Disease severity in patients with visceral leishmaniasis is not altered by co-infection with intestinal parasites.
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ABSTRACT:
SUBMITTER: Tajebe F
PROVIDER: S-EPMC5540614 | biostudies-literature | 2017 Jul
REPOSITORIES: biostudies-literature
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Disease severity in patients with visceral leishmaniasis is not altered by co-infection with intestinal parasites.
Tajebe Fitsumbrhan F Getahun Mulusew M Adem Emebet E Hailu Asrat A Lemma Mulualem M Fikre Helina H Raynes John J Tamiru Aschalew A Mulugeta Zemenay Z Diro Ermias E Toulza Frederic F Shkedy Ziv Z Ayele Tadesse T Modolell Manuel M Munder Markus M Müller Ingrid I Takele Yegnasew Y Kropf Pascale P
PLoS neglected tropical diseases 20170721 7
Visceral leishmaniasis (VL) is a neglected tropical disease that affects the poorest communities and can cause substantial morbidity and mortality. Visceral leishmaniasis is characterized by the presence of Leishmania parasites in the spleen, liver and bone marrow, hepatosplenomegaly, pancytopenia, prolonged fever, systemic inflammation and low body mass index (BMI). The factors impacting on the severity of VL are poorly characterized. Here we performed a cross-sectional study to assess whether ...[more]
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Project description:Visceral leishmaniasis (VL) is a neglected tropical disease caused by parasites from the Leishmania (L.) donovani complex. VL is characterised by uncontrolled parasite replication in spleen, liver and bone marrow, and by an impaired immune response and high systemic levels of inflammation. Monocytes have been poorly characterised in VL patients. The aim of this study was to evaluate the expression levels of markers involved in the regulation of T cell responses on different subsets of monocytes from the blood of VL patients and healthy non-endemic controls (HNEC). Monocytes can broadly be divided into three subsets: classical, intermediate and non-classical monocytes. Our results show that the percentages of all three subsets stayed similar at the time of VL diagnosis (ToD) and at the end of anti-leishmanial treatment (EoT). We first looked at co-stimulatory receptors: the expression levels of CD40 were significantly increased on classical and intermediate, but not non-classical monocytes, at ToD as compared to EoT and HNEC. CD80 expression levels were also increased on intermediate monocytes at ToD as compared to EoT and HNEC, and on classical monocytes only as compared to HNEC. The levels of CD86 were similar at EoT and ToD and in HNEC on classical and intermediate monocytes, but significantly higher at EoT on non-classical monocytes. We also looked at an inhibitory molecule, PD-L1. Our results show that the expression levels of PD-L1 were significantly higher on all three monocyte subsets at ToD as compared to HNEC, and to EoT on classical and intermediate monocytes. These results show that monocytes from the blood of VL patients upregulate both co-stimulatory and inhibitory receptors and that their expression levels are restored at EoT.
| S-EPMC11373857 | biostudies-literature
Project description:Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection results in a spectrum of clinical presentations. Evidence from Africa indicates that significantly less COVID-19 patients suffer from serious symptoms than in the industrialized world. We and others previously postulated a partial explanation for this phenomenon, being a different, more activated immune system due to parasite infections. Here, we aimed to test this hypothesis by investigating a potential correlation of co-infection with parasites with COVID-19 severity in an endemic area in Africa. Methods: Ethiopian COVID-19 patients were enrolled and screened for intestinal parasites, between July 2020 and March 2021. The primary outcome was the proportion of patients with severe COVID-19. Ordinal logistic regression models were used to estimate the association between parasite infection, and COVID-19 severity. Models were adjusted for sex, age, residence, education level, occupation, body mass index, and comorbidities. Findings: 751 SARS-CoV-2 infected patients were enrolled, of whom 284 (37.8%) had intestinal parasitic infection. Only 27/255 (10.6%) severe COVID-19 patients were co-infected with intestinal parasites, while 257/496 (51.8%) non-severe COVID-19 patients were parasite positive (p<0.0001). Patients co-infected with parasites had lower odds of developing severe COVID-19, with an adjusted odds ratio (aOR) of 0.23 (95% CI 0.17-0.30; p<0.0001) for all parasites, aOR 0.37 ([95% CI 0.26-0.51]; p<0.0001) for protozoa, and aOR 0.26 ([95% CI 0.19-0.35]; p<0.0001) for helminths. When stratified by species, co-infection with Entamoeba spp., Hymenolepis nana, Schistosoma mansoni, and Trichuris trichiura implied lower probability of developing severe COVID-19. There were 11 deaths (1.5%), and all were among patients without parasites (p = 0.009). Interpretation: Parasite co-infection is associated with a reduced risk of severe COVID-19 in African patients. Parasite-driven immunomodulatory responses may mute hyper-inflammation associated with severe COVID-19. Funding: European and Developing Countries Clinical Trials Partnership (EDCTP) - European Union, and Joep Lange Institute (JLI), The Netherlands. Trial registration: Clinicaltrials.gov: NCT04473365.
| S-EPMC8324426 | biostudies-literature
Project description:Whole genome sequencing (WGS) is increasingly used for molecular diagnosis and epidemiology of infectious diseases. Current Leishmania genomic studies rely on DNA extracted from cultured parasites, which might introduce sampling and biological biases into the subsequent analyses. Up to now, direct analysis of Leishmania genome in clinical samples is hampered by high levels of human DNA and large variation in parasite load in clinical samples. Here, we present a method, based on target enrichment of Leishmania donovani DNA with Agilent SureSelect technology, that allows the analysis of Leishmania genomes directly in clinical samples. We validated our protocol with a set of artificially mixed samples, followed by the analysis of 63 clinical samples (bone marrow or spleen aspirates) from visceral leishmaniasis patients in Nepal. We were able to identify genotypes using a set of diagnostic SNPs in almost all of these samples (97%) and access comprehensive genome-wide information in most (83%). This allowed us to perform phylogenomic analysis, assess chromosome copy number and identify large copy number variants (CNVs). Pairwise comparisons between the parasite genomes in clinical samples and derived in vitro cultured promastigotes showed a lower aneuploidy in amastigotes as well as genomic differences, suggesting polyclonal infections in patients. Altogether our results underline the need for sequencing parasite genomes directly in the host samples.
| S-EPMC6932831 | biostudies-literature
Project description:Leishmaniasis is an infectious disease in which different clinical manifestations are classified into three primary forms: visceral, cutaneous and mucocutaneous. These disease forms are associated with parasite species of the protozoan genus Leishmania. For instance, Leishmania infantum and Leishmania tropica are typically linked with visceral (VL) and cutaneous (CL) leishmaniasis, respectively; however, these two species can also cause other form to a lesser extent. What is more alarming is this characteristic, which threatens current medical diagnosis and treatment, is started to be acquired by other species. Our purpose was to address this issue; therefore, gel-based and gel-free proteomic analyses were carried out on the species L. infantum to determine the proteins differentiating between the parasites caused VL and CL. In addition, L. tropica parasites representing the typical cases for CL were included. According to our results, electrophoresis gels of parasites caused to VL were distinguishable regarding the repetitive down-regulation on some specific locations. In addition, a distinct spot of an antioxidant enzyme, superoxide dismutase, was shown up only on the gels of CL samples regardless of the species. In the gel-free approach, 37 proteins that were verified with a second database search using a different search engine, were recognized from the comparison between VL and CL samples. Among them, 31 proteins for the CL group and six proteins for the VL group were determined differentially abundant. Two proteins from the gel-based analysis, pyruvate kinase and succinyl-coA:3-ketoacid-coenzyme A transferase analysis were encountered in the protein list of the CL group.
| S-EPMC11010476 | biostudies-literature
Project description:Visceral leishmaniasis (VL) is the most severe clinical form of leishmaniasis, and if untreated may be fatal. It affects important organs of the immune system and is characterized by a specific immunosuppression, along with intense cellular activation and cytokine storm. Moreover, VL is now recognized as a systemic inflammatory response syndrome (SIRS), in which multiple cytokines and other pro-inflammatory molecules are released. The action of these inflammatory mediators may be considered risk factors for poor prognosis and death. Leptin, a hormone derived from adipose tissue, has been described with several immunoregulatory functions in vitro and in vivo Leishmania infection models, particularly for enhancing the macrophage microbicidal mechanisms. Considering that evaluation of immunologic parameters that may be associated with this clinical scenario may help to decrease VL lethality, we evaluated whether leptin is associated with VL pathogenesis. Thirty-one patients were recruited in the active phase of VL, of which 22 were followed up until one month after therapy (1mpt). Except for creatinine levels, all clinical parameters were altered in active VL patients, especially leucocyte counts and albumin and hemoglobin levels. Also, elevated levels of lipopolysaccharide (LPS), immunoglobulins (Ig)G1 and G3 anti-Leishmania and interleukins (IL)-6 and -10 were higher than in healthy individuals. In contrast, active VL patients presented diminished serum leptin levels and positive correlation with leukocytes counts and hemoglobin and albumin levels. After 1mpt, VL patients showed a significant increase in leptin levels, reaching values similar to healthy volunteers. As expected, only LPS levels remained elevated after 1mpt. These findings suggest that leptin levels are affected in Leishmania infection and the correlation with important parameters associated with the prognosis of VL points to the involvement of this molecule in VL immunopathogenesis. Additional studies are needed to evaluate the possibility of leptin as a prognostic marker of VL.
| S-EPMC6435192 | biostudies-literature
Project description:BackgroundTuberculosis and intestinal parasites are mostly affecting poor people. They are in a vicious since one is the risk factor for the other. However, the comprehensive report on the burden and co-incidence of intestinal parasites and tuberculosis in Ethiopia is scant. This systematic review and meta-analysis aimed to provide abridge conclusive evidence on the intestinal parasite-tuberculosis co-infection in Ethiopia.MethodsA total of 414 articles published in English were searched from both electronic databases (CINAHL, DOAJ, Embase, Emcare, Medline, ProQuest, and PubMed, Science Direct, and Web of Science) and other sources. The qualities of the included studies were assessed using the Joanna Briggs Institute Critical Appraisal tools and the publication bias was measured using the funnel plot and Eggers regression test. Comprehensive meta-analysis (CMA) Version 3.3.07 and Review Manager software were used to estimate pooled prevalence and associations of intestinal parasites and tuberculosis infection.ResultsEleven articles with a total of 3158 tuberculosis patients included in the analysis based on the eligibility criteria. The estimated pooled prevalence of intestinal parasites co-infection was 33% (95% CI: 23.3, 44.3) using the random-effects model. The most common intestinal parasites were Ascaris lumbricoides 10.5% (95% CI: 6.0, 17.5), Hookworm 9.5% (95% CI: 6.10, 14.4), Giardia lamblia 5.7% (95% CI: 2.90, 10.9) and Strongyloides sterocoralis 5.6% (95% CI: 3.3, 9.5). The odds of intestinal parasites infection was higher among tuberculosis patients compared to tuberculosis free individuals (OR = 1.76; 95% CI: 1.17, 2.63). A significant difference was observed among TB patients for infection with intestinal helminths (OR = 2.01; 95% CI: 1.07, 3.80) but not for intestinal protozoans when compared with their counterparts. The odds of multiple parasitic infections was higher among tuberculosis patients (OR = 2.59, 95% CI: 1.90, 3.55) compared to tuberculosis free individuals. However, intestinal parasites co-infection was not associated with HIV status among tuberculosis patients (OR = 0.97; 95% CI: 0.71, 1.32).ConclusionOne-third of tuberculosis patients are co-infected with one or more intestinal parasites, and they are more likely to be infected with intestinal helminths and multiple intestinal parasitic infections compared to TB free individuals. We recommend routine screening of tuberculosis patients for intestinal parasites. The effect of mass deworming on tuberculosis incidence would be important to be considered in future researches.Trial registrationRegistered on PROSPERO with reference number ID: CRD42019135350 .
| S-EPMC7362415 | biostudies-literature
Project description:BackgroundThe immune system plays a critical role in the development of co-infections, promoting or preventing establishment of multiple infections and shaping the outcome of pathogen-host interactions. Its ability to mediate the interplay between visceral leishmaniasis (VL) and malaria has been suggested, but poorly documented. The present study investigated whether concomitant infection with Leishmania donovani complex and Plasmodium falciparum in naturally co-infected patients altered the immunological response elicited by the two pathogens individually.ResultsCirculating levels of interferon (IFN)-?, interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12p70, IL-13, IL-17A and tumor necrosis factor (TNF) were assessed in sera of patients infected with active VL and/or malaria and healthy individuals from Gedarif State, Sudan. Comparative analysis of cytokine profiles from co- and mono-infected patients highlighted significant differences in the immune response mounted upon co-infection, confirming the ability of L. donovani and P. falciparum to mutually interact at the immunological level. Progressive polarization towards type-1 and pro-inflammatory cytokine patterns characterized the co-infected patients, whose response partly reflected the effect elicited by VL (IFN-?, TNF) and malaria (IL-2, IL-13), and partly resulted from a synergistic interaction of the two diseases upon each other (IL-17A). Significantly reduced levels of P. falciparum parasitaemia (P <0.01) were detected in the co-infected group as opposed to the malaria-only patients, suggesting either a protective or a non-detrimental effect of the co-infection against P. falciparum infection.ConclusionsThese findings suggest that a new immunological scenario may occur when L. donovani and P. falciparum co-infect the same patient, with potential implications on the course and resolution of these diseases.
| S-EPMC4024313 | biostudies-literature
Project description:Visceral leishmaniasis (also known as kala-azar) is classified as one of the most neglected tropical diseases. It is becoming a growing health problem in Ethiopia, with endemic areas that are continually spreading. The annual burden of visceral leishmaniasis (VL) in Ethiopia is estimated to be between 4,500 and 5,000 cases, and the population at risk is more than 3.2 million. There has been a change in the epidemiology of VL in Ethiopia. Over the last decades, almost all cases and outbreaks of VL were reported from arid and semi-arid parts of the country; however, recent reports indicated the introduction of this disease into the highlands. Migration of labourers to and from endemic areas, climatic and environmental changes, and impaired immunity due to HIV/AIDS and malnutrition resulted in the change of VL epidemiology. HIV spurs the spread of VL by increasing the risk of progression from asymptomatic infection towards full VL. Conversely, VL accelerates the onset of AIDS. In Ethiopia, VL epidemiology remains complex because of the diversity of risk factors involved, and its control is becoming an increasing challenge. This paper reviews the changes in epidemiology of VL in Ethiopia and discusses some of the possible explanations for these changes. The prospects for novel approaches to VL control are discussed, as are the current and future challenges facing Ethiopia's public health development program.
| S-EPMC4154678 | biostudies-other
Project description:BackgroundSouth Sudan is one of the most endemic countries for visceral leishmaniasis (VL), and is frequently affected by large epidemics. In resource-limited settings, clinicians require a simple clinical tool to identify VL patients who are at increased risk of dying, and who need specialised treatment with liposomal amphotericin B and other supportive care. The aim of this study was to develop and validate a clinical severity scoring system based on risk factors for death in VL patients in South Sudan.MethodsA retrospective analysis was conducted of data from a cohort of 6,633 VL patients who were treated in the Médecins Sans Frontières (MSF) hospital in Lankien between July 2013 and June 2015. Risk factors for death during treatment were identified using multivariable logistic regression models, and the regression coefficients were used to develop a severity scoring system. Sensitivity and specificity of score cut-offs were assessed by receiver operating characteristic (ROC) analysis.ResultsIn multivariable models, risk factors for death in adult VL patients were: anaemia (odds ratio (OR) 4.46 (95% CI 1.58-12.6) for Hb <6g/dL compared with ?9g/dL), nutritional status (OR 4.84 (2.09-11.2) for BMI <13 kg/m2 compared with ?16 kg/m2), weakness (OR 4.20 (1.82-9.73) for collapsed compared with normal weakness), jaundice (OR 3.41 (1.17-9.95)), and oedema/ascites (OR 4.86 (1.67-14.1)). For children and adolescents the risk factors were: age (OR 10.7 (6.3-18.3) for age <2 years compared with 6-18 years), anaemia (OR 7.76 (4.15-14.5) for Hb <6g/dL compared with ?9g/dL), weakness (OR 3.13 (22.8-105.2) for collapsed compared with normal weakness), and jaundice (OR 12.8 (4.06-40.2)). Severity scoring predictive ability was 74.4% in adults and 83.4% in children and adolescents.ConclusionOur evidenced-based severity scoring system demonstrated sufficient predictive ability to be operationalised as a clinical tool for rational allocation of treatment to VL patients at MSF centres in South Sudan.
| S-EPMC5638606 | biostudies-literature
Project description:Cells of the immune system are derived from hematopoietic stem cells (HSCs) residing in the bone marrow. HSCs become activated in response to stress, such as acute infections, which adapt the bone marrow output to the needs of the immune response. However, the impact of infection-adapted HSC activation and differentiation on the persistence of chronic infections is poorly understood. We have examined here the bone marrow outcome of chronic visceral leishmaniasis and show that the parasite Leishmania donovani induces HSC expansion and skews their differentiation towards non-classical myeloid progenitors with a regulatory phenotype. Our results further suggest that emergency hematopoiesis contributes to the pathogenesis of visceral leishmaniasis, as decreased HSC expansion results in a lower parasite burden. Conversely, monocytes derived in the presence of soluble factors from the infected bone marrow environment are more permissive to infection by Leishmania. Our results demonstrate that L. donovani is able to subvert host bone marrow emergency responses to facilitate parasite persistence, and put forward hematopoiesis as a novel therapeutic target in chronic infections.
| S-EPMC5560750 | biostudies-literature