, not only survived the attacks of the disease but were attacked far less often. This resistance of the elderly was a worldwide phenomenon. The most likely explanation is that an earlier pandemic so mild as to not attract attention resembled the 1918 virus closely enough that it provided protection.
See previous articles in the series:
On Pandemics: Etiology of Pandemics – Part 1
On Pandemics: Historical Considerations of Pandemics – Part 2
Figure 1: Spanish Influenza in American Army hospitals. Masks and cubicles were used at Fort Porter, where patients’ beds are reversed, so breath of one will not be directed toward another. Nov. 19, 1918.
Figure 2: Soldiers gargle with salt and water to prevent influenza. Sept. 24, 1918. Camp Dix, New Jersey, during the 1918-19 ‘Spanish’ Influenza pandemic.
Figure 3: U.S. 39th regiment in Seattle, wear masks to prevent influenza. Dec. 1918. The soldiers were on their way to France during the 1918-19 ‘Spanish’ Influenza pandemic.