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Measles was a very common childhood disease until the introduction of the MMR vaccination in 1967. It is now less common in school aged children but babies can still contract the disease. It is said to be a childhood disease because one should be immune to the virus after receiving the MMR vaccination which is administered between the ages of three to five (1). However, people of any age who have not been vaccinated can get the disease. Although it is very common it is also one of the most contagious and dangerous diseases, especially for malnourished children where it can be fatal. (2) People who are most at risk are all children and adults who have not been immunised and people that have immunodeficiency's, for example children with thymic aplasia. (2:1)
Measles is caused by a morbillivirus which is one member of a family of paramyxoviruses. Paramyxovirus is a group of RNA viruses that are responsible for the most part for acute respiratory diseases and are transmitted in an airborne or physical manner. Paramyxoviruses replicate in the cytoplasm of the host cell, its genome consists of single-stranded RNA encoding six genes. These six genes are kept separated by recurring sequences of RNA. (2:2)
Measles is a respiratory disease and is spread from person to person by droplets. The virus can spread from one person to the next through physical contact e.g. touching or kissing a person that has the virus or by breathing infected airborne droplets in the form of aerosols. The droplets are airborne secretions from the infected party's respiratory system, e.g. nose, and can travel through the air. Therefore even if the infected person is in a room away from the public, people within living space may still be infected with the virus especially if they have not been immunised for example new born babies. (3)
The virus enters the body through the upper respiratory tract and spreads by viremia. It is described as systematic virus as it does not stay localised it spreads and infects many other organs within the body. After entering the respiratory tract it stays there, in the mucosa, for around four to six days. During that time it replicates. The virus then spreads, firstly to the lymph nodes and from there enters the blood vessels. This is known as primary viremia. From the blood the virus moves into other organs e.g. the spleen and liver were it replicates again, meaning that the virus is becoming more abundant within the organ systems. A process called secondary viremia follows primary viremia. During secondary viremia, the measles virus moves back into the blood vessels and spreads to the kidney, bladder and skin. (3:1)
Measles is a viral infection that can contaminate the T cells and dendritic cells and hinder there survival and utility. This causes the immune system to become temporarily suppressed. The suppression of cell mediated immunity allows the virus to spread as cell-mediated immunity is required to control the infection. (4)
Transient immunosurppression can make a person susceptible to secondary infections. These secondary infections such as TB are said to be the foremost cause of the high death rate related with measles. Transient immunosurppression, the temporary suppression of cell-mediated immunity is not fully understood, however it is known that dysfunctions of monocytes as antigen-presenting cells may have something to do with it. (4)(5)
According to roitt and delves, "the profound fall in cell-mediated immunity which accompanies measles infection has been attributed to the specific suppression of IL-12 by viral cross linking of monocytes surface CD46." (5)
According to Rabourdin-Combe C. et al the measles virus replicates feebly in the inactive dendritic cells but intensively in CD40 activated dendritic cells. The interaction of measles infected dendritic cells with t cells induces syncytia formation. Syncytia cause's viral fusion proteins that were used by the virus to enter the cell are moved to the cell surface where they can cause the host cell membrane to fuse with near by cells causing substantial replication of the virus. Interaction between CD40-activated dendritic cells and T cells is process that can also lead to an impairment in dendritic and T cell function as well as cell death. On major impairment is that of the ability of t cells to proliferate in response on the measles virus and a second impairment is that CD40 activated dendritic cells have a decreased ability to produce IL-12. IL-12 is a cytokine that induces proliferation and INF Î³ production by Th1 and CD8 it also enhances natural killer cells and CD8 T cytotoxicity. As the production of IL-12 is decreased all these other factors are also, meaning that it is hard for the body to fight the infection. (6)
The measles virus has an incubation period of 14 days; it is only after this time that the symptoms will start to show. The first symptoms are flu like symptoms. These include; temperature of around 39°C, cough, runny nose, bronchopneumonia and conjunctivitis. There can also be some complications in the form of abdominal symptoms which include; nausea, abdominal pain and diarrhoea. Around two days from the first symptoms are noticeable small koplik spots develop inside the mouth on the oral mucosa, usually on the inside of the cheek. These spots are hard to be seen because of the area that they are in but they are circular in shape, usually an intense red colour with a white speck in the centre. These types of "spots are caused by a delayed type hypersensitivity reaction" (3:1)
The final symptom to appear is the measles rash, this to is caused by a delayed type hypersensitivity reaction. A day or to after the koplik spots appear a fine red rash will begin to develop behind the ears spreading to the face and then further down the body. (7) This rash is said to be a maculopapular rash. It appears when the virus exits the blood vessels. With this type of rash there are different types of skin lesions. The primary cause of these lesions is the destruction of cells due to virus replication. Macules and papules are lesions caused when inflammation occurs in the sensitive layer of skin or connective tissue below the epidermis known as the dermis, and when the infection is inside or close to the blood vessels. However, the vesicles and pustules occur when the virus moves from the blood vessels to the superficial layers of the skin, for example the stratum corneum and stratum lucidum. (3:1)
As mentioned earlier the MMR vaccine is the vaccination given against measles. The MMR is a dose of a mixture of three attenuated viruses. This means that they have been kept 'live' but modified into attenuated mutants so that they are harmless. In order to make these attenuated mutants harmless they are grown in conditions unlike those normal host cells, for, example procreating the virus at colder temperatures than physiological temperature. Mutants that are adapted to colder temperatures are less pathogenic that the "parental virus". Attenuated mutants work well in vaccination because they are still able to replicate to a certain extent were it is enough to provoke an immune response but overall to not replicate enough to be harmful. (3:1)
Most people in the U.K are administered with two doses of the vaccine, the first at around age one and the second around age five at school age. After the first dose over 90% of people who receive it gain immunity to the measles, therefore the second is not a booster it is a precautionary measure to ensure that all the population who received the MMR are immune to the measles virus. Immunity is gained with exposure to the antigen, in this case the measles virus. Once exposed to the antigen the immune system responds by producing antibodies, such as measles virus specific CD4 and CD8 t cells. Therefore when the body is exposed to the attenuated mutant specific CD4 t cells, also know as helper t cells are produced these cells help activate CD8 t cells which destroys cells that have been infiltrated by the disease causing organism. The body then recalls these specific antibodies, by a process known as immunological memory and every time the body is exposed to the measles virus thereafter the body will call upon the antibodies to fight the infection rapidly before it can spread throughout the body. This is the adaptive immune response.
Studies have been made that show that the immunity gained immunisation is long lasting. According to Oldstone et al. measles virus specific CD4 and CD8 t cells can still be found in the body up to thirty four years after inoculation, the study also shows that CD8 t cells and measles specific IgG stay stable but the CD4 levels tend to decrease after twenty one years. (10)
It is desired that the whole population receive the vaccination because according to playfair and Bancroft measles is one of several viral diseases that the world health organisation have targeted for eradication within the next generation. (3) This, however, is proving quite difficult due to the recent scare that the MMR vaccination is linked with autism. This has made it difficult because parents have opted out of getting their children vaccinated. (4)
Subacute sclerosing panencephalitis is a rare neurological disorder. It is seen in around four out of one hundred thousand people that have contracted the measles virus at a young age. This disorder tends to affect children and young adults. It is progressive encephalitis, acute inflammation of the brain and it affects the central nervous system. It's a persistent and slow developing viral infection caused by chronic infection of the measles virus. This could encompass an abnormal immune response to measles or even a mutant form of the virus. The measles virus can go into the brain by infiltrating lymphocytes that travel through the body during primary viremia. As mentioned previously primary viremia is when "virions are released into the blood after initial replication at the site of entry." (3:1)
People that suffer from Subacute sclerosing panencephalitis usually have contracted measles at an early age. After the measles has cleared there is a latent of 6 to 8 years before symptoms of Subacute sclerosing panencephalitis become apparent. Symptoms of Subacute sclerosing panencephalitis include behavioural changes as well as physical symptoms. There are; dementia, gradual behavioural changes and odd behaviour. The physical symptoms include myoclonic jerking, seizures, coma, and weakness in both legs and tense muscles. Some sufferers may also become blind. As the disease progresses patients slowly deteriorate. Sufferers can lose the ability to walk, due to their muscles going into spasm. Deterioration then leads on to a comatose state, and then vegetative state. The patient will die between one and three years from they are diagnosed and death is usually the result of heart failure, or the brain's incapacity to continue regulating the autonomic nervous system. (8)(9)
In conclusion there are many immunological factors that contribute to the infection and spread of the measles virus as well as helping us understand how it affects the body. For example how the symptoms arise. The study of immunology, as you can see from above, has proven extremely useful in understanding the virus and providing knowledge of what would make a suitable and effective immunisation against it, which is successful as the prevalence of the measles virus is decreasing.