Abstract
Species of the genera Trypanosoma and Leishmania are protozoan parasites responsible for a series of neglected tropical diseases. The people most affected by these parasites are the poorest living in tropical and subtropical regions of the world. Two subspecies of Trypanosoma brucei, T. b. gambiense and T. b. rhodesiense, are the causative agents of human African trypanosomiasis or sleeping sickness. Millions of people living in 36 sub-Saharan countries are at risk of acquiring the disease.(WHO 2010a) Due to increased control over the last decade, the number of reported cases has declined to under 10,000 in 2009 for the first time in 50 years (WHO 2010a). For chemotherapy, only four drugs (suramin, pentamidine, melarsoprol and eflornithine), of which three were developed >60 years ago, and one drug combination therapy (eflornithine/nifurtimox) are available (WHO 2010a; Steverding 2010). In addition, all drugs have major drawbacks including poor efficacy, significant toxicity, need for parental administration and drug resistance (Fairlamb 2003; Matovu et al. 2001; Delespaux and de Koning 2007).
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References
Almeida R, Norrish A, Levick M et al (2002) From genomes to vaccines: Leishmania as a model. Philos Trans R Soc Lond B Biol Sci 357:5–11
Alves-Ferreira M, Guimarães AC, Capriles PV et al (2009) A new approach for potential drug target discovery through in silico metabolic pathway analysis using Trypanosoma cruzi genome information. Mem Inst Oswaldo Cruz 104:1100–1110
Aurrecoechea C, Brestelli J, Brunk BP et al (2010) EuPathDB: a portal to eukaryotic pathogen databases. Nucleic Acids Res 38:D415–D419
Berg M, Van der Veken P, Goeminne A et al (2010) Inhibitors of the purine salvage pathway: a valuable approach for antiprotozoal chemotherapy? Curr Med Chem 17:2456–2481
Berriman M, Ghedin E, Hertz-Fowler C et al (2005) The genome of the African trypanosome Trypanosoma brucei. Science 309:416–422
Bhattacharyya T, Brooks J, Yeo M et al (2010) Analysis of molecular diversity of the Trypanosoma cruzi tryptomastigote small surface antigen reveals novel epitopes, evidence of positive selection and potential implications for lineage-specific serology. Int J Parasitol 40:921–928
Butler D (2005) Triple genome triumph. Nature 436:337
Camizotti LA, Yamashiro-Kanashiro EH, Cotrim PC (2009) Identification and chromosomal localization of one locus of Leishmania (L.) major related with resistance to itraconazole. Parasitol Res 105:471–478
Capriles PV, Guimarãres AC, Otto TD et al (2010) Structural modelling and comparative analysis of homologous, analogous and specific proteins from Trypanosoma cruzi versus Homo sapiens: putative drug targets for chagas’ disease treatment. BMC Genomics 11:610
Chukualim B, Peters N, Hertz Folwer C et al (2008) TrypanoCyc – a metabolic pathway database for Trypanosoma brucei. BMC Bioinformatics 9(Suppl 10):P5
Croft SL, Coombs GH (2003) Leishmaniasis – current chemotherapy and recent advances in the search for novel drugs. Trends Parasitol 19:502–508
Cuervo P, Domont GB, De Jesus JB (2010) Proteomics of trypanosomatids of human medical importance. J Proteomics 73:845–867
Delespaux V, de Koning HP (2007) Drugs and drug resistance in African trypanosomiasis. Drug Resist Updat 10:30–50
Doyle MA, MacRae JI, De Souza DP et al (2009) LeishCyc: a biochemical pathway database for Leishmania major. BMC Syst Biol 3:57
Dumonteil E, Escobedo-Ortegon J, Reyes-Rodriguez N et al (2004) Immunotherapy of Trypanosoma cruzi infection with DNA vaccines in mice. Infect Immun 72:46–53
el Kouni MH (2003) Potential chemotherapeutic targets in the purine metabolism of parasites. Pharmacol Ther 99:283–309
El-Sayed NM, Myler PJ, Bartholomeu DC et al (2005) The genome sequence of Trypanosoma cruzi, ethiologic agent of Chagas disease. Science 309:409–415
Fairlamb AH (2003) Chemotherapy of human African trypanosomiasis: current and future prospects. Trends Parasitol 19:488–494
Foti L, Fonseca Bde P, Nascimento LD et al (2009) Viability study of a multiplex diagnostic platform for Chagas disease. Mem Inst Oswaldo Cruz 104(Supp 1):136–141
Franzén O, Ochaya S, Sherwood E et al (2011) Shotgun sequencing analysis of Trypanosoma cruzi I Sylvio X10/1 and comparison with T. cruzi VI CL Brener. PLoS Negl Trop Dis 5:e984
Grisard EC, Stoco PH, Wagner G et al (2010) Transcriptomic analyses of the avirulent protozoan parasite Trypanosoma rangeli. Mol Biochem Parasitol 174:18–25
Gurunathan S, Klinman DM, Seder RA (2000) DNA vaccines: immunology, application, and optimization. Annu Rev Immunol 18:927–974
Haddad D, Bilcikova E, Witney AA et al (2004) Novel antigen identification method for discovery of protective malaria antigens by rapid testing of DNA vaccines encoding exons from the parasite genome. Infect Immun 72:1594–1602
Horn D, McCulloch R (2010) Molecular mechanisms underlying the control of antigenic variation in African trypanosomes. Curr Opin Microbiol 13:700–705
Ivens AC, Peacock CS, Worthey EA et al (2005) The genome of kinetoplastid parasite, Leishmania major. Science 309:436–442
Jackson AP, Sanders M, Berry A et al (2010) The genome sequence of Trypanosoma brucei gambiense, causative agent of chronic human African trypanosomiasis. PLoS Negl Trop Dis 4:e658
Johnston DA, Blaxter ML, Degrave WM et al (1999) Genomics and the biology of parasites. Bioassays 21:131–147
Kuboki N, Inoue N, Sakurai T et al (2003) Loop-mediated isothermal amplification for detection of African trypanosomes. J Clin Microbiol 41:5517–5524
Legrand N, Ploss A, Balling R et al (2009) Humanized mice for modelling human infectious disease: challenges, progress, and outlook. Cell Host Microbe 6:5–9
Machado FS, Tyler KM, Brant F et al (2012) Pathogenesis of Chagas disease: time to move on. Front Biosci (Elite Ed) 4:1743–1758
Magez S, Caljon G, Tran T et al (2010) Current status of vaccination against African trypanosomiasis. Parasitology 137:2017–2027
Matovu E, Seebeck T, Enyaru JC et al (2001) Drug resistance in Trypanosoma brucei spp., the causative agents of sleeping sickness in man and nagana in cattle. Microbes Infect 3:763–770
Myler PJ (2008) Searching the Tritryp genomes for drug targets. Adv Exp Med Biol 625:133–140
Ndao M (2009) Diagnosis of parasitic diseases: old and new approaches. Interdiscip Perspect Infect Dis 2009:278246
Ndao M, Spithill TW, Caffrey R et al (2010) Identification of novel diagnostic serum biomarkers for Chagas’ disease in asymptomatic subjects by mass spectrometric profiling. J Clin Microbiol 48:1139–1149
Njiru ZK, Mikosza AS, Matovu E et al (2008) African trypanosomiasis: sensitive and rapid detection of the sub-genus Trypanozoon by loop-mediated isothermal amplification (LAMP) of parasite DNA. Int J Parasitol 38:589–599
Notomi T, Okayama H, Masubuchi H et al (2000) Loop-mediated isothermal amplification of DNA. Nucleic Acids Res 28:e63
Pajot A, Michel ML, Mancini-Bourgine M et al (2006) Identification of novel HLA-DR1-restricted epitopes from the hepatitis B virus envelope protein in mice expressing HLA-DR1 and vaccinated human subjects. Microbes Infect 8:2783–2790
Peacock CS, Seeger K, Harris D et al (2007) Comparative genomic analysis of three Leishmania species that cause diverse human disease. Nat Genet 39:839–847
Pizza M, Scarlato V, Masignani V et al (2000) Identification of vaccine candidates against serogroup B meningococcus by whole-genome sequencing. Science 287:1816–1820
Rappuoli R (2000) Reverse vaccinology. Curr Opin Microbiol 3:445–450
Schroeder J, Aebischer T (2011) Vaccines for leishmaniasis: from proteome to vaccine candidates. Hum Vaccin 7:10–15
Sette A, Rappuoli R (2010) Reverse vaccinology: developing vaccines in the era of genomics. Immunity 33:530–541
Steverding D (2010) The development of drugs for treatment of sleeping sickness: a historical review. Parasit Vectors 3:15
Stober CB, Lange UG, Roberts MT et al (2006) From genome to vaccines for leishmaniasis: screening 100 novel vaccine candidates against murine Leishmania major infection. Vaccine 24:2602–2616
Subramaniam C, Veazey P, Redmond S et al (2006) Chromosome-wide analysis of gene function by RNA interference in the African trypanosome. Eukaryot Cell 5:1539–1549
Urbina JA, Docampo R (2003) Specific chemotherapy of Chagas disease: controversies and advances. Trends Parasitol 19:495–501
Velez ID, Gilchrist K, Martínez S et al (2009) Safety and immunogenicity of a defined vaccine for the prevention of cutaneous leishmaniasis. Vaccine 28:329–337
WHO (2004) Workplan of the working group on applied genomics for drugs and diagnostics; http://www.who.int/tdrold/grants/workplans/genomics.htm
WHO (2010a) African trypanosomiasis (sleeping sickness). World Health Org Fact Sheet 259: http://www.who.int/mediacentre/factsheets/fs259/en/
WHO (2010b) Chagas disease (American trypanosomiasis). World Health Org Fact Sheet 340: http://www.who.int/mediacentre/factsheets/fs340/en/index.html
WHO (2010c) Leishmaniasis. World Health Org Tech Inform; http://www.who.int/leishmaniasis/en/index.html
Yajima M, Imadome K, Nakagawa A et al (2009) T cell-mediated control of Epstein-Barr virus infection in humanized mice. J Infect Dis 200:1611–1615
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Steverding, D., Tyler, K.M., Grisard, E.C. (2012). Delivering on Promises? The Impact of Kinetoplastid Genomics on Sleeping Sickness, Chagas Disease and Leishmaniasis. In: Nelson, K., Jones-Nelson, B. (eds) Genomics Applications for the Developing World. Advances in Microbial Ecology. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-2182-5_9
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DOI: https://doi.org/10.1007/978-1-4614-2182-5_9
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