scholarly journals Visceral Leishmaniasis: Asymptomatic Facts

2021 ◽  
Author(s):  
Medhavi Sudarshan ◽  
Sumit Sharan
Keyword(s):  
Visceral Leishmaniasis ◽  
Leishmania Donovani ◽  
Clinical Symptoms ◽  
Clinical Signs ◽  
Protozoan Parasite ◽  
Diagnostic Techniques ◽  
Asymptomatic Infection ◽  
Infected People ◽  
Time Period ◽  
Almost All

Visceral Leishmaniasis (VL) caused by protozoan parasite Leishmania is a vector borne disease and infection is limited not to human but also to animals worldwide. For infection identification and prevalence in both Leishmania endemic and nonendemic regions, several serological and genetic techniques are used. Although diagnostic techniques and clinical symptoms can establish illness status, it is extremely difficult to diagnose infection in the absence of symptoms. Asymptomatic are healthy people who have an infection but are unaware of it. The epidemiology of asymptomatic Leishmaniasis is critical for its eradication. Only a small percentage of infected people are clinically suspected of having VL, as the majority of them may not show any symptoms and remain asymptomatic. Some asymptomatic infections may go away after a while, or they may linger for years, or they may develop to illness with clinical signs. Asymptomatic infection varies per endemic location, but almost all of them point to this hidden category of parasite infection. It is now critical to understand many factors such as diagnostic markers, genetic markers, and immunological markers along with different risk factors. All of these criteria, as well as some innovative techniques to diagnosing and controlling asymptomatic leishmaniasis, will be covered in this chapter. The main focus will be on asymptomatic condition of Indian Visceral Leishmaniasis, which is caused by Leishmania donovani and spreads via female sand fly P. argentipes biting. The numerous criteria that play a role in asymptomatic to symptomatic conversion in a specific time period will also be discussed in this chapter.

scholarly journals Genetic Validation of Leishmania donovani Lysyl-tRNA Synthetase Shows that It Is Indispensable for Parasite Growth and Infectivity

mSphere ◽  
2017 ◽  
Vol 2 (4) ◽  
Author(s):  
Sanya Chadha ◽  
N. Arjunreddy Mallampudi ◽  
Debendra K. Mohapatra ◽  
Rentala Madhubala
Keyword(s):  
Visceral Leishmaniasis ◽  
Leishmania Donovani ◽  
Essential Gene ◽  
Protozoan Parasite ◽  
Protein Translation ◽  
Trna Synthetase ◽  
Parasite Growth ◽  
Coding Sequences ◽  
Trna Synthetases ◽  
Aminoacyl Trna Synthetases

ABSTRACT Leishmania donovani is a protozoan parasite that causes visceral leishmaniasis. Increasing resistance and severe side effects of existing drugs have led to the need to identify new chemotherapeutic targets. Aminoacyl-tRNA synthetases (aaRSs) are ubiquitous and are required for protein synthesis. aaRSs are known drug targets for bacterial and fungal pathogens. Here, we have characterized and evaluated the essentiality of L. donovani lysyl-tRNA synthetase (LdLysRS). Two different coding sequences for lysyl-tRNA synthetases are annotated in the Leishmania genome database. LdLysRS-1 (LdBPK_150270.1), located on chromosome 15, is closer to apicomplexans and eukaryotes, whereas LdLysRS-2 (LdBPK_300130.1), present on chromosome 30, is closer to bacteria. In the present study, we have characterized LdLysRS-1. Recombinant LdLysRS-1 displayed aminoacylation activity, and the protein localized to the cytosol. The LdLysRS-1 heterozygous mutants had a restrictive growth phenotype and attenuated infectivity. LdLysRS-1 appears to be an essential gene, as a chromosomal knockout of LdLysRS-1 could be generated when the gene was provided on a rescuing plasmid. Cladosporin, a fungal secondary metabolite and a known inhibitor of LysRS, was more potent against promastigotes (50% inhibitory concentration [IC50], 4.19 µM) and intracellular amastigotes (IC50, 1.09 µM) than were isomers of cladosporin (3-epi-isocladosporin and isocladosporin). These compounds exhibited low toxicity to mammalian cells. The specificity of inhibition of parasite growth caused by these inhibitors was further assessed using LdLysRS-1 heterozygous mutant strains and rescue mutant promastigotes. These inhibitors inhibited the aminoacylation activity of recombinant LdLysRS. Our data provide a framework for the development of a new class of drugs against this parasite. IMPORTANCE Aminoacyl-tRNA synthetases are housekeeping enzymes essential for protein translation, providing charged tRNAs for the proper construction of peptide chains. These enzymes provide raw materials for protein translation and also ensure fidelity of translation. L. donovani is a protozoan parasite that causes visceral leishmaniasis. It is a continuously proliferating parasite that depends heavily on efficient protein translation. Lysyl-tRNA synthetase is one of the aaRSs which charges lysine to its cognate tRNA. Two different coding sequences for lysyl-tRNA synthetases (LdLysRS) are present in this parasite. LdLysRS-1 is closer to apicomplexans and eukaryotes, whereas LdLysRS-2 is closer to bacteria. Here, we have characterized LdLysRS-1 of L. donovani. LdLysRS-1 appears to be an essential gene, as the chromosomal null mutants did not survive. The heterozygous mutants showed slower growth kinetics and exhibited attenuated virulence. This study also provides a platform to explore LdLysRS-1 as a potential drug target.

scholarly journals Development of Vaccines against Visceral Leishmaniasis

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Krystal J. Evans ◽  
Lukasz Kedzierski
Keyword(s):  
Public Health ◽  
Visceral Leishmaniasis ◽  
Leishmania Donovani ◽  
Clinical Symptoms ◽  
Public Health Problem ◽  
Past Infection ◽  
Health Goal ◽  
Disability Adjusted Life ◽  
Life Years ◽  
Public Health Goal

Leishmaniasis is a neglected disease resulting in a global morbidity of 2,090 thousand Disability-Adjusted Life Years and a mortality rate of approximately 60,000 per year. Among the three clinical forms of leishmaniasis (cutaneous, mucosal, and visceral), visceral leishmaniasis (VL) accounts for the majority of mortality, as if left untreated VL is almost always fatal. Caused by infection withLeishmania donovaniorL. infantum, VL represents a serious public health problem in endemic regions and is rapidly emerging as an opportunistic infection in HIV patients. To date, no vaccine exists for VL or any other form of leishmaniasis. In endemic areas, the majority of those infected do not develop clinical symptoms and past infection leads to robust immunity against reinfection. Thus the development of vaccine forLeishmaniais a realistic public health goal, and this paper summarizes advances in vaccination strategies against VL.

scholarly journals LABORATORY DIAGNOSIS AND CLINICAL SIGNS OF CANINE VISCERAL LEISHMANIASIS IN DOGS EXAMINED AT THE CENTER FOR ZOONOSIS CONTROL IN CAMPO GRANDE – MS, BRAZIL

2012 ◽  
Vol 17 (4) ◽  
Author(s):  
Rodrigo Casquero Cunha ◽  
Renato Andreotti ◽  
Elaine Silva ◽  
Elisângela Pereira ◽  
Tayra Sato ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Urban Areas ◽  
Clinical Symptoms ◽  
Fluorescent Antibody ◽  
Clinical Signs ◽  
Primary Source ◽  
Laboratory Diagnosis ◽  
Leishmania Species ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mato Grosso

Visceral leishmaniasis is a type of zoonosis caused by several Leishmania species endemic to tropical, subtropical, and Mediterranean climate regions. Dogs are the primary source of infection in urban areas and can be symptomatic or asymptomatic. This study focused on the observation of clinical signs of leishmaniasis in dogs in Campo Grande, Mato Grosso do Sul, Brazil. Samples from affected animals were analyzed using indirect fluorescent antibody (IFA) tests, an enzyme-linked immunosorbent assay (ELISA), and polymerase chain reaction (PCR) assays to determine the optimal diagnostic tool for use on animals that present clinical symptoms. A predominance of clinical symptoms affecting the integumentary system was observed, and splenomegaly and hepatomegaly were the most important pathological signs. Among the diagnostic tests, the greatest agreement was seen between ELISA and IFA, followed by ELISA and PCR, and finally IFA and PCR. PCR diagnostic results showed the greatest extent of correlation with clinical signs, followed by ELISA and then IFA. When choosing a diagnostic method, veterinarians should consider the clinical signs and health status of the patient.

scholarly journals Leishmania donovani Lipophosphoglycan Increases Macrophage-Dependent Chemotaxis of CXCR6-Expressing Cells via CXCL16 Induction

2019 ◽  
Vol 87 (5) ◽  
Author(s):  
Visnu Chaparro ◽  
Louis-Philippe Leroux ◽  
Aude Zimmermann ◽  
Armando Jardim ◽  
Brent Johnston ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Leishmania Donovani ◽  
Molecular Mechanisms ◽  
Defense Mechanism ◽  
Protozoan Parasite ◽  
Parasitic Infections ◽  
Dependent Manner ◽  
Chemokine Production ◽  
Content Type

ABSTRACT CXCL16 is a multifunctional chemokine that is highly expressed by macrophages and other immune cells in response to bacterial and viral pathogens; however, little is known regarding the role of CXCL16 during parasitic infections. The protozoan parasite Leishmania donovani is the causative agent of visceral leishmaniasis. Even though chemokine production is a host defense mechanism during infection, subversion of the host chemokine system constitutes a survival strategy adopted by the parasite. Here, we report that L. donovani promastigotes upregulate CXCL16 synthesis and secretion by bone marrow-derived macrophages (BMDM). In contrast to wild-type parasites, a strain deficient in the virulence factor lipophosphoglycan (LPG) failed to induce CXCL16 production. Consistent with this, cell treatment with purified L. donovani LPG augmented CXCL16 expression and secretion. Notably, the ability of BMDM to promote migration of cells expressing CXCR6, the cognate receptor of CXCL16, was augmented upon L. donovani infection in a CXCL16- and LPG-dependent manner. Mechanistically, CXCL16 induction by L. donovani required the activity of AKT and the mechanistic target of rapamycin (mTOR) but was independent of Toll-like receptor signaling. Collectively, these data provide evidence that CXCL16 is part of the inflammatory response elicited by L. donovani LPG in vitro. Further investigation using CXCL16 knockout mice is required to determine whether this chemokine contributes to the pathogenesis of visceral leishmaniasis and to elucidate the underlying molecular mechanisms.

scholarly journals Antileishmanial Efficacy and Pharmacokinetics of DB766-Azole Combinations

2017 ◽  
Vol 62 (1) ◽  
Author(s):  
April C. Joice ◽  
Sihyung Yang ◽  
Abdelbasset A. Farahat ◽  
Heidi Meeds ◽  
Mei Feng ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Leishmania Donovani ◽  
Treatment Strategies ◽  
Parasite Burden ◽  
Pharmacokinetic Analysis ◽  
Content Type ◽  
New Treatment ◽  
Almost All

ABSTRACT Given the limitations of current antileishmanial drugs and the utility of oral combination therapy for other infections, developing an oral combination against visceral leishmaniasis should be a high priority. In vitro combination studies with DB766 and antifungal azoles against intracellular Leishmania donovani showed that posaconazole and ketoconazole, but not fluconazole, enhanced DB766 potency. Pharmacokinetic analysis of DB766-azole combinations in uninfected Swiss Webster mice revealed that DB766 exposure was increased by higher posaconazole and ketoconazole doses, while DB766 decreased ketoconazole exposure. In L. donovani-infected BALB/c mice, DB766-posaconazole combinations given orally for 5 days were more effective than DB766 or posaconazole alone. For example, 81% ± 1% (means ± standard errors) inhibition of liver parasite burden was observed for 37.5 mg/kg of body weight DB766 plus 15 mg/kg posaconazole, while 37.5 mg/kg DB766 and 15 mg/kg posaconazole administered as monotherapy gave 40% ± 5% and 21% ± 3% inhibition, respectively. Combination index (CI) analysis indicated that synergy or moderate synergy was observed in six of nine combined dose groups, while the other three were nearly additive. Liver concentrations of DB766 and posaconazole increased in almost all combination groups compared to monotherapy groups, although many increases were not statistically significant. For DB766-ketoconazole combinations evaluated in this model, two were antagonistic, one displayed synergy, and one was nearly additive. These data indicate that the efficacy of DB766-posaconazole and DB766-ketoconazole combinations in vivo is influenced in part by the pharmacokinetics of the combination, and that the former combination deserves further consideration in developing new treatment strategies against visceral leishmaniasis.

scholarly journals Canine Visceral Leishmaniasis: Dermatological Aspects and Associated Dermatoses

2018 ◽  
Vol 44 (1) ◽  
pp. 4
Author(s):  
Nayara Benites Moreira ◽  
Arleana Do Bom Parto Ferreira de Almeida ◽  
Andressa Zelenski de Lara Pinto ◽  
Emmanuelle Rosa Mutzemberg ◽  
Isabela De Godoy ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
High Frequency ◽  
Skin Diseases ◽  
Clinical Symptoms ◽  
Clinical Signs ◽  
Infectious Agent ◽  
Fungal Culture ◽  
Cutaneous Lesions ◽  
Exfoliative Dermatitis ◽  
System L

Background: Visceral leishmaniasis (VL) is a zoonotic disease caused by Leishmania chagasi (syn. L. infantum). The dog is the main reservoir for this infectious agent in the urban environment. Among the various systemic signs of viscerotropic infection by L. chagasi, cutaneous lesions, including exfoliative dermatitis, cutaneous ulcers and nodules, alopecia, papular or pustular dermatitis, and onychogryphosis, are the most common in dogs. This study aimed to describe the major cutaneous lesions, evaluate the skin parasite L. chagasi by PCR, and investigate the main dermatoses associated with this zoonosis.Materials, Methods & Results: This study evaluated 50 seropositive dogs of various breeds and sizes for VL by ELISA and IFA and for the dermatological signs associated with VL. Moreover, molecular analysis of skin fragments was performed with primers 150 and 152 for the genus Leishmania, and the species was verified as L. chagasi with RV1 and RV2 primers. Deep skin scraping for mites and fungal culture analysis were performed in all dogs. Of the 50 dogs, 15 (30%) were free of systemic or cutaneous signs; however, changes in skin and annexes were observed in 35 (70%) dogs. Thirty-one dogs (62%) presented infection with dermatophytes, 26 (83.9%) with Microsporum sp., and 5 (16.1%) with Trichophyton sp.; only one dog showed parasitism by Sarcoptes scabiei. A statistically significant association was observed between skin alterations and dermatological infection by dermatophytes (P = 0.61). Of the 29 dogs from which skin fragments were used to perform PCR with specific primers, 19 (65.5%) showed L. chagasi DNA amplification.Discussion: Symptomatic dogs are more common than asymptomatic ones; therefore, sampling was set up in the hospital for reagents dogs with clinical suspicion of this zoonosis. Dermatological signs accounted for 70% of the clinical symptoms presented by the dogs, which were evaluated as described by other authors. Exfoliative dermatitis was the most common skin lesion followed by onychogryphosis and alopecia. This is because of granulomatous or pyogranulomatous inflammation, inflammation in different structures of the skin, or deposition of immune complexes. Only few studies have described the co-existence of VL and dermatophytosis in dogs. We found dermatophyte fungal infection in more than half of the dogs (70%), most frequently Microsporum sp. followed by infection with Trichophyton sp. Regarding the clinical signs, no statistical difference was observed between the dogs with and without dermatophyte infection, which reinforces the lack of specificity in clinical signs that may hinder the diagnosis of both diseases when present as co-morbidities or in isolation. The high frequency of dermatophytosis in dogs with VL may result from a compromised immune system. L. chagasi DNA detected in 65.5% of samples tested by conventional PCR can be related to the host’s immune response, as well as to the uneven distribution of the parasite in different tissues. These results support the high frequency of skin changes and concomitant skin diseases like ringworm observed in dogs with LV, highlighting the importance of researching other differential diagnoses in endemic areas.

scholarly journals Implications of the Immune Polymorphisms of the Host and the Genetic Variability of SARS-CoV-2 in the Development of COVID-19

Viruses ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 94
Author(s):  
Jesús Zepeda-Cervantes ◽  
Daniel Martínez-Flores ◽  
Josué Orlando Ramírez-Jarquín ◽  
Ángeles C. Tecalco-Cruz ◽  
Noé Santiago Alavez-Pérez ◽  
...  
Keyword(s):  
Viral Entry ◽  
Genetic Factors ◽  
Structural Characteristics ◽  
Clinical Signs ◽  
Severe Pneumonia ◽  
Epigenetic Factors ◽  
Infected People ◽  
The World ◽  
Almost All

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the current pandemic affecting almost all countries in the world. SARS-CoV-2 is the agent responsible for coronavirus disease 19 (COVID-19), which has claimed millions of lives around the world. In most patients, SARS-CoV-2 infection does not cause clinical signs. However, some infected people develop symptoms, which include loss of smell or taste, fever, dry cough, headache, severe pneumonia, as well as coagulation disorders. The aim of this work is to report genetic factors of SARS-CoV-2 and host-associated to severe COVID-19, placing special emphasis on the viral entry and molecules of the immune system involved with viral infection. Besides this, we analyze SARS-CoV-2 variants and their structural characteristics related to the binding to polymorphic angiotensin-converting enzyme type 2 (ACE2). Additionally, we also review other polymorphisms as well as some epigenetic factors involved in the immunopathogenesis of COVID-19. These factors and viral variability could explain the increment of infection rate and/or in the development of severe COVID-19.

scholarly journals MODELING POST-KALA-AZAR DERMAL LEISHMANIASIS AS AN INFECTION RESERVOIR FOR VISCERAL LEISHMANIASIS

2019 ◽  
Vol 27 (1) ◽  
pp. 221-239
Author(s):  
ANDREA CALDERÓN ◽  
RYAN LANDRITH ◽  
NHAN LE ◽  
ILEANA MUÑOZ ◽  
CHRISTOPHER M. KRIBS
Keyword(s):  
Visceral Leishmaniasis ◽  
Leishmania Donovani ◽  
Combined Treatment ◽  
Protozoan Parasite ◽  
Bed Nets ◽  
Kala Azar ◽  
Complete Treatment ◽  
The Relationship ◽  
Incomplete Treatment ◽  
Parasite Leishmania

Visceral Leishmaniasis (VL) is a potentially fatal disease caused by the protozoan parasite Leishmania donovani. This disease is a health problem for the very poor because it results in thousands of deaths and illnesses every year. Some countries, such as India and Bangladesh, have started programs to reduce the occurrences of VL by focusing on early diagnosis and complete treatment of VL. Post-Kala-azar Dermal Leishmaniasis (PKDL) is a cutaneous manifestation of Leishmaniasis that can occur following the incomplete treatment of VL. Diagnosis and treatment of PKDL are limited in affected regions, and PKDL has been identified as a possible reservoir for infection. This study develops a mathematical model of the relationship between the level of PKDL treatment and the incidences of VL during a given period. The results indicate a nearly linear relationship between PKDL treatment rates and the percent reduction of VL incidences. With the current treatments available and considering achievable levels of treatment, the model predicts that up to 20% of VL cases could be prevented by treating new PKDL cases. Hypothetical combined treatment initiatives including bed nets and insecticide spraying are also considered. Results suggest that the population of individuals with PKDL is certainly a significant factor in the transmission of L. donovani infection, with treatment of new cases particularly important.

scholarly journals Diagnosing human asymptomatic visceral leishmaniasis in an urban area of the State of Minas Gerais, using serological and molecular biology techniques

2006 ◽  
Vol 39 (5) ◽  
pp. 421-427 ◽  
Author(s):  
Elizabeth Castro Moreno ◽  
Maria Norma Melo ◽  
José Roberto Lambertucci ◽  
José Carlos Serufo ◽  
Antero S.R. Andrade ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Urban Area ◽  
Leishmania Donovani ◽  
Venous Blood ◽  
Clinical Signs ◽  
Epidemiological Studies ◽  
Southeastern Brazil ◽  
Enzyme Linked Immunosorbent Assay ◽  
Immunochromatographic Strip ◽  
Cross Sectional

A population-based cross-sectional study was set up in Sabará country, Southeastern Brazil, to identify asymptomatic human visceral leishmaniasis in an urban area of low disease prevalence. Blood was collected on filter paper (n=1,604 inhabitants) and examined by indirect immunofluorescent test, enzyme-linked immunosorbent assay and immunochromatographic strip test. The prevalence rates of infection ranged from 2.4 to 5.6% depending on the test used. One year later, venous blood was collected in a subset of 226 participants (102 seropositive and 124 seronegative). The tests performed were IFAT, ELISA, rk39-ELISA, polymerase chain reaction and hybridization with Leishmania donovani complex probe. No clinical signs or symptoms of leishmaniasis were observed. Using hybridization as a reference test, the sensitivity and specificity of serology were respectively: 24.8 and 71% (ELISA); 26.3 and 76.3% (rk-39); 30.1 and 63.4% (IFAT). Due to disagreements, different criteria were tested to define the infection and hybridization should be considered in epidemiological studies.

scholarly journals Application of an Improved Method for the Recombinant K39 Enzyme-Linked Immunosorbent Assay To Detect Visceral Leishmaniasis Disease and Infection in Bangladesh

2005 ◽  
Vol 12 (12) ◽  
pp. 1410-1415 ◽  
Author(s):  
K. M. Kurkjian ◽  
L. E. Vaz ◽  
R. Haque ◽  
C. Cetre-Sossah ◽  
S. Akhter ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Immunosorbent Assay ◽  
Leishmania Donovani ◽  
Asymptomatic Infection ◽  
Negative Control ◽  
Original Method ◽  
Cutoff Point ◽  
Enzyme Linked Immunosorbent Assay ◽  
Standard Curve ◽  
Kala Azar

ABSTRACT Several serology-based immunoassays are used to diagnose visceral leishmaniasis (VL), a chronic protozoan parasitic disease caused by the Leishmania donovani complex. These tests are primarily designed to diagnose the most severe clinical form of VL, known as kala-azar. However, leishmanial infection is frequently asymptomatic and may manifest only as a positive serologic response or positive leishmanin skin test. We modified a previously described enzyme-linked immunosorbent assay (ELISA) that detects patient antibodies reactive with the recombinant Leishmania protein K39 (rK39) to confirm suspected kala-azar and to detect asymptomatic infection in a community study in Bangladesh. With the inclusion of a standard curve on each ELISA plate, the rK39 ELISA was more repeatable (kappa coefficient of agreement = 0.970) and more reliable compared to the original method (kappa = 0.587, P < 0.001). The cutoff point for a positive antibody response was chosen based on the 99th percentile of the ELISA distribution for the negative-control sera. However, we found that sera from all patients with active kala-azar yielded values more than twice the magnitude of this cutoff. Using receiver-operator characteristic curves, we determined a second cutoff value predictive of kala-azar. Using these criteria, the sensitivity and specificity of the modified ELISA for kala-azar were 97.0% and 98.9%, respectively, for sera from our study population. We hypothesize that individuals with antibody levels greater than the 99th percentile of the negative controls but less than the cutoff point for kala-azar have asymptomatic leishmanial infections.

Sign in / Sign up

Export Citation Format

Share Document