All You Need to Know About Influenza (Flu)

History

Influenza was first documented as a pandemic in the 16th century [1]. It was initially thought to be a bacterial infection. In 1892, Richard Pfeiffer, a German scientist, isolated an unknown bacterium from the respiratory secretions of patients with the flu and called it bacillus influenzae [7].

But, the actual causative agent was not clearly known until the early 1930s. In 1933, British virologists Wilson Smith, Christopher Andrews, and Patrick Laidrow isolated the influenza A virus from ferrets for the first time in London [1,8]. Later in 1936, Thomas Francis Jr, an American virologist, isolated the influenza B virus. In the same year, Macfarlane Burnet, an Australian virologist, discovered that the influenza virus could be grown in embryonated hens’ eggs. This discovery provided in-depth knowledge of various characteristics of the virus [1]. 

This made way for the first inactivated flu vaccine developed by American virologists Thomas Francis Jr and Jonas Salk in 1940. It was developed using fertilized chicken eggs. A couple of years later, in 1942, a bivalent vaccine was developed to protect against both influenza A and B viruses, with support from the US military [9]. It was licensed for general use in 1945 [7]. The discovery of the flu vaccine is considered one of mankind’s greatest discoveries since, even today, most flu vaccines are produced using the same process [9].

Epidemiology

Influenza has swept across the entire world throughout history and continues to infect us even today. The influenza virus, the causative agent of the disease, is a single-stranded RNA virus that belongs to the orthomyxovirus family. There are four types of influenza viruses: influenza A, B, C, and D viruses. Types A, B, and C are known to cause illness in humans, whereas type D primarily affects cattle [1,4, 5].

Influenza A and B viruses cause the most illnesses in humans [5]. Infections can be severe or mild, and infected individuals can be asymptomatic and still carry the infection [1]. Influenza B virus primarily affects children [1]. The influenza C virus is quite rare, known to cause mild illness in humans, and is not a public health concern [4].

For countries in the Northern Hemisphere, peak flu season is usually high between October, April, or May. In the Southern Hemisphere, influenza infections peak from April to September. In tropical areas, it occurs throughout the year.  People at risk of developing severe influenza-related complications include the elderly (those over 65 years of age), young children, pregnant women, and immunocompromised people, including those with chronic health issues such as heart disease or diabetes, etc. 

The World Health Organization (WHO) estimates that annual flu epidemics result in about 3 to 5 million cases of severe illness and about 290,000 to 650,000 respiratory deaths [4]. Around 9 to 45 million people in the US fall ill due to influenza yearly. Since 2010, the average number of influenza-related deaths, estimated by the Centers for Disease Control and Prevention (CDC), is 37,463. Nearly 80% of those who die due to complications caused by the disease are over 65 years of age [1].

Outbreaks

The first outbreak that fits the description of influenza occurred in 1580 in Asia. It soon spread to the rest of the world, including the Americas, Africa, and Europe. In the last 100 years, the world has seen four influenza pandemics, including the Spanish flu, Asian flu, Hong Kong flu, and the Mexican flu [10].

Spanish Flu

The influenza pandemic of 1918, the Spanish flu, is regarded as one of the deadliest pandemics of the 20th century. It claimed over 50 million lives and infected more than 500 million people worldwide. It was responsible for the deaths of around 100,000 troops in military camps and trenches during the first world war [11]. The situation was so bad that there was a waiting list for the dead to be buried. For instance, over 500 bodies were on hold in Philadelphia, US, waiting to be buried for over a week [12]. 

Songs were written about the influenza pandemic to help people cope with this scourge. For example, there was the American musician Essie Jenkins’ ‘1919 Influenza Blues’ and ‘Influenza 1918’ by South African artist Reuben Tholakele Caluza. The Spanish flu was so all-pervasive that little children jumped rope to a dark rhyme about the flu: 

I had a little bird,

Its name was Enza,

Opened up the door

And In-Flew-Enza.

—Children’s rhyme, 1918

Asian Flu

In 1957, the Asian flu, caused by a new strain of the influenza A virus (H2N2), emerged in east Asia. The Asian flu caused over one million deaths worldwide and around 116,000 deaths in the US alone, according to data provided by the CDC [13].

Hong Kong Flu

Ten years later, in 1968, the world was again pushed into a state of emergency by another pandemic, the Hong Kong flu. It was caused by a new strain of the influenza A virus (H3N2) comprising two avian influenzas A virus genes. The kind of impact created by this pandemic was close to that of the Asian flu. It caused over one million deaths worldwide and around 100,000 in the US [14].  

Mexican Flu

In 2009, the Mexican Flu was detected in the US, caused by a new strain of influenza A virus (H1N1). According to the CDC, 150,000 to 575,000 people lost their lives during the first year of the pandemic. Unlike other influenza pandemics, the Mexican flu mostly affected people under 65. Around 80% of deaths caused by the virus during this period occurred in people of this age group [15]. In the US, about 60 million people were infected by the Mexican flu. It was responsible for 270,000 hospitalizations and 12,500 deaths across the country [1].

How is it Spread?

Any person infected with an influenza virus can transmit it to other healthy individuals. An infected adult can spread the infection even before symptoms appear and up to 5-7 days after symptoms begin. Children, however, can transmit the flu virus only after symptoms appear. They remain susceptible to the transmission of the virus for up to 10 or more days following the onset of symptoms [1].

• Person-to-person influenza transmission is usually through respiratory droplets released into the air when an infected person coughs, talks, or sneezes.
• The infection also spreads when uninfected or healthy people touch surfaces contaminated with the virus and touch their eyes, mouth, or nose [1,16].

Biology of the Disease

Once the influenza virus enters the human body, it begins replicating in the respiratory tract. Although the virus is capable of replicating in other cells (including several immune cells), its replication efficiency is much higher in the respiratory epithelium. This growth can lead to lung inflammation and even pneumonia in some instances. In such severe cases, the infection can spread through the entire body, resulting in multiple organ failures [17].

Symptoms

It takes one to four days for flu symptoms to appear following exposure to the virus [1]. The most characteristic symptom of the influenza virus is a sudden rise in body temperature one to three days following the infection. Other symptoms include:

• Headache
• Muscle and joint pain
• Tiredness
• Runny nose
• Sore throat 
• Dry cough 
• Vomiting and diarrhea — more common in children than in adults [4,16,18]

The flu virus can be found in respiratory secretions for about five to ten days after the disease onset and peaks during the first three days [1]. People usually recover within a week without the need for medical attention. Some might have a severe cough lasting two or more weeks [4]. Complications from a flu infection can include:

• Pneumonia caused by a secondary bacterial infection
• Worsening of the underlying respiratory problems
• Bronchitis
• Inflammation of the ear (usually the middle ear)
• Upper airway infection [1].

Diagnosis

Testing for the flu involves collecting samples through nasal and oral swabs. Out of the different diagnostic methods available, the Rapid Influenza Diagnostic Tests (RIDTs) are a common method to detect the presence of the influenza virus. They can provide results within 10 to 15 minutes. But, RIDTs are not 100% accurate; a person can test negative and still have the infection.

Other close alternatives to RIDTs are rapid molecular assays. They can provide test results within 15 to 20 minutes and are usually more accurate than RIDTs. RT-PCR, viral culture, and immunofluorescence assays offer greater accuracy. However, these tests are performed only in some hospitals and public health laboratories [19]. Between 30% and 40% of those hospitalized due to influenza-related complications are diagnosed with acute pneumonia [17]. 

Treatment

Treatment for influenza usually focuses on relieving symptoms [4]. In severe cases, antiviral drugs are administered to reduce the disease’s severity. These drugs are more effective if administered within 24 hours from when symptoms appear [20]. Treatment is usually given for a minimum of five days. It can also be extended until the clinical condition of the patient improves [4].

Antiviral drugs, such as oseltamivir, zanamivir, peramivir, and baloxavir, are currently used to treat the flu. The choice of medicine depends on the age and clinical condition of the patient. For instance, baloxavir is used to treat uncomplicated influenza cases in patients 12 years and older. Oseltamivir is used to treat complicated cases of the disease. Also, the CDC recommends using oseltamivir to treat pregnant women with severe illnesses [20].

Prevention

According to the CDC and WHO, the flu vaccine is the most effective preventive measure to protect from an influenza infection. Influenza vaccines have been used for more than 60 years and are found to be safe and effective. But, it is important to take these vaccines every year. This is because the vaccine’s effectiveness wanes over time. Also, viruses mutate, and different strains may dominate at different times, and vaccines are regularly updated to combat circulating virus types.

While influenza vaccines are not foolproof, they are currently our best bet against getting sick with the flu. The CDC notes that in seasons when the flu vaccine viruses were similar to circulating flu viruses, the flu vaccine reduced the risk of having to go to the doctor with flu by 40% to 60%.

Annual vaccination is recommended for high-risk individuals, including children less than 5 years of age, older adults (those who are over 65 years of age), people with comorbidities, and healthcare workers. In addition to taking a flu shot, other preventive measures include:

• Wash your hands regularly
• Avoid touching your eyes, nose, and mouth with unwashed hands
• Cover your nose and mouth using tissues while sneezing or coughing
• Avoid close contact with people who are sick and isolate yourself from others when you are sick with a fever and follow your physician’s guidance
• Regularly clean and disinfect surfaces as they might be contaminated with the virus
• If you have any underlying health issues and have any flu-like symptoms, contact your healthcare provider as early as possible [4, 21].