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Visceral Leishmania

Manish K Singh, Fauzia Jamal, Amit K Dubey, Pushkar Shivam, Sarita Kumari, Pushpanjali, Ghufran Ahmed, Manas R Dikhit, S Narayan, V N R DAS, Krishna Pandey, K K Sinha, P DAS, Shubhankar K Singh
Immunoactivation depends upon the antigen potential to modulate T-cell repertoires. The present study has enumerated the effect of 61 kDa recombinant Leishmania donovani co-factor-independent phosphoglycerate mutase (rLd-iPGAM) on mononuclear cells of healthy and treated visceral leishmaniasis subjects as well as on THP-1 cell line. rLd-iPGAM stimulation induced higher expression of interleukin-1β (IL-1β) in the phagocytic cell, its receptor and CD69 on T-cell subsets. These cellular activations resulted in upregulation of host-protective cytokines IL-2, IL-12, IL-17, tumour necrosis factor-α and interferon-γ, and downregulation of IL-4, IL-10 and tumour growth factor-β...
November 15, 2017: Parasitology
Shabina Parveen, Atish Roy Chowdhury, Junaid Jibran Jawed, Suchandra Bhattacharyya Majumdar, Bhaskar Saha, Subrata Majumdar
DUSP4, an inducible protein has a substrate specificity toward ERK1/2, a component of MAP kinase which is enhanced during Leishmania infection. The DUSP4(-/-) mice show increased susceptibility towards the infection caused by Toxoplasma gondii and Leishmania mexicana. These observations emphatically established the fact that unlike DUSP1, DUSP4 has host protective role. In our study, it has been Leishmania donovani, the causative agent of visceral leishmaniasis (VL) significantly reduced the expression of DUSP4 during infection...
November 10, 2017: Microbes and Infection
Daniel S Dias, Patrícia A F Ribeiro, Vívian T Martins, Daniela P Lage, Fernanda F Ramos, Anna L T Dias, Marcella R Rodrigues, Áquila S B Portela, Lourena E Costa, Rachel B Caligiorne, Bethina T Steiner, Miguel A Chávez-Fumagalli, Beatriz C S Salles, Thaís T O Santos, Julia A G Silveira, Danielle F Magalhães-Soares, Bruno M Roatt, Ricardo A Machado-de-Ávila, Mariana C Duarte, Daniel Menezes-Souza, Eduardo S Silva, Alexsandro S Galdino, Eduardo A F Coelho
Visceral leishmaniasis (VL) represents a serious public health problem, as Leishmania infantum is one of main disease causative agents in the Americas. In a previous immunoproteomic study, the prohibitin (PHB) protein was identified in L. infantum promastigote and amastigote extracts by antibodies in asymptomatic and symptomatic VL dog sera. This protein was found to be highly conserved between different Leishmania spp., but it presented a low identity with amino acid sequences of other organisms. The aim of the present study was to evaluate the cellular response induced by the recombinant PHB (rPHB) protein in BALB/c mice, as well as in PBMCs purified from untreated and treated VL patients, as well as to evaluate its protective efficacy against an infection by L...
November 9, 2017: Cellular Immunology
K K G D U L Kariyawasam, A Selvapandiyan, H V Y D Siriwardana, A Dube, P Karunanayake, S A S C Senanayake, R Dey, S Gannavaram, H L Nakhasi, N D Karunaweera
The visceralizing potential of apparently dermotropic Leishmania donovani in Sri Lanka (L. donovani-SL) was investigated through long-term follow-up of cutaneous leishmaniasis (CL) patients and in vivo and in vitro experimental infection models. CL patients (n = 250) treated effectively with intra-lesional antimony therapy were followed-up six monthly for 4 years. There was no clinical evidence of visceralization of infection (VL) during this period. Infection of BALB/c mice with L. donovani-SL (test) through intra-dermal route led to the development of cutaneous lesions at the site of inoculation with no signs of systemic dissemination, in contrast to the observations made in animals similarly infected with a visceralizing strain of L...
November 8, 2017: Parasitology
Daniel S Dias, Vívian T Martins, Patrícia A F Ribeiro, Fernanda F Ramos, Daniela P Lage, Grasiele S V Tavares, Débora V C Mendonça, Miguel A Chávez-Fumagalli, Jamil S Oliveira, Eduardo S Silva, Dawidson A Gomes, Michele A Rodrigues, Mariana C Duarte, Alexsandro S Galdino, Daniel Menezes-Souza, Eduardo A F Coelho
In this study, a Leishmania hypothetical protein, LiHyS, was evaluated regarding its antigenicity, immunogenicity and protective efficacy against visceral leishmaniasis (VL). Regarding antigenicity, immunoblottings and an enzyme-linked immunosorbent assay using human and canine sera showed high sensitivity and specificity values for the recombinant protein (rLiHyS) in the diagnosis of VL. When evaluating the immunogenicity of LiHyS, which is possibly located in the parasite's flagellar pocket, proliferative assays using peripheral blood mononuclear cells from healthy subjects or VL patients showed a high proliferative index in both individuals, when compared to the results obtained using rA2 or unstimulated cultures...
November 8, 2017: Parasitology
Pablo Prieto Barja, Pascale Pescher, Giovanni Bussotti, Franck Dumetz, Hideo Imamura, Darek Kedra, Malgorzata Domagalska, Victor Chaumeau, Heinz Himmelbauer, Michel Pages, Yvon Sterkers, Jean-Claude Dujardin, Cedric Notredame, Gerald Frank Späth
The parasite Leishmania  donovani causes a fatal disease termed visceral leishmaniasis. The process through which the parasite adapts to environmental change remains largely unknown. Here we show that aneuploidy is integral for parasite adaptation and that karyotypic fluctuations allow for selection of beneficial haplotypes, which impact transcriptomic output and correlate with phenotypic variations in proliferation and infectivity. To avoid loss of diversity following karyotype and haplotype selection, L...
November 6, 2017: Nature ecology & evolution
Cesar Terrazas, Sanjay Varikuti, Steve Oghumu, Heidi M Steinkamp, Nurittin Ardic, Jennifer Kimble, Hira Nakhasi, Abhay R Satoskar
Ly6C(hi) inflammatory monocytes (iMO) are critical for host defense against toxoplasmosis and malaria but their role in leishmaniasis is unclear. In this study, we report a detrimental role of Ly6C(hi) iMOs in visceral leishmaniasis (VL) caused by Leishmania donovani. We demonstrate that Ly6C(hi) iMOs are continuously recruited into the spleen and liver during L. donovani infection and they are preferential targets for the parasite. Using microarray-based gene expression profiling, we show that Ly6C(hi) iMOs isolated from the infected liver and spleen have distinct phenotypic and activation profiles...
October 31, 2017: Scientific Reports
Andrea Hornemann, Denise Sinning, Sofia Cortes, Lenea Campino, Peggy Emmer, Katrin Kuhls, Gerhard Ulm, Marcus Frohme, Burkhard Beckhoff
Leishmania species are protozoan parasites and the causative agents of leishmaniasis, a vector borne disease that imposes a large health burden on individuals living mainly in tropical and subtropical regions. Different Leishmania species are responsible for the distinct clinical patterns, such as cutaneous, mucocutaneous, and visceral leishmaniasis, with the latter being potentially fatal if left untreated. For this reason, it is important to perform correct species identification and differentiation. Fourier transform infrared spectroscopy (FTIR) is an analytical spectroscopic technique increasingly being used as a potential tool for identification of microorganisms for diagnostic purposes...
October 28, 2017: Analytical and Bioanalytical Chemistry
Adil M Allahverdiyev, Rabia Cakir Koc, Melahat Bagirova, Serhat Elcicek, Serap Yesilkir Baydar, Olga Nehir Oztel, Emrah Sefik Abamor, Sezen Canim Ates, Murat Topuzogullari, Sevil Isoglu Dincer, Zeynep Akdeste
OBJECTIVE: To determine the antileishmanial vaccine effectiveness of lipophosphoglycan (LPG) and polyacrylic acids (PAA) conjugates on in vivo mice models. METHODS: LPG molecule was isolated and purified from large-scale Leishmania donovani parasite culture. Protection efficacies of LPG alone, in combination with Freund's adjuvant, in a physical mixture and in conjugate (consisting of various LPG concentrations) with PAA, were comparatively determined by various techniques, such as cultivation with the micro-culture method, assessment of in vitro infection rates of peritoneal macrophages, determination of parasite load in liver with Leishman-Donovan Units, and detection of cytokine responses...
September 2017: Asian Pacific Journal of Tropical Medicine
Isis Polianna Silva Ferreira de Carvalho, Henry Maia Peixoto, Gustavo Adolfo Sierra Romero, Maria Regina Fernandes de Oliveira
OBJECTIVE: To estimate the Brazilian direct and indirect costs of human visceral leishmaniasis (VL) in 2014. METHODS: Cost-of-illness study on the Brazilian public health system and societal perspective. VL cases registered in the Notifiable Diseases Information System in the year of 2014 were considered. Direct medical costs regarding diagnostic, treatment, and care provided to VL patients were estimated through the top-down approach. The indirect costs related to productivity loss due to premature mortality and morbidity were estimated by means of the human capital method...
October 27, 2017: Tropical Medicine & International Health: TM & IH
Muhammad Idris, Jamila Farid, Nasreen Gul, Fiaz Ahmed, Romana Irshad
Visceral Leishmaniasis (also known as Kala Azar) is a parasitic infection caused by Leishmania Donovani in the East and Leishmania Infantum in the west. It is prevalent in many countries including India, Bangladesh, Nepal, Africa and part of America. The disease follows chronic course and is usually lethal if left untreated. It has also been reported from different parts of Pakistan, including Northern areas, Districts Mansehra & Abbottabad and Hilly areas of Khyber Pukhtoonkhawah. Most the cases have been reported in paediatric population...
July 2017: Journal of Ayub Medical College, Abbottabad: JAMC
Patrick T Bunn, Marcela Montes de Oca, Fabian de Labastida Rivera, Rajiv Kumar, Chelsea L Edwards, Rebecca J Faleiro, Susanna S Ng, Meru Sheel, Yulin Wang, Fiona H Amante, Ashraful Haque, Christian R Engwerda
Many infectious diseases are characterized by the development of immunoregulatory pathways that contribute to pathogen persistence and associated disease symptoms. In diseases caused by intracellular parasites, such as visceral leishmaniasis (VL), various immune modulators have the capacity to negatively impact protective CD4(+) T cell functions. Galectin-1 is widely expressed on immune cells and has previously been shown to suppress inflammatory responses and promote the development of CD4(+) T cells with immunoregulatory characteristics...
2017: Frontiers in Immunology
Hassan Ebrahimzade-Parikhani, Mehdi Mohebali, Zabiholah Zarei, Behnaz Akhoundi, Zahra Kakoei
BACKGROUND: Since Pars Abad district had been known as a focus of visceral leishmaniasis (VL) in Ardabil Province but the prevalence of the disease in nomadic tribes has not been determined, thus, this study was conducted. METHODS: This descriptive cross-sectional study was conducted on children up to 12yr old of nomadic tribes from Pars Abad County, Ardabil Province, Iran in 2015. For each individual, a questionnaire including age, sex, clinical manifestations, history of disease, and contact with reservoir hosts of VL were completed, separately...
June 2017: Journal of Arthropod-borne Diseases
Sanchita Das, Sagnik Giri, Shyam Sundar, Chandrima Shaha
The parasite Leishmania donovani causes visceral leishmaniasis, a potentially fatal disease. These parasites survive within mammalian macrophages and express a unique set of enzymes, the tryparedoxin peroxidases for their defense against oxidative stress generated by the host. In this study, we demonstrate a differential role of two distinct enzymes, the mitochondrial (mTXNPx) and the cytosolic tryparedoxin peroxidase (cTXNPx) in defending the parasites against mitochondrial and exogenous oxidative stress during infection and drug treatment...
October 23, 2017: Antimicrobial Agents and Chemotherapy
Andrea K Pinto-Martinez, Jessica Rodriguez-Durán, Xenon Serrano-Martin, Vanessa Hernandez-Rodriguez, Gustavo Benaim
Leishmania donovani is the causing agent of visceral leishmaniasis, a common infection that affects millions of people from the most underdeveloped countries. Miltefosine is the only oral drug to treat infections caused by L. donovani. Nevertheless, its mechanism of action is not well understood. While miltefosine inhibits the synthesis of phosphatidylcholine, and also affects the parasite mitochondrion inhibiting the cytochrome C oxidase, it is to be expected that this potent drug also produces its effect through other targets...
October 23, 2017: Antimicrobial Agents and Chemotherapy
Prabin Kumar, Pragya Misra, Chandreshwar Prasad Thakur, Abhinav Saurabh, Narayan Rishi, Dipendra Kumar Mitra
Visceral leishmaniasis (VL) is a disseminated and lethal disease of reticulo-endothelial system caused by protozoan parasites Leishmania donovani and Leishmania infantum, which are known to induce host T cell suppression. To understand the impact of parasite load on T cell function, the present study was focussed on parasite load with T cell function in bone marrow of twenty-six (26) VL patients. We observed significant enrichment of Foxp3(+) (p = 0.0003) and IL-10(+) Foxp3(+) T-regulatory (Treg) cells (p = 0...
October 23, 2017: Clinical and Experimental Immunology
Belhassen Kaabi, Elyes Zhioua
During the last twenty years, zoonotic visceral leishmaniasis (ZVL) spread from the north characterized by humid, sub-humid, and semi-arid bio-climates to the arid areas located in Central Tunisia. In order to understand the eco-epidemiological factors involved in the distribution of ZVL, both a sero-epidemiological and an entomological investigation were performed in two governorates situated in two different bio-geographical areas: Bizerte in the north and Kairouan in the center. A mathematical model for transmission of ZVL was built, describing the disease dynamic in these areas...
October 16, 2017: Acta Tropica
Délia Chaves Moreira Dos Santos, Marselle Leite Silvério de Souza, Eliane Morais Teixeira, Líndicy Leidicy Alves, José Mário Carneiro Vilela, Margareth Andrade, Maria das Graças Carvalho, Ana Paula Fernandes, Lucas Antônio Miranda Ferreira, Marta Marques Gontijo Aguiar
This work aimed to optimise a new nanoemulsion (NE) formulation loaded with Amphotericin B (AmB) and to evaluate its in vivo antileishmanial activity and in vitro haemolytic toxicity. The influence of gradual increases in pressure, using a high-pressure homogeniser, was evaluated. The NE was characterised for droplet size, polydispersity index, zeta potential and encapsulation efficiency (EE). For antileishmanial activity studies, AmB-NE was administered intravenously in mice infected by Leishmania infantum chagasi, which causes Visceral Leishmaniasis (VL)...
October 18, 2017: Journal of Drug Targeting
Nilofer Naqvi, Kavita Ahuja, Angamuthu Selvapandiyan, Ranadhir Dey, Hira Nakhasi, Niti Puri
Mast Cells (MCs) are one of the first immune cells encountered by invading pathogens. Their presence in large numbers in the superficial dermis, where Leishmania is encountered, suggests that they may play a critical role in immune responses to Leishmania. In this study the interactions of Leishmania donovani, the causative agent of visceral Leishmaniasis, and Leishmania tropica, the causative agent of cutaneous Leishmaniasis with MCs were studied. Co-culture of Leishmania with Peritoneal Mast Cells (PMCs) from BALB/c mice and Rat Basophilic Leukaemia (RBL-2H3) MCs led to significant killing of L...
October 16, 2017: Scientific Reports
Aditya Verma, Vasundhra Bhandari, Deepak Kumar Deep, Shyam Sundar, Jean Claude Dujardin, Ruchi Singh, Poonam Salotra
Widespread resistance towards antimony and reports of relapses following miltefosine treatment has severely affected the management of visceral leishmaniasis (VL) in the Indian subcontinent. Paromomycin (PMM), an aminoglycoside antibiotic, has been licensed for VL treatment in India in 2007. Although its use is still restricted in the field, unraveling the molecular mechanism of resistance towards PMM is the key to preserve the drug. In this study, PMM resistant lines were selected up to 100 μM of PMM in three distinct field isolates of Leishmania donovani at promastigote stage...
October 10, 2017: International Journal for Parasitology, Drugs and Drug Resistance
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