Have you been thinking about taking a trip to Germany to see the famous Neuschwanstein Castle? Well it would be intuitive of you to make sure you are updated on your shots. The outbreak of measles has been constantly raving this country. Measles is a highly contagious disease and if not vaccinated there is an extremely large chance of one getting infected since the virus travels by way of aerosolized droplets. The virus is equipped with many virulence factors and is bound to find a host, since the virus is now being identified as endemic to the country.
The Measles virus is classified under the Paramyxoviridae in the Morbillivirus genus. The envelope around the helical nucleocapsid has proteins embedded in it called the hemugglutinin and fusion protein. Underneath the envelope is the matrix coded for the M protein. The nucleocapsid is then seen which contains the genome. Important proteins coded within the genome are L protein, P protein as well as the V and C proteins. These proteins are used in attachment, viral transcription, translation, and egression.
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The important proteins seen on the envelope of the virus the hemagglutinin (H) and fusion protein F are both glycoproteins and are specifically identified as the virus attachment proteins. The virus attaches to cells via the H protein and once the H protein has attached, it is thought to induce a conformational change which in turn activates the fusion power of the F protein. Once the F protein is activated, the virus enters the cell through fusion of the envelope and membrane of the host cell. The attachment H protein binds the receptor SLAM, a receptor expressed on immune cells such as thymocytes, activated lymphocytes, mature dendritic cells, macrophages, and platelets. (Griffin, 17). The H protein is also known to bind to receptors in epithelial cells, however the name of this receptor is not known. Once the virus has fused into the host cell, unlike other viruses the capsid does not uncode and release its contents or genome. As mentioned previously above the ribonucleoprotein complex is encapsulated by the matrix proteins. This complex and proteins encoded in the genome accounts for much of the viruses transcription and replication, however the exact involvement of these proteins are still unclear. Since then the process of replication, transcription and translation is given as an analogy from the better studied paramyxoviruse (Griffin, 83). Since the virus is negative sense, once it enters the cell the sense is immediately transcribed into the positive sense or mRNA where it can be directly translated or replicated. The P protein is thought to be a possible part of the transcription complex, while the L protein is used for translation (Murray, 572). Replication and Translation occur, after transcription and new genomes associate with the L, N, and NP proteins on viral glycoprotein or modified plasma membranes. This assembly is thought to be done by the M protein (Murray, 572). The newly created virions egress from the, and onto infect other cells. This brings us to how exactly is the measles virus able to cause disease.
The ability of a pathogen to cause disease or its pathogenicity is determined by its virulence factors. Virulence factors aid a virus in attachment, invasion, and evading the immune system. First and foremost a virus must be able to attach itself to the host's cell. Without attachment there is no means for the virus to cause a disease, and most favorably be transmitted so that it can continue to live. Starting from the molecular level, the two proteins involved in cell attachment, H protein and F protein may be considered measles primary virulence factors. These particular proteins are known to bind to CD 150 SLAM and CD46 receptors located on host's immune cells. Immune cells such as dendritic cells, b-lymphocytes, and t-lymphocytes are the cites of these receptors. CD46 is a receptor on most host cells said to be involved in the complement system, which if in normal progress, opsinizes invading pathogens aiding in the process of phagocytosis (Grifin, 35). CD46 is also identified as a costimulatory molecule during T cell receptor-mediated activation of human CD4+ T lymphocytes (griffin, 37). Since CD46 is said to be a costimulator for the T cell receptor, if CD46 is crosslinked with the H protein from the measles virus, this downregulates interleukin-12. Interlleukin-12 is responsible for a successful effector T cell response or changing an immature T cell into a mature one (Griffin, 42). Mature T cells then go on in aiding other white blood cells of the immune system. Thus the measles virus binding to the CD46 receptor can be identified as the virus's way of evading the immune system and thus causing the person to have lymphopenia or a low white blood cell count. This also aids the virus in accomplishing transcription, translation, and replication. Another important virulence factor is that the genome stays in its capsid during transcription being protected from ribonucleases. Once the virus egresses it invades neighboring cells via actin, packaged within the measles virion (Griffin, 18). It has been assumed that measles replicates in the respiratory epithelium from the luminal side before spreading in lymphatic cells. However, "studies of the attenuated virus imply that the respiratory epithelium is not a major site of replication and that the local lymph nodes are" (Meulen, 2). Thus once the virus has gone through the lymphatic system it may move by ways of the blood (viremia) and onto cells of the respiratory tract urinary tract, small blood vessels, and the CNS. A symptom associated with the replication of the virus in the lymphatic cells and the fusion of multinucleated cells is the appearance of Koplik spots. Kopik spots are a primary symptom associated with measles. Koplik spots proceeds symptoms such as high fever and respiratory tract symptoms. Around 14 days after exposure is when one starts to notice the infamous rash identified with measles. The rash can be first seen on the forehead and behind the ears but in a matter of 2 days it spreads all over the body (Meulen, 3). There are often two outcomes of a measles infection, either the rash fades and host defense develops and thus creates lifelong immunity or the person develops a secondary infection. Due to the damaging effects the virus has on the host immune cells, immunosuppression can last for weeks after the initial infection; this in turn makes the infected individual much vulnerable to opportunistic infections or secondary infections. These opportunistic infections are often fatal. Subacute Sclerosing Panencephalitis is an opportunistic infection associated with post -infections of the measles. SSPE is a slow, progressing disease that can occur from 1 to 15 years proceeding acute measles infection. Some symptoms associated with this disease are changes in personality, behavior, and memory followed by myoclonic jerks, blindness, and spasticity (Murray, 576). Another post-infectious disease associated with measles is post infectious encephalitis, characterized by demyelination of neurons. Lastly, Giant cell pneumonia without a rash is seen in immunocompromised and malnourished child who lack T-cell immunity. This disease is characterized by the development of pneumonia and bacterial superinfection (Murray, 576). These serious complications following measles along with the virus itself caused for the development of a vaccine.
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The first attempt to treating measles was done by Scottish physician Francis Home in 1749. Home tried to use the early method of variolation. Where he took the blood of someone mildy infected with the virus and injected it into someone else in hopes that they would develop antibodies as we;; as immunity against the disease. This method was proven to be unsuccessful. In 1954 the virus was successfully propagated in human and monkey cells aiding in the development of both the inactivated and live attenuated vaccine (Griffin, 192). The inactivated measles vaccine was prepared by using formalin to kill or inactivate the virus. Thus the vaccine was given the name formalin-inactivated measles vaccine (FIMV). The inactivated vaccine was first given in the United States in 1963 in a 3 dose regimen. Those who received the vaccine developed fair levels of antibodies against the H protein mentioned previously; however low levels of the complement fixing antibodies. At first glance it seemed as though the vaccine was going to be successful when first exposed to measles within months of given the vaccine. Unfortunately, antibody titers declined rapidly, and patients soon became susceptible to not acute measles but the severe atypical measles. This wild-type virus was characterized by a higher and more prolonged fever as well as severe pneumonitis and abdominal pain (Griffin, 194). Physicians then turned to the live attenuated vaccine. This vaccine was developed in chick embryo fibroblasts. This particular strain was injected into primates during pre-trial of the vaccine and produced no clinical symptoms, no detectable viremia, and no spread to the respiratory tract, but did provide immunity against the wild-type strain. The live vaccine is administered intramuscularly with at dose between 10^3 and 10^4 plaque forming units. The efficacy or ability for the vaccine to work after 1 dose is 80%-95% (Griffin, 198). The virus is now given at 2 years of age in co-vaccination with mumps and rubella. There aren't any known antiviral drugs to be effective against measles, which is not a problem as long as people get vaccinated. The problem today is getting people to get their kids vaccinated.
Although the measles vaccine has been proven to be successful for many years, outbreaks are still occurring. These outbreaks are seen in underdeveloped countries such as Africa; however the disease is also seen in industrialized countries such as Asia and Europe. Specifically, Germany has been the site of endemic outbreaks of measles in industrialized countries. The disease is seen in underdeveloped countries such as Africa for evident reasons. Reasons such as the availability of the vaccine, the vaccine not being able to be kept refrigerated, lack of trained personal, as well as personal reasons. Only one of these factors is evident in Germany and that is for personal reasons people refuse the vaccine. Now this is not seen in all the cases in Germany. Since 2005 there have been re-emerging endemics of a measles outbreak in Germany all the way until now. In 2005 the majority of the cases were seen in unvaccinated individuals. On May 19, 2006 the communicable disease control branch of Australia sent out a public health alert stating that all individuals traveling to Germany fort the World Cup should get vaccinated for measles if born during or since 1966. In 2007 the same factors occurred, 80% of the 614 cases were characterized by individuals who were unvaccinated. WHO has declared that if physicians in Germany do not press for vaccination and parents keep refusing vaccination for their children they will never be able to establish 95% coverage of herd immunity.
Measles continues to be one of the most contagious diseases seen in young children as well as the cause for hospitalization and deaths amongst the early age group. The equipped virulence factors, mode of entry, and tropism of the virus accounts for much of its successful cases documented. Although a vaccine was developed for the notorious virus cases still seem to exist. These cases are going to continue to exist if parents continuously keep choosing to not vaccinate their children. Whether its factors ranging from personal, economic, are just pure forgetfulness children will continue to suffer from this totally preventable disease if not vaccinated.