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.