Epidemiological, Diagnostic and Drug Discovery Studies of an Emerging Infection: Human Leishmaniasis

Human leishmaniasis is a vector-borne diseases, caused by the Leishmania parasite and endemic in 100 countries, including southern Europe. The clinical spectrum of Leishmania infection ranges from asymptomatic to visceral leishmaniasis (VL), the latter being fatal if not treated. The real prevalence of asymptomatic infections is unknown, the diagnosis of VL is challenging and lacks standardized methods, and also antileishmanial treatment has critical limitations. In this scenario, this study aimed (1) to determine the prevalence of asymptomatic infections in blood donors of the Bologna province, where increase of VL cases has been recently reported, (2) to compare the performance of nine different serological tests in the diagnosis of VL in northern Italy, (3) to assess the antileishmanial activity of a library of newly synthesized natural like compounds, ie chalcones. (1) The screening on samples of blood donors living in the Bologna province, shows a total prevalence of asymptomatic Leishmania infection of 11.5%, suggesting a high circulation of the parasite in this area. (2) Our findings on serodiagnosis indicate that rK39 immunochromatographic tests are insufficiently sensitive as screening tests for VL, ELISA exhibited suboptimal results in terms of sensitivity, IFAT and WB exhibited excellent sensitivity, but their cost and complexity in execution would not allow their employment as screening tests for VL. These results confirm the complexity of VL serodiagnosis and reveal the variability of diagnostic performance of serological tests. (3) Screening of 33 newly synthesized chalcones on proliferation of Leishmania promastigote and amastigote revealed that 2 compounds showed a remarkable antileishmanial potency against the parasite, a low citotoxicity against mammalian cells and they also were able to efficiently bind trypanothione reductase - a specific parasite enzyme - suggesting that these compounds should be further evaluated as antileishmanial agents.