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Influenza also known as flu that caused by influenza virus, and affect mainly the respiratory system. Influenza is known to be the main cause of diseases and death worldwide. The greatest outbreak of epidemic influenza occurs in 1918 which last for one year and killed about 40 million people around the world. This outbreak switch on the scientists to conduct more researches and studies on this infection. The challenge to the scientists was whether they can predict the new strains of flu viruses so that they can reduce the spread of such epidemic in the public health, because the flu viruses characterized by constantly changing (Collier and Oxford, 2006).
There are three types of influenza viruses which mainly found in various kinds of animals include chickens, ducks, pigs and human also.
Influenza A virus: responsible for the most common cause of serious epidemics and pandemics outbreaks.
Influenza B virus: widely circulating in human and can cause epidemics however; it causes milder diseases than influenza A.
Influenza C virus: found in animals such as dogs and pigs. It infects also respiratory tract in human with mild infection however, it does not spark epidemic.
From these viruses, Influenza type A is the most common. Influenza A genus belongs to myxovirridae family and orthomyxovirridae subfamily. It has subtypes strains, these have been all isolated from the wild bird, and generally they have all similar structure. The subtypes of influenza A labelled according to the number of H antigens (Hemagglutinin) and the number of N antigens (Neuraminidase). There are from H1 - H16 antigens, among these H1, H2, and H3 antigens are widely circulating in human. And there are from N1 - N9 different antigens, among these N1 and N2 antigens found to be more circulating in human. These subtypes resulted from mutated strains and causing different pathogenic profiles (ViralZone, 2009).
The structure of all influenza is physically similar. Influenza A genome size is 13,588 base. The viron particles are enveloped and they are either spherical or filamentous in shape, with outer layer of lipids membrane. The genome of influenza A contained on eight single RNA strands which code for eleven proteins. The eight RNA segments are HA, NA, NP, M1, M2, NS1, NEP, PA, PB1 and PB2, each has different function, some of these segments are genes of the virus (B1, PB2, PA and NP), while other segments are related to the structure of membrane such as M1 which is called matrix protein, this protein form a shell and gives strength to the lipid envelope (Richman et al., 2009).
The outer layer of lipids consists of proteins linked to sugar (glycoproteins). The glycoproteins are important in the immune response against the virus. These glycoproteins are:
Haemagglutinin (HA), playing the role of integration of the virus to the cells of the respiratory tract and thus, multiplying inside the cells and stimulating the immune system.
Neuramindase(NA), helping the virus to spread out after replication, also it has been found as a target to antiviral drugs Tamiflu and Relenza.
When the virus enters the body, it attaches or binds to the host cell receptors, releasing its RNA into the host cell. Then the genes of the virus get transcribed and translated by the cell enzymes and ribosomes. The virus uses the cell to replicate and increasing its copies, making the cell to produce new viral particles instead of producing new cellular materials. At the end, the new viral particles released and infect other cells (Collier and oxford, 2006). Replication process is shown below in figure 2.
Studies showed that, influenza A virus continuously changing by two different ways:
Antigenic drift. The virus changes gradually by antigenic drift through mutations that occurs in HN proteins and AN proteins. The immune system may not be able to recognise this new strain (Schweiger et al., 2002).
Antigenic shift. The antigen shift to influenza A, in another words the virus which is not infecting human suddenly be able to infect human by either direct transmission from the animal to human or via mixture of influenza in an animal and influenza A in human and producing the new strain of influenza A subtypes. The new virus then can cause pandemic outbreak infection (Richman et al., 2002).
Influenza viruses can be transmitted through different ways. The possible modes of transmission are:
Transmission occurs when the microorganisms transfer through direct physical contact from infected individual to uninfected one.
Transmission occurs when the microorganisms transfer through intermediate object like contaminated hands, instruments or other contaminated objects in patient's environments (Richman et al., 2002).
The transmission by droplet occurs when a large droplet > 5µm diameter transfer from infected individual during sneezing, coughing, talking or procedures such as bronchoscopy or suctioning. This droplet is deposited on the oral mucosa or nasal of un-infected host.
The transmission occurs by evaporation of large droplet containing small airborne particle of the viron, or through dust particles containing contaminated skin cells or debris and remain suspended in the air for long time. The organisms or viruses are widely spread by the air and when the new host or un-infected individual inhaled the contaminated air, the individual get infected. This is the most common way of viral transmission, and the control of air born transmission is very difficult due to the difficulty in controlling the air flow through special ventilation system.
Epidemiology of influenza A:
The surveillance of global influenza indicates that the influenza viruses are isolated from human every month somewhere in the world. The activity of influenza peaks during the month of winter in temperate regions, however influenza can occur throughout the year in tropical regions. Though the epidemiology of influenza has been investigated for many years, there are certain features such as the mode of transmission of influenza and its seasonality. However, it is generally accepted that influenza viruses are primary spread by small particles of virus from the respiratory secretion. An epidemic of influenza is the outbreak of influenza infection in specific location which can be a community, a city, or the entire country. Epidemic localized within a community often peaks within 2-3 weeks, and last for 5-10 weeks. Studies have showed that influenza A occurs unexpectedly every 10 to 40 years and children are more susceptible to influenza than adults, however and according to WHO report on H1N1 viruses the viruses of H1N1 infect younger age comparing with seasonal influenza. Nearly 3-5 millions of people get infection and around 250.000 to 500.000 death due to influenza every year (WHO, 2011). Studies have showed also that, people under the age of 18 found to be more likely to catch influenza (ScienceDaily, 2009). The history of influenza pandemics from last century to 2010 is summarized in table 3.
Pathogenesis of influenza A:
Influenza viruses attack mainly to epithelial cells of the respiratory tract. The virus receptor at HA binding site is required to bind with galactose bound sialic acid on the host cells surface, followed by fusion of the viron in the cell and release viral RNA. The virus increases its copies and replicate within the nucleus of the host cell. Abundant numbers of viral copies produced within hours, and then the infectious particles are released from the plasma membrane of the epithelial cells into the airways by budding process, allowing the virus to diffuse rapidly within the lungs. The immune system get stimulated as soon as the virus invade the host cells or the respiratory tract, stimulating B lymphocytes to release antibodies which can neutralize and attach to the virus on the mucous membrane, also the inflammatory cytokines secreted by the immune system which are the most cause of the flu symptoms (Heltzer et al., 2009).
There are several factors that determine the pathogenicity and virulence of influenza virus, these factors are:
Availability of target host cells receptors.
Presence of some enzyme in host cells that is important for viral entry and replication.
Specific immunity targeted against the viral epitopes in the host.
The ability of immune system to control effectively the viral replication without causing significant damage to the host by its inflammatory response.
Ability of the virus to bind to the host cells.
The cytopathogenic effects restriction to allow the balance between the viral replication and control of the host.
The immune-surveillance escape through recombination with various viruses strains from zoonotic disease.
Regulation of the immune response to attenuate the mechanisms of host defence effectively.
Symptoms and clinical complication of influenza A:
The most common symptoms of influenza are fever, fatigue, weakness, muscle aches, sneezing, headaches and may be a runny nose. People who are infected with influenza virus may feel very sick however, it rarely leads to serious complication except those at higher risks such as those with lung, heart, or circulation disorders. In addition, infection with influenza A may leads to further serious complications particularly with elderly and children under one year old (Walsh et al., 2002).
Bacterial infection, (Pneumonia is the most common and major serious).
Inflammation of the ear (Otitis).
Aggravate chronic respiratory disease.
Inflammation of the bronchi in infants.
Meningitis and encephalitis (inflammation of the central nervous system).
Reye's syndrome (Fatal disease, effects the brain, liver and causing hypoglycaemia and associated with consumption of aspirin by children with viral infection).
Toxic shock syndrome (sever disease caused by a toxin that produced by bacteria of staphylococcus or streptococcus).
Inflammation of heart muscles.
There are a number of tests which can help in diagnosis of influenza however; tests don't need to be carried out routinely for all patients. The preferred respiratory samples for testing influenza include:
Nasopharyngeal or nasal swab.
Nasal wash or aspirate.
The samples should be taken within the first four days of the disease. There are rapid tests that can provide the result within 15 minutes or even less. These tests are basically based on enzyme immunoassay (EIA), immune fluorescence (IF), and radioimmunoassay and can be done in the physician office however, its sensitivity is low which is about 50 - 70% and 90% specific. Thus false negative reports are common than false positive particularly during the peak of influenza activity. Rapid test also don't differentiate between influenza types (Richman et al., 2009).
Generally, routine serological testes are not recommended. Serological tests require paired acute and convalescent serum and are available only at limited number of public health laboratories.
7.1 During the outbreaks:
During outbreaks and when the influenza infection is suspected, respiratory samples are collected and tested by both rapid test and viral culture. Samples for viral culture are essential for determination of influenza A subtypes and influenza B strains and for new strains surveillance. In addition, the viral culture is useful to identify other cause of the disease (Dwyer et al., 2006).
Serological tests, type of samples used for each test and type of strains which can be detected by different tests are summarized in table 4
A range of medication are used for influenza treatment, the treatment can be used either directly to influenza virus itself or to offer relief symptoms of the disease. The main antiviral drugs used against influenza are:
Neuraminidase inhibitors (Zanamivir and oseltamivir). This type of drug prevents multiplying of the virus by inhibiting neuraminidase (Moscona A, 2005).
M2 protein inhibitors (amantadine and rimantadine), working through inhibiting M2 protein and therefore preventing replication of the virus. However, strains of influenza viruses have shown drug resistance to both groups of drugs, particularly observed in 2009, when pandemic influenza A (H1N1) showed resistance to oseltamivir or combination of zanamivir and amantadine (Jefferson et al., 2006).
Tamiflu: it is a medicine that proved clinically to stop spreading of flu inside the body. It used to treat adults and children over one year old.
Vaccination is the best way to protect against influenza, in addition measures to limit or control the spread of infection should be taken.
Washing hands frequently by soap or alcohol based hand washing is the best way to prevent the infection.
Coughs and sneezes should be contained by covering the mouth and nose when sneezing and coughing.
Avoiding crowds during the peak of influenza season is also important element to reduce the chance of infection.
It can be concluded that, influenza A viral infection is the most common cause of death and sickness among children and adults, and responsible for a serious complication of the respiratory tract. Influenza A viruses have led in last century to several pandemic outbreaks, since the flu viruses have the ability to change and mutate from time to time or become resistant to certain drugs, it is important to understanding the nature of the flu viruses and how to deal with such infection in term of prevention which is the major steps to control and limit the transmission.
The future outlook of influenza:
Since the scare of swine flu in 2009, governments in all over the world stand against the serious pandemic outbreak, making plans and procedures in place to follow the influenza outbreak. Some of these procedures are to quarantine the sick people as many as possible, and to administer a working vaccine as fast as possible. In such pandemics, actions by governments should be taken in place very fast, and as the viruses have the ability to infect millions of people within weeks, it is important for the health care to prepare to have the working vaccine against future new viruses.
Scientists and experts in pharmaceutical field are conducting more researches in the wide ranging viral technology to raise the infection response vaccination that can help if another event to breakout. So in next 20 years and due to the fast development of the viral technology, they will be or may be ready for any large scale viral outbreak. However, scientists are not sure about the possibility concerning the variety of wide viruses that can breakout any time.