Saturday, August 31, 2019
On The Last Days of My Life Essay
On The Last Days of My Life The Fantasy of My Life On the last days of my life, I want to thank God for everything, for taking care of my family and for my own safety as well. I know every second of our lives are so significant, so I want to make memories be unforgettable. Not every moment Iââ¬â¢m here for my beloved family but towards my weaknesses, they still there for me and always encouraging me to stand and never say ââ¬Ëââ¬â¢noââ¬â¢Ã¢â¬â¢. I want to thank them for giving their lots of love and care even sometimes I lose hope, they are diligent enough in explaining that life goes on whatever may happen at least I did my better than best. I also want to spend the last days of my life to those people who are very close to my heart, my gloomy friends. I want to make a big sacrifice for them and that is to see that they are happy and contented enough for what God that has given to them. I want them to be still complete even my entire presence will not be able to be there. And that is what I want for my family to be happen as well. The third is to my special someone who deserves to change and improve my entire life. I want him to be with me on the last day of my life, enjoy the last hour while singing our favorite theme song and experience the last kiss on the last minute if my life. I want him to be happy so on the last second of my life, Iââ¬â¢m giving his freedom to love another woman who will be able to continue my love and care to him. And God will be my arms in finding the fantasy of Heaven.. :â⬠) By: Jelin.. 11.08.11
Friday, August 30, 2019
Royal Danish Bearings Marketing Key Terms
Royal Danish Bearings ââ¬â Marketing Key Terms Business and Management Keyword| Definition| Relation to RDB| Market Size| The number of individuals in a certain market who are potential buyers and/or sellers of a product or service. Companies are interested in knowing the market size before launching a new product or service in an area. | The ball bearings industry has a quite large market size given the development of the automobile industry. | Market Share| A percentage of total sales volume in a market captured by a brand, product, or company. RDBââ¬â¢s market share in the business is quite large, justifying its great expansion and organic growth. | Consumer Needs| Problems that customers intend to solve with the purchase of a good or service. | Indirect consumers need automobiles, however; automobile factories require ball bearings, resulting in RDBââ¬â¢s business opportunity. | Unique Selling Point| Real or perceived benefit of a good or service that differentiates it from the competing brands and gives its buyer a logical reason to prefer it over other brands.USP is often a critical component of a promotional theme around which an advertising campaign is built. | RDBââ¬â¢s USP is its highly technologically advanced ball bearings, which are also environmentally friendly. | Competitive Advantage| A superiority gained by an organization when it can provide the same value as its competitors but at a lower price, or can charge higher prices by providing greater value through differentiation. Competitive advantage results from matching core competencies to the opportunities. RDBââ¬â¢s competitive advantage is that they are an already globally known company and they are about to invest in their Research and Development department. | Brand Loyalty| The extent of the faithfulness of consumers to a particular brand, expressed through their repeat purchases, irrespective of the marketing pressure generated by the competing brands. | Given logical ass umptions, automobile factories and companies remain loyal to RDBââ¬â¢s ball bearings, given their high quality product. | Demand| Desire for certain good or service supported by the capacity to purchase it.The aggregate quantity of a product or service estimated to be bought at a particular price. | RDBââ¬â¢s ball bearing demand is decreasing in Europe, however increasing in Brazil, China and India. | Marketing| The management process through which goods and services move from concept to the customer. It includes the 4Ps; Product, Price, Place and Promotion. | RDB plans to expand their marketing reach with the use of modern and technologically advanced media, in order to reach new customers and create brand awareness. Advertising| The activity or profession of producing information for promoting the sale of commercial products or services. | RDB is currently promoting their sales throughout their plans to expand into different countries with smaller environmentally friendly fa ctories. | Promotion| The advancement of a product, idea, or point of view through publicity and/or advertising. | RDB plans to advertise in a greater scale. | ICT| Stands for ââ¬Å"Information and Communication Technologies. ICT refers to technologies that provide access to information through telecommunications. It is similar to Information Technology (IT), but focuses primarily on communication technologies. This includes the Internet, wireless networks, cell phones, and other communication mediums. | This company is currently planning to establish a higher range of their information and communications technologies given that they require a higher advertising range. Brand Awareness| Extent to which a brand is recognized by potential customers, and is correctly associated with a particular product. Expressed usually as a percentage of target market, brand awareness is the primary goal of advertising in the early months or years of a product's introduction. | RDB has managed to cr eate brand awareness, given that they have been in the market for quite a while. They are old occupants of the market niche and their brand awareness is high. |
Thursday, August 29, 2019
Tesco Supply Chain Management Practices Case Study Essay
Tesco Supply Chain Management Practices Case Study - Essay Example They were the authors of the book known as ââ¬ËThe Machine that changed the worldââ¬â¢ which was in charge of introducing the concepts of lean production for the Toyota Company (Indu & Gupta, 2004). The experts found out that the company indulged in many unnecessary handlings whereby there would be improvements along with reductions in the costs the company incurred. They additionally found out that there were longer lead times, poor availability of products along with locations of stores. The company in turn established a system for continuous replenishment, which enabled their products to have immediate replenishment (Womack & Jones, 2006). They have also been reducing their handling of goods while also streamlining their flows. They were able to accomplish this by using dollies on wheels, which replaced shelves. The dollies could be sent from the suppliers and into their delivery Lorries and taken back to the stores. They helped in reducing the companies need for handling th e products since their products were just being loaded at the end of the companyââ¬â¢s production line and taken directly by wheels to their supermarkets (Ohno, 2005). This move helped the company in reducing their touch points for drinks by 150 locations along with the transit times. However, the multiple trips that were carried out resulted in higher costs for the company but these costs were covered by decreases in their inventory costs. The company also had agreements with other companies such as P&G, Unilever along with Coca Cola in order to alter their schedules for distribution (Womack & Jones, 2006). This in turn enabled them to reduce their lead times by fifteen days since the daily deliveries made through their wheeled pallets, which enabled the placement of their goods directly on the shelves of many of their outlets (Bicheno, 2008). The companyââ¬â¢s holding of stock reduced greatly from over four to two weeks while their service levels also improved by over six pe rcent. The companyââ¬â¢s use of lean production methods in the above aspects helped them see their profits jump from 16,452 million pounds in the year 1998 to 37,070 million pounds in the year 2005 making them the biggest grocery within the United Kingdom (Indu & Gupta, 2004). Due to the companyââ¬â¢s use of lean production systems, they were able to reduce their storage locations from five to two, their order entry locations from six to just one and their service levels from 98.5% to 99.5%. They were additionally able to reduce their throughput times from twenty to just five days, which represented a 75% reduction in their total inventory (Womack & Jones, 2006). The Tesco Company initiated a ââ¬Ëstep changeââ¬â¢ curriculum, which was used for identifying the processes in their supply chains that required transformations. This program helped the company in eliminating several of the unnecessary procedures that enabled them to save about two hundred and seventy million po unds in the years 2004 to 2005. The changes that were implemented under the program additionally helped in simplifying the operations in their stores while freeing up their employees so that they could more effectively attend to their customerââ¬â¢s needs (Ohno, 2005). The company introduced operations across docks that involved goods being loaded into one
Wednesday, August 28, 2019
What does it mean to say that the Jews are Gods chosen people Discuss Essay
What does it mean to say that the Jews are Gods chosen people Discuss with reference to the concept of covenant - Essay Example ir demographics and any other factor or variable, it is one of their religious beliefs that is more attention catching and debatable than anything else in the case of Jews. It is an observation that Jews have repeatedly emphasised on their superiority over all other creatures based on their religion. In specific, they call themselves as the covenants of God. According to the definition of the term ââ¬Ëcovenantââ¬â¢, it refers to any mutual agreement or understanding between two parties in the light of some terms and conditions enclosing some doââ¬â¢s and donââ¬â¢ts (Jospe, Madsen & Ward, pp. 52-59). Quite understandably, Jews hold the belief, based on religious historical events and their scriptures that they have an agreement with the God, which binds the God to prefer them on others. In return, Jews would have to follow the laws, rules, and regulations of the God through the prophets that He sent. In this regard, this paper is an attempt to analyse and examine the same belief of Jews as Godââ¬â¢s chosen people based on scrutiny of the concept of covenants. In addition, this paper would not merely discuss the reasons for this belief but would also try to explore the alternative views and criticism on this idea. Like any other monotheistic religion of the world, quite understandably, Jewish people believe in one God. However, they, at the same time, also are of the view that there is some sort of special pact or agreement between them and God, and that Jews are obliged to abide by the laws of God than any other people. The major reason of such belief being that it would be the Jews, leading from the front when Messiah would come back to bring order in the world near the Day of Judgment (Solomon, pp. 256-260). Moreover, for all this activity, Israel would be the center and Jews would be the vehicle. According to Jewish traditions, Abraham was first one with whom God made a covenant. According to the chapter 12 of Book of Genesis, God told Abraham, ââ¬Å"I will make you a
Tuesday, August 27, 2019
Changing our lives Essay Example | Topics and Well Written Essays - 500 words
Changing our lives - Essay Example Moreover, establishing of goals indicates how much progress has been made and how far one is from his destination. Thus, like millions of people, I have also established few goals to be achieved in my life. One of my primary goals is to seek higher professional education from the USA. Since I belong to the Middle East, proceeding to the USA for acquiring Masters Degree in International Relations is my prime ambition. It would be a token of great honor, respect and prestige when my family members, friends and relations would introduce me with others as a foreign qualified young man. It would certainly boost up my morale and I would experience the bewitching fragrance of pride and respect in my mind. Proceeding to the western societies for seeking professional education is really a pleasant dream for the Arab youth, because lucrative jobs and rapid promotions are in wait of such qualified persons on their return in their native country. During my stay in the USA, I will be able to lear n many things related to culture, civilization, society, religion and politics of the world. It is reality beyond suspicion that the USA is a multicultural society, where people belonging to divergent racial, ethnic, regional, religious and cultural groups and communities live together.
Monday, August 26, 2019
Business Strategy Essay Example | Topics and Well Written Essays - 2000 words
Business Strategy - Essay Example Yahoo was founded by Jerry Yang and David Filo in 1994, mainly as a website which featured a directory of other websites. From that beginning, it spread its operations extensively, making strong presence in certain segments, but still lay behind Google in majority of the segments, as well as in relation to market share and revenue. Actually, in 2000, Yahoo and Google had a working association, with Yahoo using Google for search results. However that was short-lived, and both the companies parted ways and importantly started competing against each other in various segments. Porterââ¬â¢s ââ¬Ëfive forces frameworkââ¬â¢ Threat of Entrants Any industrial sector will have threat from new entrants, and dot.com sector will be no exception. Actually, the dot.com sector, used to denote the companies that mainly do their operations over the internet with a website and a domain ending with .com, got originated due to the entry of new entrants particularly in Silicon Valley. This being t he case, there will be a constant threat of new entrants in this sector. New entrants are always attracted to industry sectors that are flourishing and that seem to offer the potential for healthy profits, dot.com industry fits that bill aptly. (ââ¬Å"Consulting Toolsâ⬠). They are targeting various segments in the dot.com industry from emails, video sharing and hosting, etc., Although, Google and Yahoo have consolidated their positions in these segments and hold larger market share, these new entrants by giving widespread services are minor threats. Threat of Substitutes The threat of substitutes will be found more in the dot.com industrial sector, because the lines of control and authority are blurred in the virtual world. With no worldwide authority to detect and stop copyrights infringement and other violation of trademark services, substitutes can come with similar services or slightly modified services, negatively impacting pioneers like Google and Yahoo. However, the fac t is, these two companies were also accused of coming up with substituting services, violating the rights of other players, but that were only minimal. With Internet coverage increasing, the competition for online business also increases, and using this opportunity many players are coming up with substitute services. For example, Googleââ¬â¢s Iphone has been substituted by other local mobile phone makers, likewise Youtube has many substitutes like Dailymotion, Yahoomail has been substituted by many pan-national as well as local players. ââ¬Å"The Internet creates new substitution threats by enabling new approaches to meeting customer needs and performing business functionsâ⬠(Shin). Power of Suppliers In the dot.com industry, quite uniquely, the supplier of product or services as well as user or customer of service will be maximally one and the same. That is, most of the products or services offered by the companies, like websites in search engine results, videos in Youtube , Google Adsense feature, etc., are not created ââ¬Ëin-houseââ¬â¢, instead they are sourced from the suppliers outside. Those same suppliers along with sizable common people will also utilize those services as customers. Thus, the companies by aptly hosting or collecting or arranging those things and even
Sunday, August 25, 2019
Forces of magnetism Assignment Example | Topics and Well Written Essays - 250 words
Forces of magnetism - Assignment Example Setback for magnet program occurs when hospitals lack the unison in rendering of these services to all hospitals. Programs for private and public nursing institutions do not operate at different policies. Good communication between the administration and the nurses lacks as there is no consultation in making of decisions. Endorsement of nurse empowerment goals is not successful as a result of high handedness where a nurse was fired for leading a drive for magnetic status. Changes at the hospitals leads to short-staffing and exclusion of nurses from decision making. There are complaints that the program is not monitoring compliance effectively and is used as a tool for promotion. Magnet hospitals lack improved working environment than non-magnetic hospitals (Nather, 2010). Lack of accomplishment of magnetic forces policies in hospitals or organizations will lead to enhancement of hospital policies to care for and support nurses. These policies include: zero tolerance for abuse of measures and practices, addressing nurse exhaustion adequately. Cases of assault and sexual harassment of nurses at hospitals should be pursued. Each institution should have suitable lifting equipment and no lift policies. Patient assignments in admission and discharge ought to count as 2 patients to account for the high death connected with bed turnover. Magnet hospitals ought to have needless IV systems and protected needles for safety in rendering of services (Chotaw,
Immigration from Iraq Because of Religion Assignment
Immigration from Iraq Because of Religion - Assignment Example Christians used to account for about 4% of the population but their numbers dramatically dwindled after the US invasion of the nation in 2003 (Chanaa 15). Currently, the proportion of Iraqi Christian immigrants has significantly increased owing to a number of political and social factors. First, Iraq has always given Christians a minority status in which they feel as though they are second class citizens who are vulnerable to injustices at any time. Furthermore, the law has historically minimised their ability to express themselves freely in the nation even though this has often been disguised by constitutional provisions that claim to respect the freedom of conscience (Salloum 60). In the political arena, Christians are scarcely afforded the right to become leaders in government, security organs or the military. Such institutional discrimination has ensured that Christians in this nation lack the ability to become influential in their society, so a number of them now have an even greater impetus to leave Iraq. Many Christians have not forgotten the history of oppression that they have been subjected especially in 1915, 1933, 1961 and 1975. All these attacks created numerous villages of Iraqi immigrants in Syria and other surrounding nations. The 1975 incident was accompanied by the burning of Christian villages that caused the displacement of thousands of Iraqi Christians (Rassam 23). Continued discrimination and persecution of Christians was revived in 2003 after the US-led invasion against Iraq and Afghanistan; this chaos and sectarian violence heightened in 2006.
Saturday, August 24, 2019
See attachment for essay question Example | Topics and Well Written Essays - 2500 words
See attachment for question - Essay Example This paper shall now discuss the preceding statement, examining the implications of such statement for social work practice. It shall define madness based on a technical and operational definition of the term as will now be used and applied in this paper. It shall then discuss where madness originated from, focusing on the evolution of the thought processes related to the current concept and understanding of madness. This paper shall apply madness and its concepts to social work and their work with service users. It shall also cover relevant legislation. Finally, this paper shall discuss the ethics and values of social work in relation to madness. This paper is being undertaken in order to assess and evaluate the current subject matter and how it affects the current social work practice. It ultimately aims to ensure a more profound, academics, scholarly application, and evidence-based application of the subject matter. The Cambridge Dictionaries Online (2010) defines madness as ââ¬Å"the state of being mentally ill or unable to behave in a reasonable wayâ⬠. This definition is again another generic definition of madness, one that can even easily be interchanged with the term crazy or insane. Nevertheless, the definition points out important elements about oneââ¬â¢s state of mind in this condition of madness ââ¬â which it relates to a state of being in an unreasonable or illogical state of mind. The mental processes and the normal logical thoughts of a person are compromised in times of madness; hence, in instances when one is not logically processing ideas and thoughts, some people are prone to label such person as ââ¬Ëmad.ââ¬â¢ The Encyclopedie (as cited by Foucault, 2005, p. 98) sets forth that madness means to ââ¬Å"depart from reason with confidence and in the firm conviction that one is following itâ⬠. There is a broken relationship between man and his reason and the p erson believes that his mind is
Friday, August 23, 2019
Coffee Case Study Example | Topics and Well Written Essays - 1250 words
Coffee - Case Study Example The quantity of output that is likely to be produced in a cartel depends on the strength and stability of the cartel. For instance, if the cartel decides to act as a monopoly then it has absolute authority over all its members. The following graph shows the output and price in case of a cartel arrangement (Dwivedi, 2009). The summation of individual marginal cost curves provides the marginal cost curve for the industry as a whole and the intersection of the marginal revenue and cost curves determines the equilibrium level of output and price. Once the industry has been determined then the individual firms ascertains their own level of output by matching their own marginal cost curves to the profit-maximizing level. Cartels have been banned in a number of developed countries like the U.S.A. on account of the negative impacts it has on the consumers (Marshall and Marx, 2012). In many cases it has been observed that the cartel members hide prices, charge unreasonable price and artificially constrict output and all of these reduces the welfare of the consumer. Consumers can also lose confidence in the business as cartels have been largely associated with the negative sentiments. In most of the cases the business enterprises which are not a part of the cartel are often eliminated from the business and this in turn affects the overall effectiveness of the economy as a whole. Formation of cartels has been associated with the reduction of the innovation and economic efficiency. Governments and economists of various countries thinks that cartels are ineffective because unproductive members take refuge to the cartels and are not bothered to improve their performance (Grossman, 2004). It has also been fo und that cartel members often discourage the entry of new entrants into the market and this in turn restricts the chances of economic growth and job prospects for many. In many cases the cartels have been held responsible
Thursday, August 22, 2019
Emotional Labour Essay Example for Free
Emotional Labour Essay This report investigates the shop manners and training offered to the floor sales staff at Next compared to that of those who work in the stock room. I would like to know how each environment affects the workers emotions. I think its an important question to ask because the people that work on the shop floor are constantly in contact with customers. It could be said that those that work in the stock room are not part of the stage setting and are more like the stage crew who work behind the scenes. I think it is important then to first address what emotion is. Emotion theory is centred on the relationship of the person and its environment (Lazarus, 1991 p40). This has implications on the question that I am posing as the stockroom workers interact in a different environment to their colleagues on the shop floor. There are two fundamental viewpoints to emotion the organismic and interactionalist viewpoint. The organismic model developing from the work of Charles Darwin, William James and early Sigmund Freud, Defines emotion mainly as a biological process. For Freud emotion affect is libidinal discharge, for Darwin its instinct and for James its the perception of a psychological process (Hochschild, 1983 p205) This leads organismic theorists to believe that there is a basic similarity of emotion across categories of people (Hochschild, 1983). The organismic model brings us to an elicitation-expression model (Hochschild, 1983) Interactionists believe emotion always involves a biological component but adds more points to social factors, which are present before, after and during the experience of emotion. For example why does a customer become violent when refused a refund, what in their cultural environment constitutes their response? If we conceptualise emotion as instinctive we will ignore questions about social entry. (Hochschild, 1983) Emotions are experienced by individuals and through intention or inadvertent communication may be deduced by others who are observing. (Lazarus, 1991 p40) Emotions can be a valuable source of information in determining how people are getting along. However, surface acting can disguise true emotion so you must be wary when reading emotions. Society and biological inheritance creates a pattern of behaviour that shape emotion and expressions of the individual (Lazarus, 1991 p40). I believe this statement relates to the way that shop assistants and customers are expected to behave. As you will see the training offered to the sales staff shows members of the work force how to act in a socially excepted way which is common practice in all chain stores. In a shopping environment how other people feel is a huge factor as to whether they buy something or not. Sales staff to some extent can influence this. I believe that for a customer to feel at home in a shop the sales staff need to be friendly and approachable whereby you feel even if you havent bought any thing this time you are welcome back again. I think that this is the key to the success of stores like Next and Marks and Spencers where staffs have the correct shop manners to keep the customers coming back. From interviews undertaken with staff at Next I have uncovered strict guidelines in training which each new member of staff has to go through. (I will discuss this and whether I think it is appropriate later.) Drawing on my own experience, I have worked in what you would call a downmarket clothes store and no training of shop manners was offered to me. It was my first proper job so I did feel as if I was being thrown in at the deep end. However, the shop was very small and my C.V. demonstrated that I had good people skills as I had worked on a market stall at the weekends and holidays. I assume that management didnt feel the need to train me in what they thought should be the obvious way to behave towards customers. After speaking to senior sales staff at next and sponsors, these are longer standing members of staff who train new staff using the guidelines (see Appendix), I have gathered that management wish the customer to feel that they are the most important thing and that their shopping experience is being made easier by the staff. Next seem to have thought out its training program very clearly and assigns specific amounts of time to each activity. This helps to give the impression that training is viewed as an important part of the job. I think that Next places emphasis on its training as it is a chain store and it often directs customers to local stores if the stock isnt available at the branch at which they are visiting, this calls for a sense of conformity between stores. I evaluated the training sessions which, are appropriate to the questions I am asking, by interviewing staff on how appropriate each session is, how achievable are the actions set out and how they affect emotions. The overall reaction that I had from staff was that they felt the training to be very obvious and many sponsors admitted to skipping through the training as quickly as possible because of this fact. Sponsors felt that by training staff with this obvious manner of behaviour was assuming that the trainee was, when prompted by myself, emotionally incapable of selecting the correct emotions for the customer situation. Training session 1 (Appendix Shop Manners). The trainee is told to be aware and not to get tied down in tasks when I asked staff about the reality of this they said they found it very annoying to be approached by customers when doing a job and often resented customers for bothering them. However, this is where surface acting comes into play the employee hides what they feel and pretends what they dont (Hochschild, 1983). The action is in the body language, for example the put on smile and sweet voice as it is for the people observed by Erving Goffman (cited in Hochschild, 1983 p35). The employee has to think back to their training to pick the right body language. A typical scenario: Now interrupted from a task possibly holding a huge pile of stock in their hand the employees are given a strict formula to follow, eye contact, a smile, appropriate greeting and to be friendly and sincere. This is a hard task when obviously it is inappropriate for the customer to target them and often there is another member of staff nearby doing nothing. However, the surface acting must continue as the corporate motto of The customer always comes first is relayed in your mind, plus I dont want to lose my job if they complain to head office. Company control also works along who fears whom. As with flight attendants the fear hierarchy works indirectly through customers complaining, to head office (Hochschild, 1983). This type of scenario links with the question posed by Hochschild (1983 p89) that when feelings are set by management and where workers have weaker rights to courtesy then consumers do, when deep and surface acting are forms of labour to be sold what happens to the way a person relates to her feelings or to her face? Employees said that when they were the customers they were more aware of the shop assistants emotions and tried to be more courteous. However, they may just feel as though they do this because they wish that people would do this for them. I do believe that this statement does have some truth but surely when the stage setting is different, when they are the customer and not the server they assume the actions of the customer. As on the stage as in life the person is the locus of the acting process. But when an institution is involved various acting elements are taken away from the individual and replaced by institutional mechanisms. In this case the fact that the customer comes first. The locus of acting, of emotional management, moves to the level of the institution. (Hochschild 1983 p49) The people are arranged according to institutional custom and the workers surface act in institutionally approved ways. Training Session 2 (Appendix In-Store Security) This training session makes shop assistants conscious of the need to be aware and the need for acknowledgement of the customers. You can use your training of greeting the customer in a functional way, to help reduce the comfort of shoplifters who are always aware of who is watching them. Senior staff said that it gets easier to spot thieves with practice; you get to learn their tricks of diverting your attention. Even though you have to be suspicious of certain customers you must always remember your training and be polite even if you feel that they are up to no good. Training Session 3 (Appendix Stockroom) As you can see none of the training here is connected to personal conduct, it doesnt attempt to tell you how to act where as the shop floor assistants are told to be friendly, sincere, polite, confident and have a smile. They are even told that conversations must be work related. When questioned on the reality of this last statement floor staff said they do have non-work related conversations but they are of a toned down nature to the way they would speak in private. When I asked the stockroom workers about their conversations they said that if they were in a situation to have a conversation it would be more animated then if having it on the shop floor as they are not in public. Training Session 12 (Appendix Till Service) Customer interaction is crucial at the till point. Again the trainee is told how to act, to be sincere and polite. I asked staff how easy it was to do this. A typical scenario: Its a very busy Saturday and all the tills are in operation when greeted by the customer with comments such as I have been waiting ever such a long time, you know and the like, it is difficult to be sincere and polite as there is nothing the staff can do to make the queue go any quicker. The staff member surface acts with her painted on smile and polite apologies. In the training suggestions of possible conversation are complimenting customers on their choice of purchase. Till operators said they tended to deep act in this case, only saying it if they meant it. Deep acting is a natural result of working on feeling expression is spontaneous (Hochschild 1983). As the Russian director Constantin Stanivlaski puts it a real feeling that has been self-induced (cited in Hochschild 1983 p35). The refund and exchange policy is an important part of training because it is the most likely time for customer conflict. The staff member is instructed to treat the customer in the same way as they would if they were making a purchase, this is easy if the customer has a receipt or is a well-known customer. But if the customer doesnt have a receipt it makes it harder in some cases because you have the suspicion that the customer may have stolen the garment. In this situation the staff member is advised that the best thing to do is get a manager. As formal rules that prop up an institution set limits to the emotional possibilities that staff have to feel (Hochschild 1983). The point that demonstrates this is the manager gets paid more then a shop assistant because their pay package covers them for the emotional insults, which they may receive from refusing to give a customer a refund. I asked the managers how they dealt with abusive behaviour from customers. Managers gain the experience for dealing with inconvenient customers and they assured me that it gets easier as time goes on. You have to detach what you are feeling from the situation and not let your own anger, or in some extreme cases fear get in the way. (Appendix Initial Training Requirement Chart) This gives a summary of all the training offered to the different roles at Next. As you can see all staff members that are present on the shop floor, for any point of their shift, the number one training session is shop manners. This is not part of the stockroom workers training. (Appendix Sponsors Guidelines- 6.Performance Assessment Standards) This table demonstrates that all staff working on floor cover, fitting room, till service or replenishment are those that could possibly come into contact with customers. It demonstrates that shop floor staff members are assessed on their ability to smile and make eye contact with the customer and to be aware of shoppers. Stockroom staff members, on the other hand, are assessed solely on their physical, rather then any emotional objectives. Are our feelings really our own? From the research obtained in this report it is clear to see that the staff working on the shop floor are shown how to act where as in the stock room its much more natural emotion. Institutional practice shapes the way in which shop floor workers are expected to behave. What makes some individuals prefer to work in the stock room compared to the shop floor? I asked the stockroom workers why they liked to work in the stockroom. I received comments such as. You can be more yourself as you dont have to work in uniform. I think that management enforce a strict smart dress policy on shop floor workers to help them get into the role, which they have to play; it is part of the act. In the stockroom you dont have to interact with customers. Some of the stockroom staff said the horror stories they have heard about customers puts them off working on the shop floor. As customers seem to be oblivious to the feelings of shop floor workers and assume that they are there just to serve them. The stockroom has quite a different atmosphere to the shop floor it is more relaxed, you often get shop floor sales staff coming in for a break from the hustle and bustle of the shop floor. The stockroom workers said that on many occasions sales staff come in and tell them about incidents with customers that have just happened. This helps the member of staff to calm down, as the stockroom member often is able to bring them to reality and point out that it is only a customer and not to get wound up. In the surroundings of the back office the sales floor worker is able to put the situation in context of life and go back to the act moments later. Does personality have something to do with whether you like working in the stockroom or the shop floor? From observation and asking the floor staff it seems to me that the quieter people work in the stock room. When I questioned staff members on why they enjoyed working in the stock room I deduced they dont feel the need to be on the stage acting, to them it is false they would rather be left to their own devices. I asked the floor staff whether they minded working in the stockroom as sometimes staff shortages calls for this. They said they didnt mind but preferred the interaction and liveliness of the shop floor this corresponds with previous research, which shows emotional labourers like contact with the customer. Even though customers can be very unpleasant. (MG2076 starter pack: The Survey). Sales floor staff said they wished they could work in the stockroom on days when they were feeling under the weather as the need to act in the corporate superficial way was much harder because their true emotions were harder to suppress. On days when everything is going well staff said it was a pleasure to help customers that are appreciative of their service but a customer who feels it is their right to be served can bring an end to that. This suggests that workers feelings are not their own and shop assistants surface act from day to day. I would like to investigate status and gender differences to see whether men or women are better equipped at working in either environment. Is emotion work as important for men as it is for women? (Hochschild, 1983 p 162) Hochschild believes it is not. Due to firstly lacking other resources women make a resource out of feeling. Secondly, each gender is called on to do different kinds of work, which Hochschild believes to be down to different childhood training of the heart that is given to girls and boys (Hochschild, 1983 p163). I think this gender separation at work is becoming less apparent as equal rights laws are being enforced and changing attitudes of society. At Next there is equality in the work place with men and women being treated equally with both being given the same responsibility. Thirdly, the general subordination of women leaves them more open to abuse. For example, a customer was being very rude to the floor manager on childrensware due to the fact that she refused to give the man a refund, because the garment had obviously been worn. The customer became very rude and abusive, which he thought would give him some hold over the woman. The female manager was about to give in to the customer when the shop manager, a man, noticed the disturbance and came over to assist his colleague. He refused to give the man a refund. I believe that as a man the shop manager saw the customer as a mere man and stood by the initial reaction of the female manager. The customer more intimidated by the act of the shop manager gave in very quickly and left the shop threatening I will let head office know about this. The manager was not browbeaten by this comment, as he knew the customer didnt have a leg to stand on. This situation also lends itself to the fact that a different proportion of the managed heart is enlisted for commercial use. (Hochschild, 1983 p163-164) Women make defensive use of their beauty, charm and relational skills, which due to commercial exploitation can lead them to become estranged from these capacities. For male workers it is more their ability to wield anger and make threats that is used by the company and so this the capacity which they are likely to feel estranged from. (Hochschild 1983) Conclusion Each environment has an impact on the workers emotions. The sales floor is where surface acting takes place throughout most of the working day. The stockroom is a place where deep acting is given more of a chance to occur due to the fact that the company dont suppose emotions upon its workers here. I think the training offered by Next is appropriate as it is what is institutionally expected by society. It is achievable by staff to act this way, as this is what they are getting paid to do. I think it does affect workers emotions being trained how to act because it must be hard to switch off at the end of the day. Eventually it must become instinctive to act in a socially expected way and it must become harder for staff members to express their true emotions when not at work. Bibliography * Hochschild, A. R. (1983) The Managed Heart; the commercialisation of human feeling California: University of California Press. * Lazarus, R. S. (1994) Emotion and Adaptation New York: Oxford University Press * MG2076s Starter Pack MG 2076 Louise Goldstein
Wednesday, August 21, 2019
Business environment facing lafarge cement of UK
Business environment facing lafarge cement of UK Introduction Lafarge has been a major player in the UK construction sector since entering the British market in 1987 acquiring Redland in 1997 and Blue Circle in 2001. Today, Lafarge is the market-leader in cement and holds top-ranking positions in aggregates, concrete and plasterboard. Lafarge has three sister companies in Britain Lafarge Cement UK, Lafarge Aggregates Concrete UK and Lafarge Plasterboard UK. Lafarge is passionate about customer care and proud of its active approach to sustainability and safety (Lafarge.co.uk 2009). This piece of work will explore the business environment facing Lafarge and establish a few strategic priorities going into the future. A Summary Statement of Findings This summary statement of findings analyses the UK construction industry, which is a major sector in the UK economy. The industry has a high political and social profile due to it key role in providing housing, its impact on the environment and its part as a major employer. It accounts for approximately 10% of the UK GDP and provides for over half its fixed capital investment. The industry experienced rapid growth in the 1980s but a recession in the early 1990s had severe repercussions resulting in its output plummeting, as show is Appendix . However, the volume of work already in progress cushioned the impact. The output of the UK construction industry increased from 55 million in the mid 1980s to an excess of à £110 million by 2007; a remarkable increase in real terms when considering the relative low levels of inflation. However, this increase all changed in 2008 as problems in the US sub-prime mortgage market triggered a catastrophic crash in the US banking sector, which in turn created problems in UK financial markets. This triggered a huge recession in the UK which sent the output of the UK Construction industry to fall 1.1% in 2008. The downside of the economic recession hit construction industry the hardest. This is as this industry runs on credit, more than others, and a credit squeeze affected it badly. Moreover, from the other side customers we re trying to spend as little as possible, squeezing the margins that construction companies were working on. Lafarges performance within the UK business environment during 2008 saw a decline as discussed in Appendix ?. This decline was caused by the recession that hit the UK market in early 2008; the construction sector shrank at its fastest pace since records began. This reduced government and public spending which had a major impact on Lafarge as less government spending meant less money went on the new infrastructure schemes which reduced Lafarge Contracting sales which in turn reduced material sales This had a big effect on Lafarge UK figures as they seen an immense slump in 2008 figures compared to what they were in 2007. A Review and Analysis into the Business Environment of the UK Construction Industry Business environment at Lafarge UK The best method to discover the happenings of a business environment around a company is to undertake a PESTEL analysis. By undertaking a PESTEL analysis it will help one to understand the environment within which Lafarge works better. Looking at the construction industry in general, some of the political issues surrounding them are: Political factors * The UK government is clearly pushing for more affordable housing within the country and this includes both public sector and private sector housing. So it can be said that good or decent housing needs to the people of the country is quite an important political issue. * The Government is involved with housing projects through private finance initiatives and public private partnerships, as these tend to be key aspects of housing projects involving financing, building and operating for these projects. This level of government involvement does mean that it has political implications like selecting projects or choosing partners as well as financial implications. * The UK construction industry is very large in terms of employment, revenue generation and importance to the economy. This high profile nature of the company means the Government usually takes its concerns very seriously and cannot afford to not be empathetic towards the industry. * The constantly spiralling prices of housing within the country points to the need of having affordable housing. Affordable housing schemes means more houses will be built and thus definitely have an impact on all parts of the construction industry including that of Lafarge. * The problem with a high profile industry is that it brings about a lot of regulations with it, thus needs like planning permission and so cause a lot of delay in projects involving a lot of debate and to some extent bureaucracy. Economic Factors à · The construction industry has a more than à £100 bn turnover and this making it one of the largest sectors of the country. This clearly specifies scope for Lafarge, especially as it has the reach and resources to be a big player within the industry. à · The downside of the economic recession has hit construction industry the hardest. This is as this industry runs on credit, more than others, and a credit squeeze affected it badly. Moreover, from the other side customers were trying to spend as little as possible, squeezing the margins that construction companies were working on. Although the economy is recovering but coming out of a long recession, the industry will take time to reach its pre recession levels. à · One of the implications of being part of the construction industrys that the Government is tightening the environmental norms all the time thus it adds to the financial burden of the company as they have to deal with directives, clauses and other pieces of legislation. Social Factors à · There is some skill shortage within the construction industry hence an effort is being made by all companies to hire young, talented people. This can affect Lafarge as they will need to invest time and money into the training of these individuals but as a long-term investment it is good for the company. à · The changes in society have been bringing about a change in the housing needs for people and fast. As more people are living alone, marrying later and old people living longer, distinct changes in housing pattern can be seen. This will increase the need for single occupancy housing thus this needs to be thought of by all constituents of the construction industry. à · With the ever increasing need for sustainable development, housing projects are affecting nearby retail, commercial and public buildings too. This again changes the way the industry functions or will do in the future. Technological Factors à · Regulations regarding buildings continue to add towards bettering energy efficiency and putting demand on other such technological factors in relation to buildings. This again adds to the financial burden of the companies like Lafarge and a major investment in RD results due to this. à · New and improved building materials are also a major research within the industry. The need of the hour is to come up with materials that are sustainable, good for the environment but still functional. Hence work is being carried out to satisfy the next generation of demands. à · Methods that are being used within the industry to build houses are giving rise to new methods of assembly and modulation. New improvements include developing structured insulated panels that provide thermally insulated sheet materials. For further information, Appendix offers a further review and analysis into the business environment of the UK construction industry. Lafarge does operate within the larger construction industry sector; however this section will explore the building materials sector, which is Lafarges core operating territory. This section will look at the environment for that particular sector. Sector overview As hinted in the last section that construction industry is undergoing a lot many changes and the building materials sector is no different. As emerging markets become urbanized and their demand for materials grows, so does the need to align to these markets. Within the more developed economies, environment and sustainability have become major points and as people gain awareness, companies like Lafarge will need to take those demands into consideration. Some of the key strategic directions taken by Lafarge are: Expansion of emerging markets There has been a thorough realignment in favour of emerging economies both in Europe and abroad. Around the world, cement production is growing at 5% each year which means that every year 100 million tones of cement is being consumed. Reports show that 70% of world demand is going to come from these sectors hence Lafarge will need to make itself a leading player in these markets. Lafarges current strategy in this regard is quite good, as it has acquired a lot of Cement companies in every region around the world. In fact including Asia, Africa, Central and Eastern Europe, this region contributes to 37% of its turnover and nearly half of its cement turnover. Lafarge is without doubt moving towards a strategy of more value creation. To elaborate, its programs are creating nearly 50 million tonnes of additional cement capacity by 2012. This is in addition to the aggregates and gypsum business. Reducing costs There are a lot of general costs associated with the manufacture of building products and can be broken down as follows: Energy accounts for 33% of the cost of producing cement, Raw materials (more than 50% of which are cement) represent 75% of the cost of ready-mix concrete Delivery expenses account for approximately 20% of the cost, raw materials (primarily gypsum and paper) represent 40% of the cost of plasterboard, energy, raw materials and labour represent 50% of the cost of producing aggregates. Lafarge will need to reduce all costs associated with material manufacture, especially considering the economic crisis in general. It has already started a program that reduces costs by à ¢Ã¢â¬Å¡Ã ¬200 million by the start of 2010 and over a period of three years, a cost cutting of nearly à ¢Ã¢â¬Å¡Ã ¬400 million. (see appendix ?) This is in addition to the cost cutting exercise over 2006-08 of à ¢Ã¢â¬Å¡Ã ¬400 million. It has also put a cap on expenditure at à ¢Ã¢â¬Å¡Ã ¬ 2 billion for 2009. These new financial initiatives have completely set Lafarge in a new strategic direction. Cost cutting will definitely improving the companys financial health and enable it to operate on better margins. Reducing environmental footprint of Lafarge operations If one looks at the industry in general there is a lot of waste production along with pollution, dust and other harmful ingredients in the atmosphere. Those materials that are waste derived are actively needed by the cement industry. These are used as replacement for fossil fuel and other raw materials. This measure is only taken forward if the materials can be safe to use and are of high technical quality. Along with all of this if the regulatory norms are met then these materials can be used and are a boon for the industry. The entire industry is now using over 1.4 million tonnes of waste this way and a major contributor in helping the UK government to meet its environmental targets. Coming back to Lafarge, it has been trying to reduce CO2 it produces and emits in accordance to the regulations set by governments all around the world. The current strategy of Lafarge is to improving its material making processes including modernizing plants. It also is rapidly propagating the use of alternative fuels for its production. Another important step taken by the company is moving towards sustainable construction. Building or construction of any sort does lead to consumption of huge swathes of energy and nearly 40% of all CO2 can be attributed to it. Lafarge is working hard at making better buildings using better materials and processes. Lafarge is looking at changing the lifecycle of making building products and incorporating using recyclable materials and renewable energy in order to reduce pollution. Evaluating the future impact of the UK business environment on Lafarge Some important themes have emerged from the previous sections of this piece of work that will help one to recommend future strategies to Lafarge. As far as strategic direction goes Lafarge has to align the company in two directions: First, it needs to keep investing in the emerging markets by strategically acquiring cement companies or starting Greenfield projects if needed. Its taking over of Orascom cement clearly shows that organic growth is important for the company and needs to continue in the same vein. (see appendix ?) Second, innovation via investment in RD is crucial for its long-term benefit. As companies and people grow more aware of the issues surrounding the environment, recyclable and sustainable practices, including materials processes, production needs to be incorporated. This will require a lot of effort and investment as well as a new way of thinking. Other than these main priorities the company can look at other strategic priorities for its operations. These include reducing costs further to enhance the value of the company. Lean operations within this sector will it streamline its operations. In addition, Health safety remains a big area to improve on and such activities will definitely strengthen its position in the market. Conclusion This piece of work looked at the construction industry in the UK and Lafarge materials in particular, to understand the way in which its business environment affects its operations. The work conducted a PESTEL analysis to understand the main challenges facing the construction industry in general. It then went on to conduct a sector overview of the building materials industry, where Lafarge truly operates. One also explored the strategic initiatives started by Lafarge. Finally, based on the current and future trends recommendations were made on Lafarges future strategy. REFERENCES: * Accountancy Ireland (2006), February, Vol. 38, No.1 * Anonymous Contract Journal (2006), September, ABI/INFORM Trade Industry Contract Journal, February, Vol. 442, No. 6664 * Druker, J. and White, G. (1995), Misunderstood and undervalued? Personnel management in construction, Human Resource Management Journal, 5:3, pp. 77-91. * Hollinshead, G., Nicholls, P. and Tailby, S. (1999), Employee Relations, Financial Times/Pitman, London. * Lafarge (2009). www.lafarge..co.uk [Online].[Accessed 12th Januray 2010]. * Mineral Products Association(2008). Performance 2008: A sector plan report from the cement industry. * Oxley R., Poskitt J. (1996), Management Techniques Applied to Construction Industry, Blackwell Publishing, Fifth Edition. Identifying and applying suitable business performance measures to Lafarge Lafarge had an average current ratio in 2007 in relation to its market but this decreased in 2008. Lafarges low current ratio indicates that it barely has sufficient assets available to pay its liabilities. There are many things Lafarge could do to raise there current ratio which are increasing its current assets from loans or other borrowings with a maturity of more than one year, convert non-current assets into current assets or putting profits back into the business could help. Lafarges debtor ratio represents a longer then average duration in obtaining payment for its debts owed compared to that of rival company Aggregate Industries Ltd. This indicates a struggle to obtain payment for work completed, or highlights a need to offer costly credit terms to compete with its rivals. Imposing stricter credit controls can help reduce Lafarges debtor days and improve cash flow. Alternatively, creditor ratio suggests Lafarge are paying there creditors to promptly the creditor ratio is below the market average and Lafarge are not taking advantage of the free cash flow the creditors offer. This could cause working capital issues. Lafarges weak working capital results over the past two year indicate they do not have the liquidity to meet outstanding obligations. Lafarges cash outflow is quicker than its cash inflow. However the debt to equity ratio suggests otherwise. Lafarge has no long term debt indicating strong financial strength as they can always take up debt in future to fund potential projects. A strong interest cover over 2007/2008 indicate that Lafarge has enough equity to pay its loan interest and meet its legal obligations. A zero dividend yield indicates that Lafarges shares have not matured over the past two years. Potential share holders may be discouraged by this. Its strong acid test ratio proves that current assets are not dependable on inventory-which shows strong financial integrity. A negative return on capitally employed questions Lafarges performance, although they have a strong equity base they are still making a loss. Its declining trading profit margin solidifies this by suggesting a potential loss of competitive advantage. A healthy year on year performance in return on equity indicates a strong level of profitability, high market valuation and utilization of its invested capital. A steady low dividend figure along with stable profit levels indicate a good record of using its retained earnings to generate future growth and profits. For further information, Appendix offer a complete evaluation, as well as the subsequent results of Lafarges business performance.
Tuesday, August 20, 2019
Disease Caused by Parasite of Genus Trypanosoma
Disease Caused by Parasite of Genus Trypanosoma Human trypanosomiasis caused by Trypanosoma evansi and Trypanosoma lewisi in India : A matter of concern Introduction Disease produced by the parasite of genus Trypanosoma called as trypanosomiasis. It is one of the most important hemoprotozoan diseases, widely distributed in animals and human beings. It is endemic in Africa and America, are deadly pathogens that threaten millions of people in at least 36 countries in Africa. It is estimated that approximately 60 million people are at risk and 3, 00,000 new cases found every year in Africa (WHO Report 1998). Both African and American trypanosomes rank within the top 10 in terms of global impact. Despite the impact of these parasites, how they cause disease is relatively less is understood. In Africa, the disease is commonly known as human African trypanosomiasis (HAT) or sleeping sickness whereas the American trypanosomiasis recognized as Chagas disease. They not only infect vertebrates groups (amphibians, reptiles, birds, fish, and mammals) but also many invertebrates (Crithidia, Leptomonas). Human African trypanosomiasis belongs to genus Trypanoso ma, subgenus trypanozoon. Classification phylum sacromastigophora, order kinetoplastida and the family trypanosomatidae. Genus Trypanosoma includes subgenus which is divided into major group, salivaria and stercoraria that infect vertebrates (Hoare C. A.1964). Trypanozoon (T. brucei ssp, T. evansi, T. equiperdum), Duttonella (T. vivax,T. uniforme), Nannomonas (T. congolense, T. simiae), Pycnomonas (T. suis), Tejeraia (T. rangeli) belongs to salivaria group. Under stercoraria group Herpetosoma (T. lewisi, T. musculi,T. microti), Megatrypanum (T. theileri, T. melophagium), Schizotryponum (T. cruzi, T. dionisii) come. T. brucei. brucei, T. brucei. gambiense and T. brucei. rhodesiense are the subspecies of the Trypanozoon. Sleeping sickness is caused by T. brucei. gambiense, a chronic form of HAT in West and Central Africa lasting from months to years or T. brucei. rhodesiense, an acute form of HAT in East and Southern African with a duration of weeks to months. Whereas, closely relate d parasite T. brucei. brucei is non pathogenic to humans. The American trypanosomiasis is caused by T. cruzi. rhodesiense. These forms of the disease is deadly and develop within weeks to months, the gambiense form takes year. Trypanosomes cause animal trypanosomiasis has a wide geographic distribution. Surra is caused by T. evansi and infects mainly camels, cattle, buffalos, horses, deer and other wild animals. T. b. Brucei causes nagana in tropical Africa and affects only cattle; T. vivax and T. congolense infect domestic and small animals while T.lewisi is a commensally of rats. T. equiperdum causes dourine disease in horse and donkey of India, Europe, America and North Africa. African trypanosomes are transmitted by tsetse flies, a species of Glossina, and South American trypanosomes by reduvid bugs. Normally human are resistant to animal species of Trypanosoma due to the trypanolytic factor of human serum. However, there are several cases of human infection with animal trypanosomes such as Trypanosoma evansi; Trypanosoma lewisi and Trypanosoma congolense have been discussed later in this article. This proves not just a rare cases but the beginning of new era in the history of human trypanosomes, put in dilemma whether they develop potential of new diseases of humans or just a biological accidently transmission. In Asia, first documented evidence found in 1933, human trypanosomiasis in Malaysia, a four month old infant infected with T. lewisi (Johnson P. D, 1933). Later in 1974 K. Shrivastava and colleague reported T. lewisi-like Herpetosoma infection, diagnosed in two adult patients in India during malaria eradication program. All three human Herpetosoma infected patients were recovered without treatment. More recently the cases of a two-month-old infant in the Gambia (Howie, S. et al., 2006) and India (Kaur, R. et al., 2007) infected with T. lewisi-like trypanosome is reported but Gambian case has invasion of central nervous system. One more case in Thailand is reported; Trypanosoma lewisi-like infected 45-day-old male infant was recovered with the treatment of antibiotic gentamicin (Sarataphan, N. et al., 2007). Suspected case, 40 aged female in State of west Bengal of India, infected with trypanosomiasis in January 2005 however T. evansi was concluded by considering only the fact, specie s isolated from these area is T. evansi in cattle, buffaloes, and goats (see Ref. Meeting of the Ad Hoc Group of the World Organization for Animal Health (OIE), Paris 2006). Animal trypanosomiasis Trypanosoma evansi caused to human in India, state of Maharashtra. The patient was 45 year old man and veterinary quack from Seoni village in Taluka Shindevahi of District Chandrapur from Maharashtra State. He was admitted to rural hospital; initially symptoms observed were headache, intermittent fever, disoriented, sensory scarcity, saliva dribble from mouth and violent behaviour. Blood thick smear, stained by Fields stain, examination was done by local microbiologist Mrs. Bharti U Sable; she suspects trypanosome along with plasmodium falciparum (figure 01). He was treated with antimalarial drug along with oral hematenics. She marked as the founder of Indian trypanosome, T. evansi. Later patient was transferred to the Government Medical College and Hospital (GMC) in Nagpur, India. Stained blood smear shows numerous flagellated trypanosomes parasite only, was confirmed morphologically, position of nucleus and small kinetoplast at central and posterior respectively indicate that the contributory mediator was T. evansi (Joshi, PP. et al., 2005). Anoth er unique character of T. evansi has homogenous DNA minicircles (Borst et al., 1987; Songa et al., 1990; Masiga and Gibson, 1990; Lun et al., 1992) and absence of DNA maxicircles in the kinetoplast unlike T. brucei (Borst et al., 1987; Songa et al., 1990). Several methods has been evolvedmicroscopy, card agglutination test (C. Gutierrez et. al., 2000), microhematocrit centrifugation technique (Woo, PTK 1970), enzyme-linked immunosorbent assay (Indrakamhang, P et al.1996), DNA hybridization (Viseshakul, N., Panyim, S., 1990) and polymerase chain reaction (Wuyts, N.et.al. 1994; Wuyts, N.et al.1995; Omawa, S et al 1999) for detection of T. evansi infection. To confirm morphological identification of parasite, additional test of blood, serum and cerebrospinal fluid (CSF) was done in the Department of Microbiology, Government Medical College and Hospital, Nagpur and at the Institut de Recherche pour le Dà ©veloppement in Montpellier, France. Parasitological and serological tests conducted at GMC, Nagpur, are as followed (Joshi, PP. et al., 2005): Biochemical quantitative analysis of serum was performed with less tiny significance on lipid levels, indication of Tangier disease. Tangier disease is a rare autosomal recessive genetic disorder, high density lipoprotein deficiencies associated with this disease include dramatically lowered level of APO A1 (Von Eckardstein, A., et al., 1998), was found to be non trypanolytic (Rifkin, M R. 1978a), however controversial data, fresh sera of a patient with Tangier disease is trypanolytic exhibiting bothTLF-1 and TLF-2 activity, reported (Tomlinson et al., 1995). The demonstration of specific antibodies has been employed by using card agglutination test for trypanosomiasis (CATT) for T. evansi using whole blood and serum was conducted. CATT test initially developed for T. brucei. gambiense (Diall et al., 1994). Sensitivity of CATT for T. evansi in Kenya was 65.5% (Z.K. Njiru et al.2004) and 68.6% (Ngaira et al.2003).False positive result of CATT was reported (Stijn Deborggraeve et al.2008). Mini-anion centrifugation technique is used for purification and concentration of trypanosomes using heparinised blood before and after treatment of suramin A direct latex IgM agglutination test was conducted with CSF to reveal functionless of parasite in the blood brain barrier. Sediment of CSF after centrifugation was examined by bright field microscopy for the presence of trypanosomes. Thomas chamber is used to count lymphocytes in the CSF, presence demonstrate the incursion of parasite. Molecular technique and serological tests conducted at the Institut de Recherche pour le Dà ©veloppement in Montpellier, France, are as followed (Joshi, PP. et al., 2005). Three independent PCR assay were performed using DNA of trypanosome Related to the subgenus Trypanozoon using a seminested PCR method, primer used ITS1/2 based on internal transcribed spacer (ITS) of ribosomal DNA. Related to T.brucei group using a single PCR of the 177- basepair. Amplification of T. evansi was conducted using a 994- basepair mitochondrial kinetoplast minicircle template with the primer TEV 1/2. Reference strains used are T. b.gambiense Bat 6118 and T. evansi CIRDES. PCR provided high specificity and sensitivity molecular biology technique among others for diagnosis of infectious diseases and also permits identification of micro organisms such as mycobacterium (Garcia-Quintanilla, A et al., 2002) , detection and differentiation of Entamoeba histolytica and Entamoeba dispar (Gonin, P et. al.,2003), simultaneous detection of tick-borne hemoprotozoan parasites Babesia caballi and Babesia equi in horse blood (Alhassan, A. et. al., 2005) and detection of influenza A Virus (Nicole L. Z et. al, 2006). In spite of these, PCR are not usual in some countries (Holland et al., 2001). It has been reported about reproducibility problems, for diagnosis of both human and animal trypanosomes, of PCR results (Solano et al., 2002; Malele et al., 2003). Recently a new DNA amplification method, loop-mediated isothermal amplification developed for diagnosis of species and sub-species specific trypanosomes (Thekisoe OM et al., 2007). Disease developed due to absence of trypanolytic factor in normal human serum hence immune status of patient was checked to resolve possible infection with human immunodeficiency virus (HIV). Three tests were conducted to corroborate the results of Enzyme-linked immunosorbent assay (ELISA) in India. HIV 1/2 assay Specific enzyme-linked immunosorbent assay (ELISA) NNO-LIA HIV 1/2 Score test Investigation of parasite Unusual transmission of animal trypanosomiasis, T. evansi to human requires rationalization, for this P. Truc and collaborator, 2007 studied genetic characterization of T. evansi. Generally, genetic variability of T. evansi has been detected by using isoenzyme (Gibson et al., 1983; Stevens et al., 1989), restriction fragment length polymorphism (RFLP) (Songa et al., 1990), microsatellite (Biteau et al., 2000) and random amplified polymorphic DNA (RAPD) analysis (Lun et al., 2004; Ventura et al., 2002); all these above technique found isolated T. evansi were genetically homogenous. Micro heterogeneity reported (Gibson et al., 1983; Stevens et al., 1989), may due to low-resolution techniques and no genetic exchange of T. evansi in vector like others T. brucei ssp, that leads to absence of recombination which play role for micro heterogeneity (Jenni et al.1986). Nevertheless, some genetic variability of isolated T. evansi from Kenya reported through PCR (Ngaira et al.2004, 2005; Njiru e t al.2006) and amplified fragment length polymorphism (AFLP) along with RAPD. Among later, AFLP admittance more polymorphisms, was able to differentiate and separate the Type A T. evansi into two clades (Masiga et al., 2006). Direct comparison of high-resolution molecular techniques microsatellites or simple sequence repeats (SSR) and Inter-simple sequence repeats (ISSR) PCR revealed that latter technique demonstrate greater genetic variability of T evansi isolates from different geographical area (Z.K. Njiru et al 2007). Recently molecular analysis of T. b. brucei by PCR and microsatellite PCR of reported blood slides was successfully conducted (Stijn Deborggraeve et al.2008). Isolated T. evansi has been termed into type A and type B (Masiga and Gibson, 1990). Unlike to type B detected only from Kenya, isolates type A are most copious (Borst et al., 1987). It has been shown however, that most of T. evansi from South America are dyskinetoplastic- lacking both maxicircles and minicir cles (Masiga and Gibson, 1990; Ventura et al., 2000; Schnaufer et al., 2002). Normally T. evansi diagnosed through variant surface glycoprotein (VSG) Rode Trypanozoon antigen type (RoTat) 1.2, a diagnostic antigen. Songa and Hamers, 1988 developed CATT for veterinary use, which based on RoTat 1.2 gene (Songa and Hamers, 1988). Both PCR test and serological-CATT test are highly sensitive and specific in divergent geographical region (Verloo et al., 2000), former test can be trustworthy for detection of isolates of both dyskinetoplastic and DNA minicircles in kinetoplast of T. evansi (Claes et al., 2004) also it based on RoTat 1.2 gene (Urakawa et al., 2001). On the other hand, most of T. evansi from Kenya were not detected by test, which based on VSG of T. evansi RoTat 1.2 gene because few isolates lack both RoTat 1.2 gene and their linked protein-VSG while other isolates having only RoTat 1.2 gene (Ngaira et al. 2004). Characterization of non-RoTat 1.2 T. evansi, specific PCR test developed in these 273 base pair was present in disparity to RoTat 1.2 T. evans i (J.M. Ngaira et al., 2005). Microscopic examination of dissected organs of tsetse flies was done for identification of trypanosome infections (Lloyd and Johnson, 1924). Parasites are, generally indentified in the mouthparts, salivary glands and mid-guts. Trypanosome species from vector is isolated and employed in isoenzyme electrophoresis technique for identifications (Gashumba et al., 1986). Another approach as recombinant DNA probes have been used for the identification both mature and immature trypanosomes in tsetse fly (Gibson et al., 1988; Majiwa et al., 1993).Dot-ELISA is another technique used for detecting trypanosomes in tsetse flies (Bosompem et al., 1996; Ouma, J. O et al., 2000) How T. evansi differs from other Trypanozoon The subgenus Trypanozoon includes three species, namely Trypanosoma brucei, T. evansi and T. equiperdum. T. evansi is judge against, concerning their morphological, mode of transmission, biochemical and molecular characteristics, rest of species. Bloodstream stages of these three parasites are often morphologically indistinguishable (Brun R et al., 1998; Gibson, 2003). T. evansi is mechanically transmitted of infected blood through insects of the genera Tabanus, Stomoxys, Atylotus and Lyperosia. Horseflies (Tabanus spp), Stableflies (Stomoxys spp) are the most capable vectors for the transmission of T. evansi in Indonesia and China (Luckins, 1988; Lun et al., 1993). In Africa, south and Central America, tsetse fly (Glossina spp) and vampire bats Desmodus rotundus an extra host-vector-reservoir of the T. evansi, respectively can mechanically transmitted this parasite. Direct transmissions through milk or during coitus involved T. evansi (Wang, 1988). Besides mechanical and direct tran smission of T. evansi, T. equiperdum transmitted directly during coitus and with rare possibility through bloodsucking insects (see ref. Brun, R et al.,1998). Trypanosoma brucei gambiense, sleeping sickness parasites have been able to spread through tsetse flies of palpalis group (Glossina palpalis, Glossina tachinoides) while T. b. rhodesiense was generally transmitted by tsetse of the morsitans group (Glossina morsitans, Glossina pallidipes). All 31 species of tsetse flies are able to transmit trypanosomes (Aksoy S, et al., 2003). Other major parasites T. congolense, T. vivax and T. simiae that are pathogens of domesticated animals, transmitted by tsetse fly. Both parasites, T. evansi and T. equiperdum are closely related to T. brucei, most likely developed from Trypanosoma brucei by independently deletion of kinetoplast DNA and should be regarded as two subspecies Trypanosoma brucei evansi and Trypanosoma brucei equiperdum respectively (Lai et al., 2008). Absence of maxicircles in kinetoplast DNA explained inexistence of procyclic or insect stage in these parasites and can propagate only as the mammal-infective bloodstream form (Borst et al., 1987).This facilitate to explain wide range of mechanical transmission of T. evansi outside of Africa (Lun and Desser, 1995). Procyclic form (PCF) T.brucei strain cannot survival with a partial or complete loss of kinetoplast DNA as with some Blood stream form (BSF) strains. This kinetoplast DNA deficient T.brucei strains appear naturally or induced by drugs (Schnaufer A et al.2002). Drug inducers are acriflavine, ethidium bromide, methoxy-9-ellipticine, hydroxystilbamidine, berenil, pentamidine, an trycide, and para-rosaniline, grouped as DNA intercalators and non intercalating drugs (Hajduk, 1978). Nevertheless, the existence of T. equiperdum has been complexity; Claes et al. suggested that, in fact, some strains of Trypanosoma equiperdum are actually Trypanosoma brucei and all other remaining misidentified strains such as Swiss Tropical Institute Basel (STIB) 818 are Trypanosoma evansi. However, based on PCR amplification of the fragment of DNA maxicircles in the kinetoplast, T. equiperdum Onderstepoort Veterinary Institute (OVI) and Bordeaux Trypanosoma antigen type (BoTat) 1.1 strains are T. brucei and other STIB 818, STIB 841 and STIB 842 T. equiperdum strains are not cluster together with T. evansi as it maintains maxicircles and allied genes. (Li et al., 2006). Both parasites have homogeneous minicircles. Although in all T. evansi strains maxicircles are totally lost but T. equiperdum shows more assortment, some strains seems to bear complete maxicircles with no active essential gene; others are missing one of the genes; and a few devoid the entire maxicircles (Lai et al., 2008). Unlike other DNA, T. brucei mitochondrial DNA termed kinetoplast DNA include a network of interlocked DNA rings (Liu, B. et al. 2005). This network of T. brucei ssp. comprised of several thousands of heterogeneous minicircles and several dozen of homogeneous maxicircles (Borst and Hoeijmakers, 1979). T. evansi has largely homogenous and limited heterogeneous minicircles in kinetoplast DNA (Borst et al., 1987). Results (Joshi, PP. et al., 2005; P. Truc et al., 2007) A careful examination of morphological characteristic demonstrates the presence of T. evansi. Patient had normal level of APO A-1 indicate no sign of Tangier disease. The result of CATT for T. evansi was positive suspect stalwartly presence of RoTat 1.2 gene. Latex IgM test, a diagnostic for trypanosome invasion in CSF, and lymphocytes count in the CSF indicated no invasion of parasite. An attempt to isolate and propagate trypanosome in wistar rat was failed. For molecular diagnosis of T. evansi PCR conducted, test was positive. Results of ELISAs for HIV, conducted in France and India were negative. Genetic characterization, Indian patient has homogenous DNA minicircles in kinetoplast of T. evansi of type A and devoid of SRA gene. Treatment Treatment was started 109 days after initial admission to hospital using suramin. Suramin is manufactured by Bayer and donated to WHO as Germanin, used against sleeping sickness in 1922 (Voogd et al., 1993). Suramin was used as a first stage of treatment for HAT caused by Trypanosoma brucei gambiense (chronic form) or T. b. rhodesiense (acute form). Efficacy of suramin against T. evansi infection was studied in cattle by Gill BS, Malhotra MN, 1963. It was requested and provided by Department of Public Health, Government of Maharashtra State, India and World Health Organisation respectively. As patient falls under first stage of infection, drugs have to be used pentamidine or suramin sodium. Pentamidine has more adverse effect than suramin, according to author; hence suramin was used in this patient. Drug suramin acts by interfering with enzyme of glycolytic pathway (Wierenga RK, et.al., 1987) in trypanosomes and produce hot spot, function as a signal for import into glycosome. It is preferred to give slow intravenous injection as suramin is poorly absorbed from intestine and causes intense local irritation when given intramuscularly (Voogd TE, et.al., 1993). Suramin does not cross the blood-brain barrier to kill trypanosome in the CSF however able to cure model of stage 2 diseases at a high dose greater than 80 mg per kg (Jennings FW, et.al., 1995). Follow-up study was commenced after the end of treatment and at 3rd and 6th months, all previous tests-CATT for T. evansi, latex IgM agglutination test, Mini anion-exchange centrifugation technique and examination of CSF by bright field microscopy are repeated at GMC Nagpur excepts biochemical analysis of serum for Tangier disease (P. P. Joshi et al. 2006). Tests result indicates first patient of human trypanosomiasis infected with T. evansi was recovered, Joshi and collaborators concluded that same schedule would follow in treatment if more cases observed. Suramin Suramin is less active against procyclic form of trypanosomes than bloodstream form, former normally reside in the tsetse flies (Scott AG, et.al., 1996). Suramin inhibit number of glycolytic enzyme which is essential to bloodstream form rather than procyclic form (Fairlamb AH, et.al., 1977, Fairlamb AH, et.al., 1980). Hanau and colleagues proposed other likely target of drug, competitive inhibitor of an enzyme 6-phosphogluconate dehydrogenase of pentose phosphate pathway (Hanau S, et.al., 1996). Suramin is an effective microfilaricide for Onchocerca spp. and Brugia pahangi worms (Hawking, et al., 1981; Howells, et al., 1983). It is a known ATP/UTP purine receptor (P2 receptor) antagonist (V. Ralevic and G. Burnstock, 1998). Nevertheless suramin inhibit ample varieties of enzymes like reverse transcriptase, dihydrofolate reductase, furamse, glycerol-3-phosphate dehydrogenase, hexokinase, L-a-glycerophosphate oxidase, receptor mediated uptake of low density lipoprotein, RNA polymerase and kinases, thymidine kinase, trypsin (Pà ´epin and Milord, 1994; Wang, 1995). Besides its trypanocidal activity, suramin is also useful in hormone-refractory prostate cancer, however survival rate was not affected (Small et al., 2000; Ahles et al., 2004). Suramins antitumor activity has been attributed to its inhibition of various growth factors which include platelet-derived growth factor, fibroblast growth factor, transforming growth factors alpha and beta, insulin- like growth factors 1(Stein CA,1993). Osteosarcoma is the malignant tumor of the bone; suramin exerts an inhibitory effect on osteosarcoma cell growth of established cell lines (Benini et al., 1999), newly established osteosarcoma cell lines and stimulation of osteosarcoma cells by physiological compounds, such as 1, 25-dihydroxy-Vitamin D3 (K. Trieb, H. Blahovec, 2002). Furthermore, results in an inhibiting capacity of suramin on various cell functions include production of alkaline-phosphatase or telomerase activi ty (K. Trieb, H. Blahovec, 2002). Suramin blocked CD154 (Emilio Margolles-Clark et al., 2009) from interacting with its receptor CD40 (U. Schà ¶nbeck and P. Libby, 2001; I.S. Grewal and R.A. Flavell, 1998), costimulatory interactions are therapeutically important to modulate immune responses (C.P. Larsen et al., 2006; F. Vincenti and M. Luggen, 2007). Suramin inhibited the binding of TNF-a to its receptor TNF-R1 (F. Mancini et al., 1999) and its ability to inhibit CD40-CD154 interaction was 30 fold more active compared to it (Emilio Margolles-Clark et al., 2009). Suramin has also been shown to suppress T cell activity (C. Schiller et al., 1994), antiproliferative effects on lymphoid cells (Z. Spigelman et al., 1987). Suramin can causes toxicities which include adrenal and renal insufficiency, coagulation factor abnormalities and poly-neuropathy (T.E. Voogd et al., 1993; D.J. Cole et al., 1994), at relatively high concentration inhibited the binding of IL2 to its cell surface recept or (G.B. Mills et al.,1990), greater than therapeutic use (S.A. Grossman et al., 2001; S.T. Eichhorst et al., 2004). It concentration-dependently inhibited proteolytic and phospholipase A2 (PLA2) activities of Bothrops jararacussu venom- potential to be used as antivenom, suramin also antagonise the cardiotoxic effect of Bothrops jararacussu venom in rats heart (Daniel N. Sifuentes et al., 2008). Uptake of suramin by bloodstream form of trypanosome is through receptor mediated endocytosis which is most likely route of entry (Fairlamb AH, et al., 1980). Suramin intensively bound to plasma proteins such as low density lipoproteins, albumins, globulins, fibrinogen, etc. According to Bastin et al. 1996, Coppens and Courtoy 2000 and Green et.al 2003 suggested that suramin might enter while bound to low density lipoprotein (LDL), it has high affinity to bind many serum proteins including LDL (Vansterkenburg ELM, et al., 1993). The high rate of fluid-phase endocytosis occurs in the trypanosomes of bloodstream form (Engstler, et al., 2004). This mechanism could be involved in the uptake of suramin into T. brucei that does not require specialized receptors. Trypanosomes cannot synthesise their own fatty acid and cholesterol de novo hence LDL uptake is essential for propagation (Coppens I, et al., 2000). It does not make any worse however in procyclic form, uptake of suramin is through receptor mediated endocytosis and not coupled with LDL uptake (Pal A, et al., 2002). Suramin involves inhibition of various glycolytic enzymes, effects rates of respiration as aerobic glycolysis is closely related with it in bloodstream forms (Fairlamb AH, et al., 1980, Opperdoes, F.R. et al., 1989). Diminished growth rate of trypanosome in vivo is a consequence of decrease in respiration (Fairlamb AH, et al., 1980). Suramin is also used as veterinary trypanocide; report on resistance in T. evansi that infects animals is reported (El Rayah et al., 1999, Zhou, J.L. et al., 2004). Some cases have been described of drug resistance when suramin is used against Trypanosoma brucei rhodesiense in humans (Wà ´ery, M., 1994). Suramin reduced sensitivity towards T. b. rhodesiense (Bacchi et al., 1990) and failure of treatment up to 25-30% observed (Pà ´epin and Milord, 1994, Burri, C et al., 2004). Failures of treatment are common due to misdiagnosed late stage infection (Burri et al., 2004). De Koning argued one of the reasons of suramin resistance is associated with reduction in drug uptake; molecule is large and highly charged which plasma membrane transporter takes up. Role of apolipoprotein L-1 and haptoglobin-related protein T. evansi affects mainly domesticated animals such as camels, cattle and water buffalo, spread by mechanical transmission of infected blood through insect such as tabanid flies. Due to these, it spread apart from sub-Saharan Africa to South America, North America and Asia. Normally humans are resistant to animal trypanosomes, immunity against T.brucei brucei is due to trypanolytic activity of an apolipoprotein L-1 (APOL-1) bound to high density lipoprotein (HDL) (Vanhamme L. et al., 2003). Previously it was concluded that trypanolytic activity in normal human serum was due to immunoglobin M (Aaronovitch, S. Terry, R. J. 1972). Later in 1973, Hawking and colleagues resolute there were two trypanolyic factors. These two factors differ in their activity (in vivo and vitro), molecular mass, quantity in serum and sensitivity to antagonists (Hawking et al., 1973b). HDL was identified as trypanolyic factor by Rifkin in 1978, she also characterised the two trypanolyic factors determined by Hawking (Rifkin, M. R. 1978b). Trypanolyic factors in human serum shows inhomogeneous properties (Tomlinson et al., 1995; Raper et al., 1996b). Both TLF are a subset of HDLs commonly referred to as HDL3 (Lorenz et al., 1995), contain haptoglobin-related protein (Hpr) (Smith et al., 1995) and APOL-1 (Vanhamme, L. et al., 2003).TLF-1 is a 500 kDa lipid rich while TLF-2,1000 kDa protein complex containing IgM, lipid poor HDL particle (Raper, J. et al., 1999; Lugli, E.B. et al., 2004). Apolipop rotein A-1 (APOA-1) is a component of TLF-1(Smith et al., 1995) and, although previously reported that APOA-1 could not detected in TLF-2(Tomlinson, S. et al., 1995), is a component of TLF-2 (Raper, J. et al., 1999). Previously unknown proteins, human cathelicidin antimicrobial peptide (hCAP18), glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) and paraoxonase are associated with TLF-1(Smith AB et al., 1995; Lugil E et al., 2004). APOA-1 suggests a role in trypanolysis later controversial report supporting a lytic role (Gillett, M. Owen, J. 1992a) or not favor lytic role (Rifkin, 1991; Seed et al., 1993). Later it was confirmed that APOA-1 was not toxic (Tytler, 1995) but may indirectly play role of trypanolytic (Owen et al., 1996). For trypanosomes, HDLs contain 16,000-65,000 binding site per cell having moderate affinity (Gillett, M. Owen, J. 1992b). However, binding of lytic factor, TLF-1 appeared to involve two binding site, low affinity have 65,000 and high affinity 350 binding sites (Drain et al., 2001). Host macromolecules, interact with bloodstream trypanosomes, transferrin (Borst, P.1991) and low-density lipoprotein (LDL) (Coppens, I et al., 1987) through receptor-mediated endocytosis occur at the flagellar pocket of trypanosome (Gull, K., 2003). APOL-1 is a bacterial colicins and Bcl-2 family members like protein containing pore forming domain as well as a region for the membrane insertion of it (Pà ©rez -Morga D et al., 2005, Pays E et al., 2006). APOL-1 is taken up in the parasite by endocytosis, able to kill by the parasite by forming anion selective pores in the lysosomal membrane of parasite, this pore allows the influx of chloride ions into the lysosome, subsequent cell death as a consequence of entry of water and induces uncontrolled osmotic swelling of vacuole ((Pà ©rez-Morga D et al., 2005; Pays E et al., 2006; B. Vanhollebeke et al., 2007a). APOL-1 could not be involved in apoptosis but in programmed cell death (B. Vanhollebeke et al., 2006a). Resistance of T.brucei rhodesiense and T.brucei gambiense to APOL-1 is developed which allows these parasites to infect and cause HAT. Single protein termed serum resistance-associated protein (SRA) is main reason of resistance of T.brucei rhodesiense to APOL-1.SRAP interacts strongly with APOL-1 and provide specific resistance to T.brucei rhodesiense (Xong HV et al., 1998; Gibson WC, 2005). T brucei gambiense is also resistant to APOL-1; mechanism is not understood (Pays E et al., 2006). Indian case with T. evansi infection, human serum devoid of APOL-1, reason for the absence was due to independent frameshift mutation in both APOL-1 alleles (B. Vanhollebeke et al., 2006b). Another HDL component, plays a toxic role for full trypanolytic activity of normal human serum, haptoglobin-related protein (Hpr).Indian case has normal concentration of Hpr bound HDL but short of trypanolytic activity. Hpr is a haemoglobin (Hb) binding protein induces, within acidic lysosome of T.b.brucei, Fenton like reaction between H202 and iron that lead to formation of free hydroxyl radicals, which would prompt the reaction of lipid peroxidation of lysosomal membrane (Smith AB et al., 1995; Hager KM et al., 1994; Bishop JR et al., 2001; Justin Widener et al., 2007). Nevertheless action of trypanolysis of Hpr and APOL-1, biological function is not clear. Optimal trypanolytic activity requires presence of both APOL-1 and Hpr on same subset of HDL particle (B. Vanhollebeke et al., 2007b). Vanhollebeke et al. (2007b) reported trypanosome survival assay in normal as well as mutant human sera. Survival of trypanosomes occurs in human serum devoid of APOL-1 and fetal calf serum (FCS). FCS is nonlytic and contains neither APOL-1 nor Hpr. Human serum deficient of Hpr and haptoglobin (Hp) but with normal HDL b Disease Caused by Parasite of Genus Trypanosoma Disease Caused by Parasite of Genus Trypanosoma Human trypanosomiasis caused by Trypanosoma evansi and Trypanosoma lewisi in India : A matter of concern Introduction Disease produced by the parasite of genus Trypanosoma called as trypanosomiasis. It is one of the most important hemoprotozoan diseases, widely distributed in animals and human beings. It is endemic in Africa and America, are deadly pathogens that threaten millions of people in at least 36 countries in Africa. It is estimated that approximately 60 million people are at risk and 3, 00,000 new cases found every year in Africa (WHO Report 1998). Both African and American trypanosomes rank within the top 10 in terms of global impact. Despite the impact of these parasites, how they cause disease is relatively less is understood. In Africa, the disease is commonly known as human African trypanosomiasis (HAT) or sleeping sickness whereas the American trypanosomiasis recognized as Chagas disease. They not only infect vertebrates groups (amphibians, reptiles, birds, fish, and mammals) but also many invertebrates (Crithidia, Leptomonas). Human African trypanosomiasis belongs to genus Trypanoso ma, subgenus trypanozoon. Classification phylum sacromastigophora, order kinetoplastida and the family trypanosomatidae. Genus Trypanosoma includes subgenus which is divided into major group, salivaria and stercoraria that infect vertebrates (Hoare C. A.1964). Trypanozoon (T. brucei ssp, T. evansi, T. equiperdum), Duttonella (T. vivax,T. uniforme), Nannomonas (T. congolense, T. simiae), Pycnomonas (T. suis), Tejeraia (T. rangeli) belongs to salivaria group. Under stercoraria group Herpetosoma (T. lewisi, T. musculi,T. microti), Megatrypanum (T. theileri, T. melophagium), Schizotryponum (T. cruzi, T. dionisii) come. T. brucei. brucei, T. brucei. gambiense and T. brucei. rhodesiense are the subspecies of the Trypanozoon. Sleeping sickness is caused by T. brucei. gambiense, a chronic form of HAT in West and Central Africa lasting from months to years or T. brucei. rhodesiense, an acute form of HAT in East and Southern African with a duration of weeks to months. Whereas, closely relate d parasite T. brucei. brucei is non pathogenic to humans. The American trypanosomiasis is caused by T. cruzi. rhodesiense. These forms of the disease is deadly and develop within weeks to months, the gambiense form takes year. Trypanosomes cause animal trypanosomiasis has a wide geographic distribution. Surra is caused by T. evansi and infects mainly camels, cattle, buffalos, horses, deer and other wild animals. T. b. Brucei causes nagana in tropical Africa and affects only cattle; T. vivax and T. congolense infect domestic and small animals while T.lewisi is a commensally of rats. T. equiperdum causes dourine disease in horse and donkey of India, Europe, America and North Africa. African trypanosomes are transmitted by tsetse flies, a species of Glossina, and South American trypanosomes by reduvid bugs. Normally human are resistant to animal species of Trypanosoma due to the trypanolytic factor of human serum. However, there are several cases of human infection with animal trypanosomes such as Trypanosoma evansi; Trypanosoma lewisi and Trypanosoma congolense have been discussed later in this article. This proves not just a rare cases but the beginning of new era in the history of human trypanosomes, put in dilemma whether they develop potential of new diseases of humans or just a biological accidently transmission. In Asia, first documented evidence found in 1933, human trypanosomiasis in Malaysia, a four month old infant infected with T. lewisi (Johnson P. D, 1933). Later in 1974 K. Shrivastava and colleague reported T. lewisi-like Herpetosoma infection, diagnosed in two adult patients in India during malaria eradication program. All three human Herpetosoma infected patients were recovered without treatment. More recently the cases of a two-month-old infant in the Gambia (Howie, S. et al., 2006) and India (Kaur, R. et al., 2007) infected with T. lewisi-like trypanosome is reported but Gambian case has invasion of central nervous system. One more case in Thailand is reported; Trypanosoma lewisi-like infected 45-day-old male infant was recovered with the treatment of antibiotic gentamicin (Sarataphan, N. et al., 2007). Suspected case, 40 aged female in State of west Bengal of India, infected with trypanosomiasis in January 2005 however T. evansi was concluded by considering only the fact, specie s isolated from these area is T. evansi in cattle, buffaloes, and goats (see Ref. Meeting of the Ad Hoc Group of the World Organization for Animal Health (OIE), Paris 2006). Animal trypanosomiasis Trypanosoma evansi caused to human in India, state of Maharashtra. The patient was 45 year old man and veterinary quack from Seoni village in Taluka Shindevahi of District Chandrapur from Maharashtra State. He was admitted to rural hospital; initially symptoms observed were headache, intermittent fever, disoriented, sensory scarcity, saliva dribble from mouth and violent behaviour. Blood thick smear, stained by Fields stain, examination was done by local microbiologist Mrs. Bharti U Sable; she suspects trypanosome along with plasmodium falciparum (figure 01). He was treated with antimalarial drug along with oral hematenics. She marked as the founder of Indian trypanosome, T. evansi. Later patient was transferred to the Government Medical College and Hospital (GMC) in Nagpur, India. Stained blood smear shows numerous flagellated trypanosomes parasite only, was confirmed morphologically, position of nucleus and small kinetoplast at central and posterior respectively indicate that the contributory mediator was T. evansi (Joshi, PP. et al., 2005). Anoth er unique character of T. evansi has homogenous DNA minicircles (Borst et al., 1987; Songa et al., 1990; Masiga and Gibson, 1990; Lun et al., 1992) and absence of DNA maxicircles in the kinetoplast unlike T. brucei (Borst et al., 1987; Songa et al., 1990). Several methods has been evolvedmicroscopy, card agglutination test (C. Gutierrez et. al., 2000), microhematocrit centrifugation technique (Woo, PTK 1970), enzyme-linked immunosorbent assay (Indrakamhang, P et al.1996), DNA hybridization (Viseshakul, N., Panyim, S., 1990) and polymerase chain reaction (Wuyts, N.et.al. 1994; Wuyts, N.et al.1995; Omawa, S et al 1999) for detection of T. evansi infection. To confirm morphological identification of parasite, additional test of blood, serum and cerebrospinal fluid (CSF) was done in the Department of Microbiology, Government Medical College and Hospital, Nagpur and at the Institut de Recherche pour le Dà ©veloppement in Montpellier, France. Parasitological and serological tests conducted at GMC, Nagpur, are as followed (Joshi, PP. et al., 2005): Biochemical quantitative analysis of serum was performed with less tiny significance on lipid levels, indication of Tangier disease. Tangier disease is a rare autosomal recessive genetic disorder, high density lipoprotein deficiencies associated with this disease include dramatically lowered level of APO A1 (Von Eckardstein, A., et al., 1998), was found to be non trypanolytic (Rifkin, M R. 1978a), however controversial data, fresh sera of a patient with Tangier disease is trypanolytic exhibiting bothTLF-1 and TLF-2 activity, reported (Tomlinson et al., 1995). The demonstration of specific antibodies has been employed by using card agglutination test for trypanosomiasis (CATT) for T. evansi using whole blood and serum was conducted. CATT test initially developed for T. brucei. gambiense (Diall et al., 1994). Sensitivity of CATT for T. evansi in Kenya was 65.5% (Z.K. Njiru et al.2004) and 68.6% (Ngaira et al.2003).False positive result of CATT was reported (Stijn Deborggraeve et al.2008). Mini-anion centrifugation technique is used for purification and concentration of trypanosomes using heparinised blood before and after treatment of suramin A direct latex IgM agglutination test was conducted with CSF to reveal functionless of parasite in the blood brain barrier. Sediment of CSF after centrifugation was examined by bright field microscopy for the presence of trypanosomes. Thomas chamber is used to count lymphocytes in the CSF, presence demonstrate the incursion of parasite. Molecular technique and serological tests conducted at the Institut de Recherche pour le Dà ©veloppement in Montpellier, France, are as followed (Joshi, PP. et al., 2005). Three independent PCR assay were performed using DNA of trypanosome Related to the subgenus Trypanozoon using a seminested PCR method, primer used ITS1/2 based on internal transcribed spacer (ITS) of ribosomal DNA. Related to T.brucei group using a single PCR of the 177- basepair. Amplification of T. evansi was conducted using a 994- basepair mitochondrial kinetoplast minicircle template with the primer TEV 1/2. Reference strains used are T. b.gambiense Bat 6118 and T. evansi CIRDES. PCR provided high specificity and sensitivity molecular biology technique among others for diagnosis of infectious diseases and also permits identification of micro organisms such as mycobacterium (Garcia-Quintanilla, A et al., 2002) , detection and differentiation of Entamoeba histolytica and Entamoeba dispar (Gonin, P et. al.,2003), simultaneous detection of tick-borne hemoprotozoan parasites Babesia caballi and Babesia equi in horse blood (Alhassan, A. et. al., 2005) and detection of influenza A Virus (Nicole L. Z et. al, 2006). In spite of these, PCR are not usual in some countries (Holland et al., 2001). It has been reported about reproducibility problems, for diagnosis of both human and animal trypanosomes, of PCR results (Solano et al., 2002; Malele et al., 2003). Recently a new DNA amplification method, loop-mediated isothermal amplification developed for diagnosis of species and sub-species specific trypanosomes (Thekisoe OM et al., 2007). Disease developed due to absence of trypanolytic factor in normal human serum hence immune status of patient was checked to resolve possible infection with human immunodeficiency virus (HIV). Three tests were conducted to corroborate the results of Enzyme-linked immunosorbent assay (ELISA) in India. HIV 1/2 assay Specific enzyme-linked immunosorbent assay (ELISA) NNO-LIA HIV 1/2 Score test Investigation of parasite Unusual transmission of animal trypanosomiasis, T. evansi to human requires rationalization, for this P. Truc and collaborator, 2007 studied genetic characterization of T. evansi. Generally, genetic variability of T. evansi has been detected by using isoenzyme (Gibson et al., 1983; Stevens et al., 1989), restriction fragment length polymorphism (RFLP) (Songa et al., 1990), microsatellite (Biteau et al., 2000) and random amplified polymorphic DNA (RAPD) analysis (Lun et al., 2004; Ventura et al., 2002); all these above technique found isolated T. evansi were genetically homogenous. Micro heterogeneity reported (Gibson et al., 1983; Stevens et al., 1989), may due to low-resolution techniques and no genetic exchange of T. evansi in vector like others T. brucei ssp, that leads to absence of recombination which play role for micro heterogeneity (Jenni et al.1986). Nevertheless, some genetic variability of isolated T. evansi from Kenya reported through PCR (Ngaira et al.2004, 2005; Njiru e t al.2006) and amplified fragment length polymorphism (AFLP) along with RAPD. Among later, AFLP admittance more polymorphisms, was able to differentiate and separate the Type A T. evansi into two clades (Masiga et al., 2006). Direct comparison of high-resolution molecular techniques microsatellites or simple sequence repeats (SSR) and Inter-simple sequence repeats (ISSR) PCR revealed that latter technique demonstrate greater genetic variability of T evansi isolates from different geographical area (Z.K. Njiru et al 2007). Recently molecular analysis of T. b. brucei by PCR and microsatellite PCR of reported blood slides was successfully conducted (Stijn Deborggraeve et al.2008). Isolated T. evansi has been termed into type A and type B (Masiga and Gibson, 1990). Unlike to type B detected only from Kenya, isolates type A are most copious (Borst et al., 1987). It has been shown however, that most of T. evansi from South America are dyskinetoplastic- lacking both maxicircles and minicir cles (Masiga and Gibson, 1990; Ventura et al., 2000; Schnaufer et al., 2002). Normally T. evansi diagnosed through variant surface glycoprotein (VSG) Rode Trypanozoon antigen type (RoTat) 1.2, a diagnostic antigen. Songa and Hamers, 1988 developed CATT for veterinary use, which based on RoTat 1.2 gene (Songa and Hamers, 1988). Both PCR test and serological-CATT test are highly sensitive and specific in divergent geographical region (Verloo et al., 2000), former test can be trustworthy for detection of isolates of both dyskinetoplastic and DNA minicircles in kinetoplast of T. evansi (Claes et al., 2004) also it based on RoTat 1.2 gene (Urakawa et al., 2001). On the other hand, most of T. evansi from Kenya were not detected by test, which based on VSG of T. evansi RoTat 1.2 gene because few isolates lack both RoTat 1.2 gene and their linked protein-VSG while other isolates having only RoTat 1.2 gene (Ngaira et al. 2004). Characterization of non-RoTat 1.2 T. evansi, specific PCR test developed in these 273 base pair was present in disparity to RoTat 1.2 T. evans i (J.M. Ngaira et al., 2005). Microscopic examination of dissected organs of tsetse flies was done for identification of trypanosome infections (Lloyd and Johnson, 1924). Parasites are, generally indentified in the mouthparts, salivary glands and mid-guts. Trypanosome species from vector is isolated and employed in isoenzyme electrophoresis technique for identifications (Gashumba et al., 1986). Another approach as recombinant DNA probes have been used for the identification both mature and immature trypanosomes in tsetse fly (Gibson et al., 1988; Majiwa et al., 1993).Dot-ELISA is another technique used for detecting trypanosomes in tsetse flies (Bosompem et al., 1996; Ouma, J. O et al., 2000) How T. evansi differs from other Trypanozoon The subgenus Trypanozoon includes three species, namely Trypanosoma brucei, T. evansi and T. equiperdum. T. evansi is judge against, concerning their morphological, mode of transmission, biochemical and molecular characteristics, rest of species. Bloodstream stages of these three parasites are often morphologically indistinguishable (Brun R et al., 1998; Gibson, 2003). T. evansi is mechanically transmitted of infected blood through insects of the genera Tabanus, Stomoxys, Atylotus and Lyperosia. Horseflies (Tabanus spp), Stableflies (Stomoxys spp) are the most capable vectors for the transmission of T. evansi in Indonesia and China (Luckins, 1988; Lun et al., 1993). In Africa, south and Central America, tsetse fly (Glossina spp) and vampire bats Desmodus rotundus an extra host-vector-reservoir of the T. evansi, respectively can mechanically transmitted this parasite. Direct transmissions through milk or during coitus involved T. evansi (Wang, 1988). Besides mechanical and direct tran smission of T. evansi, T. equiperdum transmitted directly during coitus and with rare possibility through bloodsucking insects (see ref. Brun, R et al.,1998). Trypanosoma brucei gambiense, sleeping sickness parasites have been able to spread through tsetse flies of palpalis group (Glossina palpalis, Glossina tachinoides) while T. b. rhodesiense was generally transmitted by tsetse of the morsitans group (Glossina morsitans, Glossina pallidipes). All 31 species of tsetse flies are able to transmit trypanosomes (Aksoy S, et al., 2003). Other major parasites T. congolense, T. vivax and T. simiae that are pathogens of domesticated animals, transmitted by tsetse fly. Both parasites, T. evansi and T. equiperdum are closely related to T. brucei, most likely developed from Trypanosoma brucei by independently deletion of kinetoplast DNA and should be regarded as two subspecies Trypanosoma brucei evansi and Trypanosoma brucei equiperdum respectively (Lai et al., 2008). Absence of maxicircles in kinetoplast DNA explained inexistence of procyclic or insect stage in these parasites and can propagate only as the mammal-infective bloodstream form (Borst et al., 1987).This facilitate to explain wide range of mechanical transmission of T. evansi outside of Africa (Lun and Desser, 1995). Procyclic form (PCF) T.brucei strain cannot survival with a partial or complete loss of kinetoplast DNA as with some Blood stream form (BSF) strains. This kinetoplast DNA deficient T.brucei strains appear naturally or induced by drugs (Schnaufer A et al.2002). Drug inducers are acriflavine, ethidium bromide, methoxy-9-ellipticine, hydroxystilbamidine, berenil, pentamidine, an trycide, and para-rosaniline, grouped as DNA intercalators and non intercalating drugs (Hajduk, 1978). Nevertheless, the existence of T. equiperdum has been complexity; Claes et al. suggested that, in fact, some strains of Trypanosoma equiperdum are actually Trypanosoma brucei and all other remaining misidentified strains such as Swiss Tropical Institute Basel (STIB) 818 are Trypanosoma evansi. However, based on PCR amplification of the fragment of DNA maxicircles in the kinetoplast, T. equiperdum Onderstepoort Veterinary Institute (OVI) and Bordeaux Trypanosoma antigen type (BoTat) 1.1 strains are T. brucei and other STIB 818, STIB 841 and STIB 842 T. equiperdum strains are not cluster together with T. evansi as it maintains maxicircles and allied genes. (Li et al., 2006). Both parasites have homogeneous minicircles. Although in all T. evansi strains maxicircles are totally lost but T. equiperdum shows more assortment, some strains seems to bear complete maxicircles with no active essential gene; others are missing one of the genes; and a few devoid the entire maxicircles (Lai et al., 2008). Unlike other DNA, T. brucei mitochondrial DNA termed kinetoplast DNA include a network of interlocked DNA rings (Liu, B. et al. 2005). This network of T. brucei ssp. comprised of several thousands of heterogeneous minicircles and several dozen of homogeneous maxicircles (Borst and Hoeijmakers, 1979). T. evansi has largely homogenous and limited heterogeneous minicircles in kinetoplast DNA (Borst et al., 1987). Results (Joshi, PP. et al., 2005; P. Truc et al., 2007) A careful examination of morphological characteristic demonstrates the presence of T. evansi. Patient had normal level of APO A-1 indicate no sign of Tangier disease. The result of CATT for T. evansi was positive suspect stalwartly presence of RoTat 1.2 gene. Latex IgM test, a diagnostic for trypanosome invasion in CSF, and lymphocytes count in the CSF indicated no invasion of parasite. An attempt to isolate and propagate trypanosome in wistar rat was failed. For molecular diagnosis of T. evansi PCR conducted, test was positive. Results of ELISAs for HIV, conducted in France and India were negative. Genetic characterization, Indian patient has homogenous DNA minicircles in kinetoplast of T. evansi of type A and devoid of SRA gene. Treatment Treatment was started 109 days after initial admission to hospital using suramin. Suramin is manufactured by Bayer and donated to WHO as Germanin, used against sleeping sickness in 1922 (Voogd et al., 1993). Suramin was used as a first stage of treatment for HAT caused by Trypanosoma brucei gambiense (chronic form) or T. b. rhodesiense (acute form). Efficacy of suramin against T. evansi infection was studied in cattle by Gill BS, Malhotra MN, 1963. It was requested and provided by Department of Public Health, Government of Maharashtra State, India and World Health Organisation respectively. As patient falls under first stage of infection, drugs have to be used pentamidine or suramin sodium. Pentamidine has more adverse effect than suramin, according to author; hence suramin was used in this patient. Drug suramin acts by interfering with enzyme of glycolytic pathway (Wierenga RK, et.al., 1987) in trypanosomes and produce hot spot, function as a signal for import into glycosome. It is preferred to give slow intravenous injection as suramin is poorly absorbed from intestine and causes intense local irritation when given intramuscularly (Voogd TE, et.al., 1993). Suramin does not cross the blood-brain barrier to kill trypanosome in the CSF however able to cure model of stage 2 diseases at a high dose greater than 80 mg per kg (Jennings FW, et.al., 1995). Follow-up study was commenced after the end of treatment and at 3rd and 6th months, all previous tests-CATT for T. evansi, latex IgM agglutination test, Mini anion-exchange centrifugation technique and examination of CSF by bright field microscopy are repeated at GMC Nagpur excepts biochemical analysis of serum for Tangier disease (P. P. Joshi et al. 2006). Tests result indicates first patient of human trypanosomiasis infected with T. evansi was recovered, Joshi and collaborators concluded that same schedule would follow in treatment if more cases observed. Suramin Suramin is less active against procyclic form of trypanosomes than bloodstream form, former normally reside in the tsetse flies (Scott AG, et.al., 1996). Suramin inhibit number of glycolytic enzyme which is essential to bloodstream form rather than procyclic form (Fairlamb AH, et.al., 1977, Fairlamb AH, et.al., 1980). Hanau and colleagues proposed other likely target of drug, competitive inhibitor of an enzyme 6-phosphogluconate dehydrogenase of pentose phosphate pathway (Hanau S, et.al., 1996). Suramin is an effective microfilaricide for Onchocerca spp. and Brugia pahangi worms (Hawking, et al., 1981; Howells, et al., 1983). It is a known ATP/UTP purine receptor (P2 receptor) antagonist (V. Ralevic and G. Burnstock, 1998). Nevertheless suramin inhibit ample varieties of enzymes like reverse transcriptase, dihydrofolate reductase, furamse, glycerol-3-phosphate dehydrogenase, hexokinase, L-a-glycerophosphate oxidase, receptor mediated uptake of low density lipoprotein, RNA polymerase and kinases, thymidine kinase, trypsin (Pà ´epin and Milord, 1994; Wang, 1995). Besides its trypanocidal activity, suramin is also useful in hormone-refractory prostate cancer, however survival rate was not affected (Small et al., 2000; Ahles et al., 2004). Suramins antitumor activity has been attributed to its inhibition of various growth factors which include platelet-derived growth factor, fibroblast growth factor, transforming growth factors alpha and beta, insulin- like growth factors 1(Stein CA,1993). Osteosarcoma is the malignant tumor of the bone; suramin exerts an inhibitory effect on osteosarcoma cell growth of established cell lines (Benini et al., 1999), newly established osteosarcoma cell lines and stimulation of osteosarcoma cells by physiological compounds, such as 1, 25-dihydroxy-Vitamin D3 (K. Trieb, H. Blahovec, 2002). Furthermore, results in an inhibiting capacity of suramin on various cell functions include production of alkaline-phosphatase or telomerase activi ty (K. Trieb, H. Blahovec, 2002). Suramin blocked CD154 (Emilio Margolles-Clark et al., 2009) from interacting with its receptor CD40 (U. Schà ¶nbeck and P. Libby, 2001; I.S. Grewal and R.A. Flavell, 1998), costimulatory interactions are therapeutically important to modulate immune responses (C.P. Larsen et al., 2006; F. Vincenti and M. Luggen, 2007). Suramin inhibited the binding of TNF-a to its receptor TNF-R1 (F. Mancini et al., 1999) and its ability to inhibit CD40-CD154 interaction was 30 fold more active compared to it (Emilio Margolles-Clark et al., 2009). Suramin has also been shown to suppress T cell activity (C. Schiller et al., 1994), antiproliferative effects on lymphoid cells (Z. Spigelman et al., 1987). Suramin can causes toxicities which include adrenal and renal insufficiency, coagulation factor abnormalities and poly-neuropathy (T.E. Voogd et al., 1993; D.J. Cole et al., 1994), at relatively high concentration inhibited the binding of IL2 to its cell surface recept or (G.B. Mills et al.,1990), greater than therapeutic use (S.A. Grossman et al., 2001; S.T. Eichhorst et al., 2004). It concentration-dependently inhibited proteolytic and phospholipase A2 (PLA2) activities of Bothrops jararacussu venom- potential to be used as antivenom, suramin also antagonise the cardiotoxic effect of Bothrops jararacussu venom in rats heart (Daniel N. Sifuentes et al., 2008). Uptake of suramin by bloodstream form of trypanosome is through receptor mediated endocytosis which is most likely route of entry (Fairlamb AH, et al., 1980). Suramin intensively bound to plasma proteins such as low density lipoproteins, albumins, globulins, fibrinogen, etc. According to Bastin et al. 1996, Coppens and Courtoy 2000 and Green et.al 2003 suggested that suramin might enter while bound to low density lipoprotein (LDL), it has high affinity to bind many serum proteins including LDL (Vansterkenburg ELM, et al., 1993). The high rate of fluid-phase endocytosis occurs in the trypanosomes of bloodstream form (Engstler, et al., 2004). This mechanism could be involved in the uptake of suramin into T. brucei that does not require specialized receptors. Trypanosomes cannot synthesise their own fatty acid and cholesterol de novo hence LDL uptake is essential for propagation (Coppens I, et al., 2000). It does not make any worse however in procyclic form, uptake of suramin is through receptor mediated endocytosis and not coupled with LDL uptake (Pal A, et al., 2002). Suramin involves inhibition of various glycolytic enzymes, effects rates of respiration as aerobic glycolysis is closely related with it in bloodstream forms (Fairlamb AH, et al., 1980, Opperdoes, F.R. et al., 1989). Diminished growth rate of trypanosome in vivo is a consequence of decrease in respiration (Fairlamb AH, et al., 1980). Suramin is also used as veterinary trypanocide; report on resistance in T. evansi that infects animals is reported (El Rayah et al., 1999, Zhou, J.L. et al., 2004). Some cases have been described of drug resistance when suramin is used against Trypanosoma brucei rhodesiense in humans (Wà ´ery, M., 1994). Suramin reduced sensitivity towards T. b. rhodesiense (Bacchi et al., 1990) and failure of treatment up to 25-30% observed (Pà ´epin and Milord, 1994, Burri, C et al., 2004). Failures of treatment are common due to misdiagnosed late stage infection (Burri et al., 2004). De Koning argued one of the reasons of suramin resistance is associated with reduction in drug uptake; molecule is large and highly charged which plasma membrane transporter takes up. Role of apolipoprotein L-1 and haptoglobin-related protein T. evansi affects mainly domesticated animals such as camels, cattle and water buffalo, spread by mechanical transmission of infected blood through insect such as tabanid flies. Due to these, it spread apart from sub-Saharan Africa to South America, North America and Asia. Normally humans are resistant to animal trypanosomes, immunity against T.brucei brucei is due to trypanolytic activity of an apolipoprotein L-1 (APOL-1) bound to high density lipoprotein (HDL) (Vanhamme L. et al., 2003). Previously it was concluded that trypanolytic activity in normal human serum was due to immunoglobin M (Aaronovitch, S. Terry, R. J. 1972). Later in 1973, Hawking and colleagues resolute there were two trypanolyic factors. These two factors differ in their activity (in vivo and vitro), molecular mass, quantity in serum and sensitivity to antagonists (Hawking et al., 1973b). HDL was identified as trypanolyic factor by Rifkin in 1978, she also characterised the two trypanolyic factors determined by Hawking (Rifkin, M. R. 1978b). Trypanolyic factors in human serum shows inhomogeneous properties (Tomlinson et al., 1995; Raper et al., 1996b). Both TLF are a subset of HDLs commonly referred to as HDL3 (Lorenz et al., 1995), contain haptoglobin-related protein (Hpr) (Smith et al., 1995) and APOL-1 (Vanhamme, L. et al., 2003).TLF-1 is a 500 kDa lipid rich while TLF-2,1000 kDa protein complex containing IgM, lipid poor HDL particle (Raper, J. et al., 1999; Lugli, E.B. et al., 2004). Apolipop rotein A-1 (APOA-1) is a component of TLF-1(Smith et al., 1995) and, although previously reported that APOA-1 could not detected in TLF-2(Tomlinson, S. et al., 1995), is a component of TLF-2 (Raper, J. et al., 1999). Previously unknown proteins, human cathelicidin antimicrobial peptide (hCAP18), glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) and paraoxonase are associated with TLF-1(Smith AB et al., 1995; Lugil E et al., 2004). APOA-1 suggests a role in trypanolysis later controversial report supporting a lytic role (Gillett, M. Owen, J. 1992a) or not favor lytic role (Rifkin, 1991; Seed et al., 1993). Later it was confirmed that APOA-1 was not toxic (Tytler, 1995) but may indirectly play role of trypanolytic (Owen et al., 1996). For trypanosomes, HDLs contain 16,000-65,000 binding site per cell having moderate affinity (Gillett, M. Owen, J. 1992b). However, binding of lytic factor, TLF-1 appeared to involve two binding site, low affinity have 65,000 and high affinity 350 binding sites (Drain et al., 2001). Host macromolecules, interact with bloodstream trypanosomes, transferrin (Borst, P.1991) and low-density lipoprotein (LDL) (Coppens, I et al., 1987) through receptor-mediated endocytosis occur at the flagellar pocket of trypanosome (Gull, K., 2003). APOL-1 is a bacterial colicins and Bcl-2 family members like protein containing pore forming domain as well as a region for the membrane insertion of it (Pà ©rez -Morga D et al., 2005, Pays E et al., 2006). APOL-1 is taken up in the parasite by endocytosis, able to kill by the parasite by forming anion selective pores in the lysosomal membrane of parasite, this pore allows the influx of chloride ions into the lysosome, subsequent cell death as a consequence of entry of water and induces uncontrolled osmotic swelling of vacuole ((Pà ©rez-Morga D et al., 2005; Pays E et al., 2006; B. Vanhollebeke et al., 2007a). APOL-1 could not be involved in apoptosis but in programmed cell death (B. Vanhollebeke et al., 2006a). Resistance of T.brucei rhodesiense and T.brucei gambiense to APOL-1 is developed which allows these parasites to infect and cause HAT. Single protein termed serum resistance-associated protein (SRA) is main reason of resistance of T.brucei rhodesiense to APOL-1.SRAP interacts strongly with APOL-1 and provide specific resistance to T.brucei rhodesiense (Xong HV et al., 1998; Gibson WC, 2005). T brucei gambiense is also resistant to APOL-1; mechanism is not understood (Pays E et al., 2006). Indian case with T. evansi infection, human serum devoid of APOL-1, reason for the absence was due to independent frameshift mutation in both APOL-1 alleles (B. Vanhollebeke et al., 2006b). Another HDL component, plays a toxic role for full trypanolytic activity of normal human serum, haptoglobin-related protein (Hpr).Indian case has normal concentration of Hpr bound HDL but short of trypanolytic activity. Hpr is a haemoglobin (Hb) binding protein induces, within acidic lysosome of T.b.brucei, Fenton like reaction between H202 and iron that lead to formation of free hydroxyl radicals, which would prompt the reaction of lipid peroxidation of lysosomal membrane (Smith AB et al., 1995; Hager KM et al., 1994; Bishop JR et al., 2001; Justin Widener et al., 2007). Nevertheless action of trypanolysis of Hpr and APOL-1, biological function is not clear. Optimal trypanolytic activity requires presence of both APOL-1 and Hpr on same subset of HDL particle (B. Vanhollebeke et al., 2007b). Vanhollebeke et al. (2007b) reported trypanosome survival assay in normal as well as mutant human sera. Survival of trypanosomes occurs in human serum devoid of APOL-1 and fetal calf serum (FCS). FCS is nonlytic and contains neither APOL-1 nor Hpr. Human serum deficient of Hpr and haptoglobin (Hp) but with normal HDL b
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