Potential antigenic targets used in immunological tests for diagnosis of tegumentary leishmaniasis: A systematic review.
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SUBMITTER: Freire ML
PROVIDER: S-EPMC8158869 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundTegumentary leishmaniasis (TL) is a parasitic disease that can present a cutaneous or mucocutaneous clinical form (CL and MCL, respectively). The disease is caused by different Leishmania species and transmitted by phlebotomine sand flies. Bolivia has one of the highest incidences of the disease in South America and the diagnosis is done by parasitological techniques. Our aim was to describe the clinical and immunological characteristics of CL and MCL patients attending the leishmaniasis reference center in Cochabamba, Bolivia, in order to gain updated clinical and epidemiological information, to evaluate the diagnostic methods used and to identify biomarkers related to clinical disease and its evolution.Methodology/principal findingsThe study was conducted from September 2014 to November 2015 and 135 patients with lesions compatible with CL or MCL were included. Epidemiological and clinical data were collected using a semi-structured questionnaire. Two parasitological diagnostic methods were used: Giemsa-stained smears and culture of lesion aspirates. Blood samples obtained from participants were used to measure the concentrations of different cytokines. 59.2% (80/135) were leishmaniasis confirmed cases (CL: 71.3%; MCL: 28.7%). Sixty percent of the confirmed cases were positive by smears and 90.6% were positive by culture. 53.8% were primo-infections. Eotaxin and monokine induced by IFN-γ presented higher serum concentrations in the MCL clinical presentation compared to CL cases and no-cases. None of the cytokines presented different concentrations between primo-infections and secondary infections due to treatment failure.Conclusions/significanceIn Bolivia, parasitological diagnosis remains the reference standard in diagnosis of leishmaniasis because of its high specificity, whereas the sensitivity varies over a wide range leading to loss of cases. Until more accurate tools are implemented, all patients should be tested by both smears and culture of lesion aspirates to minimize the risk of false negatives. Our results showed higher concentrations of several cytokines in MCL compared to CL, but no differences were observed between CL and no-cases. In addition, none of the cytokines differed between primary and secondary infections. These results highlight the need of further research to identify biomarkers of susceptibility and disease progression, in addition to looking at the local cellular immune responses in the lesions.
| S-EPMC7968743 | biostudies-literature
Project description:Serological methods should meet the needs of leishmaniasis diagnosis due to their high sensitivity and specificity, economical and adaptable rapid diagnostic test format, and ease of use. Currently, the performances of serological diagnostic tests, despite improvements with recombinant proteins, vary greatly depending on the clinical form of leishmaniasis and the endemic area. Peptide-based serological tests are promising as they could compensate for antigenic variability and improve performance, independently of Leishmania species and subspecies circulating in the endemic areas. The objective of this systematic review was to inventory all studies published from 2002 to 2022 that evaluate synthetic peptides for serological diagnosis of human leishmaniases and also to highlight the performance (e.g., sensitivity and specificity) of each peptide reported in these studies. All clinical forms of leishmaniasis, visceral and tegumentary, and all Leishmania species responsible for these diseases were considered. Following PRISMA statement recommendations, 1,405 studies were identified but only 22 articles met the selection criteria and were included in this systematic review. These original research articles described 77 different peptides, of which several have promising performance for visceral or tegumentary leishmaniasis diagnosis. This review highlights the importance of and growing interest in synthetic peptides used for serological diagnosis of leishmaniases, and their performances compared to some widely used tests with recombinant proteins.
| S-EPMC10069404 | biostudies-literature
Project description:Several controlled and uncontrolled studies addressing azole antifungal drugs for cutaneous and mucosal leishmaniasis have been published with inconclusive results. We conducted a systematic literature review of studies evaluating the efficacy and toxicity associated with azole therapy for tegumentary leishmaniasis.PRISMA guidelines for systematic reviews and the Cochrane manual were followed, and the review methodology was registered (PROSPERO; CRD42016048668). Sources included the EMBASE, Web of Science, MEDLINE, LILACS, and IBECS databases along with a manual search of references from evaluated studies. Additional resources such as Google Scholar and clinicaltrials.gov were also searched. We included all studies reporting cure rate after cutaneous or mucosal leishmaniasis treatment with systemic azole drugs, regardless of their design. R software was used to estimate global rates of success and adverse events with each drug. The main outcome of interest was clinical cure, defined as complete re-epithelialization of all lesions.A total of 37 studies involving 1259 patients that reported outcomes after fluconazole (9), ketoconazole (14) and itraconazole (15) treatments were included. Only 14 (38%) were randomized controlled trials (RCT). The pooled azole final efficacy rate was 64% (CI95%: 57-70%) for all studies and 60% (CI95%: 50-70%) (p = 0.41) if only RCTs studies were considered. Twenty-four studies were conducted in the Old World and 13 studies in the Americas. The final efficacy rate according to New and Old World were 62% (CI95%: 43-77%) and 66% (CI95%: 58-73%), respectively. The final efficacy rate of azoles according to species were 89% (CI95%: 50-98%) for L. mexicana; 88% for L. infantum (CI95%: 27-99%); 80% for L. donovani; 53% (CI95%: 29-76%) for L. major; 49% for L. braziliensis (CI95%: 21-78%); and 15% (CI95%: 1-84%) for L. tropica. The cure rates were similar among the fluconazole, ketoconazole and itraconazole group arms (p = 0.89), specifically 61% (CI95%: 48-72%), 64% (CI95%: 44-80%) 65% (CI95%: 56-72%), respectively. Adverse events during fluconazole, itraconazole and ketoconazole therapy were reported in 7% (CI95%: 3-14%), 12% (CI95% 8-19%) and 13% (CI95%: 6-29%) of treated patients, respectively, without difference among them (p = 0.35). This systematic review included studies with small samples and both non-comparative and non-randomized studies and the main limitation was the low quality of the available studies.Available evidence suggests that fluconazole, ketoconazole and itraconazole have similar and modest efficacy rates for tegumentary leishmaniasis treatment. There is insufficient evidence to support the exclusive use of azole therapy as a single agent for leishmaniasis treatment.
| S-EPMC5633178 | biostudies-literature
Project description:American tegumentary leishmaniasis (ATL) can affect the skin or mucosa (mucocutaneous leishmaniasis - MCL) including the oral cavity. MCL oral lesions are often confused with other oral diseases, delaying diagnosis and specific treatment, and increasing the likelihood of sequelae. Thus, increasing the knowledge of the evolution of ATL oral lesions can facilitate its early diagnosis improving the prognosis of healing.Evaluate the frequency of ATL oral lesion and describe its clinical, laboratory and therapeutic peculiarities.A descriptive transversal study was carried out, using data from medical records of 206 patients with MCL examined at the outpatient clinics-IPEC-Fiocruz between 1989 and 2013. Proportions were calculated for the categorical variables and the association among them was assessed by the Pearson's chi-square test. Measures of central tendency and dispersion were used for the continuous variables and their differences were assessed by both parametric (t test) and non parametric (Mann-Whitney) tests. P-values <0.05 were considered as significant.The most affected site was the nose, followed by the mouth, pharynx and larynx. Seventy eight (37.9%) have oral lesions and the disease presented a lower median of the evolution time than in other mucous sites as well as an increased time to heal. The presence of oral lesion was associated with: the presence of lesions in the other three mucosal sites; a smaller median of the leishmanin skin test values; a longer healing time of the mucosal lesions; a higher recurrence frequency; and a smaller frequency of treatment finishing and healing. When the oral lesion was isolated, it was associated with an age 20 years lower than when the oral lesion was associated with other mucosal sites.Considering the worst therapy results associated with the presence of oral lesions, we suggest that lesions in this location represent a factor of worse prognosis for MCL.
| S-EPMC4227643 | biostudies-other
Project description:BackgroundTegumentary leishmaniasis (TL) is a disease of skin and/or mucosal tissues caused by Leishmania parasites. TL patients may concurrently carry other pathogens, which may influence the clinical outcome of TL.Methodology and principal findingsThis review focuses on the frequency of TL coinfections in human populations, interactions between Leishmania and other pathogens in animal models and human subjects, and implications of TL coinfections for clinical practice. For the purpose of this review, TL is defined as all forms of cutaneous (localised, disseminated, or diffuse) and mucocutaneous leishmaniasis. Human immunodeficiency virus (HIV) coinfection, superinfection with skin bacteria, and skin manifestations of visceral leishmaniasis are not included. We searched MEDLINE and other databases and included 73 records: 21 experimental studies in animals and 52 studies about human subjects (mainly cross-sectional and case studies). Several reports describe the frequency of Trypanosoma cruzi coinfection in TL patients in Argentina (about 41%) and the frequency of helminthiasis in TL patients in Brazil (15% to 88%). Different hypotheses have been explored about mechanisms of interaction between different microorganisms, but no clear answers emerge. Such interactions may involve innate immunity coupled with regulatory networks that affect quality and quantity of acquired immune responses. Diagnostic problems may occur when concurrent infections cause similar lesions (e.g., TL and leprosy), when different pathogens are present in the same lesions (e.g., Leishmania and Sporothrix schenckii), or when similarities between phylogenetically close pathogens affect accuracy of diagnostic tests (e.g., serology for leishmaniasis and Chagas disease). Some coinfections (e.g., helminthiasis) appear to reduce the effectiveness of antileishmanial treatment, and drug combinations may cause cumulative adverse effects.Conclusions and significanceIn patients with TL, coinfection is frequent, it can lead to diagnostic errors and delays, and it can influence the effectiveness and safety of treatment. More research is needed to unravel how coinfections interfere with the pathogenesis of TL.
| S-EPMC5832191 | biostudies-literature
Project description:The search toward the establishment of novel serological tests for the diagnosis of leishmaniasis and proper differential diagnosis may represent one alternative to the invasive parasitological methods currently used to identify infected individuals. In the present work, we investigated the potential use of recombinant peroxidoxin (rPeroxidoxin) of Leishmania (Viannia) braziliensis as a potential antigen for the immunodiagnosis of human tegumentary (TL) and visceral leishmaniasis (VL) and canine visceral leishmaniasis (CVL). Linear B-cell epitope mapping was performed to identify polymorphic epitopes when comparing orthologous sequences present in Trypanosoma cruzi, the agent for Chagas disease (CD), and the Homo sapiens and Canis familiaris hosts. The serological assay (ELISA) demonstrated that TL, VL and CVL individuals showed high levels of antibodies against rPeroxidoxin, allowing identification of infected ones with considerable sensitivity and great ability to discriminate (specificity) between non-infected and CD individuals (98.46% and 100%; 98.18% and 95.71%; 95.79% and 100%, respectively). An rPeroxidoxin ELISA also showed a greater ability to discriminate between vaccinated and infected animals, which is an important requirement for the public campaign control of CVL. A depletion ELISA assay using soluble peptides of this B-cell epitope confirmed the recognition of these sites only by Leishmania-infected individuals. Moreover, this work identifies two antigenic polymorphic linear B-cell epitopes of L. braziliensis. Specific recognition of TL and VL patients was confirmed by significantly decreased IgG reactivity against rPeroxidoxin after depletion of peptide-1- and peptide-2-specific antibodies (peptide 1: reduced by 32%, 42% and 5% for CL, ML and VL, respectively; peptide-2: reduced by 24%, 22% and 13% for CL, ML and VL, respectively) and only peptide-2 for CVL (reduced 9%). Overall, rPeroxidoxin may be a potential antigen for the immunodiagnosis of TL, VL or CVL, as it has a higher agreement with parasitological assays and is better than other reference tests that use soluble Leishmania antigens for diagnosing CVL in Brazil (EIE-LVC, Bio-manguinhos, FIOCRUZ).
| S-EPMC4055673 | biostudies-literature
Project description:The serodiagnosis of human tegumentary leishmaniasis (TL) presents some problems, such as the low level of antileishmanial antibodies found in most of the patients, as well as the cross-reactivity in subjects infected by other trypanosomatids. In the present study, an immunoproteomic approach was performed aimed at identification of antigens in total extracts of stationary-phase promastigote and amastigote-like forms of Leishmania (Viannia) braziliensis using sera from TL patients. With the purpose of reducing the cross-reactivity of the identified proteins, spots recognized by sera from TL patients, as well as those recognized by antibodies present in sera from noninfected patients living in areas where TL is endemic and sera from Chagas disease patients, were discarded. Two Leishmania hypothetical proteins and 18 proteins with known functions were identified as antigenic. The study was extended with some of them to validate the results of the immunoscreening. The coding regions of five of the characterized antigens (enolase, tryparedoxin peroxidase, eukaryotic initiation factor 5a, β-tubulin, and one of the hypothetical proteins) were cloned in a prokaryotic expression vector, and the corresponding recombinant proteins were purified and evaluated for the serodiagnosis of TL. The antigens presented sensitivity and specificity values ranging from 95.4 to 100% and 82.5 to 100%, respectively. As a comparative antigen, a preparation of Leishmania extract showed sensitivity and specificity values of 65.1 and 57.5%, respectively. The present study has enabled the identification of proteins able to be employed for the serodiagnosis of TL.
| S-EPMC4622107 | biostudies-literature
Project description:BackgroundTegumentary Leishmaniasis (TL) is a neglected disease with worldwide distribution and considered a public health problem, especially in Latin America. In Colombia, the governmental epidemiological surveillance system (SIVIGILA) is responsible for collecting information on the presentation of cases of TL from each of the municipalities and departments. In absence of a study compiling and analyzing currently available metadata of TL in Colombia, this study describes the geospatial-temporal distribution of TL and identifies the regions of the country on which prevention measures should be established in order to control the disease.Methodology/principal findingsThis is an exploratory descriptive analysis of the distribution of TL in Colombia. Information was collected on new cases of the disease during the years 2007-2016 from the Colombian reporting system (SIVIGILA). Incidence calculations were made based on population estimates by departments and biogeographical regions. Time evolution is shown in biennial maps. A 10-year series was analyzed, showing that the Amazon region is the most affected in terms of incidence, while the Andean region has the highest number of cases with a high variability among the departments that make it up. In those departments where there is a greater reported diversity of vector species, a large number of cases was observed.Conclusions/significanceTransmission dynamics of TL in Colombia in the past 10 years have been variable, with a greater concentration of cases in the central and southern departments. The present study contributes to improve the understanding of the patterns of distribution of TL in Colombia and can be a basis for future studies of impact evaluation of Health policies in the country and the region.
| S-EPMC5906026 | biostudies-literature
Project description:The current reliable recommended test for coronavirus disease 2019 (COVID-19) diagnosis is quantitative reverse-transcription polymerase chain reaction (RT-qPCR). Rapid antigen test devices could be useful as they are less expensive, faster without the need of specialized laboratories to perform the test. We report the performances of two rapid immunochromatographic antigen testing devices compared with RT-qPCR for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection in nasopharyngeal samples. We carried out a lateral-flow tests study on 401 nasopharyngeal swab samples from nonduplicated suspected COVID-19 subjects. An equal volume of universal transport medium tubes-containing samples (dilution ratio = 1:15) were added to the manufacturer's extraction buffer solution (dilution ratio = 1:2) and analyzed on BioSpeedia COVID19Speed-Antigen Test and on Abbott Panbio™ COVID-19 Ag Rapid Test, devices. Qualitative results were compared to those obtained by the RT-qPCR (Allplex™ SARS-CoV-2 Assay Seegene). Based on our data, the overall sensitivity for BioSpeedia and Panbio devices was estimated at 65.5% and 75.0%, respectively. The sensitivity was greater for cycle threshold values less than 25 achieving 90.4 and 96.8 for BioSpeedia and Panbio devices, respectively. A perfect specificity of 100.0% was observed for both devices.
| S-EPMC8242554 | biostudies-literature
Project description:New therapeutic strategies for visceral leishmaniasis (VL) have been studied, and the development of an immunotherapeutic agent that modulates the host's immune response is necessary. The aim of this study was to evaluate in vitro the bioactive extracts of photosynthetic microorganisms (PMs) for their leishmanicidal/leishmanistatic and immunomodulatory potentials. Bioactive extracts from PMs (Arthrospira platensis and Dunaliella tertiolecta) were obtained by sonication. Reference drugs, miltefosine (MTF) and N-methylglucamine antimoniate (SbV), were also evaluated. The selectivity index (SI) of treatments was determined by assays of inhibitory concentration (IC50) in Leishmania infantum cells and cytotoxic concentrations (CC50) in human peripheral blood mononuclear cells by the MTT method. The immune response was evaluated in healthy human cells by the production of cytokines and nitric oxide (NO) and the gene expression of Tbx21, GATA3, RORc, and FOXP3, using four concentrations (CC50, ½ CC50, ¼ CC50, and IC50) for in-vitro stimulation. Based on the data obtained, we observed that the extracts of D. tertiolecta (SI = 4.7) and A. platensis (SI = 3.8) presented better results when compared to SbV (SI = 2.1). When analyzing the immune response results, we identified that the extracts of PMs stimulated the production of cytokines of the Th1 profile more than the reference drugs. The extracts also demonstrated the ability to stimulate NO synthesis. Regarding gene expression, in all concentrations of A. platensis extracts, we found a balance between the Th1/Th2 profile, with the average expression of the Tbx21 gene more than the GATA3 in the highest concentration (CC50). Regarding the extract of D. tertiolecta, we can observe that, in the lowest concentrations, a balance between all the genes was present, with the average expression of the GATA3 gene being lower than the others. The best result was found in the ½ CC50 concentration, stimulating a balanced positive expression between the Th1×Th17×Treg profiles, with a negative expression of GATA3. Thus, PM extracts showed promising results, presenting low toxicity, leishmanicidal/leishmanistatic activity, and induction of the immune response, which could be potential therapeutic candidates for VL.
| S-EPMC9280147 | biostudies-literature