Magnitude of unreported kala-azar cases in a highly endemic district of Bihar, India: A positive impact of Indian elimination programme.

BACKGROUND & OBJECTIVES: In India, kala-azar surveillance is weak and no public-private partnership exists for disease containment. Estimate of disease burden is not reliably available and still cases are going to private providers for the treatment. The present study aimed to assess the magnitude of kala-azar cases actually detected and managed at private set-up and unreported to existing health management information system. METHODS: Institution based cross-sectional prospective pilot study was conducted. List of facilities was created with the help of key informants. The information about incidence of kala-azar cases were captured on monthly basis from July 2010 to June 2011. Rapid diagnostic strip test (rk-39) or bone marrow/splenic puncture were applied as laboratory methods for the diagnosis of kala-azar. Descriptive statistics as well as chi-square test for comparison between proportions was conducted. RESULTS: Overall availability of private practitioners (PPs) was 4.59/1,00,000 population and maximum PPs (46; 93.9%) were from qualified category. The median years of medical practice was 25 yr (inter quartile-range [18, 28]). Interestingly, only a small proportion (240; 19%) of cases was managed by PPs. Amongst the PPs, only low proportion (32; 18.2%) managed >2 cases per month. The mean number of kala-azar suspects and cases identified varied significantly between different PPs' professions with p <0.048 and p <0.032, respectively. A highly significant difference (p <0.0001) was observed for kala-azar case load between qualified and unqualified practitioners. A small proportion (38; 15.8%) of kala-azar cases was not present in the public health system record. INTERPRETATION & CONCLUSION: Still sizeable proportions of cases are going to PPs and unrecorded into government surveillance system. A mechanism need to be devised to involve at least qualified PPs in order to reduce treatment delay and increase case detection in the region.

Vaccine potential of HLA-A2 epitopes from Leishmania Cysteine Protease Type III (CPC).

Although the precise host-defence mechanisms are not completely understood, T-cell-mediated immune responses are believed to play a pivotal role in controlling parasite infection. In this study, the potential HLA*A2 restricted peptides were predicted and the ability of peptides to bind HLA-A*02 was confirmed by a MHC stabilization assay. Two of the peptides tested stabilized HLA-A*02: (a) LLATTVSGL (P1) and (b) LMTNGPLEV (P3). The potential of the peptides to generate protective immune response was evaluated in patients with treated visceral leishmaniasis as well as in healthy control subjects. Our data suggest that CD8+ T-cell proliferation against the selected peptide was significantly higher compared to unstimulated culture conditions. The stimulation of peripheral blood mononuclear cells with epitopes individually or as a cocktail upregulated IFN-γ production, which indicates its pivotal role in protective immune response. The IFN-γ production was mainly in a CD8+ T-cells-dependent manner, which suggested that these epitopes had an immunoprophylactic potential in a MHC class I-dependent manner. Moreover, no role of the CD3+ T cell was observed in the IL-10 production against the selected peptides, and no role was found in disease pathogenesis. Further studies on the role of these synthetic peptides may contribute significantly to developing a polytope vaccine idea towards leishmaniasis.

Exploring novel KDR inhibitors based on pharmaco-informatics methodology.

Kinase-insert domain-containing receptor (KDR) is one of the important mediators of Vascular endothelial growth factor (VEGF) function in endothelial cells. Inhibition of KDR can be therapeutically advantageous for treatment of a number of diseases. The present study focuses on exploring novel KDR inhibitors by means of pharmaco-informatics methodologies. Three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis by atom-based pharmacophore mapping over a set of 85 molecules provides a proposition regarding the molecular fingerprint that can be optimized for designing more active inhibitors. The model was statistically validated with Q(2) = 0.865 for training and r(2) = 0.789, Pearson-r = 0.903 for test set molecules; r(2)(0.925) by external validation suggests model robustness and indicates it as a strong query for screening any compound library. Virtual screening shows the importance of active site and hinge region residue for interaction with KDR inhibitors. Remarkably the retrieved hits contain a urea backbone, implicating urea derivatives as promising candidate for designing KDR inhibitors. The hydrophobicity of active site, which has until now been overlooked, has been raised into the picture by this study. This can impact on KDR drug development. The study thus quantifies crucial structural requirements necessary for a favourable interaction with the receptor binding site while the cooperative pattern provides important structural clues to chemists for framing potent medicinal agents in future.