pathogens using reactive nitrogen and oxygen intermediates. they effectively subvert the production of reactive oxygen species. in this way the amastigotes are able to survive and replicate inside these primary immune systems. the parasites manipulate the cell signalling pathway of the macrophages, such as down-regulating of jak/stat signalling, no and tnf-α production, and also by blocking the nf-κb-dependent pathway. there are two major mechanisms of immune evasion such as induction of immune suppressive il-10 responses and the generation of poor and functionally impaired cd8(+) t-cell responses. treatment the conventional treatment method is an intravenous injection with antimony compounds, such as pentostam. unfortunately, these chemotherapeutics are so poisonous that about 15% of the patients die from the treatments. to compound the situation, drug resistance has evolved in the parasites against the traditional antimonials. according to rough estimates, about 40% of patients in india are already resistant to this therapy. another antimicrobial drug amphotericin b is also commonly used. liposomal amphotericin b (l-amb) has been a drug of choice in india, but is practically useless in africa because of low effectiveness in the african strain of the parasite. further, amphotericin b has severe adverse effects. its acute effects includes nausea, vomiting, rigors, fever, hypertension or hypotension, and hypoxia, and its chronic effect is nephrotoxicity. in 1999, an anticancer drug miltefosine was demonstrated to be highly effective (95% cure rate) among indian patients. this was the first time an oral drug is effective for visceral leishmaniasis. clinical trials showed that the new drug is relatively harmless. the most adverse effects were only vomiting and diarrhoea in 20–28% patients, which were rather mild. the drug has been officially approved in india. the recommended dosage is 100 mg per day over a period of four weeks. evolution l. donovani is now considered to be a species complex as indicated by different pathological symptoms occurring in different geographical areas where the species of the vector sandfly are also different. however, none of the parasites are morphologically distinguishable, except by molecular analysis, making them cryptic species. molecular data show that genotype is strongly correlated with geographical origin. dna sequencing of different geographical strains indicates that the protozoan complex can be classified into two valid taxa, l. donovani and l. infantum. the genus leishmania most likely originated in south america, from where it migrated to asia. l. donovani and l. infantum diverged ~1 mya, with further divergence of infraspecific genetic groups between 0.4 and 0.8 mya.