Laboratory of Professor Michael A. Miles
Current participants (subject to change):
Dr Matthew Yeo
Dr Martin Llewellyn
Dr Michael D. Lewis (attached to Professor John Kelly's research group)
Louisa Messenger
Tapan Bhattacharyya
Nidia Acosta (overseas research student, Paraguay)
Dr Isabel Mauricio (collaborator, Institute of Hygiene and Tropical Medicine, Lisbon)
Dr Andrew Falconar (visiting research fellow)
Dr James Patterson (visiting research fellow)
Professor Chris Schofield (honorary staff)
Dr Michael W. Gaunt (collaborator)
Urvish Mistry (visiting research volunteer)
RESEARCH INTERESTS
Molecular genetics of Trypanosoma cruzi, and the epidemiology and control of Chagas Disease
Objectives:
- Understand divergence between the major intraspecific subdivisions of T. cruzi
- Characterise naturally occurring and experimentally derived T. cruzi hybrids
- Investigate mechanisms and importance of genetic exchange in T. cruzi
- Investigate multiclonality in T. cruzi infections
- Relate the natural diversity and population genetics of T. cruzi to the epidemiology and control of Chagas disease
- Strengthen European and international collaboration in research on T. cruzi and Chagas disease
Relevant website
ChagasEpiNet www.ki.se/chagaspinet
Examples of recent and key historical publications
Franzen, O., Ochaya, S., Sherwood, E., Lewis, M.D., Llewellyn, M.S., Miles, M.A., Andersson, B., 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.
Hamilton, P.B., Lewis, M.D., Cruickshank, C., Gaunt, M.W., Yeo, M., Llewellyn, M.S., Valente, S.A., Maia da Silva, F., Stevens, J.R., Miles, M.A., Teixeira, M.M. 2011. Identification and lineage genotyping of South American trypanosomes using fluorescent fragment length barcoding. Infect Genet Evol 11, 44-51
Lauthier, J.J., Tomasini, N., Barnabe, C., Rumi, M.M., D'Amato, A.M., Ragone, P.G., Yeo, M., Lewis, M.D., Llewellyn, M.S., Basombrio, M.A., Miles, M.A., Tibayrenc, M., Disque, P. 2011. Candidate targets for Multilocus Sequence Typing of Trypanosoma cruzi: validation using parasite stocks from the Chaco Region and a set of reference strains. Infect Genet Evol
Lewis, M.D., Llewellyn, M.S., Yeo, M., Acosta, N., Gaunt, M.W., Miles, M.A. 2011 Recent, independent and anthropogenic origins of Trypnosoma cruzi hybrids. PLoS Negl Trop Dis 5, e1363
Llewellyn, M.S., Rivett-Carnac, J.B., Fitzpatrick, S., Lewis, M.D., Yeo, M., Gaunt, M.W., Miles, M.A. 2011. Extraordinary Trypanosoma cruzi diversity within single mammalian reservoir hosts implies a mechanism of diversifying selection. Int J Parasitol 41, 609-614
Yeo, M., Mauricio, I.L., Messenger, L.A., Lewis, M.D., Llewellyn, M.S., Acosta, N., Bhattacharyya, T., Diosque, P., Carrasco, H.J., Miles, M.A. 2011. Multilocus sequence typing (MLST) for lineage assignment and high resolution diversity studies in Trypanosoma cruzi. PLoS Negl Trop Dis 5, e1049
Zingales, B., Miles, M.A., Cammpbell, D.A., Tibayrenc, M., Macedo, A.M., Teizeira, M.M., Schijman, A.G., Llewellyn, M.S., Lages-Silva, E., Machado, C.R., Andrade, S.G., Sturm, N.R. 2011. The revised Trypanosoma cruzi subspecific nomenclature: rationale, epidemiological relevance and research applications. Infect Genet Evol
Bhattacharyya, T., Brooks, J., Yeo, M., Carrasco, H.J., Lewis, M.D., Llewellyn, M.S., Miles, M.A. 2010. Analysis of molecular diversity of the Trypanosoma cruzi trypomastigote small surface antigen reveals novel epitopes, evidence of positive selection and potential implications for lineage-specific serology. Int J Parasitol 40, 921-928
Miles, M.A., 2010. Orally acquired Chagas disease: lessons from an urban school outbreak. J Infect Dis 201, 1282-1284
Ocana-Mayorga, S., Llewellyn, M.S., Costales, J.A., Miles, M.A., Grijalva, M.J., 2010. Sex, subdivision and domestic dispersal of Trypnanosoma cruzi lineage I in southern Ecuador. PLoS Negl Trop Dis 4, e915
Lewis, M.D., Llewellyn, M.S., Gaunt, M.W., Yeo, M., Carrasco, H.J., Miles, M.A., 2009. Flow cytometric analysis and microsatellite genotyping reveal extensive DNA content variation in Trypanosoma cruzi populations and expose contrasts between natural and experimental hybrids. Int J Parasitol
Llewellyn, M.S., Miles, M.A., Carrasco, H.J., Lewis, M.D., Yeo, M., Vargas, J., Torrico, F., Diosque, P., Valente, V., Valente, S.A., Gaunt, M.W., 2009. Genome-scale multilocus microsatellite typing of Trypanosoma cruzi discrete typing unit I reveals phylogeographic structure and specific genotypes linked to human infection. PLoS Pathogens 5, e1000410
Yeo, M., Acosta, N., Llewellyn, M., Sanchez, H., Adamson, S., Miles, G.A.J., Lopez, E., Lewis, M.D., Carrasco, H.J., da Silva Valente, S.A., de Costa Valente, V., de Arias, A.R., Miles M.A., 2007. Resolution of muticlonal infectinos of Trypanosoma cruzi from naturally infected triatomine bugs and from experimentally infected mice by direct plating on a sensitive solid medium. Int J Parasitol 37, 111-120
Gonzalez, N., Patterson, J.S., Gaunt, M.W., 2005. Origins of Chagas disease: Didelphis species are natural hosts of Trypanosoma cruzi I and armadillos hosts of Trypansoma cruzi II, including hybrids. International Journal for Parasitilogy 35, 225-233
Gaunt, M.W., Yeo, M., Frame, I.A., Stothard, J.R., Carrasco, H.J., Taylor, M.C., Mena, S.S., Veazey, P., Miles, G.A.J., Acosta, N., de Arias, A.R., Miles, M.A., 2003. Mechanism of genetic exchange in American trypanosomes. Nature 421, 936-939
Miles, M.A., Feliciangeli, M.D., de Arias, A.R., 2003. American trypanosomiasis (Chagas' disease) and the role of molecular epidemiology in guiding control strategies. BMJ 326, 1444-1448
Coura, J.R., Junqueira, A.C., Fernandes, O., Valente, S.A., Miles, M.A., 2002. Emerging Chagas' disease in Amazonian Brazil. Trends Parasitol 18, 171-176
Stothard, J., Frame, I., Miles, M., 1999. Genetic diversity and genetic exchange in Trypanosoma cruzi: dual drug-resistant "progeny" from episomal transformants. Memorias do Instituto Oswaldo Cruz 94, 189-193
Carrasco, H.J., Frame, I.A., Valente, S.A., Miles, M.A., 1996. Genetic exchange as a possible source of genomic diversity in sylvatic populations of Trypanosoma cruzi. Am J Trop Med Hyg 54, 418-424
Chapman, M., Baggaley, R., Godfrey-Fausset, P., Malpas, T., White, G., Canese, J., Miles, M., 1984. Trypanosoma cruzi from the Paraguayan Chaco: isoenzyme profiles of strains isolated at Makthlawaiya. Journal of Protozoology 31, 482-486
Miles, M.A., 1983. The epidemiology of South American Trypanosomiasis - biochemical and immunological approaches and their relevance to control. Trans R Soc Trop Med Hyg 77, 5-23
Miles, M.A., Arias, J.R., Valente, S.A., Naiff, R. D., de Souza, A.A., Povoa, M.M., Lima, J.A., Cedillos, R.A., 1983. Vertebrate hosts and vectors of Trypanosoma rangeli in the Amazon Basin of Brazil. Am J Trop Med Hyg 32, 1251-1259
Schofield, C.J., Apt, W., Miles, M.A., 1982. The ecology of Chagas disease in Chile. Ecol Dis 1, 117-129
Miles, M., Cedillos, R., Povoa, M., de Souza, A., Prata, A., Macedo, V., 1981. Do radically dissimilar Trypanosoma cruzi strains (zymodemes) cause Venezuelan and Brazilian forms of Chagas' disease? The Lancet 317, 1338-1340
Miles, M.A., de Souza, A.A., Povoa, M., 1981. Chagas disease in the Amazon Basin III. Ecotypes of ten triatomine bug species (Hemiptera: Reduviidae) from the vicinity of Belem, Para State, Brazil. J Med Entomol 18, 266-278
Miles, M.A., Lanham, S.M., de suoza, A.A., Povoa, M., 1980. Further enzymic characters of Trypanosoma cruzi and their evaluation for strain identification. Transactions of the Royal Society of Tropical Medicine and Hygiene 74, 221-237
Miles, M.A., 1979. Transmission cycles and the heterogeneity of Trypanosoma cruzi. Academic Press
Miles, M.A., Souza, A., Povoa, M., Shaw, J.J., Lainson, R., Toye, P.J., 1978. Isozymic heterogeneity of Trypanosoma cruzi in the first autochthonous patients with Chagas' disease in Amazonian Brazil. Nature 272, 819-821
Miles, M.A., Toye, P., Oswald, S., Godfrey, D., 1977. The identification by isoenzyme patterns of two distinct strain-groups of Trypanosoma cruzi, circulating independently in a rural area of Brazil. Transactions of the Royal Society for Tropical Medicine and Hygiene 71, 217-225
Miles, M.A., Castro, C., Macedo, V., Draper, C.C., 1975. Letter: Trypanosoma cruzi - prenatal transfer of maternal antibody in man. Trans R Soc Trop Med Hyg 69, 286
Miles, M.A., 1972. Trypanosoma cruzi - milk transmission of infection and immunity from mother to young. Parasitology 65,1-9
Molecular genetics of Leishmania and the epidemiology and control of leishmaniasis
Objectives
- Devise new molecular methods for taxonomic and population genetics research on Leishmania, in particular on the Leishmania donovani complex and the subgenus Viannia
- Improve molecular methods for the rapid identification of Leishmania
- Reevaluate the taxonomy of the L.donovani complex and clarify its evolutionary history
- Investigate the presence and epidemiological importance of genetic exchange in the Leishmania donovani complex
- Investigate the relevance of canine and other reservoir hosts to the control of visceral leishmaniasis
- Strengthen European and international collaboration in research on leishmaniasis
Relevant website
LeishEpiNetSA www.leishdomus.org/history.htm
Examples of recent and key historical publications
Sadlova, J., Yeo, M., Seblova, V., Lewis, M.D., Mauricio, I.L., Volf, P., Miles, M.A., 2011. Visualisation of Leishmania donovani fluorescent hybrids during early stage development in the sand fly vector. PLoS ONE 6, e19851
Kuhls, K., Alam, M.Z., Cupolillo, E., Ferreira, G.E., Mauricio, I.L., Oddone, R., Feliciangeli, M.D., Wirth, T., Miles, M.A., Schonian, G., 2011. Comparative microsatellite typing of new world leishmania infantum reveals low heterogeneity among populations and its recent old world origin. PLoS Negl Trop Dis 5, e1155
Miles, M.A., Yeo, M., Mauricio, I.L., 2009. Genetics. Leishmania exploit sex. Science 324, 187-189
Kuhls, K., Chicharro, C., Canavate, C., Cortes, S., Campino, L., Haralambous, C., Soteriadou, K., Pratlong, F., Dedet, J.P., Mauricio. I.L., Miles, M.A., Schaar, M., Ochsenreither, S., Radtke, O.A., Schonian, G., 2008. Differentiation and Gene Flow among European Populations of Leishmania infantum MON-1. PLoS Negl Trop Dis 2, e261
Lukes, J., Mauricio, I.L., Schonian, G., Dujardin, J-C., Soteriadou, K., Dedet, J-P., Kuhls, K., Tintaya, K.W.Q., Jirku, M., Chocholova, E., Haralambous, C., Pratlong, F., Obornik, M., Horak, A., Ayala, F.J., Miles, M.A., 2007. Evolutionary and geographical history of the Leishmania donovani complex with a revision of current taxonomy 10.1073/pnas.0703678104. Proceedings of the National Academy of Sciences 104, 9375-9380
Mauricio, I.L., Gaunt, M.W., Stothard, J.R., Miles M.A., 2007. Glycoprotein 63 (gp63) genes show gene conversion and reveal the evolution of Old World Leishmania. Int J Parasitol 37, 565-576
Nolder, D., Roncal, N., Davies, C.R., Llanos-Cuentas, A., Miles, M.A., 2007. Multiple hybrid genotypes of Leishmania (viannia) in a focus of mucocutaneous Leishmaniasis. Am J Trop Med Hyg 76, 573-578
Zemanova, E., Jirku, M., Mauricio, I.L., Horak, A., Miles, M.A., Lukes, J., 2007. The Leishmania donovani complex: genotypes of five metabolic enzymes (ICD, ME, MPI, G6PDH, and FH), new targets for multilocus sequence typing. Int J Parasitol 37, 149-160
Mauricio, I.L., Yeo, M., Baghaei, M., Doto, D., Pratlong, F., Zemanova, E., Dedet, J-P., Lukes, J., Miles, M.A., 2006. Towards multilocus sequence typing of the Leishmania donovani complex: Resolving genotypes and haplotypes for five polymorphic metabolic enzymes (ASAT, GPI, NH1, NH2, PGD). International Journal for Parasitology 36, 757-769
Mauricio, I.L., Stothard, J.R., Miles, M.A., 2000. The strange case of Leishmania chagasi. Parasitol Today 16, 188- 189
Vexenat, J.A., Olliaro, P.L., Fonseca de Castro, J.A., Cavalcante, R., Furtado Campos, J.H., Tavares, J.P., Miles, M.A., 1998. Clinical recovery and limited cure in canine visceral leishmaniasis treated with aminosidine (paromomycin). Am J Trop Med Hyg 58, 448-453
de Gorgolas, M.., Miles, M.A., 1994. Visceral leishmaniasis and AIDS. Nature 372, 734
Almeida, M.C., Cuba-Cuba, C.A., Moraes, M.A., Miles, M.A., 1996. Dissemination of Leishmania (Viannia) braziliensis. J Comp Pathol 115, 311-316
Belli, A.A., Miles, M.A., Kelly, J.M., 1994. A putative Leishmania panamensis/Leishmania braziliensis hybrid is a causative agent of human cutaneous leishmaniasis in Nicaragua. Parasitology 109 (Pt 4), 435-442
Almeida, M.C., Cuba, C.A., de Sa, C.M., Pharoah, M.M., Howard, K.M., Miles, M.A., 1993. Metcyclogenesis of Leishmania (Viannia) braziliensis in vitro: evidence that lentil lectin is a marker of complement resistance and enhanced infectivity. Trans R Soc Trop Med Hyg 87, 325-329
Howard, M.K., Sayers, G., Miles, M.A., 1987. Leishmania donovani metacyclic promastigotes: transformation in vitro, lectin agglutination, complement resistance, and infectivity. Exp Parasitol 64, 147-156
Cuba Cuba, C.A., Miles, M.A., Vexenat, A., Barker, D.C., McMahon Pratt, D., Butcher, J., Barreto, A.C., Marsden, P.D., 1985. A focus of mucocutaneous leishmaniasis in Tres Bracos, Bahia, Brazil: characterisation and identification of Leishmania stocks isolated from man and dogs. Trans R Soc Trop Med Hyg 79, 500-507
Arias, J.R., Naif, R.D, Miles, M.A., de Souza, A.A., 1981. The opossum, Didelphis marsupialis (Marsupialia: Didelphidae), as a reservoir host of Leishmania braziliensis guyanensis in the Amazon Basin of Brazil. Trans R Soc Trop Med Hyg 75, 537-541
Miles, M.A., Lainson, R., Shaw, J.J., Povoa, M., de Souza, A.A., 1981. Leishmaniasis in Brazil: XV. Biochemical distinction of Leishmania mexicana amazonensis, L. braziliensis braziliensis and L. braziliensis guyanensis - aetiological agents of cutaneous leishmaniasis in the Amazon Basin of Brazil. Trans R Soc Trop Med Hyg 75, 524-529
Miles, M.A., Povoa, M.M., de Souza, A.A., Lainson, R., Shaw, J.J., 1980. Some methods for the enzymic characterization of Latin American Leishmania with particular reference to Leishmania mexicana amazonensis and subspecies of Leishmania hertigi. Trans R Soc Trop Med Hyg 74, 243-252
Ecology, population genetics and control of triatomine bugs

Picture: Linschcosteu
Objectives
- To understand the ecology, behaviour, population structure and associated trypanosomatid infections of triatomine bug species in the context of control of Chagas disease
- Give research support to the international control effort against Chagas disease via the ECLAT triatomine research network
Examples of recent and key historical publications
Abad-Franch, F., Ferraz, G., Campos, C., Palomeque, F.S., Grijalva, M.J., Aguilar, H.M., Miles, M.A., 2010. Modeling disease vector occurrence when detection is imperfect: infestation of Amazonian palm trees by triatomine bugs at three spatial scales. PLoS Negl Trop Dis 4, e620
Fitzpatrick, S., Feliciangelis, M.D., Sanchez-Martin, M.J., Monteiro, F.A,. Miles, M.A., 2008. Molecular Genetics Reveal That Silvatic Rhodnius prolixus Do Colonise Rural Houses. PLoS Negl Trop Dis 2, e210
Yeo, M., Acosta, N., Llewellyn, M., Sanchez, H, Adamson, S., Miles, G.A.J., Lopez, E., Gonzalez, N., Patterson, J.S., Gaunt, M.W., 2005. Origins of Chagas disease: Didelphis species are natural hosts of Trypanosoma cruzi 1 and armadillo hosts of Trypanosoma cruzi II, including hybrids. International Journal for Parasitology 35, 225-233
Coura, J.R., Junqueira, A.C., Fernandes, O., Valente, S.A., Miles, M.A., 2002. Emerging Chagas disease in Amazonian Brazil. Trends Paradsitol 18, 171-176
Cuba, C.A., Abad-Franch, F., Roldan Rodriguez, J., Vargas Vasquez, F., Pollack Velasquez, L., Miles, M.A., 2002. The triatomines of northern Peru, with emphasis on the ecology and infection by trypanosomes of Rhodnius ecuadoriensis (Triatominae). Mem Inst Oswaldo Cruz 97, 175-183
Galvao, C., Patterson, J.S., Da Silva Rocha, D., Jurberg, J., Carcavallo, R., Rajen, K., Ambrose, D.P., Miles, M.A., 2002. A new species of Triatominae from Tamil Nadu, India. Med Vet Entomol 16, 75-82
Gaunt, M., Miles, M., 2000. The ecotypes and evolution of triatomine bugs (triatominae) and their associated trypanosomes. Memorias do Instituto Oswaldo Cruz 95, 557-565
Valente, V.C., Valente, S.A, Noireau, F., Carrasco, H.J., Miles, M.A., 1998. Chagas disease in the Amazon Basin: association of Panstrongylus geniculatus (Hempitera: Reduviidae) with domestic pigs. J Med Entomol 35, 99-103
Miles, M.A., Arias, J.R., de Souza, A.A., 1983. Chagas disease in the Amazon Basin: V. Periurban palms as habitats of Rhodnius robustus and Rhodnius pictipes - triatomine vectors of Chagas' disease. Mem Inst Oswaldo Cruz 78, 391-398
Miles, M.A., Arias, J.R., Valente, S.A., Naiff, R.D., de Souza, A.A., Povoa, M.M., Lima, J.A., Cedillos, R.A., 1983. Vertebrate hosts and vectors of Trypanosoma rangeli in the Amazon Basin of Brazil. Am J Trop Med Hyg 32, 1251-1259
Miles, M.A., de Souza, A.A., Povoa, M.M., 1982. The ecotope of Panstrongylus megistus (Hemiptera, Reduviidae) in the Horto Forest (Rio de Janeiro). Rev Bras Biol 42, 31-35
Miles, M.A., de Souza, A.A., Povoa, M.M., 1981. Chagas disease in the Amazon Basin III. Ecotopes of ten triatomine bug species (Hemiptera: Reduviidae) from the vicinity of Belem, Para State, Brazil. J Med Entomol 18,266-278
Miles, M.A., de Souza, A.A., Povoa, M.M., 1981. Mammal trapping and nest location in Brazilian forest with an improved spool and line. J Zool 195, 331-347
Ecology and control of tsetse flies (Glossina)
Objectives
The LTTR network was formed in 2004 as an association of research scientists and control personnel with common interests in promoting activities in support of initiatives to control tsetse and interrupt transmission of African trypanosomiasis. the network has an underlying theme of promoting collaborative research and training to improve understanding of the biology and control of tsetse, and in support of control and surveillance activities directed against the disease and its insect vectors - especially in association with the PATTEC initiative of the African Union.
Relevant websites
Leverhulme Trust Tsetse Research Network lttrn.lshtm.ac.uk
Publications by LTTRN members 2010
Awa, D.N., Achukwi, M.D., 2010. Livestock pathology in the central African region: some epidemiological considerations and control strategies. An Health Res Rev 2010 Jan15: 1-10
Beadell, J.S., Hyseni, C., Abila, P.P., Azabo, R., Enyaru, J.C., Ouma, J.O., Mohammed, Y.O., Okedi, L.M., Aksoy, S., Caccone, A., 2010. Phylogeography and population structure of Glossina fuscipes fuscipes in Uganda: implications for control of tsetse. PLoS Negl Trop Dis 2010 Mar 16;4(3):e636
Bouyer, J., Ravel, S., Guerrini, L., Dujardin, J.P., Sidibe, I, Vreysen, M.J., Solano, P., De Meeus, T., 2010. Population structure of Glossina palpalis gambiensis (Diptera: Glossinidae) between river basins in Burkina Faso: consequences for area-wide integrated pest management. Infect Genet Evol. 2010 Mar;10(21):321-8. Epub 2010 Jan 7
Courtin, F., Rayaisse, J.B., Tamboura, I., Serdebeogo, O., Koudougou, Z., Solano, P., Sidibe, I., 2010. Updating the northern tsetse limit in Burkina Faso (1949-2009): impact of global change. Int J Environ Res Public Health. 2010 Apr;7(4):1708-1719. Epub 2010 Apr 15
Enyaru, J.C., Ouma, J.O., Malele, I.I., Matovu, E., Masiga, D.K., 2010. Landmarks in the evolution of technologies for identifying trypanosomes in tsetse flies. Trends Parasitol. 2010 Aug;26(8):388-394. Epub 2010 Jun 9
Kone, N., De Meeus, T., Bouyer, J. Ravel, S., Guerrini, L, N'goran, E.K., Vial, L., 2010. Population structuring of the tsetse Glossina tachinoides resulting from landscape fragmentation in the Mouhoun River basin, Burkina Faso. Medical and Veterinary Entomology 2010 Jun;24(2):162-168. Epub 2010 Feb 4
Kone, N., N'goran, E.K., Sidibe, I., Kombassere, A.W., Bouyer, J., 2010. Spatio-temporal distribution of tsetse and other biting flies in the Mouhoun River basin, Burkina Faso. Medical and Veterinary Entomology 2011 Jun;25(2):156-168. doi: 10.1111/j.1365-2915.2010.00938.x. Epub 2010 Dec 27
Solano, P., Ravel, S., de Meeus, T., 2010. How can tsetse population genetics contribute to African trypanosomiasis control? Trends Parasitol; 26(5):255-263. Epub 2010 Mar 2