Wednesday, October 16, 2019

Marketing mix strategy Essay Example | Topics and Well Written Essays - 750 words

Marketing mix strategy - Essay Example Various researches show that the popularity of energy drinks is continuously increasing and most importantly they are giving tough challenges to the soft drinks. Over the past few years consumers have become more inclined towards the energy drinks. According to data provided by P&C Nielson Scantrack, energy drinks occupy almost 23% in the entire market of beverages.3 Considering all these facts, Frucor should introduce one or two new flavors of ‘V’ within the next fiscal year. Furthermore, the company should introduce the new flavors in a completely new package. The ‘V-Orange’ can be introduced in a completely newly designed ‘can’ or ‘bottle’. Since, energy drinks are ‘impulsive’ product, attractive cans or bottles should be introduced. Currently, the energy drink is available in the form of 250 ml cans and 500 ml bottles. In order to, go through more into the market, Frucor should introduce more product sizes. ... In simple words demand of energy drinks is increasing in a consistent manner. In such a situation, the company should not lower the prices so that more profits can be made. However, the company should introduce some attractive schemes. For instance, it can reduce the price by 2-3% in case of bulk purchase. Furthermore, special price can be offered whenever at least three different flavors are purchased together. Place V energy drinks reach the final customers i.e. the consumers through various distributors. There are some big distributors like Metro Beverage Co and Kelly’s Distributors that sells V energy drinks to the retailers.4 The important fact is that V is only sold in the markets of Australia and New Zealand. However, in order to remain competitive in the global energy drinks market in the long run, Frucor should focus on the foreign market. Initially it should target the developing economies like China, India and Russia. Consumers, in these countries are becoming stron ger in terms of their spending power. As a result, it is quite likely that the energy drinks will be more in demand in these countries. Frucor should try to form strategic alliances with some of the major distributors in these markets. In fact the company can get itself involved into some joint ventures with some of the local beverage companies that will produce the product on behalf of Frucor. A strong distribution network in the developing nations can give sustainable competitive advantage to both ‘V’ as well as its owner. Promotion In this marketing driven business world, promotion is viewed as one of the most crucial aspects for achieving long term success. The company should focus on online interface to promote the brand V. Energy drinks are likely to be consumed mainly by the

Marketing Essay Example | Topics and Well Written Essays - 2000 words - 4

Marketing - Essay Example CLASS NUMBER: †¦4†¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦. TITLE/TOPIC OF ASSIGNMENT: †¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Marketing 100 Situational Analysis†¦/Target Market Identification Report and Collage †¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦.†¦.. Please read the following and sign where indicated DECLARATION: I/We declare the attached assignment is my/our own work and has not previously been submitted for assessment. This work complies with Curtin College rules concerning plagiarism and academic misconduct. [Refer to the Policy library on www.curtincollege.edu.au for full details on our Plagiarism and Student Misconduct polices.] I/We have retained a copy of this assignment for my own records. Signed: ____Wang Jue__________________________________________ Date___10 December 2010___________ This document is current at 31/08/2010. Page 1 of 1 1.0 Situation Analysis 1.1 Current Marketing Mix 1.1.1 Current Product Sunsilk Co-Creations-Addictive Brill iant Shine Shampoo is one of new Sunsilk’s Co-creations hair care line products. It consists of chemical as well as natural ingredients. The ingredients of the shampoo were chosen to achieve healthy shine, to co-create Sunsilk’s most advanced Addictive Brilliant Shine formulation for healthy hair that dazzles with shine (Unilever in Australia, 2011). Therefore, consumers benefit from buying a product in the form of healthy hair and â€Å"brilliant shine†. The company has teamed up with Jamal Hammadi from LA hair dresser to Hollywood stars and famous for his natural approach to achieve healthy shine (Unilever in Australia, 2011). It has inherent to all Sunsilk products cambered package, so customers can easily identify the shampoo as Sunsilk’s product. The bottle has red color and a big symbolic sign â€Å"!† on the front. The package developed by Brown Inc. (Brown Inc. 2011) makes product look modern and even hi-tech. This features distinct the pro duct from other shampoos and attract customers at the same time. Sunsilk Co-Creations-Addictive Brilliant Shine Shampoo is a part of hair care complex consisting of the shampoo and conditioner. Therefore, customers are given reason to by the shampoo together with the conditioner. The main targeted groups of customers are females between 16 to 40 with middle and high income level. Other groups of customers also might buy the product. Sunsilk Shampoo might be classified as staple goods because customers can use it regularly although they easily switch to another similar shampoo if the one is absent. Therefore, the shampoo is a star product of Unilever’s new product line. Its modern, professional and high-tech. It has original features that attract customers however; people can easily identify one of Sunsilk’s products. Customers can use it regularly although they easily switch to another similar shampoo if the one is absent. 1.1.2 Current Pricing The shampoo market is hi gh-competitive. There are many brands but in fact the most of them are owned by a few corporations such as Unilever, Procter&Gamble and Schwarzkopf. Sunsilk brand belongs to Unilever, the second biggest shampoo market company in the world. Unilever (2011) claims to practice value-based pricing. This means that the price is set based on the value a customer receives using the product. The primary importance of this kind of pricing is to encourage demand through setting the price according to customers feeling of the real value of the

Tuesday, October 15, 2019

Project Management- MGMT412 - 1304B - 01 unit 2 Essay

Project Management- MGMT412 - 1304B - 01 unit 2 - Essay Example Product scope description: Winsome Company is under the management of a sister company known as Winsome’s sister company. The products and raw materials used by the company are purchased from different manufactures. They brand the products, educate the sales representatives and market them to the targeted audiences. In addition, the team will be required to attend the quarterly branch manager sales events to present the new kind of product they will be offering in the market to their respective audiences. The results the project will produce will entail all these sales deliverables required for the launching of the new products through research into different departments and consultation with various department heads (Harrington & McNellis, 2006). Acceptance criteria: The acceptance criteria for the introduction of the new product into the market will entails creating product specifications, producing photographs of the product in question, producing their pricing structures f or the new products and highlight the sources of their marketing materials. Stages will be involved in the acceptance criteria as goals for the Winsome Company and the new product will be reviewed by the different departments and government bodies concerned. ... The new product will be passed through the review to confirm the manufacturing process and the test the new product to be released into the market. Lastly, the product will be passed through exit criteria for reviews which will involve changes, signatures and putting the deliverables under the configuration management system. Deliverables: The project deliverables for the business will involve set quantitative objectives for the team. Secondly, the composite sales objectives will be reconciled. Lastly, to create an efficient marketing plan that will involve adjusting the qualitative of composite objectives into marketing plan objectives (Hougham & Association for Project Management, 2004). Project Exclusions: The project will not produce other deliverables that are not concerned with the sales and marketing on the new product that will be produced by the company. Its major emphasis will only be centered to focus on the sales and marketing activities conducted by the company. Constrai nts: However, in writing for the company the scope statement, there are unforeseen barriers that might hinder my process and result to poor sales and marketing strategy for the product to be produced by the company. Lack of funds might affect the process because it will hinder the research process thus interfere with the formulation of the deliverables required for the sales of the new product into the market. Time might also be a barrier to the process because the project duration might not be sufficient enough to allow for a thorough research of the sales deliverables required by the company. Assumptions: Reconciling the sales objectives may however lead to a waste of the company resources or poor management decisions for the company and the entire sales

How did the wars between the French Republic and the monarchies of Research Paper

How did the wars between the French Republic and the monarchies of Europe lead to the Terror and the Napoleonic Empire - Research Paper Example This war was later dominated by Napoleon who fought against the seven coalitions of European states. The origin of this war trace back to the ousting of the monarchy Louis XVI by the revolution (Wilde 1). The revolution installed a government that was not favorable with the rest of Europe. This led to ideological differences as the monarchies and empires were against the newly instituted rule. There was objection from the families and relatives of affected individuals. The nations of central Europe were against declaration issued by Austria and Prussia in 1791 of restoring the monarchy as they had an interest of dividing Poland amongst them (Waller 75). In fact, they changed the wording of declaration of Pillnitz so that they could avoid war. However, France misunderstood the document and launched a protective mechanism against the nations on April 1792 (Wilde 1). Initially, the war was faced by difficulties especially after an invading Germany took Verdum and moved close to Paris. H owever, the French managed to push the advancing enemies back. On November 19 of the same year, the National Convention assisted people who were willing to regain their lost freedom (Wilde 1). This was a justification to the creation of allied buffer zones around France. On December 15 on the same year, they made a vow that the revolutionary laws of France were to be advanced abroad by use of their armies. Additionally, France engaged in an initiative of territorial expansion. They felt that they would be protected by opposing and overthrowing any king in authority. Consequently, the association of European state came together to oppose these developments as a first coalition (Waller 75). This led to combat that lasted over two decades that eventually led to the fall of the revolution. This paper seeks to focus on how the war led to the terror and the Napoleonic Empire. Reign of Terror The war between the French republic and monarchies of Europe led to the rise of the reign of terro r. This reign lasted from 1789 to 1799. When France went to war against Austria, there was a need for more men to fight the approaching enemy. As a result, Danton that called for more men to join the French army instituted a convention. This led to serious revolts that were against the deliberations of the convention. Major revolts were experienced in Vendee as the peasants defied the authority of the meeting and design of revolution (Bastille Day History 1). They agitated for the reestablishment of the monarchy. They led to rise of civil war between the Vendeen and the guards of the established republic. As a result, over 100, 000 people died (Bastille Day History 1). On April 6 1793, a committee was created and led to the establishment of the new government led by Robespierre. Serious measures were put to counter resistance locally and French military defeats in Belgium. The Girondists were accused of military crisis, and 22 of its members were guillotined (Bastille Day History 1) . This was the decline of the true revolution ideas. The reign of terror spread to the rest of the country on September 1793. Consequently, hundreds of French were killed to instill frightening trend of anger and decadence. Those perceived to be the enemy of the revolution were arrested and executed without trial. This led to the death of over 40,000 people in a period of 15 months (Bastille Day History 1). The period after this saw the death of many other people through Guillotine. One of those was the wife of

Unified of the American Constitution Essay Example for Free

Unified of the American Constitution Essay What was the original intent of the U.S. Constitution? Why did Alexander Hamilton want to create a more powerful centralization of federal government? What is the difference between Democratic-Republican and Federalist? Analyzing and resolving constitutional issues was an ongoing process during the eighteenth century. According to Jack Rakove â€Å"†¦ from a historical perspective this book, guidelines, approval around the constitution, form political worries about reviewing in 1780, the Constitution and the clarification of the scope that the debate on the role of the original intent of the constitutional debate should be interpreted to play. † 1 Also Rakove thinks the federal constitution must be developed to address the representatives of the executive power and the rights and constitutional concepts in a way reflecting the highest law. The federal convention or intense political debate followed. Similar to Rakove, some people believed the Constitution could give people clearer rules to tell them what they were supposed to do or not. In addition, the Constitution could also prohibit the government from what they should not do. The government needs to guarantee freedom for people, and what rights belong to people couldn’t be violated. The Constitution also remains above the government; while maintaining above the people, its like a barrier to prevent the government from expanding. The Constitution could guarantee justice and equity for what the government sometimes did, like being secretive, and corrupt, which violates and ignores the Constitution by following the money of corporations, lobbyists, and bankers that are destroying our country, freedoms, economy, and our way of life. It provides a set of hard-fast rules for the creation and perpetuation of a Legislature, an Executive, and a Judiciary Branch. According to Madison, he was the person strongly argued for the central of the government that would unify the country and he was the most important person to write and creation of the Constitution. People call him Father of the Constitution. He thought a representative government suppose governed by those smaller states. The  power should be limited by the Federal Government because those specific areas know what they wanted and had representatives their interests. So the best way to vote was elect representatives was social system, citizens because they lived in same of the territory, it would be easier for them to agree to work together to realize their ideas. The government should protect different rights because through their representative institutions pronunciation sounds more in line with the interests of human society and the decision of the people were subject to their own interests, such as the freedom of speech, religion and the press. Alexander Hamilton believed the new U.S. administration should be divided into three divisions: Congress executive, legislative and judicial powers. 2 The government divided into three sections would provide checks and balances to prevent any one branch from becoming too powerful, and that by working together in three different branches can concentrate power in the state. He also believed that serving the life of good character, or, more precisely, would give stability to the administrative offices on the other hand, that short-term services only encourage politicians to focus on re-election, rather than the rule in this country. Hamilton also thought people should have bicameral: one is upper chamber, called the Senate, including the elite aristocracy of the country, and one is lower chamber, called the General Assembly. Would be the seat of democracy for the American people, Senator Election life’s by the House of Lords and the elected representatives of the elected term of three years. According to George Washington, â€Å"from all classes of Citizens, The reflection on the days of difficulty and danger which are past is rendered the more sweet, from a consciousness that they are succeeded by days of uncommon prosperity and security. One says George Washington was a very passionate, very proud man. In this sense, he was seen as a quiet man. His pride came from a sense of honor. This was reflected in; he would do everything, and He showed humility, when he was appointed commander of the Continental Army s commander in chief, he said he did not think he had the ability to task, but it needed to start with all his strength. He also had a heart of gratitude and sincere attitude. He respected the views of the  Congress; he would make every effort to live up to their expectations. His believed in public service his entire life, if you sport or tooted his horn† to get the job, then you are not eligible to sow themselves. In conclusion, the differences between Jam es Madison, Alexander Hamilton, and George Washington were James Madison believed in a limited federal government, and Alexander Hamilton believed in a strong, extensive federal government. George Washington was friends with Alexander Hamilton, and George Washington was also a Federalist, so he believed in a strong central government because George Washington believed that if our nation would survive then we would need a strong government and the government needed rules to go by or they would basically rule over Americans. But they all have their different ways to seeing and saying the same ideas about the constitution in the eighteenth century. On the other hand, the similarity between James Madison, Alexander Hamilton, and George Washington were having similar ideas about the constitution in eighteenth century. They all want to make the unification of the constitution of U.S. because it can protect all of our rights of its citizens. One could argue about the Federalists was more important than the Republicans because the Federalists make the country more organized and clearer rule for all the people in the U.S. This is the agreement for the most important power of the constitution because the process of drafting and ratification of the Constitution led to the victory of the Enlightenment philosophy: the full definition and addressing social and political issues of integrity and ability of the human rational nature of man and society personalities and beliefs. Indeed, the Constitution itself is perhaps best understood as an Enlightenment document, also because it reflects the target, order, freedom and justice and the general welfare of its preamble and its explicit and implicit promises, the concept of limited government, civil liberties , Church and State, military strength limitations, as well as the separation of an open society.

Monday, October 14, 2019

Marriage in Jane Austens Pride and Prejudice Essay Example for Free

Marriage in Jane Austens Pride and Prejudice Essay The intricate nexus of marriage, money and love in Jane Austens society is unfolded through the development of plots and characters of her novel Pride and Prejudice. In the nineteenth centurys rural England, marriage was a womans chief aim, both financially and socially. Financially because of womens dependent position marriage was the only honourable position, infinitely preferable to the dependence of precarious shabby-genteel spinsterhood. Money was, therefore, a very significant aspect of Austens society, especially when marriage was concerned. A single man of large fortune was naturally considered as a nice thing for the unmarried girls. Partners were chosen for what might now seem unemotional reasons: fortune and connections, similar to, but preferably better than ones own. By representing a series of marriages, Austen in this novel unearths and elucidates different aspects of the role of marriage, money and love in her society. Austen was a realist and painted her time as they were. In this novel, love and money-based Darcy-Elizabeth marriage is the most successful one whereas the marriage of Elizabeths parents, Mr. and Mrs. Bennet, is one of the faulty ones. Mr. Bennet married his wife being captivated and tempted by her youth, beauty and physical appearance. He forgot that the first appeal of a pretty face does not last long unless serenity of mind and sweetness of temper provide more enduring powers of attraction. Moreover, Mrs. Bennet inherited no property. So, form every point of view, this marriage is a failure. Mr. Bennet, therefore, always has to endure her weak understanding, vulgarity to such and extreme degree that he has nothing to revel in except confining himself to his library all the day, and thus eluding the necessary rituals of family and society. Charlottes loveless matrimony for financial security with the pompous Collins is another interesting marriage. Being twenty-seven and plain looking and realizing that it is her last chance, she accepts the grotesque Mr. Collins, to whom the role of romance and love in life is beyond the reach. He only wants a wife, because in the eyes of the society it is time for him to settle and be married. Charlotte knows that apart from some kind of security and happiness, marriage gives a woman a position. She has few hopes of happiness in marriage beyond the material comfort it can give and so she marries Collins who is inferior in intelligence, only for the home and position he offers, as she believes Happiness in marriage is entirely a matter of chance. The marriage and money theme operates in a baffling way when Elizabeth herself comes to marry. When she sees Pemberly, her prejudice against Darcy begins to be subdued and later by accepting him she makes the most glorious match of and of Austens heroines. The fact that Darcy has then thousand pounds a year is not to be ignored; it emphasizes the perfect adjustment between personal and social ambition achieved by Elizabeth. [Actually Jane Austen understood better than any other of her contemporary English novelists the degree to which social and personal behaviors and even emotion depend on the economic framework of the society.] Moreover, in her marriage with Darcy, affection and understanding, financial security and social engagement are juxtaposed. But to achieve all these material things she has never turned herself into a husband-hunting butterfly despite her mothers inducement. Although she is aware of the fact that in her society a senile spinster, without any fortune, is faced with the prospect of a bleak future full of deprivation and humiliation, still she is the bold heroine who at first showed courage to refuse two marriage proposals. To Austen, sexuality was far less vital to relationships than its counterpart, affection. Therefore, Lydias ex-based marriage with the seductive but penniless Wickham later turns out to be an unsuccessful ones. Wickhams plausible appearance even overwhelmed Elizabeth once. His former interest in Miss King and her â‚ ¤ 10,000 dowry alludes to the role of money in marriage. He only takes Lydia to London only for physical enjoyment. As a consequence, their marriage ends in his going to enjoy himself in London and Lydias patent failure in managing her household financially despite Darcy and Elizabeths continuous help. The Bingley-Jane marriage is another example of good marriage, like the Darcy- Elizabeth marriage, where mutual understanding, romance and financial  stability are combined. Their affection-based marriage works as both are perfectly amiable, modest and gentle. The established marriage of the Gardiners is too shadowy to have a dramatic role. We are only dimly aware of it as a satisfactory relationship between two apparently similar type of persons. In Pride and Prejudice we experience different marriages in the light of one another. Austen presents all the material for an al-round understanding and view: Jane and Elizabeth, combing love and marriage, Charlotte marries for safety, Lydia repenting at leisure. The married couples are equally varied, from well-matched like the Gardiners to ill-suited like the Bennets. The novel says in effect that the real object of love and marriage is not only financial security or physical passion or romance, but also the self-development that true relationships bring about. A marriage can only become an institution when it provides for the fulfillment of both men and womens aspirations, sanctified by love and validated by prudence that both Elizabeth Bennet and Mr. Collins can live on, the former drinking deep draughts of lifes fullness, the later continuing to sip its littleness. The richness of Pride and Prejudice lies in that exploration of life and marriage by Jane Austen.

Sunday, October 13, 2019

N. Fowleri Diagnosis, Treatment and Prevention

N. Fowleri Diagnosis, Treatment and Prevention Historical Aspect: Naegleria Fowleri (N. Fowleri ) is a free living, thermophilic protozoan that is a human specific pathogen that attacks the central nervous system. It can be found in contaminated freshwater sources. It enters through the nose and travels to the brain causing primary amoebic meningoencephalitis1. It was first observed in 1899 and later named after Dr. M. Fowler, who observed the first reported fatal cases of acute pyogenic meningitis in Australia in 19652. While these infections have been identified as early as the 19th century it is challenging to identify because it mimics many of the symptoms of bacterial meningitis[1]. Primary amoebic meningoencephalitis (PAM) is a necrotizing and hemorrhagic meningoencephalitis3. The symptoms begin 1-9 days after the onset of infection these symptoms include fever, nausea, headache and vomiting. The initial symptoms mimic those of bacterial meningitis, the later symptoms are unique to this disease. Later symptoms include neck stiffness, hallucinations, seizures, an inability to focus, lack of balance and eventually coma and death. The mortality rate for this disease is 95%. The disease progresses quickly and leads to death within 12 days of the initial infection1. While this infection has a high mortality rate, it is very rare. There have been 300 reported cases of PAM worldwide in the last 40 years4. It is important to note that this conditioned is often misdiagnosed so these numbers are estimates. In the United States there have been 138 cases in the last 50 years1. This infection was once a condition that plagued developing countries but the incidence is spreading all over the world. Researchers suspect that the increased temperatures due to global warming, increased use of public water sources due to scarcity and an overall increase in aquatic recreational activities are to blame3,18. While swimming and other aquatic recreational activities help proliferate this disease so do rituals. Aga Khan University in Pakistan noticed an increased number of deaths caused by PAM in young males that had no history of swimming, but were devout Muslims. Those who practice this faith pray five times a day and before every prayer, they perform ablution, ablution is the washing of the hands, face, ears, nose, mouth, arms and feet. While cleansing the nose, water is forced up the nose putting individuals performing this practice with inadequately purified water at a greater risk for PAM3. Religious festivals like the Kumbh Mela where Hindus gather and swim in the Ganges river put those who participate at risk of developing diseases like PAM caused by N. Fowleri 3. In addition to religious practices, therapeutic interventions like the Neti pot increase the risk of PAM. Nasal irrigation systems like the Neti pot work to relieve the symptoms of sinusitis and cold. It works by removing debris and mucus from the nasal passages. The recommendation is that the water should be boiled or mixed with a non-ionized sodium chloride. Basic structure: N. Fowleri are a part of the free living amoeba that cause infections in the central nervous system. Some of the other protists are Acanthamoeba spp and Balamuthia mandrillas. Naegleria fowleri have been classified by modern techniques which analyze morphology, biochemical pathway and molecular phylogeny2. The modern approach classifies N. Fowleri as a part of the super group Excavata, in the group Heterolobosea and a part of the family Vahlkampfiidae. Although the genome for N. Fowleri is not yet completed there are some studies producing information about its molecular and genetic characteristics. N. Fowleri s genus includes more than 40 species, but N. Fowleri is the only one that is known to cause disease in humans. De Jonckheere created the most popular identification system for N. Fowleri . The identification system uses genetic markers like internal transcribed spacers (ITS1) and 5.8S rDNA 2. This identification system revealed at least 8 different genotypes. The genotypes are dispersed among different continents America (I,II,III), Europe (III,IV,V,VI,VIII), Oceania (V), and Asia (II,III). Of the eight genotypes only four have been found in humans, types 1-42. Naegleria are a part of the group heteroloboseans that have a three-phased lifecycle. They are first amoeba, then flagellate and lastly cyst formation5. N. Fowleri reproduces in the amoeba form via binary fission to produce the cyst and the flagellate forms. The entire cell cycle is 8 hours, N. Fowleri spends 28 minutes in M phase, 180 minutes in G1, 183 minutes in S phase, and 90 minutes in G22. In the amoeba form, the trophozoite ranges in size from 15-25 Â µm. Trophozoites also have cytoplasmic projections called food cups which allow phagocytosis of bacteria, yeast, erythrocytes and cellular waste. Trophozoites are the form of the amoeba that can feed and divide, they are also the form that enter the human host6.Trophozoites will transition into the flagellate stage after being exposed to a saline solution2. The flagellates cannot feed or divide, the transition also involves a change in shape from pleomorphic to pear shaped with a pair of flagella. The flagella have the typical 9+2 structure and are surrounded by a cytoplasmic membrane. The 9+2 flagella structure describes the cross- sectional arrangement of microtubules that make up the flagella. There are nine doublet outer tubules and two central singlet tubules7. The cyst form is resistant to most disinfection. The cyst formation is spherical, smooth, double walled and refractive. They measure about 20Â µm. The material of the cyst wall is synthesized and packaged by the rough endoplasmic reticulum2. Route of Transmission: N. Fowleri is a thermophilic amoeba, its optimal temperature ranges from 1150 to 1220 F. N. Fowleri can typically be found in warm freshwater like lakes and rivers, warm water from industrial parks, or inadequately chemically treated water, other warm water sources like water heaters and soil. In their natural environment N.Fowleri phagocytize cyanobacteria and eubacteria to regulate levels. Samples from the lakes of the southern United States reveal that N. Fowleri introphozoite formis present during the summer. During the winter months N. Fowleri in cyst form survive in freshwater sources, but no form of N. Fowleri can withstand freezing temperatures1 . Most cases of PAM are caused by swimming in warm freshwater, from drinking water, recreational activities, ritual abulation and sinus irrigation systems1. Infection occurs when water containing N. Fowleri gets into the nose. The amoeba enters the nose and travels along the olfactory nerve, through a bony plate in the skull called the cribriform plate3. Once it reaches the brain it causes meningoencephalitis, cerebral edema and results in herniation. The olfactory bulbs and orbitofrontal cortices become necrotic and hemorrhagic. The data on both humans and mice support the conclusion that death is ultimately caused by increased intracranial pressure and herniation3. Swimming in water containing N. Fowleri increases the risk for PAM but age and sex are also risk factors. From the 1962- 2015 there have been 138 reported cases of PAM in the United States, 114 of the cases have been children around the age of 12. Nearly 75% of the infections have affected males1. Certain behaviors are associated with an increased risk of infection, those infected individuals reported participating in water related activities like swimming, diving and head dunking1. Although N. Fowleri can be transmitted through water it cannot be transmitted through aerosols or droplets, or via person to person contact. N. Fowleri can be found in other organs of the body, such as the heart, lung, spleen and thyroid1. Pathogenesis: N. Fowleri enter the human host through the nose which provides access to the brain. Within eight hours of infection N. Fowleri is present in the mucus layer of the olfactory epithelium. Within 24 hours N. Fowleri are in the olfactory bulb and present in the cribriform plate. By 96 hours neutrophil polymorphs cause a severe inflammatory response in the olfactory bulb which leads to brain tissue damage3. Contact dependent mechanisms are N. Fowleri mediated pathogenic processes. The primary mechanism of pathogenesis in N. Fowleri is adhesion. Adhesion allows for movement and chemotaxis in the nasal mucosa and assists N. Fowleri with disease progression. Adhesins are expressed on the surface of N. Fowleri, the adhesins are integrin like proteins surrounded by adhesion like structures. Fibronectin binding protein, protein kinase C and NFa1 are important to interrupting the host mediated cytotoxicity3. In an experiment testing cytopathicity of N. Fowleri, a culture would bind to Fibronectin and in the presence protein kinase C the ability of the amoeba to adhere increased8. N. Fowleri also produces Reactive Oxygen Species (ROS) which damage the host cell. Following cell damage, N. Fowleri uses phagocytosis and amoebastomes to assist N. Fowleri in breaking down and consuming the cells through a sucker structure on its surface. These processes are mediated via actin and involve the polymer ization of monomeric G-actin and filamentous F-actin. Studies have found that a membrane protein Mp2CL5 may also play a role in pathogenicity, without this protein N.Fowleri are nonpathogenic3 .This protein is suspected to aid in pathogenicity by navigating the environment, and movement toward food sources9. In addition to contact dependent mechanisms of pathogenicity, N.Fowleri also utilizes contact independent mechanisms. N-PFP is a cytolytic pore forming protein that depolarizes the cell membrane and decreases the integrity. Naegleriapores A and B are pore forming polypeptides that are very similar in structure and function. Both are antimicrobial and cytolytic polypeptides3. The enzymes phospholipase A, A 2 and C are present in patients with PAM. Phospholipases are responsible for the demyelination of white matter. Sphingomyelinase, neuroaminidase, elastase and proteolytic enzymes are responsible for demyelinating nerve tissue. N. Fowleri are hemolytic due to the heat shock protein 70 which is unaffected by salt concentrations, chelating agents, pH and temperature extremes3,10. This protein is present in the cytoplasm, pseudopodia and phagocytic food cups. There are many other factors associated with the pathogenicity of N. Fowleri and others that are suspected to have an effect on t he pathogenicity. On the onset of infection the hosts innate immune system attempts to reduce the pathogens cytotoxicity. During the early infection the body releases mucin which surrounds the N.Fowleri trophozoites to prevent cytotoxicity. In the later infection eosinophils and neutrophils surround the N. Fowleri cells to prevent cytotoxicity. Inflammation increases over time, although there are not many cells that penetrate the host epithelium. The inflammation and polymorph nuclear cells from the host response damage cerebral tissue2 . Diagnosis, Treatment, Prevention: Diagnosis of N. Fowleri is heavily dependent on laboratory techniques. The most effective way to diagnose N. Fowleri requires cerebrospinal fluid (csf) which is conducted while the patient is living and brain biopsy which is conducted post-mortem11. Different laboratory tests are utilized to analyze the specimen. When PAM is suspected, samples can be wet mounted and placed under a microscope to identify trophozoites12. Polymerase chain reaction is a method that can be used to amplify DNA, to identify the presence of N. Fowleri DNA in a sample11. Another laboratory technique involves antigens that were developed from mouse monoclonal antibodies (mAbs) against N. Fowleri . When indirect immunofluorescence assays are used mAbs react to N.Fowleri from specific geographic regions13. The infection due to PAM progresses quickly and as previously stated, mimics symptoms of bacterial meningitis. Even with the advances in laboratory diagnostics most cases are diagnosed post mortem making effective treatment elusive. One successful case study provides an example of effective diagnosis and treatment of this condition. On July 13, 2013, a 12 year-old girl presented to Arkansas Childrens Hospital vomiting, having trouble holding up her head and was unable to open her eyes. A few days prior to hospitalization the patient had been playing in a local water park. During her hospitalization she experienced hallucinations, and thirst. A spinal tap was performed which ruled out bacterial meningitis. The laboratory identified N. Fowleri trophozoites in the patients cerebrospinal fluid. After determining the infection was PAM caused by N. Fowleri, physicians initially treated the patient with antibiotics and antifungals like Amphotericin B, Rifampin, Fluconazole, Dexamethasone an d Azithromycin .None of these treatments improved the condition of the patient. The hospital petitioned the Center for Disease Control (CDC) to allow the use of a new experimental drug available for the treatment of N.Fowleri14. The drug Miltesfosine was given 36 hours after the initial diagnosis, physicians also lowered the patients body temperature to 93.2 F0 to reduce cerebral edema and intracranial pressure. After 18 days in the ICU there was no N. Fowleri found in her system. The patient experienced a full but gradual recovery over the next fifty five days. After seven days the patient was able to write her name, in fourteen days she was able to speak in one and two syllable words. She also underwent both speech and physical therapy14. This patient is one of the three known survivors of PAM. While the virulence factors and the degree of recovery that surround the other two cases of survival are unknown. The prompt diagnosis, treatment with Miltesfosine within thirty six hours and maintaining a low body temperature for this patient played significant roles in effectively treating this infection14. Although the first case of N. Fowleri was over 50 years ago, the mortality rate for this disease continues to increase due to water scarcity which increases use of water from public sources. As previously stated this condition is either diagnosed post mortem or misdiagnosed. The development of a standard microbial treatment will aid in the reduction of high mortality rates14. In the three cases of survival the patients were all intially treated with amphotericin B, rifampcin, fluconazole, dexamethasone and phenytoin during the first week of infection15. In 1969 a patient survived PAM with the successful treatment of amphotericin B. The patient in 2013 was initially treated with amphotericin B and it was ineffective. Miltesfosine effectively treated this patients PAM14. Other drugs with the potential to treat PAM have been tested, and some have been proven effective while others have not. Clotrimazole a drug that has been used as an antifungal had potential to treat PAM but under further study was deemed ineffective16. In developing countries like Pakistan where water is in short supply and ablution is common practice the danger of becoming infected with N. Fowleri is greatly increased. Water sources in these countries include wells or water storage tanks which are often contaminated with N. Fowleri 17. In order to prevent infection the World Health Organization (WHO) encourages that water storage units and wells be regularly tested to ensure proper disinfection. Public health organizations have also encouraged the use of nose clips while swimming in lakes and other freshwater sources, and boiling water that is used for ablution17. Chlorine disinfection regimens prevent against most pathogens in drinking water systems however free living amoeba like N. Fowleri survive most disinfection. The cyst form of N. Fowleri is resistant to most disinfection and are associated with biofilm that can build up in drinking water systems. N. Fowleri have been isolated in drinking water systems in Australia, the United States and Pakistan, in both Australia and the United States they maintain chlorine levels of 0.5mg/L at all times in the drinking water18.To test the amount of chlorine needed to eliminate N. Fowleri, researchers conducted an experiment using two separate sites, a pre re-chlorination site and a post re-chlorination site, both sites were monitored before and after re-chlorination for a year. The results were that after chlorination of greater than 1mg/L at each site, in the post re-chlorination site the amoeba were gone within 60 days. The pre re-chlorination site would have seasonal flares of N.Fowleri but the c hlorine levels eliminated the protozoan and prevented further spread. Overall chlorine levels above 1mg/L result in the elimination of N.Fowleri in drinking water systems18. Summary of current areas of research notes: N. Fowleri is a rare pathogen that was discovered over fifty years ago. Since its discovery still not much is known about this pathogen. Future research into this pathogen will focus on patient complaint diagnosis and treatment, expanding the drugs that are used, biomarkers, and drug targets. In order to determine whether the patient has contracted PAM due to N.Fowleri the patients csf is tested and if the test is negative for bacterial cultures and the patient has a history of swimming or other aquatic activities, then the patient tests positive for N.Fowleri. Extracting csf can increase the pressure in the patients brain and lead to herniation of the brain. Because N. Fowleri travels to the brain via the nasal passage, the proposed route of diagnosis is collecting a nasal sample. Research confirms that N.Fowleri can be collected in both csf and nasal cultures3. Drugs administered through the nasal cavity, through the transcribial route would be delivered across the cribifrom plate to the inferior portion of the frontal lobe. This is the site where N. Fowleri attacks and spreads to the central nervous system. Drugs like amphotericin B do not decrease the minimum inhibitory concentration (mic) when administered intravenously. By potentially administering the drug transcribialy, the drug passes the blood barrier which would allow the drug to be more potent, trail the route of N.Fowleri, attack the site of infection, allow the lethal dose of drug to achieve the mic without venous drainage, and lastly to avoid symptoms of intravenous drug administration 15. There are clinically approved drugs that have promising amoebicidal effects. These drugs interrupt the mechanisms and processes of the amoeba. Digoxin and proyclidine both exhibit amoebicidal properties. Digoxin treats atrial fibrillation and heart rhythm disorder by helping the heart beat stronger and with more rhythm19. Proyclidine is used to treat Parkinsons and other diseases that cause involuntary muscle movement20. In order for further testing of the amoebicidal effects of these drugs to continue to be studied more drugs that have the potential to be amoebicidal must be identified and screened for tests to go from in vitro testing to in vivo testing. There has not been a lot of emphasis on finding drugs that treat N. Fowleri because the condition is rare and affects populations in the developing world. Biomarkers for PAM have been challenging to identify because little is known about N. Fowleris pathophysiology. Mass spectrometry, NMR and other tools of analysis are being utilized to identify biomarkers. Researchers are also making biochemical profiles of individuals in populations that contracted the disease against those who did not. These profiles will include information on the individuals age, gender, ethnicity and factors that predispose them to this condition3. This condition is rare and because of its rarity has been studied infrequently. With limited time and resources N.Fowleri is funded and studied less frequently than conditions that affect larger populations like Malaria or the Zika virus. The range of drugs used to treat patients with PAM is severely limited, researchers are developing drugs that would inhibit different processes of N.Fowleri. The drug pathways are hydrolytic enzymes that invade the host cells, glycocytic enzymes that are expressed differently by the pathogen, thiol based redox metabolism pathway, oxidative stress pathway, trypanothione pathways, and encystation and excystation pathways3. Bibliography 1. 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