Disease Caused by Parasite of Genus Trypanosoma
Disclaimer: This dissertation has been submitted by a student. This is not an example of the work written by our professional dissertation writers. You can view samples of our professional work here.
Any opinions, findings, conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of UK Essays.
Human trypanosomiasis caused by Trypanosoma evansi and Trypanosoma lewisi in India : A matter of concern
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 Trypanosoma, 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 related 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, species 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). Another 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 evolved--microscopy, 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 Développement 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 Développement 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 et 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 minicircles (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. evansi (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 transmission 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, antrycide, 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 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 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). Suramin's 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 activity (K. Trieb, H. Blahovec, 2002). Suramin blocked CD154 (Emilio Margolles-Clark et al., 2009) from interacting with its receptor CD40 (U. Schönbeck 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 receptor (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 rat's 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). Apolipoprotein 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 (Pérez -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 ((Pérez-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 bound APOL-1 promotes lysis of trypanosomes. Improvement of trypanolytic activity in both FCS and human serum devoid of APOL-1 after supplement of recombinant APOL-1 however no trypanolytic activity was restored in FCS after addition of recombinant Hpr or Hp. Human serum devoid of Hpr and Hp give evidence of delayed trypanolytic process also Hpr prevent binding of trypanosome lytic factor to trypanosome at 4oc, signifying that Hpr act as ligand to mediate the binding process of trypanosome lytic factor to a specific Hp/Hpr surface receptor of parasite. Drain and colleagues (2001) reached to these conclusions previously. It was proposed that APOL-1 and Hpr acts synergistically as a trypanolytic (Shiflett AM et al., 2005), however, this view was debated (Pays E et at., 2006). Vanhollebeke, et al. (2007) data also contradict this issue.
Man is protected from T. b. brucei because of the balance ratio between haptoglobin related protein and haptoglobin (Smith AB, Hajduk SL, 1995). Hp, an acute phase response protein whose level increase in mice after 3 days of infection with T.brucei (Pluschke et al., 1986) and during systemic tissue injury (Stadnyk AW; Gauldie, J., 1991).On the other hand there is a decrease of haptoglobin in hemolytic anemia patients (Nosslin, B. F. and Nyman, M.1958). Smith and collaborators reported that level of trypanolytic activity increased in hemolytic anemia patient while haptoglobin level decreased as compared with healthy patient (Smith AB, Hajduk SL, 1995). An excess Hp was able to inhibit most of the trypanolytic activity of normal human serum (Smith AB, Hajduk SL, 1995; Raper J, Nussenzweig V, Tomlinson S, 1996b).Serum particles TLF-1 and TLF-2 are present at a similar concentration (Raper et al., 2001), also contain some common protein. Both would differ on the natural inhibitor properties of normal constituent of human serum, Hp. Hp targeted TLF-1, but not on TLF-2, at lesser concentration than present in normal human serum (Tomlinson et al., 1995; Raper et al., 1996a, b, 1999; Barker et al., 2001), hence TLF-2 would be a lytic factor (Raper et al., 2001). Analogous result of inhibiting of trypanolytic activity was obtained from excess recombinant Hpr (Vanhollebeke B et al., 2007b).It is tempting to speculate that both Hp and Hpr would interfere with TLF activity only when they are in surplus.
Hpr is 91% similar to Hp, having very high affinity for Hb (Nielsen MJ et al., 2006). CD163 scavenger receptor removes complexes of Hp and Hb from the circulation during intravascular hemolysis (Kristiansen M et al., 2001). However Hpr-Hb complex does not response to CD163 scavenger receptor (Nielsen MJ et al., 2006; 2007) and remain unaffected by hemolysis (Kristiansen M et al., 2001; Nielsen MJ et al., 2007) Scavenger receptor for lipoproteins could be involved in trypanosome lytic factor uptake (Green HP et al., 2003). Presence of Hpr, allows trypanolytic particles to bind to trypanosomes at specific surface receptor of parasite, in trypanolytic particle. It has been suggested that optimal uptake of TLF requires combination of both scavenger and specific receptor.
Serological screening of local population (Shegokar, et al., 2006)
After evolution of new zoonotic disease of T. evansi, 1806 local persons were screened serologically. Card agglutination test for trypanosomiasis (T. evansi) is a serological screening test that consists of stained reagent along with variable antigen types of trypanosomes. Variant surface glycoprotein (VSG) - Rode Trypanozoon antigen type (RoTat) 1.2 used. On a card, a drop of heparinised whole blood mixed with a drop of reagent. If blood is infected, trypanosomes in reagent will agglutinate in presence of specific antibodies. If test was positive for whole blood, test for serum dilution of 1:2, 1:4, 1:8, 1:16, and 1:32 conducted.
Animal trypanosomiasis Trypanosoma evansi caused to human in India, state of west Bengal. (See Ref. Meeting of the Ad Hoc Group of the World Organization for Animal Health (OIE), Paris 2006).
Second suspected human case of T. evansi was reported in January 2005. Blood smear examination of 40 year old woman was done in rural laboratory; foresee trypanosomes. It was further confirmed by School of Tropical Medicine, Kolkata (West Bengal state) and Institute of Post Graduate Medical Research and Training, Kolkata, India. She died after two days admission to hospital. Only Trypanosoma species, which observed in cattle of this area, is T. evansi. This help to conclude that isolated species from patient was T. evansi. CATT having Ro Tat 1.2- antigen of T. evansi measured further Trypanosma antibodies level in blood of general population of different areas of West Bengal, results in different distribution of positive antibody (Ankita sarkar et.al., 2008)
- World Health Organization, 1998. Control and surveillance of African trypanosomiasis. World Health Organ Tech Rep Ser 881.
- Hoare CA. Morphologic and taxonomic studies on mammalian trypanosomes. X. Revision of the systematics. J Protozool 1964; 11:200-207
- Johnson PD. A case of infection by Trypanosoma lewisi in a child. Trans R Soc Trop Med Hyg 1933; 26: 467-468
- Shrivastava KK, Shrivastava GP. Two cases of Trypanosoma (Herpetosoma) species infection of man in India. Trans R Soc Trop Med Hyg 1974; 68: 143-144.
- Hawking F. The resistance of Trypanosoma congolense, T.vivax and T. evansi to human plasma.Trans R Soc Trop Med Hyg 1978; 72: 405-407.
- Truc P, Jamonneau V, N'Guessan P, N'Dri L, Diallo PB, Cuny G.Trypanosoma brucei spp. and Trypanosoma congolense: mixed human infection in Côte d'Ivoire. Trans R Soc Trop Med Hyg 1998; 92: 537-538.
- Howie, S. et al. (2006) A Gambian infant with fever and an unexpected blood film. PLoS Med. 3 (e355), 1508-1512
- Kaur, R. et al. (2007) A rare case of trypanosomiasis in a two month old infant in Mumbai. India. J. Commun. Dis. 39, 71-74
- Nachai Sarataphan, Montakan Vongpakorn, Bandit Nuansrichay, Nonglux Autarkool, Tiemjan Keowkarnkah, Pranee Rodtian, Roger W. Stich and Sathaporn Jittapalapong. Diagnosis of a Trypanosoma lewisi-like (Herpetosoma) infection in a sick infant fromThailand. J. Med. Microbiol.2007; 56:1118-1121
- Joshi PP, Shegokar V, Powar S, Herder S, Katti R, Salkar S, Dani V, Bhargava A, Jannin J, Truc P. Human trypanosomiasis caused by Trypanosoma evansi in India: the first case report. Am. J. Trop.Med. Hyg 2005; 73: 491-495
- Tomlinson S, Jansen AM, Koudinov A, Ghiso JA, Choi-Miura NH, Rifkin MR, Ohtaki S, Nussenzweig V. High-density- lipoprotein-independent killing of Trypanosoma brucei by human serum. Mol Biochem Parasitol 1995; 70:131-138.
- Gill BS, Malhotra MN. Prophylactic activity of suramin complexes in surra (Trypanosoma evansi). Nature 1963; 200: 285-286.
- Wierenga RK, Swinkels B, Michels PA, Osinga K, Misset O, Van Beeumen J et al. (1987). Common elements on the surface of glycolytic enzymes from Trypanosoma brucei may serve as topogenic signals for import into glycosomes. EMBO J 6: 215-221.
- Voogd TE, Vansterkenburg ELM, Wilting J, Janssen LHM. Recent research on the biological activity of suramin. Pharmacol Rev.1993; 45: 177-203.
- Jennings FW (1995). Suramin treatment of experimental Trypanosoma brucei infection of the central nervous system. Trans R Soc Trop Med Hyg 89: 677.
- Scott AG, Tait A, Turner CMR (1996). Characterisation of cloned lines of Trypanosoma brucei expressing stable resistance to MelCy and suramin. Acta Tropica 60: 251-262.
- Fairlamb AH, Bowman IBR (1977). Trypanosoma brucei - suramin and other trypanocidal compounds effects on Sn-glycerol-3-phosphate oxidase. Exp Parasitol 43: 353-361.
- Fairlamb AH, Bowman IBR (1980). Uptake of the trypanocidal drug suramin by bloodstream forms of Trypanosoma brucei and its effect on respiration and growth-rate in vivo. Mol Biochem Parasitol 1: 315-333.
- Hanau S, Rippa M, Bertelli M, Dallocchio F, Barrett MP (1996).6-Phosphogluconate dehydrogenase from Trypanosoma brucei.Kinetic analysis and inhibition by trypanocidal drugs. Eur J Biochem 240: 592-599.
- Bastin P, Stephan A, Raper J, SaintRemy JM, Opperdoes FR, Courtoy PJ (1996). An M(r) 145000 low-density lipoprotein (LDL)-binding protein is conserved throughout the Kinetoplastida order. Mol Biochem Parasitol 76: 43-56.
- Coppens I, Courtoy PJ (2000). The adaptative mechanisms of Trypanosoma brucei for sterol homeostasis in its different life-cycle environments. Annu Rev Microbiol 54: 129-156.
- Green HP, Del Pilar Molina Portela M, St Jean EN, Lugli EB, Raper J (2003). Evidence for a Trypanosoma brucei lipoprotein scavenger receptor. J Biol Chem 278: 422-427
- Vansterkenburg ELM, Coppens I, Wilting J, Bos OJM, Fischer MJE, Janssen LHM et al. (1993). The uptake of the trypanocidal drug suramin in combination with low-density lipoproteins byTrypanosoma brucei and its possible mode of action. Acta Trop 54:237-250
- Pal, A., Hall, B.S., Field, M.C., 2002. Evidence for a non-LDL mediated entry route for the trypanocidal drug suramin in Trypanosoma brucei. Mol. Biochem. Parasitol. 122, 217-221.
- El Rayah IE, Kaminsky R, Schmid C, El Malik KH (1999). Drug resistance in Sudanese Trypanosoma evansi. Vet Parasitol 80:281-287.
- Zhou, J.L., Shen, J., Liao, D.J., Zhou, Y.Z., Lin, J.J., 2004. Resistance to drug by different isolates Trypanosoma evansi in China. Acta Trop. 90, 271-275.
- W´ery, M., 1994. Drug used in the treatment of sleeping sickness (human African trypanosomiasis: HAT). Int. J. Antimicrob.Agents 4, 227—238.
- P´epin, J., Milord, F., 1994. The treatment of human African trypanosomiasis. Adv. Parasitol. 33, 1-47.
- Burri, C.,Keyser, J., Brun, R., 2004. Current chemotherapy of human African trypanosomiasis. In: Maudlin, I., Holmes, P.H., Miles, M.A. (Eds.), TheTrypanosomiases. CABI Publishing, Cambridge, USA, pp. 403-420.
- Vanhamme L, Paturiaux-Hanocq F, Poelvoorde P, et al. Apolipoprotein L-I is the trypanosome lytic factor of human serum.Nature 2003;422:83-7.
- Perez-Morga D, Vanhollebeke B, Paturiaux-Hanocq F, Nolan DP, Lins 10L, Homble F, Vanhamme L, Tebabi P, Pays A, Poelvoorde P, et al. (2005) Science 309:469-472.
- Pays E, Vanhollebeke B, Vanhamme L, Paturiaux-Hanocq F, Nolan DP, Perez-Morga D (2006) Nat Rev Microbiol 4:477-486.
- Pérez-Morga D, Vanhollebeke B, Paturiaux-Hanocq F, et al. Apolipoprotein L-I promotes trypanosome lysis by forming.pores in lysosomal membranes. Science 2005; 309: 469-72.
- Pays E, Vanhollebeke B, Vanhamme L, Paturiaux-Hanocq F, Nolan DP, Pérez- Morga D. The trypanolytic factor of human serum. Nat Rev Microbiol 2006; 4:477-86.
- Xong HV, Vanhamme L, Chamekh M, et al. A VSG expression site-associated gene confers resistance to human serum in Trypanosoma rhodesiense. Cell 1998; 95:839-46.
- Gibson WC. The SRA gene: the key to understanding the nature of Trypanosoma brucei rhodesiense. Parasitology 2005; 131:143-50.
- Nielsen MJ, Petersen SV, Jacobsen C, Oxvig C, Rees D, et al.(2006) Haptoglobin-related protein is a high-affinity hemoglobin-binding plasma protein. Blood 108: 2846-2849.
- Kristiansen M, Graversen JH, Jacobsen C, Sonne O, Hoffman HJ, et al.(2001) Identification of the haemoglobin scavenger receptor. Nature 409:198-201
- Nielsen MJ, Petersen SV, Jacobsen C, Thirup S, Enghild JJ, et al. (2007) A unique loop extension in the serine protease domain of haptoglobin is essential for CD163 recognition of the haptoglobin-hemoglobin complex. J Biol Chem 282: 1072-1079.
- Vanhollebeke B, Nielsen MJ, Watanabe Y, Truc P, Vanhamme L, et al.(2007b) Distinct roles of haptoglobin-related protein and apolipoprotein L-I in trypanolysis by human serum. Proc Natl Acad Sci U S A 104: 4118-4123.
- Drain J, Bishop JR, Hajduk SL (2001) J Biol Chem 276:30254-30260.
- Shiflett AM, Bishop JR, Pahwa A, Hajduk SL (2005) J Biol Chem 280:32578-32585.
- Pays E, Vanhollebeke B, Vanhamme L, Paturiaux- Hanocq F, Nolan DP, Perez-Morga D (2006) Nat Rev Microbiol 4:477-486.
- Hawking, F., Jennings, T., Louis, F.J., Tuira, E., 1981.The mechanisms which affect the periodic cycle of pacific Wuchereria bancrofti microfilariae. J. Helminthol. 55, 95-100.
- Howells, R.E., Mendis, A.M., Bray, P.G., 1983.The mode of action of suramin on the filarial worm Brugia pahangi. Parasitology 87, 29-48.
- Opperdoes, F.R. et al.1989.Unique properties of glycosomal enzymes. In Parasites: Molecular Biology, Drug and Vaccine Design (Agabian, N. and Cerami, A., eds), pp. 233-246, Wiley-Liss.
- Ahles, T.A., Herndon, J.E., Small, E.J., Vogelzang, N.J., Kornblith, A.B., Ratain, M.J., Stadler, W., Palchak, D., Marshall, M.E., Wilding, G., Petrylak, D., Holland, J.C., 2004. Quality of life impact of three different doses of suramin in patients with metastatic hormone-refractory prostate carcinoma - results of intergroup 0159/Cancer and Leukemia Group B 9480.Cancer 101, 2202-2208.
- Small, E.J., Meyer, M., Marshall, M.E., Reyno, L.M., Meyers, F.J., Natale, R.B., Lenehan, P.F., Chen, L., Slichenmyer,W.J., Eisenberger, M., 2000. S uramin therapy for patients with symptomatic hormone-refractory prostate cancer: Results of a randomized phase III trial comparing suramin plus hydrocortisone to placebo plus hydrocortisone. J. Clin. Oncol. 18, 1440-1450.
- Bacchi, C.J., Nathan, H.C., Livingston, T., Valladares, G., Saric, M., Sayer, P.D., Njogu, A.R., Clarkson, A.B., 1990. Differential susceptibility to DL-alpha-difluoromethylornithine in clinical isolates of Trypanosoma brucei rhodesiense. Antimicrob. Agents Chemother. 34, 1183-1188.
- De Koning, H.P., 2001b. Uptake of pentamidine in Trypanosoma brucei brucei is mediated by three distinct transporters: implications for crossresistance with arsenicals. Mol. Pharmacol. 59, 586-592.
- Aaronovitch, S. & Terry,R. J. (1972).The trypanolytic factor in human serum. Transactions of the Royal society of Tropical Medicine and Hygiene.66,344.
- Hawking, F.(1973a).Trypanocidal substances in human serum.Transactions of the Royal Society of Tropical Medicine and Hygiene. 67,262.
- Hawking, F.(1973b). The differentiation of Tryoanosoma rhodesiense from T. brucei by means of human serum. Transactions of the Royal Society of Tropical Medicine and Hygiene, 67, 517-527.
- Rifkin, M. R. (1978a). Identification of the trypanocidal factor in normal human serum: high density lipoprotein. Proceedings of the National Academy of Sciences of the USA, 75, 3450-3454.
- Rifkin, M. R. (1978b). Typanosoma brucei: some properties of the cytotoxic reaction induced by normal human serum. Experimental Parasitology, 46, 189-206.
- Tomlinson, S., Jansen, A. M., Koudinov, A., Ghiso, J. A., Choi-Miura, N. H., Rifkin, M. R., Ohtaki, S. & Nussenzweig, V.(1995). High-denisty-lipoprotein-independent killing of Trypanosoma brucei brucei by human serum. Molecular and Biochemical Parasitology, 70, 131 - 138.
- Raper, J., Nussenzweig, V. & Tomlinson, S. (1996). The main lytic factor of Typanosoma brucei brucei in, normal human serum is not high density lipoprotein. Journal of Experimental Medicine, 183, 1023-1029.
- Von Eckardstein, A., Chirazi, A., Schuler-Luttmann, S., Walter, M., Kastelin, J., Geisel, J., Real, J., Miccoli, R., Noseda, G., Hobbel, G. & Assmann, G. (1998). Plasma and fibroblasts of Tangier disease patients are disturbed in transferring phospholipids onto apoliporotein A-I. Journal of Lipid Research, 39, 987-998.
- Raper , J. , R. Fung , J. Ghiso , V. Nussenzweig , and S. Tomlinson . 1999. Characterization of a novel trypanolytic factor in human serum. Infect.Immun. 67: 1910 - 1916.
- Lugli, E.B., M. Pouliot, M.P. Molina-Portela, M.R. Loomis and J.Raper. 2004. Characterization of primate trypanosome lytic factors. Mol. Biochem. Parasitol. 138: 9 - 20.
- Rifkin, M. (1991). Typanosoma brucei: cytotoxicity of host high-density lipoprotein is not mediated by apolipoprotein A-I. Experimental Parasitology, 72, 216-218. Seed, J., Sechelski, J. B., Ortiz, J. C. & Chapman, J. F. (1993).
- Relationship between human serum trypanocidal activity and host resistance to the African trypanosome. Journal of Parasitology, 79, 226-232.
- Tytler, E., Moore, D. R., Pierce, M. A., Hager, K. M., Esko, J. D. & Hajduk, S. L.(1995). Reconstitution ofthe trypanosome lytic factor from components of a subspecies of human high density lipoproteins.Molecular and Biochemical Parasitology, 69, 9 -17.
- Owen, J. S.,Lorenz, P. & Betschart, B. (1996).HDL particles as the trypanosome-killing factor in human serum: an exclusive or inconclusive role? Parasitology Today, 12, 250-251.
- V.Ralevic and G. Burnstock (1998).Receptors for purines and pyrimidines. Pharmacol Rev 50, 413-492.
- U.Schönbeck and P.Libby,(2001).The CD40/CD154 receptor/ligand dyad. Cell Mol Life Sci 58, pp. 4-43.
- I.S.Grewal and R.A.Flavell,(1998). CD40 and CD154 in cell mediated immunity. Annu Rev Immunol 16, 111-135.
- C.P.Larsen, S.J.Knechtle, A. Adams,T. Pearson and A.D. Kirk, (2006). A new look at blockade of T-cell costimulation: a therapeutic strategy for long-term maintenance immunosuppression, Am J Transplant 6, 876-883.
- F. Vincenti and M.Luggen, (2007). T cell costimulation:a rational target in the therapeutic armamentarium for autoimmune diseases and transplantation, Annu Rev Med 58,347-358.
- Emilio Margolles-Clark, M. Caroline Jacques-Silva, Lakshmi Ganesan, Oliver Umland, Norma S. Kenyon, Camillo Ricordi, Per-Olof Berggren and Peter Buchwald. Suramin inhibits the CD40-CD154 costimulatory interaction: A possible mechanism for immunosuppressive effects
- F. Mancini, C.M. Toro, M. Mabilia, M. Giannangeli, M. Pinza and C. Milanese, (1999). Inhibition of tumor necrosis factor alpha(TNF-alpha)/ TNF-alpha receptor binding by structural analogues of suramin, Biochem Pharmacol 58, 851-859.
- G.B. Mills, N. Zhang, C. May, M. Hill and A. Chung, Suramin prevents binding of interleukin 2 to its cell surface receptor: a possible mechanism for immunosuppression, Cancer Res 50 (1990), 3036-3042
- S.A. Grossman, S. Phuphanich, G. Lesser, J. Rozental, L.B. Grochow and J. Fisher et al., Toxicity, efficacy, and pharmacology of suramin in adults with recurrent high-grade gliomas, J Clin Oncol 19 (2001), 3260-3266.
- S.T. Eichhorst, A. Krueger, S. Müerköster, S.C. Fas, A. Golks and U. Gruetzner et al., Suramin inhibits death receptor-induced apoptosis in vitro and fulminant apoptotic liver damage in mice, Nat Med 10 (2004), 602-609.
- C. Schiller, A. Spittler, M. Willheim, Z. Szepfalusi, H. Agis and M. Koller et al.,(1994). Influence of suramin on the expression of Fc receptors and other markers on human monocytes and U937 cells, and on their phagocytic properties, Immunology 81, 598-604.
- T.E.Voogd, E.L.Vansterkenburg, J.Wilting and L.H.Janssen, Recent research on the biological activity of suramin,(1993). Pharmacol Rev 45, 177-203.
- D.J. Cole, S.E. Ettinghausen, H.I. Pass, D.N. Danforth, M.W. Linehan and C.W. Myers et al., (1994).Postoperative complications in patients receiving suramin therapy, Surgery 116, 90-95.
- Z. Spigelman, A. Dowers, S. Kennedy, D. DiSorbo, M. O'Brien and R. Barr et al., Antiproliferative effects of suramin on lymphoid cells, Cancer Res 47 (1987), 4694-4698.
- Daniel N.Sifuentes, Camila Z.El-kik, Hilmar D.Richardo, Marcelo A. et al. (2008). Ability of suramin to antogonise the cardiotoxic and some enzymatic activities of Bothrops jararacussu venom, Toxion, volume 51, issue 1, 28-36.
- Stein CA. Suramin:a novel antineoplastic agent with multiple potential mechanisms of action. Cancer Res 1993, 53, 2239-2248.
- K. Trieb, H. Blahovec; (2003). Suramin suppresses growth, alkaline-phosphatase and telomerase activity of human osteosarcoma cells in vitro. The International Journal of Biochemistry & Cell Biology 35, 1066-1070.
- B. Vanhollebeke, E. Pays, The function of apolipoproteins L, Cell. Mol. Life Sci. 63 (2006a) 1937-1944
- B. Vanhollebeke , Truc P, Poelvoorde P, Pays A, Joshi PP, et al. (2006b) Human Trypanosoma evansi infection linked to a lack of apolipoprotein L-I. N Engl J Med 355: 2752-2756.
- B. Vanhollebeke, L. Lecordier, D. Pe´rez-Morga, A. Amiguet-Vercher, E. Pays, Human serum lyzes Trypanosoma brucei by triggering uncontrolled swelling of the parasite lysosome, J. Eukaryot. Microbiol. 54 (2007a) 448-451.
- Vanhollebeke B, Nielsen MJ, Watanabe Y, Truc P, Vanhamme L, et al.(2007b) Distinct roles of haptoglobin-related protein and apolipoprotein L-I in trypanolysis by human serum. Proc Natl Acad Sci U S A 104: 4118-4123.
- Smith AB, Hajduk SL (1995) Proc Natl Acad Sci USA 92:10262-10266.
- Smith AB, Esko JD, Hajduk SL (1995) Science 268:284-286.
- Raper, J., Nussenzweig, V.,Tomlinson, S., 1996a.Lack of correlation between haptoglobin concentration and trypanolytic activity of normal human serum. Mol. Biochem. Parasitol. 76, 337-338.
- Raper, J., Nussenzweig, V. & Tomlinson, S. (1996b).The main lytic factor of Typanosoma brucei brucei in, normal human serum is not high density lipoprotein. Journal of Experimental Medicine, 183, 1023-1029.
- Barker, C., Barbour, K. W., Berger, F. G., Hajduk, S. L., 2001.Activity of human trypanosome lytic factor in mice. Mol. Biochem. Parasitol. 117, 129-136.
- Raper, J., Portela, M.P., Lugli, E., Frevert, U., Tomlinson, S., 2001.Trypanosome lytic factors:novel mediators of human innate immunity. Curr. Opin. Microbiol. 4, 402-408.
- Hager KM, Pierce MA, Moore DR, Tytler EM, Esko JD, et al. (1994) Endocytosis of a cytotoxic human high density lipoprotein results in disruption of acidic intracellular vesicles and subsequent killing of African trypanosomes. J Cell Biol 126: 155-167
- Bishop JR, Shimamura M, Hajduk SL (2001) Insight into the mechanism of trypanosome lytic factor-1 killing of Trypanosoma brucei brucei. Mol Biochem Parasitol 118: 33-40.
- Widener J, Nielsen MJ, Shiflett A, Moestrup SK, Hajduk S, (2007) Hemoglobin is a co-factor of human trypanosome lytic factor. PLoS Pathog 3(9) e129
- Pluschke, G., Jenni, L., Van Alphen, L. and Lefkovits, I. (1986) Clin. Exp. Immunol. 66, 331-339.
- Stadnyk, A. W. and Gauldie, J. (1991) Immunol. Today 12, A7-A12
- Lorenz, P., Owen, J.S., Hassall, D.G., 1995b. Human serum resistant Trypanosoma brucei rhodesiense accumulates similar amounts of fluorescently-labelled trypanolytic human HDL3 particles as human serum sensitive T.b. brucei. Mol. Biochem. Parasitol. 74, 113-118.
- Raper, J., Portela, M.P., Lugli, E., Frevert, U., Tomlinson, S., 2001.Trypanosome lytic factors: novel mediators of human innate immunity.Curr. Opin. Microbiol. 4, 402-408.
- Gillett, M. & Owen, J. (1992a).Comparison of the cytolytic effects in vitro on Typanosoma brucei brucei of plasma, high density lipoproteins, and apolipoprotein A-I from hosts both susceptible (cattle and sheep) and resistant (human and baboon) to infection. Journal of Lipid Research, 33, 513-523
- Gillett, M.P., Owen, J.S., 1992b.Characteristics of the binding of human and bovine high-density lipoproteins by bloodstream forms of the African trypanosome, Trypanosoma brucei brucei. Biochim. Biophys. Acta. 1123, 239-248.
- Borst, P.1991.Transferrin receptor, antigen variation and the prospect of a trypanosome vaccine. Trends Genet. 7, 307-309.
- Coppens, I., P. Baudhuin, F. R. Opperdoes and P. J. Courtoy. 1988. Receptor for the host low density lipoproteins on the hemoflagellate Trypanosoma brucei: purification and involvement in the growth of the parasite. Proc. Natl. Acad. Sci. USA. 85:6753-6757.
- Gull, K., 2003.Host-parasite interactions and trypanosome morphogenesis: a flagellar pocketful of goodies. Curr. Op. Microbiol. 6, 365-370.
- P.P. Joshi, A. Chaudhari, V.R. Shegokar, R.M. Powar, V.S. Dani, A.M. Somalwar, J. Jannin, P. Truc. Treatment and follow-up of the first case of human trypanosomiasis caused by Trypanosoma evansi in India.Trans R Soc Trop Med Hyg (2006) 100, 989—991.
- 74th General Session, International Committee World Health Organization for animal health (OIE), Paris, 21-26 may 2006. Vijay R Shegokar, Rajaram M Powar, Jean Jannin, Philippe Truc, et al. (2006) Am. J. Trop. Med. Hyg., 75(5), 869-870.
- Gibson, W.C., Wilson, A.J., Moloo, S.K., 1983.Characterisation of Trypanosoma (Trypanozoon) evansi from camels in Kenya using isoenzyme electrophoresis.Res. Vet. Sci. 34, 114-118.
- Stevens, J.R., Nunes, V.L., Lanham, S.M., Oshiro, E.T., 1989. Isoenzyme characterization of Trypanosoma evansi isolated from capybaras and dogs in Brazil. Acta Tropica 46, 213-222.
- Songa, B.E., Paindavoine, P., Wittouck, E., Visehakul, N., Muldernams, S., Steinert, M., Hamers, R., 1990.Evidence for kinetoplast and nuclear DNA homogeneity in Trypanosoma evansi isolates. Molecular Biochemical Parasitology 43, 167-180.
- Biteau, N., Bringaud, F., Gibson, W., Truc, P., Baltz, T.Characterisation of Trypanozoon isolates using a repeated coding sequence and microsatellite markers. Molecular and Biochemical Parasitology. 2000; 105: 185-201.
- Lun, Z.R., Li, A.X., Chen, X.G., Lu, L.X., Zhu, X.Q. Molecular profiles of Trypanosoma brucei, T. evansi and T. equiperdum stocks revealed by the random amplified polymorphic DNA method. Parasitology Research. 2004; 92: 335-340.
- Ventura, R.M., Takeda, G.F., Silva, R.A.M.S., Nunes, V.L.B., Buck, G.A., Texeira, M.M.G. Genetic relatedness among Trypanosoma evansi stocks by random ampliWcation of polymorphic DNA and evaluation of a synapomorphic DNA fragment for species-speciWc diagnosis. International Journal for Parasitology. 2002; 32: 53-63.
- Borst,P., Fase-Fowler, F., Gibson, W.C.,.Kinetoplast DNA of Trypanosoma evansi. Mol Biochem Parasitol. 1987; 23: 31-88.
- Masiga, D.K., Gibson, W.C. Specific probes for Trypanosoma (Trypanozoon) evansi based on kinetoplast DNA minicircles. Mol Biochem Parasitol. 1990; 40: 279-284.
- Lun, Z.R., Brun, R., Gibson, W.Kinetoplast DNA and molecular karyotypes of Trypanosoma evansi and Trypanosoma equiperdum from China.Mol Biochem Parasitol. 1992: 50: 189-196.
- Jenni, L., Marti, S., Schweizer, J., Betschart, B., Le Page, R.W.,Wells, J.M., Tait, A., Paindavoine, P., Pays, E., Steinert, M. Hybrid formation between African trypanosomes during cyclical transmission. Nature.1986; 322: 173-175.
- Masiga, D.K., Gibson, W.C. Specific probes for Trypanosoma (Trypanozoon) evansi based on kinetoplast DNA minicircles. Mol Biochem Parasitol. 1990; 40: 279-284.
- Masiga, D.K., Ndung'u, K., Tweedie, A., Tait, A., Turner, C.M. Trypanosoma evansi: Genetic variability detected using amplified restriction fragment length polymorphism (AFLP) and random amplified polymorphic DNA (RAPD) analysis of Kenyan isolates. Exp. Parasitol. 2006;114: 147-153
- Z.K. Njiru, C.C. Constantine, P.K. Gitonga , R.C.A. Thompson, S.A. Reid. Genetic variability of Trypanosoma evansi isolates detected by inter-simple sequence repeat anchored-PCR and microsatellite. Vet Parasitol.2007; 147: 51-60.
- Songa, E., Hamers, R. A card agglutination test (CATT) for veterinary use based on early VAT RoTat 1.2 of Trypanosoma evansi. Ann.Soc. Belgr. Med. Trop. 1988; 68:233-240
- Schnaufer, A., Domingo, G.J., Stuart, K. Natural and induced dyskinetoplastic trypanosomatids: how to live without mitochondrial DNA. Int. J. Parasitol. 2002; 32: 1071-1084.
- Ventura, R.M., Takata, C.S., Silva, R.A., Nunes, V.L., Takeda, G.F., Teixeira, M.M. Molecular and morphological studies of Brazilian Trypanosoma evansi stocks: the total absence of kDNA in trypanosomes from both laboratory stocks and naturally infected domestic and wild mammals. J. Parasitol. 2000; 86: 1289-1298.
- Urakawa, T., Verloo, D., Moens, L., Buscher, P., Majiwa, P.A. Trypanosoma evansi: Cloning and expression in Spodoptera frugiperda [correction of fugiperda] insect cells of the diagnostic antigen RoTat 1.2. Exp Parasitol. 2001; 99: 181-189.
- Claes, F., Radwanska, M., Urakawa, T., Majiwa, P.A., Goddeeris, B., Buscher, P. Variable surface glycoprotein RoTat 1.2 PCR as a specific diagnostic tool for the detection of Trypanosoma evansi infections. Kinetoplastid. Biol. Dis. 2004; 17:3.
- Ngaira, J.M., Njagi, E.N.M., Ngeranwa, J.J.N., Olembo, N.K. PCR amplification of RoTat 1.2 VSG gene in Trypanosoma evansi isolates in Kenya. Vet. Parasitol.2004; 120: 23-33.
- Ngaira, J.M., Bett, B., Karanja, S.M., Njagi, E.N.M. Evaluation of antigen and antibody rapid detection tests for Trypanosoma evansi infection in camels in Kenya. Vet. Parasitol.2003; 114:131-141.
- Ngaira, J.M., Olembo, N.K., Njagi, E.N., Ngeranwa, J.J.The detection of non-RoTat 1.2 Trypanosoma evansi. Exp. Parasitol.2005; 110: 30-38.
- Njiru, Z.K., Constantine, C.C., Masiga, D.K., Reid, S.A., Thompson, R.C., Gibson, W.C. Characterization of Trypanosoma evansi type B. Infect. Genet. Evol.2006; 6: 292-300.
- Z.K. Njiru, C.C. Constantine, J.M. Ndung'u, I. Robertson, S. Okaye, R.C.A. Thompson, S.A. Reid. Detection of Trypanosoma evansi in camels using PCR and CATT/T. evansi tests in Kenya. Veterinary Parasitology. 2004; 124: 187-199.
- Diall, O., Bajyana-Songo, E., Magnus, E., Kouyate, B., Diallo, B., Van Meirvenne, N., Mamers, R. Evaluation d'un test serologique d'agglutination directe sur carte dans le diagnostic de la trypanosomes cameline a Trypanosoma evansi. Rev. Sci. Tech.1994; 13: 793-800.
- Stijn Deborggraeve, Mathurin Koffi, Vincent Jamonneau, Frank A. Bonsu, Richard Queyson, Pere P. Simarro, Piet Herdewijn, Philippe Büscher. Molecular analysis of archived blood slides reveals an atypical human Trypanosoma infection. Diag. Micro. Inf. Dis.2008; 6: 428-433.
- Lun, Z.R., Fang, Y., Wang, C.J., Brun, R. Trypanosomiasis of domestic animals in China. Parasitology Today.1993; 9: 41-45.
- Luckins,A.G. Trypanosoma evansi in Asia. Parasitology Today.1988; 4:137-141.
- Aksoy, S., Gibson, W.C., Lehane, M.J. Interactions between tsetse and trypanosomes with implications for the control of trypanosomiasis. Advances in Parasitology. 2003:1-83.
- Lun, Z.R. and Desser, S.S. Is the broad range of host geographical distribution of Trypanosoma evansi attributable to the loss of maxicircle kinetoplast DNA? Parasitol. Today.1995; 11:131-133.
- Lai, D.H., Hashimi, H., Lun, Z. R., Ayala, F. J., Lukes?, J. Adaptations of Trypanosoma brucei to gradual loss of kinetoplast DNA: Trypanosoma equiperdum and Trypanosoma evansi are petite mutants of T. brucei. Proc. Natl. Acad. Sci. U. S. A. 2008; 105:1999-2004.
- Brun, R., Hecker, H., Lun, Z. R. Trypanosoma evansi and T. equiperdum: distribution, biology, treatment and phylogenetic relationship. Vet Parasitol. 1998; 79:95-107.
- Wang, Z.L., 1988. The similarities and differences of the characteristics between T. equiperdum and T. evansi. Bul. Vet. Col. (PLA) (Chinese) 8, 300-303.
- Gibson, W. Species concepts for trypanosomes: from morphological to molecular definitions? Kinetoplastid Biol. Dis. 2003; 2, 10.
- Claes, F., Buscher, P., Touratier, L. Goddeeris, B. M. Trypanosoma equiperdum: master of disguise or historical mistake? Trends Parasitol. 2005; 21:316-321
- Li, F. J., Lia, D.H., Lukes?, J., Chen, X. G., Lu, Z. R. Doubts about Trypanosoma equiperdum strains classed as Trypanosoma brucei or Trypanosoma evansi. Trends Parasitol.2006; 22:2:55-56.
- Schnaufer, A., Domingo, G. J., Stuart, K. Natural and induced dyskinetoplastic trypanosomatids: how to live without mitochondrial DNA. Int. J. Parasitol. 2002; 32:1071-1084
- Hajduk, S.L., 1978. Influence of DNA complexing compounds on the kinetoplast of trypanosomatids. Prog. Mol. Subcell. Biol. 6, 158-200.
- Liu, B., Liu, Y., Motyka, S. A., Agbo, E. E. C., Englund, P. T. Fellowship of the rings: the replication kinetoplast DNA. Trends Parasitol. 2005; 21: 363-369.
- Borst, P., Hoeijmakers, J.H.J. Kinetoplast DNA. Plasmid.1979; 2: 20-40.
Cite This Dissertation
To export a reference to this article please select a referencing stye below:Reference Copied to Clipboard.Reference Copied to Clipboard.Reference Copied to Clipboard.Reference Copied to Clipboard.Reference Copied to Clipboard.Reference Copied to Clipboard.Reference Copied to Clipboard.