Diagnosis and Treatment
Diagnosis
Influenza is a common illness which is often mistaken for the common cold because of overlapping symptoms. Diagnosis can therefore be difficult as both are associated with general symptoms such as :
General Symptoms Influenza in addition is often characterised by :
head ache myalgia
rhinitis severe malaise
sore throat fever
productive cough Gastrointestinal symptoms
non- productive cough
Treatment
Flu Vaccination
Due to the high mutation rate of the influenza virus which alters the antigenic glycoprotein envelope, it is impossible to acquire permanent immunity by vaccination or anti viral treatments. Immunisation however can be achieved for particular strains of the influenza virus through vaccination and is a method of immunoprophylaxis and infection control. The flu vaccination is recommended for the young, elderly or those in high risk of secondary complications after flu infection although the general population may also benefit. The vaccination consists of either attenuated or inactivated strains of virus which are injected directly into the blood stream. This stimulates the individual's own immune response to produce specific antibodies and is therefore an example of active immunity. As the virus is inactivated, vaccinated individuals do not endure the full extent of symptoms usually experienced during infection. It is important to use a good quality vaccine as a vaccine insufficiently matched to the circulating strain could accelerate viral mutation. The exact strains used vary each year depending on which viruses have been identified as a public health concern by the World Health Organisation. To understand the principle of flu vaccination therefore a basic understanding of active immunity is required.
Image courtesy of Flickr under a Creative Commons License.
Active Immunity
Clonal Selection
The adaptive immune system tailors a unique and specific response to a large variety of pathogens and the clonal selection theory is thought to underlie this magnificently diverse response. This theory suggests that during immune system development an organism randomly generates a vast range of lymphocytes, each displaying different antigen receptors and secreting specific antibodies. If however a lymphocyte encounters its specific antigen, for example by binding to a foreign hemagglutinin molecule, the naïve cell is stimulated to rapidly proliferate and differentiate into effector and memory cells, selectively producing many identical clones with the same specific antigen receptor and antibody. In this way the influenza vaccine stimulates the organisms natural defence system to increase the number of lymphocytes able to protect against a specific viral strain. How the immune system pre empts the structure of foreign antigens without ever having seen them is a mystery!
(1) A stem cell undergoes differentiation during development to produce a large range of lymphocytes which display varying antigen receptors (2). Some of these antigens may cause an auto immune response binding to the bodies own proteins. These lymphocytes are destroyed (3). Other lymphocytes mature but remain inactive (4). A few of these lymphocytes encounter antigens which correspond to their receptors and are activated (5). This induces rapid proliferation of lymphocytes which all secrete the same antibody, building an immunity against a specific antigen. This is clonal selection (6).
Clonal Selection. Image courtesy of Wikipedia under the terms of the GNU Free Documentation License.
Memory Cells
But how then is vaccination any better than catching the flu directly? Memory cells hold the key to this answer. The first encounter and response with a particular antigen described above is termed a primary immune response. If infected with the same strain of virus weeks, months or even years later, a vaccinated person produces a faster and greater immune response, a sign of immunological memory. This is due to a population of lymphocytes produced upon primary encounter with the antigen. Instead of developing into active effector cells, these lymphocytes called memory cells are set aside in preparation for a secondary infection. As these lymphocytes have already multiplied and differentiated during clonal selection to produce antigen specific antibodies, a secondary infection is dealt with quickly and more efficiently than the primary response. The individual may either experience mild symptoms or be asymptomatic and unaware of infection. The direct injection of antibodies on the other hand is an example of passive immunity and does not activate the host's own immune system. As a result the immunity conferred does not create memory lymphocytes and is therefore only temporary.
Initial primary response and memory cell mediated secondary repsonses. Image courtesy of https://en.wikipedia.org/wiki/File:Immune_response.jpg#file under the terms of the GNU Free Documentation License.
Anti- Viral Treatments
Although vaccination against influenza is an effective prophylactic treatment, anti viral drugs are simultaneously used for individuals with medical conditions such as pulmonary and cardiac disease or for those who are predisposed to further bacterial infections such as pneumonia.
Neuraminidase inhibitors
Neuraminidase (NA) is an antigenic glycoprotein found on the cell of the influenza virus (see structure) and is a potential target for medicinal intervention. The neuraminidase inhibitors Zanamivir and Oseltmavir (commercially known as Tamiflu) are sialic acid analogues which bind to NA receptors. NA is responsible for cleaving sialic acid receptors and facilitating new viral particles from budding off from the host cell. By blocking NA sialic acid binding sites these drugs cause viral aggregation which prevents release and spreading of the virus in the host organism. At present however neither drug is recommended for prophylactic use and their clinical effectiveness for preventing bacterial infections is disputed.
M2 inhibitors
M2 is a proton ion channel present in the outer envelope of the virus. By conducting H+ which acidifies the pH, it facilitates virus uncoating in the endosome (see structure). M2 inhibitors such as Amantadine and Rimantadine block the proton ion channel thereby preventing acidification of the endosome. In consequence this prevents uncoating of the virus and nuclear import of the RNA for replication and transcription. Therefore by preventing the replication of virus particles, infection can be minimised. M2 inhibitors are beneficial for those at risk of developing complications, however are not used by the general population due to caution against drug resistance and their neurological side effects.
Tamiflu promotion featuring a hermetic environment. Image courtesy of https://en.wikipedia.org/wiki/File:Tamiflu-display-trailer-miami.jpg under the terms of the GNU Free Documentation License.