## Leishmaniasis

Yesterday I heard a talk by Ingrid Müller from Imperial College about leishmaniasis, a disease caused by protozoa of the genus Leishmania. The genus is named after the Scottish pathologist and army medical officer William Leishman. The life cycle of the parasite is of a similar type to that of the organism which causes malaria. Humans are infected by the bite of a sand fly (instead of mosquito in the case of malaria) and the individual infected in this way then passes on the parasite to other sand flies taking blood meals. While the malaria parasite makes its way to red blood cells the preferred target of Leishmania are macrophages, where it lives in certain vesicles. In this sense it is similar to the tuberculosis bacterium and has to meet similar challenges, such as not being digested. There are different forms of leishmaniasis. The cutaneous form, which is the most common, affects the skin and is cleared by the immune system after some time. Another, the visceral form, is much more serious. In the latter case the parasite damages internal organs and may be fatal if not treated. It could be said that cutaneous leishmaniasis is not a very serious disease, compared to many others. Unfortunately even when the lesion on the skin heals it can leave the affected person seriously disfigured. Thus there is a strong motivation for combatting it. Not surprisingly leishmaniasis is only common in parts of the world where poverty is widespread (Africa, South America, India) although cases do also occur in southern Europe. In parts of India the visceral form is known under the name kala azar. Searching for this disease on the internet you find a relatively large number of sites relating to dogs. What is behind this is the following. Dogs can also be affected by these parasites. When dog-lovers bring stray dogs from Spain to Germany (for instance) there exists an appreciable risk that the dogs may bring the parasites with them. Thus care is necessary.

Leishmaniasis is much less well-known than malaria and the available scientific knowledge of the disease and (as a natural consequence) the available treatments are much more rudimentary. What treatments there are are expensive, which is particularly problematic in the regions where they are necessary. Leishmaniasis is also much less common than malaria but in fact no up to date and reliable epidemiological data is available so that it is not clear how common it is. Infections of mice with Leishmania have been a popular model system in immunology. The cutaneous and visceral forms have been associated with Th1 and Th2 type responses respectively in the past. According to the speaker this association is controversial. A simple picture would be that a Th1 response results in a high concentration of interferon $\gamma$ which activates macrophages and thus allows them the kill the parasites infecting them. It was mentioned in the talk that macrophages can also be activated in a different way by IL4 (the typical Th2 cytokine) in what is called alternative activation. This leads to production of the enzyme arginase which metabolises arginine. In the talk evidence was presented that the resulting metabolites can serve as raw materials for the replication of the parasite in the hostile environment of the phagosome. This has been supported by showing that parasite growth can be accelerated by adding metabolites downstream of arginine, such as ornithine. What I heard in this talk has contributed to my opinion that while the Th1-Th2 axis is useful for generating ideas for understanding various diseases it is necessary to keep in mind that it is likely to be an oversimplification of a complex state of affairs.