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 (P ´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 (W ´ery, M., 1994). Suramin reduced sensitivity towards T. b. rhodesiense (Bacchi et al., 1990) and failure of treatment up to 25-30% observed (P ´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 (P ´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 (W ´ery, M., 1994). Suramin reduced sensitivity towards T. b. rhodesiense (Bacchi et al., 1990) and failure of treatment up to 25-30% observed (P ´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

Psychological Perspectives of Understanding Essay

Introduction This booklet will introduce you to the main psychological perspectives to the understanding of a child’s behaviour development. Each perspective will be described in as much detail as possible, and the theorist that are linked to them. The main perspectives are; * Psychodynamic * Freud * Behaviourist * Skinner * Cognitive * Piget * Humanist * Rogers, Maslow, Cooley and mead * Social learning The psychodynamic perspective This perspective is very much based on the early work of Sigmund Freud. It is believed that behaviour is made from a child’s subconscious feelings, which all come from life experiences. It is viewed as a child’s problem as an outward and visible symptom of invisible conflicts. All the conflicts may come from trauma, loss, or from a strained/troubled relationship with parents or carers. Children do not have any inner resources that help them understand their feelings completely so they may be shown in inappropriate and difficult behaviour. Sigmund Freud said that â€Å"when a child’s too painful or too difficult feelings are left untalked about, they leak out in difficult and challenging behaviour or in neurotic symptoms.† The source of a painful feeling is buried under a defensive mechanism that is very hard to find in a child; because of this most children do not understand why they are behaving this way. A psychodynamic assessments are always carried out by psychiatrist as they use techniques that are designed to provide an insight into their past. To do this they use the response of the child to make inferences about sub-conscious motives for behaviour. Once they have understood the child’s behaviour the psychologists will start an intervention which will help the child express their feelings instead of it coming through their behaviour. These can be done through the following;  * Build a supportive relationship with a significant adult * Help the child to talk about what they are feeling in an secure environment * Express painful feeling through drama, storytelling, play or cartoons The behaviourist perspective This perspective is based from the work Skinner. It was said â€Å"Law of Effect† is the behaviour that leads to strengthened behaviour which is ignored or unsatisfying which is all weakened. Behaviourists claim that all behaviour of children are learned and can be changed by systems, such as rewards or punishment. There are two types of rewards behaviourists use, these are informal and formal. * Informal – acknowledgement or praise * Formal – clear targets for example stickers, tokens or points which all then lead to bigger rewards. The behaviourists also claimed that the behaviour requires a scientific approach which is completely based on objectivity and experimentation. The methods they were use were considered to be unscientific, so instead it was all placed on observations on their behaviour rather than a searches for the cause of the behaviour through the child’s past. Behavioural assessments in schools involve observation and recording of a child’s behaviour. When they are observing it is all taken down on an observation checklist, which includes the following titles; * Antecedent * Behaviour * Consequences All this is then used to form a baseline for a post-intervention can be assessed. The Cognitive perspective This perspective shows how a child’s develops understanding what is around them. This refers to different mental activities such as; * Listening * Speaking * Learning * Understanding All the theories of cognitive development concentrate on developments of  their intellectual skills. All the skills that we have are the ones that have been learnt through cognitive development. If none of the children have cognitive skills then they wouldn’t be able to put past experiences or plan future events, cognitive development is very much concerned with how the mental processes work and develop. There were two psychologists who studied cognitive development, there name was Jean Piaget and Lev Vygotsky. Jean Piaget was a psychologist who looked at a child’s developing their reasoning skills. Piaget carried out detailed observations of them and as his work started taking shape on how our understanding a child’s intellectual skills and as a result of this he has made changes in education. Piaget understood that cognitive developments occurred in stages, his research concentrated on how children learn and start to gain an understanding of their stage of development to be able to learn new concepts. He identified a four-stage process of cognitive development all the way through childhood. He stated that every child would go through each stage but not at the same time, but he also said that some children would sometimes never reach the later stages. The four stages are; * Sensorimotor stage (0-2 years) * Children at very young ages start to learn by their own activity and movement. Everything babies touch or see they put into their mouths or hold them tight and they examine them closely. A child develops an understanding through something called schema. Schema is a mental construction which contains all the information a child has about a particular aspect of the world. * Pre-operational stage (2-7 years) * At this stage children start to show evidence of thinking but it’s not logical thinking, they are not able to perform mental operations. Children will start to use symbolic behaviour such as pretend play, language and drawings. * Concrete operations stage (7-11 years) * At this stage children are able to understand any ideas in a much more logical way but they sometimes still find it hard to understand concepts. * Formal operational stage (age 12 to adult) * At this stage children are able to think in a way which is more abstract and logical way, they can use reasoning skills; they are applying a general principle to a particular situation. Children are more flexible in the way they think. There are two people who have been highly interested in cognitive styles of therapy. Aaron Beck and Albert Ellis, Aaron Beck has used methods of cognitive behavioural therapy to treat many people who have or are suicidal, depressed or may have personality disorders. Whereas Albert Ellis looked at the different ways to change their behaviour my using methods of Rational Emotive Behavioural Therapy, he used this to show his patients that their feelings were results of different habits by conditioning rather than being realistic. Therapists that use this approach use training and role-play techniques to modify their behaviour. The humanist perspective This perspective makes positive aspects of development and growth, this emphasises a person’s unique experiences to a personal thoughts. There are four psychologists that are specialised in this perspective, these four are; * Carl Rogers * Rogers developed the concept on self-esteem. According to him everyone has an idea of what someone’s ideal self should be. He believed that if your image of your self is the same as your ideal self then you have good self-esteem. Rogers said that the development of self-esteem all depends on positive regard from others, the effect of a child’s self-esteem will come from their parents’ unconditional love and affection. Children will start to cope with different situations as they get older, for example a sense of achievement or failure in either sports or their educational skills. Rogers also considered cultural factors, gender and physical attributes to come to his conclusion. * Abraham Maslow * Maslow’s theory is based on individuals that are being motivated through seeking to develop through five levels of need. The most basic needs are physiological which are survival instinct, which is then followed by safety needs, belonging and loving needs, self-esteem needs and at the very top is personals achievements and growth. * Cooley * Cooley proposed â€Å"looking glass† theory, which means that the behaviour from children to others acts like a looking glass which gives us a reflection of ourselves. It raises people’s self-esteem. * Mead * Mead had the view that everyone has two aspects â€Å"I† and â€Å"me†. This means that â€Å"I† is the social responses of individual and â€Å"me† being the responses and attitudes of others. It was important of the communication with others for the development of self-esteem. The Social learning perspective Social psychology looks at aspects of development such as behaviour such as being in a group, leadership, non-verbal behaviour and aggression. The social perspective looks at the environment, interactions with others that have influenced the child’s behaviour and attitudes. Bandura theory emphasises on the environment and the social steps of learning. His view is that it would be part of a child’s self development, is what they have observed and imitated from people around them.

How Has 4-h Impacted Your Life for a College Essay Samples at a Glance

How Has 4-h Impacted Your Life for a College Essay Samples at a Glance Details of How Has 4-h Impacted Your Life for a College Essay Samples My principal role is to answer people's questions and assist them with technological difficulties. Any recognition from a preceding employer is the sort of proof an upcoming employer is interested in. Our whole life is the procedure of learning and gaining new useful understanding. With an expertly trained group of consumer representatives and an on-line catalog of our very best products, Crown Awards is the ideal source for excellent teacher appreciation awards. Scholarship sponsors start looking for applicants with vision and motivation, so they may ask about your targets and aspirations. If you visit the trouble of offering awards, recognize them for the huge deal they are for your employee recipients. You may also have taken formal training. Finding How Has 4-h Impacted Your Life for a College Essay Samples on the Web There are a few work interview questions you simply know you should prepare for. College gives me an opportunity to test out what I would like to do. To start with, school is a difficult matter to concentrate on. These gorgeous company teacher appreciation awards are the ideal method to recognize your employees they can cherish for a lifetime! There are amazing qualities in my personal character and the following are just a few of the numerous. To put it simply, an academic essay may be an evidence of the depth of your research procedures and the rest of the activities which you have executed so you can support the content of your written output. The bulk of the study's youth planned to leave the rural region to find employment. 4-H has produced a significant impact on my life. A Secret Weapon for How Has 4-h Impacted Your Life for a College Essay Samples The call to action is made urgent with the debut of time certain incentives. While in high school there are lots of goals that I need to set for myself. The perfect ending is extremely memorable. When it's too long make the vital cuts. How Has 4-h Impacted Your Life for a College Essay Samples If you would like excellent paper essay examples, reach out to us here today and we'll do our very best to offer you the most suitable support. The motive of your essay is crucial to be regarded as as it can identify whether you may be of help to the individuals who want a distinct educational reference. When you're finished writing, you will need to make sure your essay still adheres to the prompt. You should find the correct resources for your essay and patience when finding the most suitable inspiration to write. The rules for writing a superb essay are not any different. Generally speaking, employing the debut of the essay to paint a scene or mood can be quite powerful. Stephen's essay is rather effective. Richard's essay wouldn't be appropriate in all situations. To assist you write from an audience perspective, identify either an actual person or the sort of person who is probably to be listening to you. If that is your very first speech, take all of the time you will need. The point of a descriptive essay is to describe an individual, place or anything in vivid detail so the reader can create a photo in mind of what's being written. The fundamental speech format is straightforward. 5StarEssays academic writing professionals are prepared to aid you. For college applications, you can want to have a 10-step course on college application essay writing to find out more. Remember that all scholarship applications are different, and that means you might need to design your essay to ful fill those particular requirements. Your academic essay should evoke an emotion that is needed to spark different ideas, opinions and other types of responses. Learning how to compose a speech is straight forward once you learn how to write out loud. Observing the tips, you will locate a sample award letter. Start brainstorming now, and you might find yourself a winner! Begin the essay in an easy to comprehend way and language.

Why to People Commit Crimes Essay - 927 Words

People commit crimes for various reasons. These various reasons got to do with social, economic, and cultural reason. These factors trigger an individual to do criminal activities. Social reasons are peer pressure, and school failure. Economic reasons are poverty. Cultural reasons are hatred. The combination of these factors is behind a person who commits crimes. To start with, people commit crime because of social reasons. The social reasons are poor parenting skills, peer influence, drugs, and education failure. Poor parenting skills includes when children are neglected or abused. Also when there are parents who have a permissive or a neglecting style of parenting. Permissive style is when they have no control over their children†¦show more content†¦Alcohol and drugs can trigger you to do stupid things that you will later regret in life or make you do things that you never wanted to do. People can learn from previous experience. Education is a big part of committing crimes. Education is important because it will let you know the right from wrong in life. Lack of school gives an anti-social development. Also, when don’t have any education it’s going to be hard for you to find a job that would pay you good or to find a job that you like. Its helps people overcome any situation. These social reasons trigger people to commit crime. In addition to social reasons there are also economic reasons for people to commit crime. Some of these reasons are poverty and lack of job. There are people who have a large family to maintain but do not have enough money to do so. There are some people who cannot find jobs. This will drive a person to steal. People don’t have to do illegal things in order to maintain their family people can try to get government benefits. If people cannot afford their kids what they want can drive their kids to go and steal what they want. Lack of jobs can get people to get aggressive. It also makes people to take the wrong direction. There are people that do drug trafficking or do illegal jobs for someone else such has kidnapping, committing murder, and etc. People that commit these crimes end up in prison. But even though they do go there theyShow MoreRelatedWhy People Commit The Crime Essay1538 Words   |  7 Pagescriminal justice process. Criminological theory is important be cause most of what is done in criminal justice is based on criminological theory, whether we or the people who propose and implement policies based on the theory know it or not. In criminology, examining why people commit the crime is very important in the ongoing debate on how crime should be handled or committed. Several criminological theories that best describe the cause for juvenile delinquency is social disorganization, strain, socialRead MoreWhy People Commit Crimes1403 Words   |  6 Pagesperson has it own opinion. Crime is the human conduct in violation of the criminal laws of a state, the federal government, or a local jurisdiction that has the power to make such laws, according with Schmalleger. The criminal behavior is the antisocial acts that a person commits for different reasons. This means that the person violated laws constantly for a long or short time period. There are many reasons why criminals commit crimes. Some of the criminals commit crimes for necessity, o thers forRead MoreWhy People Commit Crimes?1255 Words   |  6 PagesWhy People Commit Crimes Author: admin Monday, 22 Sep 2014 It is known that people commit crimes for various reasons, such as social factors, economic and cultural reasons. All these factors have negative impact on the individuals and trigger them to be involved in criminal activities. For example, social factors are focused on the role of society in the life of an individual. The reasons of many crimes are concluded in peer pressure, school failure, prejudices and stereotyping, etc. Economic reasonsRead MoreWhy People Commit Crime?1417 Words   |  6 PagesThroughout History, there have been many speculations as to why people commit crime. Criminologists, Psychologists, Sociologists and even Biologists have all, at one time or another claimed to have an explanation. However, there is one underlying explanation that has been maintained across centuries, presented by various theorists, and to this day, is widely perceived as truthful. That is the explanation that a certain propensity to commit crime exists within the lower classes of society that does notRead MoreWhy People Commit The Crimes2635 Words   |  11 Pages Introduction There are many different theories out there of why people commit the crimes they do. In fact there are several theories that are apart of the different aspects of those theories. For hundreds of years people have been trying to figure out what causes people to engage in deviant behavior. It has been a field that has changed the way it has looked at why criminals commit the crimes that they do. The theory that I am going to be covering in this paper is that of the Strain TheoryRead MoreWhy People Commit Crime? Essay1621 Words   |  7 Pageswhen offenders desist, or stop, committing crime. Desistance from crime exists when an individual has an absence of criminal behavior in their lives for a sustained period of time. By studying desistance, there is a better understanding of what causes individuals to commit crime; as well as, a better understanding as to why certain individuals discontinue their lives of crime. The criminal justice field often encompasses, serving justice by locking people up and keeping the â€Å"bad guys† away from theRead MoreWhy People Commit Crimes?933 Words   |  4 PagesCrime has been around for as long as humans have had law. 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Identify and explore 3 theories of crime and evaluate their key strengths and weaknesses Discuss the role of rehabilitation in the justice system (using three theories of crime to back up) The Oxford Dictionary defines a crime as an action or omission, which constitutes an offence and is punishable by law . Criminological studies look into why individuals commit crime and why they behave the way they do in certain situations. By understanding this, one is able to