Neisseria+meningitidis

**Title**: //Neisseria meningitis//; Taming the Global Epidemic

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//Neisseria meningitidis// is a bacterium that is one of three bacteria to cause bacterial meningitis. It is one of two human pathogenic species of //Neisseria// and the only one to cause bacterial meningitis. //N. meningitidis// is not a normal microbiota, however it does inhabit around ten percent of the human population asymptomatically during non-epidemic years. There are thirteen different serotypes, with only five being human pathogenic, and two of those, A and B, are considered epidemic causing around the world. Serotype A affects sub-Saharan Africa for the most part, while many developed countries experience problems with serotype B, which poses problems of its own in structural similarity to a human glycoprotein. Vaccines and antibiotics are being researched and are in different stages of testing. The different pathogenic serotypes make finding a universal vaccine extremely difficult. ======

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//Neisseria meningitidis// is a Gram negative encapsulated meningococcal bacterium. [2] It is one of only two human pathogenic species //of Neisseria. N. meningitidis//’ specific ecological niche is the human naso- pharynx, and is never found living outside of the nasal and throat tract. [1] The fact that //N. meningitidis// is an obligate human pathogen, that is it cannot be cultured outside of the human naso-pharynx, has made research regarding prevention or treatment beneficial to help those afflicted with bacterial meningitis. During a non epidemic, anywhere from 5-15% of humans are non-symptomatic carriers of //N. meningitidis//, which means many are most likely unaware that their nose and throat are being used as a breeding ground for a potentially deadly disease. [1] ======



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Meningitis is an infection and inflammation of the meninges, the outer membranes that protect the central nervous system; the brain and spinal cord. There are two different sources of meningitis; bacterial and viral. Bacterial meningitis is relatively common, but extremely serious. If treated immediately, there is a 15% death rate and 10% or more die within 48 hours of symptoms emerging even if they have been treated. If a patient survives, chances are he or she will carry the repercussions throughout the rest of their life. Bacterial meningitis can result in brain damage, hearing loss, learning or mental disabilities and limb amputation. [2] The people in developed countries that are most affected are very young children, and young adults. Bacterial meningitis is caused when //N. meningitidis// crosses the blood-brain barrier and infects the meninges. [4] ======



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//Neisseria meningitis// has thirteen chemically different serotypes that are currently known to scientists. A serotype is a subdivision of a virus that is unique with a protein or protein component which would in turn determine the different antigen specificity. [3] Out of the thirteen that are known, only serotypes A, B, C, Y, and W-135 are harmful to humans. [2] ======

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In developing countries, //N. meningitidis// is even more of a problem. In sub-Saharan Africa, //N. meningitidis// is such a health problem that many people refer to that area as the “meningitis belt.”[5]There are many explosively fast moving epidemics that occur in this belt. The darker areas have the higher number of //N. meningitidis// caused bacterial meningitis. These cases are generally caused by one serotype. 90% of the bacterial meningitis occurrences in the meningitis belt are caused by the capsular polysaccharide group A strains of //N. meningitidis.// [4] A conjugate vaccine for Group A has been developed and is now in the second phase of clinical trials in Africa. So far, this new vaccine has shown promising results. After preliminary tests it does appear to be safe for human use, as well as produce an immune response in many of the vaccinated. The hope is that the widespread use of this vaccine, once it has been approved for widespread distribution, is that serotype A will no longer cause epidemics in sub-Saharan Africa. [4] The one worry on the minds of medical professionals however, is that once serotype A is no longer the largest threat, that space might open up for a new, unpreventable serotype to take over and cause further damage. ======



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In developed countries, serotype B is most prevalent. Alone, serotype B accounts for 32%of bacterial meningitis in the United States, anywhere from 45%-80% of cases in the United Kingdom, and 50% of all cases in the rest of the world, excluding sub-Saharan Africa. [1] Serotype B has a capsular polysaccharide that is indistinguishable from polysialic acid, which is present in human glycoproteins. [1] This enables the bacterium to multiply safely, with no human immune response. However, even if a response were to occur, because it is identical to the self-antigen, the immune response would result in autoimmunity, and the body would begin to fight itself. This makes it extremely difficult for a vaccine to be licensed and publicly distributed. To make a universal vaccine, the genome had to be sequenced. [1] Scientists are now working on a vaccine against serotype B using exposed surface proteins inside the outer membrane vesicles. This has only been tested in vitro, and there is minimal confidence that the results will enable further development of a vaccine available to humans. [1] ======

For serotype B, there is a medicine in pill format called Rifampin that can be prescribed by a medical professional. When taken every day for months at a time, it eliminates bacteria, including //N. meningitidis// that cause bacterial meningitis as well as the bacteria that cause tuberculosis. It also prevents the transmission of the bacteria or disease to others. Rifampin, however, does not treat infections caused by //N. meningitidis//; it just tries to prevent them. [6] An antibiotic prophylaxis such as Ceftriaxone or Ciprofloxacin should be administered immediately after possible exposure to the bacterium. [4] Casual encounters are not high risk for contracting bacterial meningitis. People in close relativity to an infected individual, such as family members or classmates in day-care/school are the ones that should seek medical attention. //N. meningitidis// is not passed as rapidly as the flu or a cold, but through direct contact with a patient’s saliva or other respiratory fluids. [4] Coughing and kissing spread much of the harmful bacterium, but any exchange of saliva could be problematic including children chewing on toys, or the administration of CPR.

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A vaccination for serotype B is not routinely administered in adults of middle aged children in the United States currently, but more effective vaccines are being developed or tested. The vaccine that is currently used is recommended for teens entering college and beginning life in the dormitories.[4] It is an OMP, an outer membrane protein vaccine. [2] It is not currently used widely for a couple reasons. First, it is not effective in children under two years old, one of the largest groups that are fatally affected by //N. meningitids// induced bacterial meningitis. But more importantly, the current vaccine does not induce immunological memory; it does not last for years. [2] This would cause the price of constant administration of the vaccine to be too high to be a universal vaccination. Scientists believe that a development of a polysaccharide conjugated to a carrier protein could be effective in children. [2] This is hopeful because it is similar to the vaccine for serotype A, currently having positive test results in sub-Saharan Africa. ======

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Serotype C is the second most common harmful serotype in the developed world. [2] The United Kingdom, Ireland and Canada have been using a newly developed vaccine for serotype C, creating a positive response in infants and young children. Because of the high success rate of 90%, scientists have been researching and working to make this vaccine accessible for the world. [2] ======

The latest endeavor for scientists is to attempt to develop a universal vaccine for meningococcal diseases. The way that they plan to develop this vaccine is through a newly developed process coined as reverse vaccinology.[8] The steps for reverse vaccinology are relatively vague. The entire genome must be sequenced for this to occur. Using the sequenced genome, a computer predicts vaccine candidates. They are tested and ideally DNA vaccine recombinant proteins are expressed. The next step would be to test immunogenicity in animals, and if those results are promising, a vaccine is developed. [8] So far for the universal vaccine of //Neiserria meningitides//, they are still in the animal testing phase. They have developed a vaccine that induces bacterial antibodies from aluminum hydroxide that is 78% effective in testing. [8] With the addition of CpG oligonucleotides the results increased to 90% positive results. [8] Both of these tests have been administered to rats, and the hope is that human clinical trials will be next.



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What this means is that the number of bacterial meningitis cases caused by Neisseria meningitidis could be drastically cut, if not eliminated. Of course there are many determining factors, and the vaccine would need to be scrutinized intensely before massive human distribution. The long term effects and risk potential need to be assessed, as well as the potential side effects and cost of massive production. Even though there are many steps before we can see a massive reduction in this bacterium, the universal vaccine is definitely an optimistic stride in the fight against bacterial meningitis.======

Literature Cited [1]: Rappuloi, Rino. //A Universal vaccine for serogroup B meningococcus.// Published online in //Proceedings of the National Academy of Sciences of the United States of America. (//May 12, 2006//)// [2] Rappuoli, Rino. //Vaccination against __Neisseria meningitidis__ Using Three Variants of the Lipoprotein GNA1870.// Published in //the Journal of Experimental Medicine.// (March 17, 2003) [3] Arneson, Phil. //Online Glossary of Technical Terms.// [4] Oregon Department of Public Health. //Meningococcal Disease Fact Sheet; Acute and Communicable Disease Prevention.// Oregon.gov. (March 2009) [5]LaForce, F. Marc. //Epidemic meningitis due to Group A Neisseria meningitidis in the African meningitis belt: A persistent problem with an imminent solution.// Published in //Science Direct.// B13-B19. (May 27, 2009) [6] PubMed Health. // Rifampin. // [|National Center for Biotechnology Information],  [|U.S. National Library of Medicine]. (October 1, 2010) [7] //The Truth About Your Immune System; Vaccines and your health.// Harvard Health Publications, Harvard Medical School. (2010)   [8] Rappuoli, Rino. //Reverse vaccinology, a genome-based approach to vaccine development.// Pubilshed in Science Direct. (March 2001) Images: 1. Lowry, S. SEM //Neisseria meningitidis.// Getty Images. University Ulster. 2. [5]LaForce, F. Marc. //Epidemic meningitis due to Group A Neisseria meningitidis in the African meningitis belt: A persistent problem with an imminent solution.// Published in //Science Direct.// B13-B19. (May 27, 2009) 3. Todar, Kenneth. //Meningococcal Meningitis.// Published in //Lectures in Microbiology at University of Wisconsin.// (2006)