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  • 1.
    Abate, E.
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet. University of Gondar, Ethiopia.
    Elias, D.
    University of Southern Denmark, Denmark.
    Getachew, A.
    University of Gondar, Ethiopia.
    Alemu, S.
    University of Gondar, Ethiopia.
    Diro, E.
    University of Gondar, Ethiopia.
    Britton, S.
    Karolinska Hospital, Sweden.
    Aseffa, A.
    Armauer Hansen Research Institute, Ethiopia.
    Stendahl, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Schön, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet. Kalmar County Hospital, Sweden.
    Effects of albendazole on the clinical outcome and immunological responses in helminth co-infected tuberculosis patients: a double blind randomised clinical trial2015Ingår i: International Journal of Parasitology, ISSN 0020-7519, E-ISSN 1879-0135, Vol. 45, nr 2-3, s. 133-140Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Despite several review papers and experimental studies concerning the impact of chronic helminth infection on tuberculosis in recent years, there is a scarcity of data from clinical field studies in highly endemic areas for these diseases. We believe this is the first randomised clinical trial investigating the impact of albendazole treatment on the clinical and immunological outcomes of helminth co-infected tuberculosis patients. A randomised, double-blind, placebo-controlled trial of albendazole (400 mg per day for 3 days) in helminth-positive tuberculosis patients was conducted in Gondar, Ethiopia. The primary outcome was clinical improvement (Delta TB score) after 2 months. Among secondary outcomes were changes in the levels of eosinophils, CD4+ T cells, regulatory T cells, IFN-gamma, IL-5 and IL-10 after 3 months. A total of 140 helminth co-infected tuberculosis patients were included with an HIV co-infection rate of 22.8%. There was no significant effect on the primary outcome (Delta TB score: 5.6 +/- 2.9 for albendazole versus 5.9 +/- 2.5 for placebo, P = 0.59). The albendazole-treated group showed a decline in eosinophil cells (P = 0.001) and IL-10 (P = 0.017) after 3 months. In an exploratory analysis after 12 weeks, the albendazole treated group showed a trend towards weight gain compared with the placebo group (11.2 +/- 8.5 kg versus 8.2 +/- 8.7 kg, P = 0.08)). The reductions in eosinophil counts and IL-10 show that asymptomatic helminth infection significantly affects host immunity during tuberculosis and can be effectively reversed by albendazole treatment. The clinical effects of helminth infection on chronic infectious diseases such as tuberculosis merit further characterisation. (C) 2014 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

  • 2.
    Elshafie, Amir I.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Åhlin, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Håkansson, Lena Douhan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Elghazali, Gehad
    El Safi, Sayda Hassan
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Venge, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Activity and turnover of eosinophil and neutrophil granulocytes are altered in visceral leishmaniasis2011Ingår i: International Journal of Parasitology, ISSN 0020-7519, E-ISSN 1879-0135, Vol. 41, nr 3-4, s. 463-469Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Visceral leishmaniasis (VL) is a health issue in Sudan. Our aim was to investigate the involvement of eosinophils and neutrophils in VL by serum and plasma measurements of eosinophil cationic protein (ECP) and myeloperoxidase (MPO) and some key cytokines and chemokines. Blood was collected from 125 VL patients and 181 healthy Sudanese controls from the same rural area. Results showed reduced eosinophil and neutrophil counts in the VL group (P = 0.0001 and P = 0.002, respectively). Serum-ECP levels were higher in the controls (P < 0.0001), while plasma MPO levels were higher in the VL group (P < 0.0001). Levels of IL-5, granulocyte macrophage-colony stimulating factor (GM-CSF) and IL-17 were increased among the VL group (P < 0.0001, P = 0.017 and P = 0.03, respectively), whereas eotaxin and IL-8 levels were reduced (P < 0.0001 and P = 0.002, respectively). Positive correlations were found between IL-8 and ECP/MPO (P < 0.0001). We conclude that eosinophil and neutrophil turnover and activity are increased in subjects in rural areas of Sudan. In VL the turnover was further increased, but the relatively low secretory activity of eosinophils and neutrophils in VL may relate to the reduced production and availability of the chemokines eotaxin and IL-8. The combined assay of ECP and MPO in serum and plasma provides further insight into the mechanisms of eosinophil and neutrophil involvement in disease and constitutes a novel approach to the study of disease processes.

  • 3.
    Emery-Corbin, Samantha J.
    et al.
    Walter & Eliza Hall Inst Med Res, Populat Hlth & Immun Div, Melbourne, Vic, Australia.
    Vuong, Daniel
    Microbial Screening Technol, Smithfield, NSW, Australia.
    Lacey, Ernest
    Microbial Screening Technol, Smithfield, NSW, Australia;Macquarie Univ, Fac Sci, Chem & Biomol Sci, N Ryde, NSW, Australia.
    Svärd, Staffan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Ansell, Brendan R. E.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Jex, Aaron R.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi. Univ Melbourne, Fac Vet & Agr Sci, Melbourne, Vic, Australia.
    Proteomic diversity in a prevalent human-infective Giardia duodenalis sub-species2018Ingår i: International Journal of Parasitology, ISSN 0020-7519, E-ISSN 1879-0135, Vol. 48, nr 11, s. 817-823Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Giardia duodenalis a species complex of gastrointestinal protists, with assemblages A and B infective to humans. To date, post-genomic proteomics are largely derived from Assemblage A, biasing understanding of parasite biology. To address this gap, we quantitatively analysed the proteomes of trophozoites from the genome reference and two clinical Assemblage B isolates, revealing lower spectrum-to-peptide matches in non-reference isolates, resulting in significant losses in peptide and protein identifications, and indicating significant intra-assemblage variation. We also explored differential protein expression between in vitro cultured subpopulations putatively enriched for dividing and feeding cells, respectively. This data is an important proteomic baseline for Assemblage B, highlighting proteomic differences between physiological states, and unique differences relative to Assemblage A. 

  • 4.
    Eriksson, Jenny
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Reimert, Claus
    Kabatereine, Narcis
    Kazibwe, Francis
    Ireri, Edmund
    Kadzo, Hilda
    Eltahir, Hanan
    Mohamed, Abdelrahim
    Vennervald, Birgitte
    Venge, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    The 434(G>C) polymorphism within the coding sequence of Eosinophil Cationic Protein (ECP) correlates with the natural course of Schistosoma mansoni infection2007Ingår i: International Journal of Parasitology, ISSN 0020-7519, E-ISSN 1879-0135, Vol. 37, nr 12, s. 1359-1366Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Schistosomiasis is a chronic parasitic infection with over 200 million people infected worldwide. In Schistosoma mansoni infections, parasite-derived eggs get trapped in the liver, causing the formation of granulomas, which may develop into periportal fibrosis and portal hypertension, and thus severe morbidity. Eosinophil cationic protein (ECP) is a secretory protein of eosinophil granulocytes that efficiently kills the larval stage of S. mansoni, but also affects fibroblast functions. We have investigated the prevalence of the ECP gene polymorphism 434(G>C) in two African populations, from an S. mansoni endemic area in Uganda (n = 297) and from a non-endemic area in Sudan (n - 78), and also compared these with a Swedish population (n = 209). The genotype frequencies in the Ugandan population differed significantly from both the Sudanese and Swedish populations (P < 0.001). In the Ugandan population there was a significant association between genotype and prevalence of infection (P = 0.03), with lower prevalence in subjects with the GG genotype compared with GC (P = 0.02) and CC (P = 0.03). There was also a trend towards an association with periportal fibrosis (P = 0.08) in the Ugandan population. This suggested association was confirmed when the predominant tribe (n = 212) was analysed separately (P = 0.004). Our results suggest that ECP may be an important protein, both in the immune response against S. mansoni and in the development of periportal fibrosis. The results also suggest genetic selection towards the ECP 434CC genotype in populations living in S. mansoni endemic areas.

  • 5.
    Ma'ayeh, Showgy Y.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Knörr, Livia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Svärd, Staffan G.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Transcriptional profiling of Giardia intestinalis in response to oxidative stress2015Ingår i: International Journal of Parasitology, ISSN 0020-7519, E-ISSN 1879-0135, Vol. 45, nr 14, s. 925-938Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Giardia intestinalis is a microaerophilic parasite that infects the human upper small intestine, an environment that is fairly aerobic with reactive oxygen species being produced to fight off the parasite. It is quite perplexing how Giardia, lacking conventional eukaryotic antioxidant machinery (e.g. catalase, superoxide dismutase and glutathione peroxidase), can cope with the oxidative stress in this environment. We used transcriptomics (RNA sequencing and quantitative PCR) to study giardial gene expression changes in response to oxygen (O-2; 1 h) and hydrogen peroxide (H2O2; 150 mu M, 500 mu M and 1 mM for 1 h). The results showed phenotypic and transcriptional differences between Giardia isolates of different genotypes (WB, assemblage A and GS, assemblage B), with GS being more tolerant to H2O2 and exhibiting higher basic transcript levels of antioxidant genes (e.g. NADH oxidase lateral transfer candidate, peroxiredoxin 1 (Prxl) and thioredoxin (Trx)-like proteins). Cysteine is a major antioxidant in Giardia and its role in oxidative defense could be highlighted here by the up-regulation of gene transcripts encoding the cysteine-rich variable surface proteins (VSPs) and high cysteine membrane proteins (HCMPs). Genes in the thioredoxin system (Prxl, Trx and Trx reductase) occupied a central role in the gene expression response to oxidative stress, together with genes encoding metabolic (NADPH-producing enzymes, glutathione and glycerol biosynthetic enzymes) and O-2-consuming nitric oxide detoxification enzymes (e.g. nitroreductase, flavohemoprotein and a flavodiiron protein). This study reveals the intricate network of genes associated with the oxidative stress response in Giardia, and provides a stepping-stone towards future studies at the protein level.

  • 6. Reiner, David S.
    et al.
    Ankarklev, Johan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Troell, Karin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Palm, Daniel
    Bernander, Rolf
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolution, genomik och systematik, Molekylär evolution.
    Gillin, Frances D.
    Andersson, Jan O.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Svärd, Staffan G.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Synchronisation of Giardia lamblia: identification of cell cycle stage-specific genes and a differentiation restriction point2008Ingår i: International Journal of Parasitology, ISSN 0020-7519, E-ISSN 1879-0135, Vol. 38, nr 8-9, s. 935-944Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The intestinal parasite Giardia lamblia undergoes cell differentiations that entail entry into and departure from the replicative cell cycle. The pathophysiology of giardiasis depends directly upon the ability of the trophozoite form to replicate in the host upper small intestine. Thus, cell proliferation is tightly linked to disease. However, studies of cell cycle regulation in Giardia have been hampered by the inability to synchronise cultures. Here we report that Giardia isolates of the major human genotypes A and B can be synchronised using aphidicolin, a mycotoxin that reversibly inhibits replicative DNA polymerases in eukaryotic cells. Aphidicolin arrests Giardia trophozoites in the early DNA synthesis (S) phase of the cell cycle. We identified a set of cell cycle orthologues in the Giardia genome using bioinformatic analyses and showed that synchronised parasites express these genes in a cell cycle stage-specific manner. The synchronisation method also showed that during encystation, exit from the ordinary cell cycle occurs preferentially in GZ and defines a restriction point for differentiation. Synchronisation opens up possibilities for further molecular and cell biological studies of chromosome replication, mitosis and segregation of the complex cytoskeleton in Giardia.

  • 7. Resende, Mafalda
    et al.
    Ditlev, B
    Nielsen, A
    Bodevin, Sabrina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Bruun, Silas
    Pinto, V
    Clausen, Henrik
    Turner, Louise
    Theander, G
    Salanti, Ali
    Dahlbäck, Madeleine
    Chondroitin sulphate A (CSA)-binding of single recombinant Duffy-binding-like domains is not restricted to Plasmodium falciparum Erythrocyte Membrane Protein 1 expressed by CSA-binding parasites2009Ingår i: International Journal of Parasitology, ISSN 0020-7519, E-ISSN 1879-0135, Vol. 39, nr 11, s. 1195-1204Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Individuals living in areas with high Plasmodium falciparum transmission acquire immunity to malaria over time and adults have a markedly reduced risk of contracting severe disease. However, pregnant women constitute an important exception. Pregnancy-associated malaria is a major cause of mother and offspring morbidity, such as severe maternal anaemia and low birth-weight, and is characterised by selective accumulation of parasite-infected erythrocytes (IE) in the placenta. A P. falciparum protein named VAR2CSA, which belongs to the large P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) family, enables the IE to bind chondroitin sulphate A (CSA) in the placenta. Knock-out studies have demonstrated the exclusive capacity of VAR2CSA to mediate IE binding to CSA, and it has been shown that four of the six Duffy-binding-like (DBL) domains of VAR2CSA have the ability to bind CSA in vitro. In this study, we confirm the CSA-binding of these DBL domains, however, the analysis of a number of DBL domains of a non-VAR2CSA origin shows that CSA-binding is not exclusively restricted to VAR2CSA DBL domains. Furthermore, we show that the VAR2CSA DBL domains as well as other DBL domains also bind heparan sulphate. These data explain a number of publications describing CSA-binding domains derived from PfEMP1 antigens not involved in placental adhesion. The data suggest that the ability of single domains to bind CSA does not predict the functional capacity of the whole PfEMP1 and raises doubt whether the CSA-binding domains of native VAR2CSA have been correctly identified. (C) 2009 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

  • 8.
    Weidner, Jessica M.
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Barragan, Antonio
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Tightly regulated migratory subversion of immune cells promotes the dissemination of Toxoplasma gondii2014Ingår i: International Journal of Parasitology, ISSN 0020-7519, E-ISSN 1879-0135, Vol. 44, nr 2, s. 85-90Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    While the spread of Toxoplasma gondii within the infected human or animal host is associated with pathology, the pathways of dissemination have remained enigmatic. From the time point of entry into the gut, to the quiescent chronic infection in the central nervous system, Toxoplasma is detected and surveyed by immune cells that populate the tissues, for example dendritic cells. Paradoxically, this protective migratory function of leukocytes appears to be targeted by Toxoplasma to mediate its dissemination in the organism. Recent findings show that tightly regulated events take place shortly after host cell invasion that promote the migratory activation of infected dendritic cells. Here, we review the emerging knowledge on how this obligate intracellular protozoan orchestrates the subversion of leukocytes to achieve systemic dissemination and reach peripheral organs where pathology manifests.

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