Pradeep Das

Publications (88)288.17 Total impact

• Article: Structure prediction of gBP21 protein of L. donovani and its molecular interaction

  Ganesh Chandra Sahoo, Md. Yousuf Ansari, Manas Ranjan Dikhit, M. Kannan, Sindhuprava Rana, Pradeep Das
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  ABSTRACT: Visceral leishmaniasis (Kala-azar) is a fatal disease caused by the obligate intracellular parasite Leishmania donovani and the available drugs for the treatment are few, and are frequently associated with side effects and toxicity. RNA editing is one of the essential metabolic processes in the kinetoplastids, where the pre-mRNAs are edited post-transcriptionally by the guide RNAs with the addition or deletion of uridine residues. The aim is to block the gBP21 protein involved in RNA editing process thereby other direct and indirect protein activity is reduced and ultimately the editing process in L. donovani is disturbed and it will inhibit the growth. RNA editing factors are RNA-linked proteins essential for in vivo editing i.e. mitochondrial RNA binding protein1 (MRP 1) originally called as gBP21. The model of L. donovani gBP21 (gBP21Ldv) showed that this protein bears an anti-parallel ß sheet (segregated α and ß regions) with ß-ß-ß-ß-α-ß-ß-ß-ß-α-type topology (“whirly” transcription-factor fold). Each of the four ß strands within a given ß-ß-ß-ß-α repeats and form a curved anti-parallel ß-sheet that packs perpendicularly against the sheet from the other repeat. Among all of the computationally screened compounds by the GLIDE program (Schrödinger) and GOLD program hyperoside1a, posaconazole, quercetin, and pentanediol, 427 exhibited higher binding affinities with the modeled gBP21 protein of L. donovani. Ligandfit program (DSv2.5) revealed that DNA, RNA polymerase inhibitors acyclovir, mitomycin C, and daunorubicin have better binding affinity towards gBP21Ldv. These compounds may be given in combination with miltefosine (first line therapy) against patients with VL and other associated disorders like anemia.
  Journal of biomolecular structure & dynamics 06/2013; · 4.99 Impact Factor
• Article: Effectiveness of miltefosine treatment in targeting anti-leishmanial HO-1/Nrf-2-mediated oxidative responses in visceral leishmaniasis patients.

  Sushmita Das, Krishna Pandey, Vidya N Rabidas, Abhishek Mandal, Pradeep Das
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  ABSTRACT: OBJECTIVES: Miltefosine, an alkylphosphocholine anti-cancer drug, exhibits direct activity against Leishmania donovani and also promotes anti-leishmanial host immunomodulatory functions. Nuclear factor-erythroid 2-related factor 2 (Nrf-2), a redox-sensitive transcription factor, regulates the host stress responses leading to effective microbial clearance by a positive effect on haem oxygenase-1 (HO-1) enzyme expression/activity. We aimed to investigate the role of miltefosine in regulating HO-1/Nrf-2-mediated oxidative responses in visceral leishmaniasis (VL) patients in vivo and in vitro. METHODS: Splenic aspirate and bone marrow aspirate cells of VL patients (n = 23) were used in the study. RT-PCR of HO-1, Nrf-2 translocation analysis and HO-1 ELISA were used to investigate the HO-1/Nrf-2-mediated modulation of oxidative responses by miltefosine in vivo. Fluorometric measurement of reactive oxygen species (ROS) was performed, determination of glutathione peroxidase (GPx) activity was performed, and bilirubin and superoxide dismutase (SOD) levels were determined. The in vitro HO-1/Nrf-2-dependent anti-leishmanial effect of miltefosine was assessed by the use of specific inhibitors/inducers and subsequent microscopic measurement of parasite killing and Th1/Th2 cytokine regulation by ELISA. RESULTS: Increased levels of transcript and serum HO-1, Nrf-2 nuclear translocation, serum bilirubin, GPx and SOD activity in untreated VL patients were reversed after miltefosine chemotherapy. The effectiveness of miltefosine for positive induction of ROS via NADPH correlated with a decrease in HO-1/ERK/Nrf-2-dependent parasite load. Furthermore, HO-1 blockade by miltefosine led to suppression of interleukin-10 and transforming growth factor-β, but enhanced interleukin-12 and tumour necrosis factor-α production, in VL patients. CONCLUSIONS: The antioxidant promoting property of L. donovani is crucial for protection against the mounting redox threat in the host. Therefore, these findings provide direct evidence for targeting HO-1/Nrf-2 as an anti-leishmanial approach for chemotherapy in human VL.
  Journal of Antimicrobial Chemotherapy 05/2013; · 5.07 Impact Factor
• Article: Diagnosis of Visceral Leishmaniasis in Bihar India: Comparison of the rK39 Rapid Diagnostic Test on Whole Blood Versus Serum.

  Greg Matlashewski, Vidya Nand Ravi Das, Krishna Pandey, Dharmendra Singh, Sushmita Das, Ayan Kumar Ghosh, Ravindra Nath Pandey, Pradeep Das
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  ABSTRACT: Antibody-detecting rapid diagnostic tests (RDTs) against rK39 are available to aid in the diagnosis of visceral leishmaniasis (VL). Although these rK39 RDTs have been developed, validated and approved for use with serum, they are universally performed using whole blood. It was therefore necessary to determine whether this RDT is as sensitive on whole blood as on serum. In this study we compared the rK39 RDT on serum and blood samples from 624 individuals with symptoms of VL attending the outpatient clinic at the Rajendra Memorial Research Institute of Medical Sciences, Patna, India. A total of 251 cases (40%) were both serum and blood-positive and 26 cases (4%) were identified as blood-negative and serum-positive. These 26 individuals in general had low titer antibodies against rK39 as determined by ELISA and follow-up on most of these individuals revealed none had persistent VL symptoms. The Cohen kappa index comparing blood and serum was 0.88 indicating excellent concordance. Although the concordance was excellent, it is possible to miss rK39 positive individuals when using blood and the titer of anti-rK39 antibodies is low. We recommend that when an individual from an endemic area has obvious clinical symptoms of VL and the whole blood rK39 RDT is negative, that the test should be redone 2-3 weeks later if the symptoms persist.
  PLoS Neglected Tropical Diseases 05/2013; 7(5):e2233. · 4.69 Impact Factor
• Article: Appraisal of Phlebotomus argentipes habitat suitability using a remotely sensed index in the kala-azar endemic focus of Bihar, India.

  Shreekant Kesari, Gouri Sankar Bhunia, Nandini Chatterjee, Vijay Kumar, Rakesh Mandal, Pradeep Das
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  ABSTRACT: Visceral leishmaniasis, or kala-azar, is recognised as a serious emerging public health problem in India. In this study, environmental parameters, such as land surface temperature (LST) and renormalised difference vegetation indices (RDVI), were used to delineate the association between environmental variables and Phlebotomus argentipes abundance in a representative endemic region of Bihar, India. The adult P. argentipes were collected between September 2009-February 2010 using the hand-held aspirator technique. The distribution of P. argentipes was analysed with the LST and RDVI of the peak and lean seasons. The association between environmental covariates and P. argentipes density was analysed a multivariate linear regression model. The sandfly density at its maximum in September, whereas the minimum density was recorded in January. The regression model indicated that the season, minimum LST, mean LST and mean RDVI were the best environmental covariates for the P. argentipes distribution. The final model indicated that nearly 74% of the variance of sandfly density could be explained by these environmental covariates. This approach might be useful for mapping and predicting the distribution of P. argentipes, which may help the health agencies that are involved in the kala-azar control programme focus on high-risk areas.
  Memórias do Instituto Oswaldo Cruz 04/2013; 108(2):197-204. · 2.15 Impact Factor
• Article: Spatial and temporal variation and hotspot detection of kala-azar disease in Vaishali district (Bihar), India.

  Gouri Sankar Bhunia, Shreekant Kesari, Nandini Chatterjee, Vijay Kumar, Pradeep Das
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  ABSTRACT: BACKGROUND: An improved understanding in transmission variation of kala-azar is fundamental to conduct surveillance and implementing disease prevention strategies. This study investigated the spatio-temporal patterns and hotspot detection for reporting kala-azar cases in Vaishali district based on spatial statistical analysis. METHODS: Epidemiological data from the study area during 2007--2011 was used to examine the dynamic space-time pattern of kala-azar outbreaks, and all cases were geocoded at a village level. Spatial smoothing was applied to reduce random noise in the data. Inverse distance weighting (IDW) is used to interpolate and predict the pattern of VL cases distribution across the district. Moran's I Index (Moran's I) statistics was used to evaluate autocorrelation in kala-azar spatial distribution and test how villages were clustered or dispersed in space. Getis-Ord Gi* (d) was used to identify the hotspot and cold spot areas within the study site. RESULTS: Mapping kala-azar cases or incidences reflects the spatial heterogeneity in the incidence rate of kala-azar affected villages in Vaishali district. Kala-azar incidence rate map showed most of the highest endemic villages were located in southern, eastern and northwestern part of the district; in the middle part of the district generally show the medium occurrence of VL. There was a significant positive spatial autocorrelation of kala-azar incidences for five consecutive years, with Moran's I statistic ranging from 0.04-0.17 (P <0.01). The results revealed spatially clustered patterns with significant differences by village. The hotspots showed the spatial trend of kala-azar diffusion (P < 0.01). CONCLUSIONS: The results pointed to the usefulness of spatial statistical approach to improve our understanding the spatio-temporal dynamics and control of kala-azar. The study also showed the north-western and southern part of Vaishali district is most likely endemic cluster region. To employ exact and geographically suitable risk-reduction programmes, apply of such spatial analysis tools should suit a vital constituent in epidemiology research and risk evaluation of kala-azar.
  BMC Infectious Diseases 02/2013; 13(1):64. · 3.12 Impact Factor
• Article: Proteome changes associated with Leishmania donovani promastigote adaptation to oxidative and nitrosative stress.

  Abul Hasan Sardar, Sudeep Kumar, Ashish Kumar, Bidyut Purkait, Sushmita Das, Abhik Sen, Manish Kumar, Kislay Kumar Sinha, Dharmendra Singh, Asif Equbal, Vahab Ali, Pradeep Das
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  ABSTRACT: Phagocytic cells produce reactive oxygen and nitrogen species (ROS & RNS) as the most common arsenal to kill intracellular pathogens. Leishmania, an obligate intracellular pathogen also confronts this antimicrobial assault during the early phase of infection but nevertheless is able to survive these attacks and proliferate in macrophage. Adaptation of Leishmania to the toxic effects of ROS and RNS, involves a rapid change in the parasite proteome to combat the host defense response that macrophage mount in combating pathogen. To understand the events associated with combating ROS and RNS species, we performed a proteomic analysis of L. donovani promastigotes treated with sub-lethal doses of menadione (ROS), S-nitroso-N-acetylpenicillamine (RNS) or combination of both compounds. Proteomic changes triggered by these reagents were evaluated by iTRAQ labeling and subsequent LC-MALDI-TOF/TOF-MS analysis. Across the 3 stress conditions, the quantitative analysis identified changes in the proteins which encompass ~20% of the parasite proteome. Major changes were observed in enzymatic machinery of pathways involved in maintaining redox homeostasis, trypanothione metabolism, oxidative phosphorylation, superoxide metabolism, mitochondrial respiration process and other essential metabolic pathways. These observations shed light on how Leishmania promastigotes counter ROS and RNS affects during the initial stage of infection.
  Journal of Proteomics 01/2013; · 4.88 Impact Factor
• Article: Comparative analysis of serum zinc, copper, magnesium, calcium and iron level in acute and chronic patients of visceral leishmaniasis.

  Chandra S Lal, Sanjay Kumar, Alok Ranjan, Vidya N Rabidas, Neena Verma, Krishna Pandey, Rakesh B Verma, Sushmita Das, Dharmendra Singh, Pradeep Das
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  ABSTRACT: PROJECT: Chronic visceral leishmaniasis (VL) is an increasingly common problem in disease endemic states of India. Identification of prognosis risk factor in patients with VL may lead to preventive actions, toward decreasing its mortality in chronic individuals. Though serum Zinc levels are decreased in patients of VL, limited information is available regarding trace elements status in acute and chronic VL patients. The present study was undertaken to compare serum trace elements concentrations in acute and chronic VL patients. PROCEDURE: Acute (mean age=28.64years), chronic (mean age=23.68years) VL patients and healthy controls (mean age=23.05years) who agreed to provide blood specimens for laboratory investigations participated in this study. Serum zinc (Zn), copper (Cu), iron (Fe), magnesium (Mg) and calcium (Ca) were measured spectrophotometrically using chemistry analyzer. RESULTS: Serum Zn concentration was comparatively much decreased in chronic VL than to acute ones (p=0.007) while serum Mg was higher in chronic VL than acute (p=0.002) ones. There was no statistically significant difference between acute and chronic VL in serum concentrations of Cu, Fe and Ca. CONCLUSIONS: Serum Zn levels were much decreased and serum Mg were increased in chronic VL as compared to acute cases. The serum concentrations of Fe and Ca did not show any difference between two groups. The serum Cu was increased in both groups but more in chronic ones. Serum Zn and Mg could be a potential prognosis factor for chronic VL patients. We hypothesize zinc supplementation as a chemo preventive agent for chronic VL cases, particularly in endemic areas.
  Journal of Trace Elements in Medicine and Biology 11/2012; · 1.68 Impact Factor
• Article: Active case detection in national visceral leishmaniasis elimination programs in Bangladesh, India, and Nepal: feasibility, performance and costs.

  M Mamun Huda, Siddhivinayak Hirve, Niyamat Ali Siddiqui, Paritosh Malaviya, Megha Raj Banjara, Pradeep Das, Sangeeta Kansal, Chitra Kumar Gurung, Eva Naznin, Suman Rijal, Byron Arana, Axel Kroeger, Dinesh Mondal
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  ABSTRACT: BACKGROUND: Active case detection (ACD) significantly contributes to early detection and treatment of visceral leishmaniasis (VL) and post kala-azar dermal leishmaniasis (PKDL) cases and is cost effective. This paper evaluates the performance and feasibility of adapting ACD strategies into national programs for VL elimination in Bangladesh, India and Nepal. METHODS: The camp search and index case search strategies were piloted in 2010-11 by national programs in high and moderate endemic districts respectively. Researchers independently assessed the performance and feasibility of these strategies through direct observation of activities and review of records. Program costs were estimated using an ingredients costing method. RESULTS: Altogether 48 camps (Bangladesh-27, India-19, Nepal-2) and 81 index case searches (India-36, Nepal-45) were conducted by the health services across 47 health center areas (Bangladesh-4 Upazillas, India-5 PHCs, Nepal-38 VDCs). The mean number of new case detected per camp was 1.3 and it varied from 0.32 in India to 2.0 in Bangladesh. The cost (excluding training costs) of detecting one new VL case per camp varied from USD 22 in Bangladesh, USD 199 in Nepal to USD 320 in India. The camp search strategy detected a substantive number of new PKDL cases. The major challenges faced by the programs were inadequate preparation, time and resources spent on promoting camp awareness through IEC activities in the community. Incorrectly diagnosed splenic enlargement at camps probably due to poor clinical examination skills resulted in a high proportion of patients being subjected to rK39 testing. CONCLUSION: National programs can adapt ACD strategies for detection of new VL/PKDL cases. However adequate time and resources are required for training, planning and strengthening referral services to overcome challenges faced by the programs in conducting ACD.
  BMC Public Health 11/2012; 12(1):1001. · 2.00 Impact Factor
• Source

  Available from: Ashish Kumar

  Article: Evaluation of rK-39 Strip Test Using Urine for Diagnosis of Visceral Leishmaniasis in an Endemic Region of India.

  Dharmendra Singh, Krishna Pandey, Vidya Nand Rabi Das, Susmita Das, Neena Verma, Alok Ranjan, Sekhar Chandra Lal, Kamal Roshan Topno, Shubhankar Kumar Singh, Rakesh Bihari Verma, Ashih Kumar, Abul Hasan Sardar, Bidyut Purkait, Pradeep Das
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  ABSTRACT: The definitive diagnosis of visceral leishmaniasis (VL) requires invasive procedures for demonstration of parasites in tissue smear or culture. These procedures need expertise and laboratory supports and cannot be performed in the field. The aim of the present study was to evaluate the existing rK-39 immunochromatographic nitrocellulose strips test (ICT) with some modification in human urine for diagnosis of VL. The test was performed on both sera and urine samples on the same 786 subjects (365 confirmed VL and 421 control subjects). The sensitivity of the rK-39 ICT in serum was 100%, whereas the specificity was 93.8%, 100%, and 96.2% in healthy controls from endemic, non-endemic, and other infectious diseases, respectively. However, in urine samples, the test showed 96.1% sensitivity and 100% specificity. Considering sensitivity and feasibility of the test in the field, rK-39 ICT using urine samples can be an alternative to conventional invasive VL diagnosis.
  The American journal of tropical medicine and hygiene 11/2012; · 2.59 Impact Factor
• Article: Agar barrier method for removal of yeast and other fungal contamination from Leishmania promastigotes culture.

  Anil Kumar Gupta, Shyam Narayan, Shubhankar Kumar Singh, Ajit Kumar Thakur, Pradeep Das
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  ABSTRACT: The present study explains a novel method of Leishmania promastigotes culture decontamination. The method is based on motility of Leishmania promastigotes across agar barrier which facilitates decontamination from yeast and other non motile contamination. This is inexpensive, easy, rapid and reliable physical method and is able to save valuable isolates in culture.
  Pathogens and global health. 11/2012; 106(7):418-20.
• Article: Seasonal relationship between normalized difference vegetation index and abundance of the Phlebotomus kala-azar vector in an endemic focus in Bihar, India.

  Gouri S Bhunia, Shreekant Kesari, Nandini Chatterjee, Nicolás Frutos, Rakesh Mandal, Gonzalo Peralta, Vijay Kumar, Pradeep Das
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  ABSTRACT: Remote sensing was applied for the collection of spatio-temporal data to increase our understanding of the potential distribution of the kala-azar vector Phlebotomus argentipes in endemic areas of the Vaishali district of Bihar, India. We produced monthly distribution maps of the normalized difference vegetation index (NDVI) based on data from the thematic mapper (TM) sensor onboard the Landsat-5 satellite. Minimum, maximum and mean NDVI values were computed for each month and compared with the concurrent incidence of kala-azar and the vector density. Maximum and mean NDVI values (R2 = 0.55 and R2 = 0.60, respectively), as well as the season likelihood ratio (X2 = 17.51; P <0.001), were found to be strongly associated with kala-azar, while the correlation with between minimum NDVI values and kala-azar was weak (R2 = 0.25). Additionally, a strong association was found between the mean and maximum NDVI values with seasonal vector abundance (R2 = 0.60 and R2 = 0.55, respectively) but there was only a marginal association between minimum NDVI value and the spatial distribution of kala-azar vis-à-vis P. argentipes density.
  Geospatial health 11/2012; 7(1):51-62. · 3.00 Impact Factor
• Article: Corrigendum to "Role of remote sensing, geographic bioinformatics system and bioinformatics in kala-azar epidemiology" [originally published as J Biomed Res 2011, 25(6):373-384; doi:10.1016/S1674-8301(11)60050-X].

  Gouri Sankar Bhunia, Manas Ranjan Dikhit, Shreekant Kesari, Ganesh Chandra Sahoo, Pradeep Das
  Journal of biomedical research. 09/2012; 26(5):371.
• Source

  Available from: Marleen Boelaert

  Article: A Global Comparative Evaluation of Commercial Immunochromatographic Rapid Diagnostic Tests for Visceral Leishmaniasis.

  Jane Cunningham, Epco Hasker, Pradeep Das, Sayda El Safi, Hiro Goto, Dinesh Mondal, Margaret Mbuchi, Maowia Mukhtar, Ana Rabello, Suman Rijal, Shyam Sundar, Monique Wasunna, Emily Adams, Joris Menten, Rosanna Peeling, Marleen Boelaert
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  ABSTRACT: Background. Poor access to diagnosis stymies control of visceral leishmaniasis (VL). Antibody-detecting rapid diagnostic tests (RDTs) can be performed in peripheral health settings. However, there are many brands available and published reports of variable accuracy. Methods. Commercial VL RDTs containing bound rK39 or rKE16 antigen were evaluated using archived human sera from confirmed VL cases (n = 750) and endemic non-VL controls (n = 754) in the Indian subcontinent (ISC), Brazil, and East Africa to assess sensitivity and specificity with 95% confidence intervals. A subset of RDTs were also evaluated after 60 days' heat incubation (37°C, 45°C). Interlot and interobserver variability was assessed. Results. All test brands performed well against ISC panels (sensitivity range, 92.8%-100%; specificity range, 96%-100%); however, sensitivity was lower against Brazil and East African panels (61.5%-91% and 36.8%-87.2%, respectively). Specificity was consistently > 95% in Brazil and ranged between 90.8% and 98% in East Africa. Performance of some products was adversely affected by high temperatures. Agreement between lots and readers was good to excellent (κ > 0.73-0.99). Conclusions. Diagnostic accuracy of VL RDTs varies between the major endemic regions. Many tests performed well and showed good heat stability in the ISC; however, reduced sensitivity against Brazilian and East African panels suggests that in these regions, used alone, several RDTs are inadequate for excluding a VL diagnosis. More research is needed to assess ease of use and to compare performance using whole blood instead of serum and in patients coinfected with human immunodeficiency virus.
  Clinical Infectious Diseases 08/2012; 55(10):1312-1319. · 9.15 Impact Factor
• Article: Delimitation of kala-azar risk areas in the district of Vaishali in Bihar (India) using a geo-environmental approach.

  Gouri Sankar Bhunia, Nandini Chatterjee, Vijay Kumar, Niyamat Ali Siddiqui, Rakesh Mandal, Pradeep Das, Shreekant Kesari
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  ABSTRACT: Remote sensing and geographical information technologies were used to discriminate areas of high and low risk for contracting kala-azar or visceral leishmaniasis. Satellite data were digitally processed to generate maps of land cover and spectral indices, such as the normalised difference vegetation index and wetness index. To map estimated vector abundance and indoor climate data, local polynomial interpolations were used based on the weightage values. Attribute layers were prepared based on illiteracy and the unemployed proportion of the population and associated with village boundaries. Pearson's correlation coefficient was used to estimate the relationship between environmental variables and disease incidence across the study area. The cell values for each input raster in the analysis were assigned values from the evaluation scale. Simple weighting/ratings based on the degree of favourable conditions for kala-azar transmission were used for all the variables, leading to geo-environmental risk model. Variables such as, land use/land cover, vegetation conditions, surface dampness, the indoor climate, illiteracy rates and the size of the unemployed population were considered for inclusion in the geo-environmental kala-azar risk model. The risk model was stratified into areas of "risk"and "non-risk"for the disease, based on calculation of risk indices. The described approach constitutes a promising tool for microlevel kala-azar surveillance and aids in directing control efforts.
  Memórias do Instituto Oswaldo Cruz 08/2012; 107(5):609-20. · 2.15 Impact Factor
• Source

  Available from: Mukta Rani

  Article: Combination of paromomycin and miltefosine promotes TLR4-dependent induction of antileishmanial immune response in vitro.

  Sushmita Das, Mukta Rani, Krishna Pandey, Ganesh Chandra Sahoo, Vidya Nand Rabidas, Dharmendra Singh, Pradeep Das
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  ABSTRACT: To evaluate the in vitro activity of antileishmanial drugs, paromomycin and miltefosine, to generate Th-1-biased immunomodulation in hosts against intracellular Leishmania donovani. In silico protein-ligand interaction and in vitro drug-cell interaction assays were performed. Interaction assays of TLR4-deficient HEK293 cells and HEK293 cells engineered to express either TLR4 or TLR2 with different concentrations of miltefosine and/or paromomycin sulphate were performed for 48 h. Differentially transfected human peripheral blood monocyte-derived macrophages (PBMFs) were treated with the drugs, and nuclear factor (NF)-κB promoter activity was measured using a κB-luciferase reporter construct. PBMFs were infected with L. donovani. Cultures were incubated with miltefosine or paromomycin sulphate over different concentrations, as mono-treatment or combined. The in vitro antileishmanial effect of the drugs on macrophage-bound L. donovani amastigotes was measured in terms of parasite killing and production of tumour necrosis factor-α (TNF-α) and nitric oxide. Computational studies reveal that paromomycin and miltefosine interact with TLR4. Both drugs, as monotherapy or in combination, induce release of TNF-α and nitric oxide in a TLR4-dependent manner. Interestingly, the TLR4-dependent action of the drugs leads to NF-κB promoter activation through MyD88. In vitro, both the drugs kill macrophage-bound L. donovani by inducing release of TNF-α and nitric oxide in a TLR4-dependent manner. The in vitro activity of paromomycin and miltefosine against host cells is TLR4 dependent. This has implications for: (i) evaluation of in vitro activity of combinational antileishmanial therapy; (ii) the evaluation of drug susceptibility of clinical isolates; and (iii) the standardization of in vitro antileishmanial assays for determining toxicity in hosts.
  Journal of Antimicrobial Chemotherapy 07/2012; 67(10):2373-8. · 5.07 Impact Factor
• Article: Telehealth: a perspective approach for visceral leishmaniasis (kala-azar) control in India.

  Gouri Sankar Bhunia, Shreekant Kesari, Nandini Chatterjee, Vijay Kumar, Pradeep Das
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  ABSTRACT: Visceral leishmaniasis, also known as kala-azar, is a vector borne disease caused by the protozoan parasite, L. donovani. Poor and neglected populations in Indian sub-continent are particularly affected by this disease. Due to the diversity of epidemiological situations, no single diagnosis, treatment, or control will be suitable for all. Control measures through case findings, treatment, and vector control are seldom used, even where they could be useful. Modern tools like telehealth, using space technology, have now come in handy to address issues of disease surveillance, control checking, and evaluation. The present study focuses on telehealth as a current vector control strategy, perspectives on diagnosis, treatment, and control of visceral leishmaniasis as these deserve more attention and research.
  Pathogens and global health. 07/2012; 106(3):150-8.
• Article: Clinical epidemiologic profile of a cohort of post-kala-azar dermal leishmaniasis patients in Bihar, India.

  Vidya Nand Rabi Das, Alok Ranjan, Krishna Pandey, Dharmendra Singh, Neena Verma, Sushmita Das, Chandra S Lal, Naresh K Sinha, Rakesh B Verma, Niyamat A Siddiqui, Pradeep Das
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  ABSTRACT: Post-kala-azar dermal leishmaniasis (PKDL) has important public health implications for transmission of visceral leishmaniasis (VL). Clinical and epidemiologic profiles of 102 PKDL patients showed that median age of males and females at the time of diagnosis was significantly different (P = 0.013). A significant association was observed between family history of VL and sex of PKDL patients (χ(2) = 5.72, P < 0.01). Nearly 33% of the patients showed development of PKDL within one year of VL treatment. The observed time (median = 12 months) between appearance of lesions and diagnosis is an important factor in VL transmission. A significant association was observed between type of lesions and duration of appearance after VL treatment (χ(2) = 6.59, P = 0.001). Because PKDL was observed during treatment with all currently used anti-leishmanial drugs, new drug regimens having high cure rates and potential to lower the PKDL incidence need to be investigated.
  The American journal of tropical medicine and hygiene 06/2012; 86(6):959-61. · 2.59 Impact Factor
• Article: Leishmania donovani: CD2 biased immune response skews the SAG mediated therapy for a predominant Th1 response in experimental infection.

  Sanjiva Bimal, Sukrat Sinha, Shubhankar K Singh, Shyam Narayan, Vikash Kumar, Neena Verma, Alok Ranjan, P K Sinha, V N R Das, K Pandey, Shantanu K Kar, Pradeep Das
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  ABSTRACT: We have evaluated the effect of combining CD2 with conventional antimonial (sb) therapy in protection in BALB/c mice infected with either drug sensitive or resistant strain of Leishmania donovani with 3×10(7) parasites via-intra-cardiac route. Mice were treated with anti CD2 adjunct SAG sub-cutaneously twice a week for 4 weeks. Assessment for measurement of weight, spleen size, anti-Leishmania antibody titer, T cell and anti-leishmanial macrophage function was carried out day 0, 10, 22 and 34 post treatments. The combination therapy was shown boosting significant proportion of T cells to express CD25 compared to SAG monotherapy. Although, the level of IFN-γ was not statistically different between combination vs monotherapy (p=0.298) but CD2 treatment even alone significantly influenced IFN-γ production than either SAG treatment (p=0.045) or with CD2 adjunct SAG treatment (p=0.005) in Ld-S strain as well as in Ld-R strain. The influence of CD2 adjunct treatment was also documented in anti-leishmanial functions in macrophages. As shown, the super-oxide generation began enhancing very early on day 10 after SAG treatment with CD2 during which SAG action was at minimum. Interestingly, the super-oxide generation ability remained intact in macrophage after treatment with immuno-chemotherapy even in mice infected with Leishmania resistant strain. Unlike SAG treatment, treatment of SAG with CD2 also led to production of nitric oxide and TNF-α, resulting in resulting in most effective clearance of L. donovani from infected macrophages. Our results indicate that CD2, which can boost up a protective Th1 response, might also be beneficial to enable SAG to induce Macrophages to produce Leishmanicidal molecules and hence control the infection in clinical situation like Kala-azar. Drug resistance is the major impedance for disease control but the encouraging results obtained after infecting mice with resistant strain of the parasite strongly imply that this drug can be effective even in treating resistant cases of Kala-azar.
  Experimental Parasitology 05/2012; 131(3):274-82. · 2.12 Impact Factor
• Article: Localization of kala-azar in the endemic region of Bihar, India based on land use/land cover assessment at different scales.

  Gouri Sankar Bhunia, Shreekant Kesari, Nandini Chatterjee, Vijay Kumar, Pradeep Das
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  ABSTRACT: Land cover, a critical variable in the epidemiology of kala-azar, can be remotely characterized by customizing and integrating "state-of-the-art" imagery at different spatial scales from different sensors onboard satellites. A study was conducted at four levels (national, state, district and village) investigating the role of land use/land cover (LULC) for leishmaniasis transmission resulting in a framework highlighting the links between LULC and areas endemic for the disease. Distribution maps were analysed by a probabilistic approach (Bayesian classifier) which produced a set of "suitability estimates" based on the probability of sand fly presence. The development of a sound knowledge of each link in the predicted sequence of satellite views offering an extraordinary opportunity to support the mapping of kala-azar endemicity and stratification of areas suitable for sand fly habitats across the country as well as at the local scale.
  Geospatial health 05/2012; 6(2):177-93. · 3.00 Impact Factor
• Article: Tuberous sclerosis with visceral leishmaniasis: a case report

  Krishna Pandey, PrabhatK Sinha, VidyanandR Das, Nawin Kumar, Sanjiva Bimal, RakeshB Verma, Neena Verma, ChandraS Lal, RoshanK Topno, NA Siddiqui, Dharmendra Singh, Pradeep Das
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  ABSTRACT: IntroductionVisceral leishmaniasis, a tropical infectious disease, is a major public health problem in India. Tuberous sclerosis, a congenital neuro-ectodermosis, is an uncommon disease which requires life long treatment. Case presentationA 15-year-old Indian patient, presented to the outpatient department of our institute with a high-grade fever for two months, splenomegaly and a history of generalized tonic-clonic convulsions since childhood. The clinical and laboratory findings suggested visceral leishmaniasis with tuberous sclerosis. The patient was treated with miltefosine and antiepileptics. ConclusionThe patient responded well and in a follow up six months after presentation, she was found free of visceral leishmaniasis and seizures. Diagnosis and treatment of this rare combination of diseases is difficult.
  Journal of Medical Case Reports 04/2012; 3(1):1-4.