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Influenza is a respiratory disease that occurs as a result of infection with influenza Virus. Influenza is one of the most main causes of illness and death today in all over the world, because it is one of the most important infectious diseases facing the world. The combined between pneumonia and influenza considered one of the top ten causes of death in the United States. In addition the history of the great epidemic which occurred in 1918 to 1919 and killed more than 20 million people around the world has prompted scientists to conduct more studies and research on these viral infections. So far, the assets of strains of the flu and the epidemiological behaviour are not fully understood. However, the inability to predict the new strains of flu represents a serious challenge to public health and programs that reduce the spread of such epidemics. There are three types of flu viruses infect humans are influenza A, influenza B and Influenza C. Several studies show that influenza type A virus is the most common seen, which is the main cause of many serious epidemics and the pandemics. Influenza A infects humans, horses, goats, pigs, birds and some other animals. Based on studies conducted on flu pandemics that hit people in the past, all of these pandemics were caused by influenza A(1). Influenza A identified in pigs in 1918, which coincided with a human flu pandemic 1918-1919.However, even though influenza A viruses have many similarities, but that is not mean they are same. Each influenza A viruses are genetically designed to infect that species. Genetic mutations may occur to some strains of influenza A virus with a different pathogenic dangerous and some of these mutations occur in the same species, but do not move to other species. On the other hand, some of the virus after mutation moves to other species, causing them serious pathogenic.
Genus: Influenza A
The virus reproduces only within the cells of living tissue and not affect by antibiotics such as penicillin that used to treat bacterial infections. Influenza virus is spherical and its size is equal to one thousandth of a millimetre, and genetic material of the virus consists of RNA, which contains 8 genes and the enzyme "polymerase" which plays a vital role in the proliferation of the virus. Influenza virus consists of an internal membrane made from protein surrounding the nuclear material of the virus. While, the outside membrane made from lipid, which project prominent glycoprotein spikes of two types:
Haemagglutinin (HA): which plays a key role in the ability of the virus to infect cells of the respiratory tract infection by fusion with cell's receptors and multiply inside the cell. This molecule is more parts of the virus's ability to stimulate the immune system, and the ability of body resistance measured by the level of Haemagglutinin resistance.
Neuraminidase (NA): works to spread out the virus after replication in respiratory system throughout the body(1).
The structure of the influenza A virus:
PB2: Transcriptase: cap binding
PA : Transcriptase : protease activity
NP: Nucleoprotein: RNA binding; part of transcriptase complex; nuclear/ cytoplasmic transport of vRNA
NA: Neuraminidase: release of virus
M1: Matrix protein: major component of virion
M2: Intergral membrane protein-ion channel
NS1: Non-structural: nucleus; effects on cellular RNA transport, splicing, translation. Anti-iterferon protein.
NS2: Non-structural: nucleus+cytoplasm, function uknown
Influenza virus is a class of viruses that contain RNA as a genetic material. Influenza virus multiplies inside the host cell and uses the material of this cell to reproduce hundreds of copies of the virus. When the virus combined with cell membrane, the RNA of the virus enters inside the cell. Then the cell enzymes and ribosomes transcribe and translate the viral genes. In this way, virus multiplies inside the cell. Thus, the host cell produces hundreds of new virus particles, rather than the production of new cellular material. Therefore, the new virus particles excreted outside the host cells to infect new cells.
Drift and Shift:
Several studies indicate that, the influenza A viruses are continuously evolving, and can change by two different ways: Antigenic Drift and Antigenic Shift.
Influenza A virus changes by antigenic drift all the time. Antigenic drift change is small and gradual change through mutations that through mutations occur in two of the genes that contain the genetic material which produce surface proteins, hemagglutinin and neuraminidase. However, this mutation produces new strains of the virus, which may not be recognized by antibodies to earlier influenza strains. When a person is infected by certain strain of influenza virus, his immune system produces antibodies specific to this strain, but if he infected by the virus evolving, these antibodies do not affect on the new strain of the virus. This explains why people got infected more the one time by influenza virus.
Antigenic shift refers to sudden shift of the influenza A virus subtypes from a virus that is unable to infect humans to the virus able to infect humans. It can occur either by direct transmission between animal and human or by mixing between animal influenza A and human influenza A virus genes to produce a new strain of influenza A subtypes in a process known as genetic reassortment. Thus, the new virus can infect human causing pandemic of influenza A .
Influenza A viruses further classified into subtypes based upon the characteristics of the surface proteins Haemagglutinin (HA) and Neuraminidase (NA). At least 16 different HA and 9 different NA. All 16 HA and 9 NA subtypes of type A viruses are maintained in aquatic birds. Widely circulating human influenza A viruses seem to have been limited to three H (H1, H2 and H3) and two neuraminidase (N1 and N2) subtypes. Recently, purely avian viruses including H5N1, H9N2 and H7N7 subtypes have been directly transmitted to humans.
Table1 shows Influenza A subtypes isolated from different species.
Serotypes of influenza A viruses which have been confirmed in humans, and caused a number of deaths,are:
H1N1: caused Spanish flu in 1918, and the 2009 flu pandemic
H2N2: Caused Asian Flu in 1957
H3N2: Caused Hong Kong Flu in 1968
H5N1: A current pandemic threat
H7N7: Zoonotic potential
H1N2: endemic in human and pigs
There are many ways that influenza virus can be transmitted, primarily by direct contact with infected person. The infected person can spread the infections before symptoms appear (within 24-48 hours) and the ability to continue to spread the virus to the third or fourth day after onset of symptoms. Additionally, influenza can be transmitted by contact with contaminated materials such as doorknobs and toys which has been sneezed upon or coughed on by infected person. Influenza spreads rapidly among the people particularly in crowded circumstances.Most transmission occurs in a short time before or after the appearance of flu symptoms on an infected person (3). Moreover, individuals can be infected by inhalation of virus-laden aerosols. However, it can spread rapidly by sneezing and coughing especially in medical settings, classrooms and airports. Whereas, nasal discharges (droplets) are the most common source of virus transmission by contaminated materials or direct contact. Several studies have suggested a possible relationship between influenza virus transmission and with significant contact between people and infected animals, although this association is still controversial. Influenza A virus is highly contagious and spreads rapidly affecting the respiratory system.
Influenza A virus infect humans virtually every winter in some parts of the world and throughout the year in tropical regions. Global epidemiology of influenza A occurs unexpectedly every 10-40 years. Several studies have shown that, children are infected more than older age. Recent studies indicate that changes in the haemagglutinin and neuraminidase surface antigens are responsible for the appearance of novel strains that evade host immunity and cause re-infections. According to The World Health Organization, the H1N1 virus affects younger age compared with seasonal influenza in all categories- those who are most frequently infected, requiring intensive care, hospitalized and dying (1). It has been estimated that, 3-5 million of people worldwide are infected by influenza and 250 000 to 500 000 deaths yearly due to influenza (2). According to study published in December 30, 2009 by The New England Journal of Medicine, young people who are under 18 years are more likely to catch influenza from an infected person in their household than adults (3). Three pandemics of influenza occurred in the last century. In 1918, "Spanish" influenza (H1N1) caused an estimated 40 million deaths in less than a year(4). While, In 1957, "Asian" influenza (H2N2) caused an estimated 70,000 deaths in the US alone and in 1968 more than 30,000 people were killed in the US by new subtypes of influenza A virus (H3N2).
After transmission through inhalation of droplets, the virus attacking the respiratory tract cells and seize the host cell to replicate itself, which further increase the number of viruses. Innate immune response, delay the spread of the virus in the respiratory tract, which gave time for the host cells to stimulate the immune system to attack invading viruses. B-lymphocytes release antibodies that can neutralize and bind to the virus on the mucous membrane. While T-lymphocytes dispose of the infected cells, which have become a source of the new virus particles production. The body's immune system secretes inflammatory cytokines, which are responsible for most of the symptoms caused by the flu. Virus remains limited in the upper respiratory tract but in certain circumstances and depend on the response of the immune system of an infected person may spread to the rest of the respiratory system. And therefore, the circulating cytokines cause most symptoms of flu such as fever, muscle pain and malaise. Influenza A is a self-limited disease. But in the absence of full immunity to one subtype of Influenza, such as the emergence of a new strain of H1N1, even a young people may die within 24-48 hours of onset of symptoms, and the inflammatory response to the virus may cause acute respiratory distress. A weakened immune system with the very young and the elderly may lead to viral pneumonia, or bacterial infections. Study done on Children's Hospital of Philadelphia between influenza patients and with the patients suffer from moderate influenza, respiratory syncytial virus and healthy individuals shows that the immune paralysis seen in the patients with influenza. On the other hand, the immune paralysis was not seen in the patients with respiratory syncytial virus. This finding may explain the reason of why a quarter of children who die from influenza die because of bacterial infections that attack the body due to weakness of immune system during influenza virus infection (3).
Influenza A virus infects mammals, man, pigs, birds, pets and horses. Influenza A is a major human pathogen, which is associated with pandemics and epidemics. Several studies have pointed out that, pigs and birds are played an important role in the reserve and the genetic development (mutation) of influenza A virus. These finding may explains the pandemic of human influenza because these outbreaks have appeared in the beginning with the people who are connect to these animals.
The incubation period of influenza A virus is from 2-3 days and may become contagious within a day from the incubation period. However, symptoms continue from 3-7 days, but in some cases, symptoms have persisted to 3 weeks.
Runny or stuffy nose
Complications may occur in the upper or lower respiratory tract because of influenza A or due to other infections (secondary complications). However, influenza A virus infections may cause serious complications with the elderly, children and with the people who suffer from medical problem.
Complications of influenza A virus:
Pneumonia: is one of the common complications, perhaps because of the influenza A virus or because of secondary complications such as viral or bacterial infections. The incidence of viral pneumonia is few, but most complications because of the difficulty of treatment. However, pneumonia is one of the causes of death after influenza infection. Bacterial pneumonia usually occurs in patients with chronic chest disease or heart disease.
Aggravate or exacerbate chronic respiratory diseases
Croup and inflammation of the bronchi in infants and children vanity
Convulsions ( due to fever)
Toxic shock syndrome
Inflammation of the muscular and heart muscle
During a pandemic influenza A diagnosis can be made on the basis of clinical symptoms. In most cases, influenza A can be diagnosed based on symptoms alone. But sometimes it is useful to conduct a laboratory tests to determine the type of virus and its appropriate treatment.
Table 1 shows the virous laboratory tests of influenza A
Laboratory diagnostic tests
Time for results
Paired Acute and Convalescent Serum Samples
Influenza Enzyme Immuno- Assay (EIA)
Rapid Diagnostic Tests
Directigen A (Becton-Dickinson)
There are for antiviral medications have been approved for treating influenza A virus infections: zanamivir, oseltamivir, amantadine and rimantadine.
Table shows antiviral Medications for Treatment of Influenza A
Prevention and control
Influenza surveillance, prevention and treatment are the three options available for control of influenza. These options differ in how they are applied from one country to the other.
Surveillance: 50 years ago, The World Health Organization (WHO) has established a global program to control influenza. Today there are 110 control centres for influenza in 80 countries to monitor and track influenza and therefore the composition of their early warning system to prevent cases of epidemic spread of the virus. Together, the centres also collect information about the virus and its spread and samples to determine its properties. We use this information to determine the components of the annual influenza vaccine by the World Health Organization.
Until recently there was no effective medicine for the treatment of influenza. However , to prevent influenza virus infection immunization (vaccination) was used to control the influenza virus infections especially for groups of patients that are characterized by the seriousness of exposure to influenza A virus such as the elderly and patients with asthma.
Since influenza A viruses have the ability to constantly changing and the immune system can't recognize the virus evolving. Thus, the influenza replicate each season, so the vaccine has to be changed annually based on the epidemic of the new virus.
Doctors usually recommended to give influenza vaccine to people who are characterized by the seriousness of exposure to complications from influenza A virus, or those who have chronic diseases such as:
The elderly ( greater than 65 years)
Chronic respiratory diseases including asthma
Chronic heart disease
Chronic renal failure
Diabetes and other endocrine disorders
Studies have shown that young adults who got influenza A vaccination, 70% to 90% of them had been prevented from influenza A virus after vaccination. On the other hand, vaccination in the elderly is less effective but contributes to reducing the severity of the disease and the risk of dangerous complications. Moreover, studies have shown that vaccination of older people reduces the percentage of hospital admissions by 70% and death by 85%.
How can limit the spread of influenza?
Infected people have to stay at home and followed up by specialists.
Quarantine for six days on the people who have had contacts with infected persons without taking preventive action.
The use of masks that prevent the transmission of the virus.
Since the virus can be in the hands prevention action is necessary, such as washing hands with soap repeatedly after sneezing or contact one of the infected person, cover the mouth and nose when coughing or sneezing, avoiding spitting on the ground .
Stay away from crowded places.
In order to reduce the spread of influenza from animals:
Quarantine the infected animals, and then kill it after that.
Clean the tools after used to avoid the infection when used in other places.
Separation of animal species during the breeding each species in isolation from the other type.
Encourage the people to inform about infected animals as soon as.
Influenza A is one of the most dangerous infectious diseases affecting humans and a number of animals. However, influenza A virus has led to several pandemics in the last century. Since the influenza virus is able to change each time, so it requires a new vaccine in each time of mutation. Governments should take several precaution and prevention steps to control the spread of infections by influenza A virus. Therefore, scientists should conduct many researches and studies to find out the effective medicines against this virus and to assume the occurrence of new influenza A pandemics. Moreover, a lot of work and communications between stakeholders and the people must be to reduce the incidence of new influenza A pandemic.