Influenza

Cause

Influenza is an infectious disease caused by an enveloped RNA virus belonging to the Orthomyxoviridae family, which mainly affects the upper respiratory tracts (nose, throat and bronchi) and sometimes the lungs. Humans can be infected with three types of influenza virus: A, B and C. Type A viruses infect humans and various animal species, and the reservoir hosts are avian species (wild waterfowl, poultry) and various mammals, particularly pigs. Type A viruses are classified into subtypes designated HxNy, based on their hemagglutinin (H) and neuraminidase (N) surface proteins. Type B viruses almost exclusively infect humans. There are two type B virus lineages: B-Yamagata and B-Victoria. Type A and B viruses are responsible for seasonal outbreaks while type C viruses generally cause a very mild disease.

Only type A viruses have pandemic potential.

Symptoms and disease development

The first symptoms appear 1 to 4 days after contamination. Infection generally lasts one week and is characterized by the sudden onset of fever, muscle ache, headache, a general feeling of fatigue or weakness, and respiratory signs (dry cough, sore throat and runny nose).

Most infected individuals recover within a week with symptomatic treatment (antipyretics, hydration, cough medicine and rest). Some vulnerable individuals are at risk of developing severe influenza that may lead to hospitalization in intensive care, respiratory support or even death, for example people over the age of 65, pregnant women, the morbidly obese (BMI>40 kg/m2), diabetics, immunodeficient patients, people with chronic conditions (cardiovascular diseases, respiratory diseases), and infants.

Please note that influenza should not be confused with influenza-like illness

• Influenza is the infection caused by an influenza virus, which has the same symptoms as influenza-like illness.
• Influenza-like illness is a range of symptoms (fever, respiratory signs, aches, headache, etc.) caused by a respiratory virus that may be different from influenza, for instance respiratory syncytial virus (RSV), rhinovirus, parainfluenza virus or adenovirus.
• If necessary, doctors may take a respiratory sample for laboratory testing during an influenza-like illness to establish whether or not it is influenza.

Transmission

Influenza viruses enter the body through airborne transmission via the nose or throat. They are easily spread by aerosol transmission via microdroplets ejected when infected individuals cough, sneeze or speak. The viruses can also be spread by hand (hand transmission), when people touch a contaminated surface and then bring their hands close to their nose, which is why barrier measures (masks, hand washing) are so important during outbreaks. Influenza viruses replicate in the respiratory epithelium, where new viral particles are produced. Viral replication is localized and leads to necrosis of the ciliated respiratory epithelium which is accompanied by excessive bronchial mucus secretion.

Cold temperatures aid influenza virus survival which partly explains why outbreaks occur in winter in temperate climates.

Immune response

During infection, the innate immune response leads to the production of inflammatory cytokines, which are responsible for most influenza symptoms. The adaptive or specific immune response primarily involves induction of cytotoxic T lymphocytes that eliminate infected cells, and B lymphocytes that produce antibodies which will neutralize the virus.

Treatment

Treatment is symptomatic and good hygiene habits limit the spread. A specific antiviral treatment may also be prescribed. The antivirals available in France are neuraminidase* inhibitors. Oseltamivir (Tamiflu®), which is effective against type A and B viruses, can be taken orally. It reduces disease duration and symptom severity if taken early, i.e. within 48 hours following the onset of symptoms. It can also reduce the risk of complications and death. Another neuraminidase inhibitor, zanamivir (Relenza®) can be administered intravenously in hospital in the event of resistance to oseltamivir.

These antivirals are prescribed as curative medicine, and oseltamivir can also be given as a preventive measure in some situations (an outbreak in a nursing home for example).

*Neuraminidase: viral surface glycoprotein with enzyme activity that enables newly-formed viral particles to be released and spread in the mucus.

Prevention and vaccination

• Prevention

In the event of an outbreak, personal protective measures are needed to avoid becoming infected or infecting others, i.e. wearing a mask, using disposable tissues, coughing and sneezing into your arm or sleeve, washing your hands regularly and airing your home. If you are ill, avoid contact with vulnerable individuals.

• Vaccination

In addition to hygiene measures, the annual influenza vaccine is the most effective means of protection and it reduces severe forms of influenza.

It is strongly recommended for the most vulnerable individuals (see above), but also for medical staff, people in nursing homes and for all other people in direct contact with vulnerable individuals. The vaccine is effective for 6 to 9 months.

Influenza viruses are constantly undergoing genetic changes, so the composition of the influenza vaccine has to be changed every year to incorporate the most recent circulating strains. The vaccine's efficacy depends above all on the age and immune status of the vaccinated individual, as well as the similarity between the selected vaccine strains and circulating influenza viruses.

Vaccine development

The WHO Global Influenza Surveillance and Response System includes WHO Collaborating Centers and Reference Centers for Influenza from all over the world. It is responsible for monitoring the evolution of viruses circulating among humans and rapidly identifying new strains. Based on the information collected by the network, WHO recommends the vaccine composition it believes will be effective against the most recent circulating strains. There are two meetings each year: one in February to determine the influenza vaccine for the northern hemisphere, and one in September to determine the vaccine preparation for the southern hemisphere. Influenza vaccines are quadrivalent. They contain representative strains of the two virus A subtypes, A(H1N1)pdm09 and A(H3N2), and two B virus lineages, B-Yamagata and B-Victoria, responsible for seasonal outbreaks.

Epidemiology

Type A and B influenza viruses cause seasonal outbreaks in humans. Influenza generally occurs in winter in temperate countries but influenza viruses circulate all year round in tropical and subtropical countries. Only type A influenza is responsible for pandemics due to new viruses, which are unknown to the population and against which most people have no protection.

• Seasonal influenza

Influenza outbreaks vary according to the season. They occur in temperate regions between November and April in the northern hemisphere, and between April and October in the southern hemisphere. Although there are influenza outbreaks every year, they remain unpredictable. No one knows when they will begin, how long they will last and which viruses will circulate. It is also impossible to predict how strong or severe an outbreak will be. In France, seasonal influenza affects 2 to 8 million people each year and claims 10,000 to 15,000 lives.

• Pandemics

A pandemic is an outbreak which is not contained and rapidly spreads across the world. It is caused by the emergence of a new type A influenza virus subtype (following a major genetic modification) to which the majority of the population is immunologically naive. Pandemics have a devastating impact in terms of morbidity, mortality and socio-economic aspects. But these pandemics are rare. There were three in the 20th century:

• the most severe, the 1918 pandemic, or "Spanish flu", caused by the H1N1 subtype, spread across the world and was responsible for 20 to 50 million deaths between 1918 and 1919;
• the Asian flu of 1957, caused by the H2N2 subtype;
• and the 1968 "Hong Kong" flu, caused by the H3N2 subtype

In 1977, during the outbreak of Russian flu, H1N1 subtype viruses were reintroduced to humans and circulated alongside H3N2 subtype viruses.

In 2009, the year of the last influenza pandemic, the virus responsible was a new variant of the H1N1 subtype, resulting from genetic exchanges (called reassortments) between a human virus, an avian virus and two swine viruses. Since 2009, this A(H1N1)pdm09 virus has replaced the previous A(H1N1) viruses and together with A(H3N2) and type B viruses is responsible for seasonal outbreaks.

• Avian/zoonotic influenza

The term zoonotic influenza is used when an influenza virus is spread from animals to humans. For influenza A viruses, infections due to viruses from animal reservoirs are possible in exceptional cases. These zoonotic infections vary in severity. They can cause relatively mild infections (e.g. H3N2v swine virus, H9N2 avian virus) or highly lethal forms (e.g. H5N1 and H7N9 avian viruses). These viruses are general incapable of human-to-human transmission. The term avian influenza is used for cases of infection caused by avian influenza viruses which have been able to cross the species barrier and infect humans.

In poultry, the influenza virus mainly replicates in the digestive and respiratory tracts. This is why large quantities of the virus are excreted in droppings and contaminate the environment. The H5 and H7 subtype avian viruses are classified as low pathogenic (LP) or highly pathogenic (HP) for poultry. Transmission to humans requires prolonged exposure to infected poultry or contaminated environments, and human-to-human transmission is inefficient. Among these avian viruses, HP A(H5N1) and HP and LP A(H7N9) are responsible for most cases. Other avian viruses, such as A(H5N6) viruses, are responsible for severe sporadic human cases, while A(H5N8) viruses have never been detected in humans.

To factor in the risk of imported cases in France, Santé publique France updates the list of countries with endemically-circulating influenza viruses with zoonotic potential, and suspected cases of infection are assessed according to the recommendations of France’s High Council for Public Health (HCSP).

October 2019