Professor Paul Bates
Chair in Biomedicine
Office C41, Bowland North
Division of Biomedical and Life Sciences
Faculty of Health and Medicine
Tel: +44 1524 593718
Fax: +44 1524 593192
The leishmaniases are tropical infectious diseases that occur in many parts of the world, including Central and South America, Africa, Southern Europe and Asia. The true scale of the disease is severely under-reported, but estimates of the number of people infected at any one time range from 12 to 20 million, with some 350 million exposed to the risk of infection. The World Health Organisation has targeted leishmaniasis as a priority for research, being one of the "Neglected Tropical Diseases". Although populations living in the tropics and sub-tropics are at the highest risk of infection, visitors and tourists also occasionally become infected with leishmaniasis.
There are three main forms of disease: cutaneous leishmaniasis, mucocutaneous leishmaniasis and visceral leishmaniasis. All are transmitted by the bites of small blood feeding insects called phlebotomine sand flies.
Cutaneous leishmaniasis or "oriental sore" results in skin lesions or ulcers, up to several centimetres across. Although in most cases these will eventually resolve and self-cure, they always leave behind an unsightly scar that may be on a sensitive site such as the face. Also some patients can suffer from multiple or persistent cutaneous lesions.
Mucocutaneous leishmaniasis or "espundia" is a more serious form of the disease. It initially appears the same as cutaneous disease, but in some patients the infection spreads to the soft cartilage of the nose and palate. This gradually becomes eroded and if left untreated causes severe facial disfigurement.
The most deadly form is visceral leishmaniasis or "kala azar". Here the infection spreads to the internal organs, particularly the spleen and liver, which can become grossly enlarged as a result. Advanced visceral leishmaniasis is almost always fatal unless treated with drugs.
These different forms of leishmaniasis are all caused by various species of Leishmania, single-celled parasites that live inside human macrophages. This is particularly remarkable because macrophages are a key component of the immune response and are normally very effective at killing foreign micro-organisms. However, in patients that do overcome the infection their macrophages are eventually able to kill the parasites within and control the infection. Such individuals show resistance to re-infection, giving hope that vaccines might be developed against leishmaniasis. This is one of our key research aims and in particular understanding a crucial event in the Leishmania life cycle, the transmission of the infection when the parasite, human host and sand fly vector come together.
One of our major interests is to investigate the role that a parasite secretory product known as promastigote secretory gel (PSG) plays in this process. PSG enhances transmission by creating a "blocked fly", forcing the sand fly to regurgitate PSG into the skin along with the parasites, helping to establish the infection. Other interests include the biochemistry and chemotherapy of leishmaniasis and the development of parasite identification and diagnostic tools. We are also investigating the response of the sand fly host to Leishmania infection using a genomics approach, and are engaged in a project to sequence the genome of Lutzomyia longipalpis, the vector of visceral leishmaniasis in South America. The epidemiology of this disease is also being investigated in the field and laboratory with colleagues in Brazil.
Our research has been supported by funds from The Wellcome Trust, World Health Organisation and Medical Research Council.
Rogers, M.E., Kropf, P., Choi, B.-S., Dillon, R.J., Podinovsaia, M., Bates, P.A. and Müller, I. (2009). Proteophosphoglycans regurgitated by Leishmania-infected sand flies target the L-arginine metabolism of host macrophages to promote parasite survival. PLoS Pathogens 5(8), e1000555.
Sant’Anna, M.R.V., Jones, N.G., Hindley, J.A., Mendes-Sousa, A.F., Dillon, R.J., Cavalcante, R.R., Alexander, J.B. and Bates, P.A. (2008). Blood meal identification and parasite detection in laboratory-fed and field-captured Lutzomyia longipalpis by PCR using FTA databasing paper. Acta Tropica 107, 230-237.
Rogers ME, Hajmová M, Joshi MB, Sadlova J, Dwyer DM, Volf P and Bates PA (2008). Leishmania chitinase facilitates colonization of sand fly vectors and enhances transmission to mice. Cellular Microbiology 10: 1363-1372.
Ranasinghe S, Rogers ME, Hamilton JGC, Bates PA and Maingon RDC (2008). A real time PCR assay to estimate Leishmania chagasi load in its natural sand fly vector Lutzomyia longipalpis. Transactions of the Royal Society for Tropical Medicine and Hygiene 102: 875-882.
Sant’Anna MRV, Alexander JB, Bates PA and Dillon RJ (2008). Gene silencing in phlebotomine sand flies: xanthine dehydrogenase knock down by dsRNA micro-injections. Insect Biochemistry and Molecular Biology 38: 652-660.
Bates PA (2008). Leishmania sand fly interaction: progress and challenges. Current Opinion in Microbiology 11: 340-344.
Siriwardana HVYD, Noyes HA, Beeching NJ, Chance ML, Karunaweera ND and Bates PA (2007). Leishmania donovani is the agent of cutaneous leishmaniasis in Sri Lanka. Emerging Infectious Diseases 13: 476-478.
Rogers ME and Bates PA (2007). Leishmania manipulation of sand fly feeding behavior results in enhanced transmission. PLoS Pathogens 3: 818-825.
Jariyapan N, Choochote W, Jitpakdi A, Harnnoi T, Siriyasatein P, Wilkinson MC and Bates PA (2007). Salivary gland proteins of the human malaria vector, Anopheles Dirus B (Diptera: Culicidae). Revista do Instituto de Medicina Tropical de São Paulo 49: 5-10.
Bates PA (2007). Transmission of Leishmania metacyclic promastigotes by phlebotomine sand flies. International Journal for Parasitology 37, 1097-1106.
Dillon RJ, Ivens AC, Churcher C, Holroyd N, Quail MA, Rogers ME, Soares MB, Bonaldo MF, Casavant TL, Lehane MJ and Bates PA (2006). Analysis of expressed sequence tags from Lutzomyia longipalpis sand flies infected with Leishmania sp. and its contribution towards understanding of the insect vector-parasite relationship. Genomics 88: 831-840.
Rogers ME, Sizova OV, Ferguson MAJ, Nikolaev AV and Bates PA (2006). Synthetic glycovaccine protects against the bite of Leishmania-infected sand flies. Journal of Infectious Diseases 194: 512-518.
Al-Mohammed HI, Chance ML and Bates PA (2005). Production and characterisation of stable amphotericin-resistant amastigotes and promastigotes of Leishmania mexicana. Antimicrobial Agents and Chemotherapy 49: 3274-3280.
Joshi MB, Rogers ME, Shakarian AM, Yamage M, Al-Harthi SA, Bates PA and Dwyer DM (2005). Molecular characterization, expression and in vivo analysis of LmexCht1: the chitinase of the human pathogen Leishmania mexicana. Journal of Biological Chemistry 280: 3847-3861.
Jamjoom MB, Ashford RW, Bates PA, Chance ML, Kemp SJ, Watts P and Noyes HA (2004). Leishmania donovani is the only cause of visceral leishmaniasis in East Africa; previous descriptions of L. infantum and “L. archibaldi” from this region are a consequence of convergent evolution in the isoenzyme data. Parasitology 129: 399-409.
Rogers ME, Ilg T, Nikolaev AV, Ferguson MAJ and Bates PA (2004). Transmission of cutaneous leishmaniasis by sand flies is enhanced by regurgitation of fPPG. Nature 430: 463-467.