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  • 1. Albrecht, Letusa
    et al.
    Moll, Kirsten
    Blomqvist, Karin
    Normark, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Chen, Qijun
    Wahlgren, Mats
    var gene transcription and PfEMP1 expression in the rosetting and cytoadhesive Plasmodium falciparum clone FCR3S1.22011Inngår i: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 10, artikkel-id 17Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The pathogenicity of Plasmodium falciparum is in part due to the ability of the parasitized red blood cell (pRBC) to adhere to intra- vascular host cell receptors and serum-proteins. Binding of the pRBC is mediated by Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), a large multi-variant molecule encoded by a family of approximate to 60 var genes. Methods: The study of var gene transcription in the parasite clone FCR3S1.2 was performed by semi-quantitative PCR and quantitative PCR (qPCR). The expression of the major PfEMP1 in FCR3S1.2 pRBC was analysed with polyclonal sera in rosette disruption assays and immunofluorecence. Results: Transcripts from var1 (FCR3S1.2(var1); IT4var21) and other var genes were detected by semi-quantitative PCR but results from qPCR showed that one var gene transcript dominated over the others (FCR3S1.2var2; IT4var60). Antibodies raised in rats to the recombinant NTS-DBL1a of var2 produced in E. coli completely and dosedependently disrupted rosettes (approximate to 95% at a dilution of 1/5). The sera reacted with the Maurer's clefts in trophozoite stages (IFA) and to the infected erythrocyte surface (FACS) indicating that FCR3S1.2var2 encodes the dominant PfEMP1 expressed in this parasite. Conclusion: The major transcript in the rosetting model parasite FCR3S1.2 is FCR3S1.2var2 (IT4var60). The results suggest that this gene encodes the PfEMP1-species responsible for the rosetting phenotype of this parasite. The activity of previously raised antibodies to the NTS-DBL1a of FCR3S1.2var1 is likely due to cross-reactivity with NTS-DBL1 alpha of the var2 encoded PfEMP1.

  • 2.
    Lemma, Hailemariam
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Löfgren, Curt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    San Sebastian, Miguel
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Adherence to a six-dose regimen of artemether-lumefantrine among uncomplicated Plasmodium falciparum patients in the Tigray Region, Ethiopia2011Inngår i: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 10, s. 349-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: In 2004, Ethiopia switched its first-line treatment of uncomplicated Plasmodium falciparum malaria from sulphadoxine-pyrimethamine to a fixed artemisinin-based combination therapy (ACT), artemether-lumefantrine (AL). Patient adherence to AL regimen is a major determining factor to achieve the desired therapeutic outcome. The aim of this study was to measure patient adherence levels to the six-dose AL regimen for the treatment of uncomplicated P. falciparum malaria and to identify its determinant factors in rural areas of the Tigray region, Ethiopia

    METHODS: The study was conducted under routine health service delivery at health posts level. Patients/caregivers were not informed about their home visit and were traced on the day after they finished the AL regimen. By combining the response to a structured questionnaire and the tablet count from the blister, adherence level was classified into three categories: definitely non-adherent, probably non-adherent and probably adherent. Reasons for being definitely non-adherent were also assessed. For the purpose of examine risk factors, definitely non-adherent and probably non-adherent was merged into a non-adherent group. Variables found significantly associated (p < 0.05) with the adherence level on the univariate analysis were fitted into a multivariate logistic regression model.

    RESULTS: Out of the total initially enrolled 180 patients, 86.1% completed the follow-up. Out of these, 38.7% were classified as probably adherent, 34.8% as probably non-adherent, and 26.5% were definitely non-adherent. The most common reasons that definitely non-adherents gave for not taking the full dose were "too many tablets" (37.3%) and to "felt better before finished the treatment course" (25.5%). The adherence of the patients was associated with the ownership of a radio (adjusted odd ratio, AOR: 3.8; 95% CI: 1.66-8.75), the belief that malaria can be treated traditionally (AOR: 0.09; 95% CI: 0.01-0.78) and a delay of more than one day in seeking treatment after the onset of fever (AOR: 5.39; 95% CI: 1.83-15.88).

    CONCLUSION: The very low adherence to AL found in this study raises serious concerns for the malaria control in the region. The implementation of a monitoring adherence system is essential to ensure long-term treatment efficacy.

  • 3. Lover, Andrew A
    et al.
    Sutton, Brett A
    Asy, Angelina J
    Wilder-Smith, Annelies
    Institute of Public Health, University of Heidelberg, Germany.
    An exploratory study of treated-bed nets in Timor-Leste: patterns of intended and alternative usage.2011Inngår i: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 10, s. 199-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: The Timor-Leste Ministry of Health has recently finalized the National Malaria Control Strategy for 2010-2020. A key component of this roadmap is to provide universal national coverage with long-lasting insecticide-treated nets (LLINs) in support of achieving the primary goal of reducing both morbidity and mortality from malaria by 30% in the first three years, followed by a further reduction of 20% by end of the programme cycle in 2020 1. The strategic plan calls for this target to be supported by a comprehensive information, education and communication (IEC) programme; however, there is limited prior research into household and personal usage patterns to assist in the creation of targeted, effective, and socio-culturally specific behaviour change materials.

    METHODS: Nine separate focus group discussions (FGDs) were carried out in Dili, Manatuto, and Covalima districts, Democratic Republic of Timor-Leste, in July 2010.These focus groups primarily explored themes of perceived malaria risk, causes of malaria, net usage patterns within families, barriers to correct and consistent usage, and the daily experience of users (both male and female) in households with at least one net. Comprehensive qualitative analysis utilized open source analysis software.

    RESULTS: The primary determinants of net usage were a widespread perception that nets could or should only be used by pregnant women and young children, and the availability of sufficient sleeping space under a limited number of nets within households. Both nuisance biting and disease prevention were commonly cited as primary motivations for usage, while seasonality was not a significant factor. Long-term net durability and ease of hanging were seen as key attributes in net design preference. Very frequent washing cycles were common, potentially degrading net effectiveness. Finally, extensive re-purposing of nets (fishing, protecting crops) was both reported and observed, and may significantly decrease availability of nighttime sleeping space for all family members if distributed nets do not remain within the household.

    CONCLUSIONS: Emphasizing that net usage is acceptable and important for all family members regardless of age or gender, and addressing the complex behavioural economics of alternative net usages could have significant impacts on malaria control efforts in Timor-Leste, as the country's programmes make progress towards universal net coverage.

  • 4. Reuterswärd, Philippa
    et al.
    Bergström, Sofia
    Orikiiriza, Judy
    Lindquist, Elisabeth
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Bergström, Sven
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Svahn, Helene Andersson
    Ayoglu, Burcu
    Uhlén, Mathias
    Wahlgren, Mats
    Normark, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Ribacke, Ulf
    Nilsson, Peter
    Levels of human proteins in plasma associated with acute paediatric malaria2018Inngår i: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 17, artikkel-id 426Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The intimate interaction between the pathophysiology of the human host and the biology of the Plasmodium falciparum parasite results in a wide spectrum of disease outcomes in malaria. Development of severe disease is associated with a progressively augmented imbalance in pro- and anti-inflammatory responses to high parasite loads and sequestration of parasitized erythrocytes. Although these phenomena collectively constitute common denominators for the wide variety of discrete severe malaria manifestations, the mechanistic rationales behind discrepancies in outcome are poorly understood. Exploration of the human pathophysiological response by variations in protein profiles in plasma presents an excellent opportunity to increase the understanding. This is ultimately required for better prediction, prevention and treatment of malaria, which is essential for ongoing elimination and eradication efforts.

    Results: An affinity proteomics approach was used to analyse 541 paediatric plasma samples collected from community controls and patients with mild or severe malaria in Rwanda. Protein profiles were generated with an antibody-based suspension bead array containing 255 antibodies targetting 115 human proteins. Here, 57 proteins were identified with significantly altered levels (adjusted p-values < 0.001) in patients with malaria compared to controls. From these, the 27 most significant proteins (adjusted p-values < 10−14) were selected for a stringent analysis approach. Here, 24 proteins showed elevated levels in malaria patients and included proteins involved in acute inflammatory response as well as cell adhesion. The remaining three proteins, also implicated in immune regulation and cellular adhesivity, displayed lower abundance in malaria patients. In addition, 37 proteins (adjusted p-values < 0.05) were identified with increased levels in patients with severe compared to mild malaria. This set includes, proteins involved in tissue remodelling and erythrocyte membrane proteins. Collectively, this approach has been successfully used to identify proteins both with known and unknown association with different stages of malaria.

    Conclusion: In this study, a high-throughput affinity proteomics approach was used to find protein profiles in plasma linked to P. falciparum infection and malaria disease progression. The proteins presented herein are mainly involved in inflammatory response, cellular adhesion and as constituents of erythrocyte membrane. These findings have a great potential to provide increased conceptual understanding of host-parasite interaction and malaria pathogenesis.

  • 5.
    Surowiec, Izabella
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Gouveia-Figueira, Sandra
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Orikiiriza, Judy
    Lindquist, Elisabeth
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Bonde, Mari
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Magambo, Jimmy
    Muhinda, Charles
    Bergström, Sven
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Normark, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    The oxylipin and endocannabidome responses in acute phase Plasmodium falciparum malaria in children2017Inngår i: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 16, artikkel-id 358Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Oxylipins and endocannabinoids are low molecular weight bioactive lipids that are crucial for initiation and resolution of inflammation during microbial infections. Metabolic complications in malaria are recognized contributors to severe and fatal malaria, but the impact of malaria infection on the production of small lipid derived signalling molecules is unknown. Knowledge of immunoregulatory patterns of these molecules in malaria is of great value for better understanding of the disease and improvement of treatment regimes, since the action of these classes of molecules is directly connected to the inflammatory response of the organism.

    Methods: Detection of oxylipins and endocannabinoids from plasma samples from forty children with uncomplicated and severe malaria as well as twenty controls was done after solid phase extraction followed by chromatography mass spectrometry analysis. The stable isotope dilution method was used for compound quantification. Data analysis was done with multivariate (principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA (R)) and univariate approaches (receiver operating characteristic (ROC) curves, t tests, correlation analysis).

    Results: Forty different oxylipin and thirteen endocannabinoid metabolites were detected in the studied samples, with one oxylipin (thromboxane B2, TXB2) in significantly lower levels and four endocannabinoids (OEA, PEA, DEA and EPEA) at significantly higher levels in infected individuals as compared to controls according to t test analysis with Bonferroni correction. Three oxylipins (13-HODE, 9-HODE and 13-oxo-ODE) were higher in severe compared to uncomplicated malaria cases according to the results from multivariate analysis. Observed changes in oxylipin levels can be connected to activation of cytochrome P450 (CYP) and 5-lipoxygenase (5-LOX) metabolic pathways in malaria infected individuals compared to controls, and related to increased levels of all linoleic acid oxylipins in severe patients compared to uncomplicated ones. The endocannabinoids were extremely responsive to malaria infection with majority of this class of molecules found at higher levels in infected individuals compared to controls.

    Conclusions: It was possible to detect oxylipin and endocannabinoid molecules that can be potential biomarkers for differentiation between malaria infected individuals and controls and between different classes of malaria. Metabolic pathways that could be targeted towards an adjunctive therapy in the treatment of malaria were also pinpointed.

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