Influenza Exclusive: Symptoms, Detection, Vaccines and Updates

 

 

Influenza, commonly known as flu, is a highly contagious respiratory condition caused by influenza viruses belonging to the family Orthomyxoviridae. It is also considered one of the leading causes of mortality globally as serious complications can develop with influenza particularly among the high-risk people such as those with a chronic medical condition, immunity compromised individuals and children under the age of 5. With seasonal influenza occurring annually around the winter months, the transmission of the infection can occur rapidly particularly in the crowd.

The contagious period lasts for 4 days and commonly affects the nose, throat and sometimes the lungs. Once an individual becomes infected, the influenza virus attaches to the epithelial cells continuing to replicate in the respiratory tract as the immune system responds by eventually destroying the infected host cells. Also, the viral infection can further encourage complication such as the development of a secondary bacterial infection by providing sites for adhesion and by impairing immune response. However, once the infection subsides, with the loss of the cell lining of the respiratory tract, the recovery process can take up to a month for the regeneration of the epithelium.

The only preventive measure is with a vaccine that is only effective for one year due to the high mutation of the influenza viruses. According to the recommendations and updates of WHO, one or more vaccine components are changed every year in order to effectively target the seasonal viruses. And hence, the genetic characterization plays a vital role in order to better understand how the viruses are evolving and developing resistance to the antiviral drugs.

To learn more about the structure and characterization of Influenza virus, read Influenza Series: How does Influenza virus act?

Seasonal and Pandemic Influenza

Seasonal Influenza

Seasonal influenza is characterized by the acute respiratory infection caused by influenza viruses every year, particularly prevalent during the winter months. The influenza viruses are designated into four types; A, B, C and D although A and B viruses predominantly affect humans and cause seasonal epidemics. Based on the antigenic properties of their envelope proteins, type A is further divided into various subtypes. According to WHO, the currently circulating seasonal influenza A virus subtypes are A(H1N1) and A(H3N2). Also, the two types of B viruses currently circulating as seasonal influenza viruses are Victoria lineage and Yamagata lineage, named after the place where they were initially detected. The type C is not considered much of a disease burden and hence only influenza A and B are included in the seasonal influenza vaccines. The influenza D viruses mostly affect the cattle population without causing illness among people.

Pandemic Influenza

Pandemic influenza occurs as a global epidemic when a new influenza virus emerges, affecting humans who have little or no immunity to it. The pandemic influenza cannot be predicted and the severity of it can range from mild to severe causing death. The recent pandemic caused by influenza A (H1N1) occurred in 2009 and according to WHO, it is estimated to have caused around 100,000 to 400,000 deaths internationally. Currently, there is no pandemic influenza virus circulating the globe.

Avian and other Zoonotic Influenza

The avian, swine and other zoonotic influenza viruses can also affect humans and in most of the cases, influenza (H5N1) and A(H7N9) develop from a direct contact with the infected animals; live or dead. The infection may be mild or progress rapidly to severe pneumonia, acute respiratory distress syndrome, sepsis with shock or death. The incubation period, the severity of the infection and the clinical outcome varies among the patients. Among most of the individuals with A(H5) or A(H7N9) viruses, the infection is often aggressive and the case fatality rate is often much higher than the normal seasonal influenza.

Epidemiology

According to WHO, acute lower respiratory infections are considered the second most common illness and the third cause of death globally. According to WHO, 5% to 15% of the global population are infected annually making it one of the leading causes of mortality next to AIDS. An estimated 650,000 deaths occur annually that are related to the respiratory diseases from seasonal influenza according to the new estimates marking an increase on the previous estimate of 250,000 to 500,000 dating from over ten years ago. And, according to the United States Centers for Disease Control and Prevention (US-CDC) most of the deaths occur in the poorest regions of the world among people over the age of 75.

To learn more about WHO recommendations to combat Influenza, read Influenza Series: Recommendations and Actions Initiated by WHO. 

Global Influenza Activity

The influenza transmission normally appears in the winter months of the northern hemisphere temperate region and the duration of the season varies by country annually. Although the season can begin as early as October, the peaks are usually around January or February. Less frequently, tropical regions also experience influenza epidemics particularly, during the rainy season.

To learn more about the seasonal flu activity in Canada, read Influenza Series: Canadian Flu Season News Updates.

To learn more about the seasonal flu activity in the United States, read Influenza Series: US Flu Season News Updates.

Transmission

The transmission of the virus occurs through respiratory droplets of the infected individual when they cough and sneeze. The transmission is also possible by touching the surface contaminated with the virus and then touching the mouth or the nose. Affected individuals may be able to pass on the infection even before they are aware of their sickness. The contagious period is usually the initial 3 – 4 days after the infection and those with a weakened immune system such as young children could continue to infect others for an even longer time.

Clinical Characteristics

The clinical features of influenza are almost indistinguishable from other respiratory viral infections. However, influenza is characterized by the onset of sudden increase in temperature that can continue to an average of 3 days, chills, pharyngeal irritation and headaches. Additional symptoms include headache, limb ache, faintness, fatigue and dry cough. In the case of an existing asthma condition, wheezing may also be evident. Vomiting and diarrhea are particularly more common among children than the adults and the younger children could excrete the viruses earlier and over an extended period of time. One of the serious outcomes of influenza is death over a short period of time and primary influenza pneumonia.

People at high risk

Some of the health and age factors that contribute to an individual developing serious complication from the flu include;

• Asthma
• Chronic lung disease
• Blood disorders
• Heart disease
• Kidney disorders
• Endocrine disorders
• Liver disorders
• People with a weakened immune system such as HIV patients
• Other individuals also considered as high risk from the flu include people aged 65 and older, children under the age of 5 and pregnant women

Pathogenesis of Influenza

When the influenza virus enters the respiratory tract, it attaches to the epithelial cells and continues to replicate in the upper and the lower respiratory tract. The RNA of the virus is identified by toll-like receptor (TLR)7 and retinoic acid-inducible gene-I (RIG-I) thus inducing the production of type I IFNs and activating antiviral host responses. However, the influenza A virus (IAV) can deviate from the innate immune response by interfering with RIG-1 signaling pathway. With the progression of the infection, cell damage occurs within the airways, up-regulating the generation of toxins and an increased inflammation response is generated within the host. In a continued effort to control the infection, the immune system destroys the infected host cells with the production of perforin by Natural Killer (NK) cells and the production of reactive oxygen species from macrophages and neutrophils. The virally induced destruction of immune cells prevents the clearance of the infection and further promoting the development of the infection.

To learn more about subtypes of Influenza, read Influenza A, Influenza B, Influenza C  and Influenza D.

Detection Methods

In order to reduce the number of influenza-associated morbidity and mortality, an accurate and early diagnosis is vital to initiate antiviral therapy. Some of the several approaches used for the diagnosis of influenza infections in humans include nucleic acid amplification tests, advanced molecular detection (AMD), serological testing, viral isolation in cell culture, rapid molecular assays and immunofluorescence assay, etc. For the detection of the flu virus, ideally, the samples require to be collected within the initial 3 – 5 days of illness. In the case of a critically ill patient who has tested negative on the sample collected from the upper respiratory tract, a lower respiratory tract specimen should be collected to detect influenza viruses by reverse transcription polymerase chain reaction (RT-PCR) test.

Virus culture

The embryonated eggs are inoculated, cytopathic effect is monitored and the infection is confirmed by specific antibody staining. However, the rapid tests and PCR-based tests are capable of detecting the virus with comparatively more sensitivity and specificity.

Commercial rapid influenza diagnostic tests (RIDTs)

This antigen detection assays can identify the viruses within 15 minutes but the accuracy of the tests can differ based on the respiratory specimen collected such as the throat swab or nasal swab.

Immunofluorescence

These antigen detection assays can deliver the results in approximately 2 to 4 hours. The direct and indirect fluorescent antibody staining assays can identify A and B influenza viral antigens although the subtyping of the viruses is not possible.

Rapid molecular Assays

This is a new kind of molecular influenza diagnosis that uses the specimen from the upper respiratory tract. The use of isothermal nucleic acid amplification can deliver results within 15 minutes and RT-PCR can yield results in approximately 20 minutes.

To learn more about screening methods for Influenza, read Influenza Series: Evolution of screening tests. 

Clinical Management

Individuals not from the high-risk group are generally provided symptomatic relief and advised to remain indoors to prevent the spread of infection to others. However, when treatment with antiviral drugs for uncomplicated human influenza is initiated within two days of sickness, it can help reduce the symptoms and the risk of developing complications such as pneumonia. Among the high-risk individuals, the early initiation of treatment can help prevent the onset of severe illness requiring hospitalization.

The three FDA approved anti-viral drugs recommended by CDC:

• Oseltamivir (trade name Tamiflu) available as a liquid suspension or as a pill for the treatment of individuals 14 days old or older and to be taken twice a day for a period of five days.
• Zanamivir (trade name Relenza) comes in powder form and is used for the treatment of individuals 7 years and older but not recommended for those with breathing conditions such as asthma. It is also to be taken twice a day for a period of five days although hospitalized individuals may require the treatment for longer than 5 days.
• Peramivir (trade name Rapivab) is administered intravenously and is recommended for early treatment of flu for individuals 2 years and older.

To learn more about figting influenza, read Influenza Series: Combating Influenza. 

To learn more about evolution of treatment options, read Influenza Series: Evolution of treatment options.

 Complications

The complications of influenza can affect any individual and include pneumonia, bronchitis, sinus infections, ear infections and deterioration of chronic medical conditions such as congestive heart failure. One of the most common complications of influenza is the secondary bacterial infection. Staphylococcus aureus has been considered as one of the important cause of bacterial pneumonia presenting a high rate of mortality. Viral infections encourage bacterial infection by impairing immune responses, providing sites for adhesion, causing cell and tissue destruction thereby enabling the spread of bacteria and to develop an invasive infection. It is estimated that the majority of individuals with influenza continue to develop pneumonia and bacteria such as Haemophilus influenzae and Staphylococcus aureus can cause post-influenza pneumonia.

Among the pregnant women, it can cause severe illness with an increased risk of hospitalization, premature labor and delivery. In the case of an asthma condition, an asthma attack can be provoked or the deterioration of asthma symptoms can also occur. People with a compromised immune system are at a greater risk of developing more serious complications such as pneumonia and death. Hence, the only preventive method for influenza and the complications associated with it is with vaccination, particularly for the high-risk individuals.

Antigenic Characterization, Genome Sequencing and Genetic Characterization

Antigenic Characterization

Antigens are the structures present on the surface of the viruses that are recognized by the immune system for the production of antibodies. Antigenic properties describe the immune response triggered by the antigens of the virus and antigenic characterization is the analysis of the virus’ antigenic properties.

Genome Sequencing

Influenza viruses constantly undergo genetic changes and the Center for Disease Control and Prevention regularly monitors the genetic changes of the viruses. The information gathered is vital to determine if existing vaccines and antiviral drugs will be effective against the new influenza viruses. The influenza A and B are RNA viruses with eight gene segments consisting of nucleotides that are designated by the letters A, U, C or G. The genome sequencing determines the order of the nucleotides in the virus’ genome. Every year CDC conducts full genome sequencing on viruses from the clinical samples with particular focus on sequencing the two gene segments, i.e., the hemagglutinin (HA) and neuraminidase (NA). These two segments are responsible for the two primary surface proteins of the viruses which determine important properties including how they respond to antiviral drugs.

Genetic Characterization

The libraries of gene sequences enable the comparison of currently circulating influenza with the older viruses and those used in vaccines. This process of comparison of genetic sequences is called genetic characterization and is performed year round by CDC. This characterization helps determine how the viruses are evolving, developing resistance to antiviral drugs, how the flu viruses are related to each other and how the influenza vaccine could offer protection against an influenza virus.

Infection Control

One of the most effective preventive measures of influenza is through vaccination. Because of the high mutation of the virus, one particular vaccine is only effective for about a year. The WHO updates the recommendation for the vaccine every year, with a change in one or more vaccine components to effectively target the viruses most commonly expected to circulate for the season. According to WHO, vaccination is recommended annually before the season particularly for the high-risk groups such as the health care workers and those at the most risk of developing health complications from the infection.

Types of Influenza Vaccines

The vaccine production usually takes around 6 months and vaccine for the seasonal influenza is based on the propagation of viruses in embryonated eggs or cell cultures.  According to WHO/Europe, the two types of influenza vaccine available are the inactivated influenza vaccines (IIV) and live attenuated influenza vaccines (LAIV). The trivalent vaccines were traditionally produced to prevent the infection against three different seasonal influenza viruses (both IIV and LAIV). Although this is still evident in most of the countries, the present trivalent vaccines contain influenza A (H3N2), pandemic A(HINI) and 1 of 2 influenza B lineage viruses. However, in some countries, the quadrivalent vaccines are available that protect against 4 different viruses.

Inactivated influenza vaccines (IIV)

IIV is derived from highly purified, egg-grown viruses and the three types of inactivated vaccines are; whole virus vaccines, split virus and subunit vaccines. Inactivated influenza vaccines are recommended for individuals over 6 months, those with chronic medical conditions and pregnant women.

Live attenuated influenza vaccines (LAIV)

The LAIV is also grown in egg culture and is made from weakened viruses. This vaccine is recommended for individuals aged 2 – 49 years without any underlying medical conditions and is normally administered as a single nasal spray. 

To learn more about the recent developments in vaccination, read Influenza Series: Vaccines Used for Treating Influenza and Flu-Related Illnesses. 

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