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af Edholm, K., Lidman, C., Andersson, S., Solders, G. & Paucar, M. (2019). Clinical Reasoning: Leg weakness and stiffness at the emergency room. Neurology, 92(6), E622-E625
Open this publication in new window or tab >>Clinical Reasoning: Leg weakness and stiffness at the emergency room
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2019 (English)In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 92, no 6, p. E622-E625Article in journal, Editorial material (Other academic) Published
Abstract [en]

A 48-year-old woman from the Maghreb came to the emergency department with insidious gait difficulties, urgency, and constipation starting 6 months prior to the visit. The patient's complaints consisted of weakness, stiffness, and pain in her legs. Her medical history consisted of Hashimoto thyroiditis and breast cancer, with the latter having motivated surgery 4 months prior to admission. Histopathologic examination had demonstrated ductal cancer sensitive to estrogen and mapping with sentinel node biopsy ruled out metastasis. For that reason, the patient was treated with local radiation given weekly over 1 month and treatment with tamoxifen was started. Physical examination upon admission demonstrated weakness and spasticity in both legs. Reflexes were brisk; bilateral nonsustained foot clonus and Babinski sign were also present. Bilateral dorsal flexion was reduced, but vibration and sensation to touch and pinprick were normal. Sphincter tonus was reduced; systemic manifestations such as myalgias, fever, skin rashes, uveitis, sicca, and arthritic joints were absent.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2019
National Category
Neurology
Identifiers
urn:nbn:se:oru:diva-73609 (URN)10.1212/WNL.0000000000006885 (DOI)000462355900021 ()30718330 (PubMedID)2-s2.0-85061059563 (Scopus ID)
Funder
Stockholm County Council
Available from: 2019-04-10 Created: 2019-04-10 Last updated: 2019-04-10Bibliographically approved
Esbjörnsson, J., Månsson, F., Kvist, A., da Silva, Z. J., Andersson, S., Fenyö, E. M., . . . Norrgren, H. (2019). Long-term follow-up of HIV-2-related AIDS and mortality in Guinea-Bissau: a prospective open cohort study. The Lancet HIV, 6(1), E25-E31
Open this publication in new window or tab >>Long-term follow-up of HIV-2-related AIDS and mortality in Guinea-Bissau: a prospective open cohort study
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2019 (English)In: The Lancet HIV, ISSN 2405-4704, E-ISSN 2352-3018, Vol. 6, no 1, p. E25-E31Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: HIV type 2 (HIV-2) is considered more benign and has fewer pathogenic consequences than HIV type 1 (HIV-1) for most infected individuals. However, reliable estimates of time to AIDS and mortality among those with HIV-2 infection are absent. We therefore aimed to compare the time to AIDS and mortality, and the CD4 T-cell dynamics between those infected with HIV-1 and HIV-2.

METHODS: We did a prospective open cohort study. We included all police officers with regular employment from police stations in both urban and rural areas of Guinea-Bissau since Feb 6, 1990. We continued to include participants until Sept 28, 2009, and follow-up of HIV-1-positive and HIV-2-positive individuals continued until Sept 28, 2013. We collected blood samples at enrolment and at scheduled annual follow-up visits at police stations. We analysed longitudinal data from individuals infected with HIV-1 and HIV-2 according to time to AIDS, time to death, and T-cell dynamics. Time of HIV infection was estimated as the mid-timepoint between last HIV-seronegative and first HIV-seropositive sample. Data from an additional 2984 HIV-uninfected individuals from the same population were analysed to assess the effect of natural mortality on HIV-related mortality.

FINDINGS: 872 participants tested HIV positive during the 23-year study period: 408 were infected with HIV-1 (183 infected before and 225 infected after enrolment) and 464 were infected with HIV-2 (377 before and 87 after enrolment). The median time from HIV infection to development of AIDS was 6·2 years (95% CI 5·4-7·1) for HIV-1 infection and 14·3 years (10·7-18·0) for HIV-2 infection (p<0·0001). The median survival time after HIV infection was 8·2 years (95% CI 7·5-8·9) for HIV-1 infection and 15·6 years (12·0-19·2) for HIV-2 infection (p<0·0001). Individuals who were infected with HIV-1 or HIV-2 before enrolment showed similar results. Comparison with uninfected individuals indicated limited confounding contribution from natural mortality. Mean CD4 percentages were higher in individuals with HIV-2 than in those with HIV-1 during early infection (28·0% [SE 1·3] vs 22·3% [1·7]; p=0·00094) and declined at a slower rate (0·4% [0·2] vs 0·9% [0·2] per year; p=0·028). HIV-2-infected individuals developed clinical AIDS at higher mean CD4 percentages (18·2%, IQR 7·2-25·4) than HIV-1-infected individuals (8·2%, 3·0-13·8; p<0·0001).

INTERPRETATION: Our results show that both HIV-1-infected and HIV-2-infected individuals have a high probability of developing and dying from AIDS without antiretroviral treatment.

Place, publisher, year, edition, pages
The Lancet Publishing Group, 2019
National Category
Public Health, Global Health, Social Medicine and Epidemiology Infectious Medicine Immunology in the medical area
Identifiers
urn:nbn:se:oru:diva-69991 (URN)10.1016/S2352-3018(18)30254-6 (DOI)000455110700011 ()30392769 (PubMedID)
Funder
Sida - Swedish International Development Cooperation AgencySwedish Research Council, 350-2012-6628 2016-01417 2016-02285 321-2012-3274Swedish Society for Medical Research (SSMF)Region Skåne
Note

Funding Agency:

Medical Faculty at Lund University

Available from: 2018-11-07 Created: 2018-11-07 Last updated: 2019-01-23Bibliographically approved
Thulin Hedberg, S., Eriksson, L., Demontis, M. A., Mölling, P., Sundqvist, M., Taylor, G., . . . Andersson, S. (2018). Droplet digital PCR for absolute quantification of proviral load of human T-cell lymphotropic virus (HTLV) types 1 and 2. Journal of Virological Methods, 260, 70-74
Open this publication in new window or tab >>Droplet digital PCR for absolute quantification of proviral load of human T-cell lymphotropic virus (HTLV) types 1 and 2
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2018 (English)In: Journal of Virological Methods, ISSN 0166-0934, E-ISSN 1879-0984, Vol. 260, p. 70-74Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Human T-lymphotrophic virus (HTLV) types 1 and 2 cause lifelong infection whereby most infected individuals are asymptomatic whilst a minority develop infection-related disease. These latter patients invariably have been found to have high proviral load (PVL). Therefore, infected patients are monitored by determining the proportion of lymphocytes that are infected with HTLV-1/2. An increase in PVL has been shown to represent an increasing risk of developing HTLV-associated diseases. Monitoring of PVL requires a reliable and sensitive method. In this study assays based on droplet digital PCR (ddPCR) were established and evaluated for detection and quantification of HTLV-1/2.

OBJECTIVES: To develop two parallel assays to detect the tax genes and determine the PVL of HTLV-1 and -2.

STUDY DESIGN: Sixty-seven clinical samples from patients infected with HTLV-1 or HTLV-2 were analysed. The samples had previously been analysed with a qPCR and a comparison between ddPCR and qPCR was performed. The specificity of the assays were determined by analyzing samples from 20 healthy blood donors.

RESULTS: The ddPCR was a stable and sensitive method for detection and quantification of HTLV-1 and -2. When comparing the qPCR and ddPCR the correlation was high (Pearsons correlation coefficient 0.96). The variability of the ddPCR was very low with intra-assay coefficient of variation (CV) of 0.97-3.3% (HTLV-1) and 1.7-8.2% (HTLV-2) and inter-assay CV of 1.8-6.1% (HTLV-1) and 1.2-12.9% (HTLV-2).

CONCLUSIONS: The ddPCR reliably quantified HTLV DNA in clinical samples and could be a useful tool for monitoring of PVLs in HTLV-infected individuals.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Absolute quantification, Clinical monitoring, Droplet digital PCR - ddPCR, Human T-cell lymphotropic virus – HTLV, Pro-viral load – PVL
National Category
Microbiology in the medical area Clinical Laboratory Medicine
Identifiers
urn:nbn:se:oru:diva-68507 (URN)10.1016/j.jviromet.2018.07.003 (DOI)000442057400012 ()30006102 (PubMedID)2-s2.0-85050084367 (Scopus ID)
Available from: 2018-08-16 Created: 2018-08-16 Last updated: 2018-08-31Bibliographically approved
Viegas, E. O., Tembe, N., Nilsson, C., Meggi, B., Maueia, C., Augusto, O., . . . Sandström, E. (2018). Intradermal HIV-1 DNA immunization using needle-free ZetajetTM injection followed by HIV-modified vaccinia virus Ankara vaccination is safe and immunogenic in Mozambican young adults: a phase I randomized controlled trial. AIDS Research and Human Retroviruses, 34(2), 193-205
Open this publication in new window or tab >>Intradermal HIV-1 DNA immunization using needle-free ZetajetTM injection followed by HIV-modified vaccinia virus Ankara vaccination is safe and immunogenic in Mozambican young adults: a phase I randomized controlled trial
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2018 (English)In: AIDS Research and Human Retroviruses, ISSN 0889-2229, E-ISSN 1931-8405, Vol. 34, no 2, p. 193-205Article in journal (Refereed) Published
Abstract [en]

We assessed safety and immunogenicity of HIV-DNA priming using Zetajet<sup>TM</sup>, a needle-free device intradermally followed by intramuscular HIV-MVA boosts, in 24 healthy Mozambicans. Volunteers were randomized to receive three immunizations of 600 µg (n = 10; 2 x 0.1mL) or 1200 µg (n = 10; 2 x 0.2mL) of HIV-DNA (3 mg/mL), followed by two boosts of 10<sup>8</sup>pfu HIV-MVA. Four subjects received placebo saline injections. Vaccines and injections were safe and well tolerated with no difference between the two priming groups. After three HIV-DNA immunizations, IFN-γ ELISpot responses to Gag were detected in 9/17 (53%) vaccinees, while none responded to Env. After the first HIV-MVA, the overall response rate to Gag and/or Env increased to 14/15 (93%); 14/15 (93%) to Gag and 13/15 (87%) to Env. There were no significant differences between the immunization groups in frequency of response to Gag and Env or magnitude of Gag responses. Env responses were significantly higher in the higher-dose group (median 420 vs 157.5 SFC/million PBMC, p=0.014). HIV-specific antibodies to subtype C gp140 and subtype B gp160 were elicited in all vaccinees after the second HIV-MVA, without differences in titers between the groups. Neutralizing antibody responses were not detected. Two (13%) of 16 vaccinees, one in each of the priming groups, exhibited antibodies mediating antibody-dependent cellular cytotoxicity to CRF01_AE. In conclusion, HIV-DNA vaccine delivered intradermally in volumes of 0.1-0.2 mL using Zetajet<sup>TM</sup> was safe and well tolerated. Priming with the 1200 µg dose of HIV-DNA generated higher magnitudes of ELISpot responses to Env.

Place, publisher, year, edition, pages
Mary Ann Liebert, 2018
Keywords
HIV, vaccine, Mozambique, HIV-DNA, HIV-MVA
National Category
Infectious Medicine Immunology in the medical area
Identifiers
urn:nbn:se:oru:diva-61451 (URN)10.1089/AID.2017.0121 (DOI)000417253800001 ()28969431 (PubMedID)2-s2.0-85041709186 (Scopus ID)
Note

Funding Agencies:

NIH  AI064518 

European and Developing Countries Clinical Trials Partnership  CT.200633111.007 

Regional HIV/AIDS Team for Africa, Embassy of Sweden, Lusaka  

Sida  2150012801 

Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc.  W81XWH-07-2-0067  W81XWH-11-0174 

U.S. Department of Defense (DOD)  

U.S. National Institutes of Health  NCT01407497 

Pan African Clinical Trials Registry  PACTR201106000304583 

Available from: 2017-10-19 Created: 2017-10-19 Last updated: 2018-09-14Bibliographically approved
Kumakech, E., Andersson, S., Wabinga, H., Musubika, C., Kirimunda, S. & Berggren, V. (2017). Cervical cancer risk perceptions, sexual risk behaviors and sexually transmitted infections among Bivalent Human Papillomavirus vaccinated and non-vaccinated young women in Uganda-5 year follow up study. BMC Women's Health, 17, Article ID 40.
Open this publication in new window or tab >>Cervical cancer risk perceptions, sexual risk behaviors and sexually transmitted infections among Bivalent Human Papillomavirus vaccinated and non-vaccinated young women in Uganda-5 year follow up study
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2017 (English)In: BMC Women's Health, ISSN 1472-6874, E-ISSN 1472-6874, Vol. 17, article id 40Article in journal (Refereed) Published
Abstract [en]

Background: Previous studies were conflicting regarding the associations between HPV vaccination, cervical cancer risk perceptions, high-risk sexual behaviors and STIs. This study compared the HPV-vaccinated and non-vaccinated young women in Uganda regarding cervical cancer risk perceptions, high-risk sexual behaviors, syphilis and HIV infections 5 years after vaccine implementation.

Methods: This was a population-based comparative cross-sectional survey conducted in Uganda. The 438 participants were sexually active young women aged 15-24 years and mean age was 18.6 (SD 1.4). The majority (53.0%) were HPV-vaccinated in 2008 without assessment of sexual activity prior to HPV vaccination. Upon verbal assessment of sexual activity at the time of follow-up, data were collected using a questionnaire and laboratory testing of blood samples for syphilis and HIV infections.

Results: There were no significant differences between the HPV-vaccinated and non-vaccinated groups regarding the prevalence of high-risk sexual behaviors, syphilis and HIV infections. Cervical cancer risk perceptions and age at sexual debut were nonetheless significantly lower among the vaccinated group compared to their non-vaccinated counterparts. However, HPV vaccination was not significantly associated to cervical cancer risk perceptions and early age at sexual debut in multivariate logistic regression analysis.

Conclusions: We found no associations between HPV vaccination, cervical cancer risk perceptions, high-risk sexual behaviors, syphilis and HIV infections among young women in Uganda 5 years after vaccine implementation. Young girls in the study population were found to be sexually active at a young age, affirming the importance of targeting girls of younger age for HPV vaccination.

Place, publisher, year, edition, pages
BioMed Central, 2017
Keywords
Bivalent Human Papillomavirus (HPV) vaccination, cervical cancer risk perceptions, sexual risk behaviors, Sexually transmitted infections, Young women, Uganda
National Category
Obstetrics, Gynecology and Reproductive Medicine
Research subject
Obstetrics and Gynaecology
Identifiers
urn:nbn:se:oru:diva-58100 (URN)10.1186/s12905-017-0394-y (DOI)000402564800002 ()28576143 (PubMedID)2-s2.0-85020029260 (Scopus ID)
Funder
Sida - Swedish International Development Cooperation Agency
Available from: 2017-06-19 Created: 2017-06-19 Last updated: 2018-07-31Bibliographically approved
Viegas, E. O., Augusto, O., Ismael, N., Kaliff, M., Lillsunde-Larsson, G., Ramqvist, T., . . . Andersson, S. (2017). Human papillomavirus prevalence and genotype distribution among young women and men in Maputo city, Mozambique. BMJ Open, 7(7), Article ID e015653.
Open this publication in new window or tab >>Human papillomavirus prevalence and genotype distribution among young women and men in Maputo city, Mozambique
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2017 (English)In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 7, no 7, article id e015653Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: Human papillomavirus (HPV) is a well-known cause of cervical cancer, the second most frequent cancer in female African populations. This study aimed at determining the prevalence of HPV infections and the genotype distribution in young adults aged 18-24, in Maputo city, Mozambique, and to assess the suitability of commercially available HPV vaccines.

METHODS: This cross-sectional study was conducted between 2009 and 2011 at a youth clinic in Maputo Central Hospital. Cervical and urethral samples were obtained from 236 women and 176 men, respectively. Demographic and behavioural data were collected using structured questionnaires. HPV genotyping was performed for 35 different high, probably or possibly high-risk and low-risk HPV types using the CLART Human Papillomavirus 2.

RESULTS: HPV prevalence was 168/412 (40.8%; 95% CI 36.0 to 45.5) and was significantly higher in women than in men (63.6%vs10.2%). HPV52 was the most frequent type found in women, followed by HPV35, -16,-53, -58,-6 and -51. In men, HPV51 ranked the highest, followed by HPV6, -11,-52, -59 and -70. HIV infection and sexual debut before 18 years of age were associated with multiple HPV infections (OR 3.03; 95% CI 1.49 to 6.25 and OR 6.03; 95% CI 1.73 to 21.02, respectively). Women had a significantly higher HPV infection prevalence than men (p<0.001). The 9-valent HPV vaccine would cover 36.8% of the high-risk genotypes circulating in women in this study, compared with 26.3% and 15.8% coverage by the bivalent and quadrivalent vaccines, respectively.

CONCLUSION: This study confirmed the high burden of HPV infections in young women in Maputo city, Mozambique. The HPV prevalence was associated with high-risk sexual behaviour. Sex education and sexually transmitted infection prevention interventions should be intensified in Mozambique. Only a proportion of the high-risk HPV genotypes (37%) were covered by currently available vaccines.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2017
Keywords
Epidemiology, INFECTIOUS DISEASES, Molecular diagnostics, Public health, SEXUAL MEDICINE
National Category
Obstetrics, Gynecology and Reproductive Medicine Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:oru:diva-61759 (URN)10.1136/bmjopen-2016-015653 (DOI)000410203700116 ()28716790 (PubMedID)2-s2.0-85025065144 (Scopus ID)
Note

Funding Agencies:

Regional HIV/AIDS Team for Africa, Embassy of Sweden, Lusaka - Sweden (Sida)  2150012801 

Regional HIV/AIDS Team for Africa, Embassy of Sweden, Lusaka - Norway (Sida)  2150012801 

Available from: 2017-10-25 Created: 2017-10-25 Last updated: 2018-08-31Bibliographically approved
Kalbina, I., Lagerqvist, N., Moiane, B., Ahlm, C., Andersson, S., Strid, Å. & Falk, K. I. (2016). Arabidopsis thaliana plants expressing Rift Valley fever virus antigens: Mice exhibit systemic immune responses as the result of oraladministration of the transgenic plants. Protein Expression and Purification, 127, 61-67
Open this publication in new window or tab >>Arabidopsis thaliana plants expressing Rift Valley fever virus antigens: Mice exhibit systemic immune responses as the result of oraladministration of the transgenic plants
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2016 (English)In: Protein Expression and Purification, ISSN 1046-5928, E-ISSN 1096-0279, Vol. 127, p. 61-67Article in journal (Refereed) Published
Abstract [en]

The zoonotic Rift Valley fever virus affects livestock and humans in Africa and on the Arabian Peninsula.The economic impact of this pathogen due to livestock losses, as well as its relevance to public health,underscores the importance of developing effective and easily distributed vaccines. Vaccines that can bedelivered orally are of particular interest.

Here, we report the expression in transformed plants (Arabidopsis thaliana) of Rift Valley fever virusantigens. The antigens used in this study were the N protein and a deletion mutant of the Gn glycoprotein.Transformed lines were analysed for specific mRNA and protein content by RT-PCR and Westernblotting, respectively. Furthermore, the plant-expressed antigens were evaluated for their immunogenicityin mice fed the transgenic plants. After oral intake of fresh transgenic plant material, a proportionof the mice elicited specific IgG antibody responses, as compared to the control animals that were fedwild-type plants and of which none sero-converted.

Thus, we show that transgenic plants can be readily used to express and produce Rift Valley Fever virusproteins, and that the plants are immunogenic when given orally to mice. These are promising findingsand provide a basis for further studies on edible plant vaccines against the Rift Valley fever virus.

Place, publisher, year, edition, pages
San Diego, USA: Elsevier, 2016
Keywords
Antigen production, Arabidopsis thaliana, Rift valley fever virus, Plant vaccine, Transformation
National Category
Immunology in the medical area Immunology Biochemistry and Molecular Biology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Biochemistry; Immunology
Identifiers
urn:nbn:se:oru:diva-51367 (URN)10.1016/j.pep.2016.07.003 (DOI)000382181300009 ()27402440 (PubMedID)2-s2.0-84978634507 (Scopus ID)
Projects
Vaccinutveckling och vaccinproduktion
Funder
Knowledge FoundationStiftelsen Olle Engkvist Byggmästare
Note

Funding Agencies:

Swedish International Development Cooperation Agency (SIDA)

Örebro University's Faculty for Business, Science and Technology

Sparbanksstiftelsen Nya

Available from: 2016-07-17 Created: 2016-07-17 Last updated: 2018-01-10Bibliographically approved
Malm, K., Andersson, S. & Sundqvist, M. (2016). Evaluation of the Veris MDx (TM) system for quantification of Hepatitis B DNA and Hepatitis C and HIV-1 RNA in a medium sized University Hospital. Journal of Clinical Virology, 82, S27-S27
Open this publication in new window or tab >>Evaluation of the Veris MDx (TM) system for quantification of Hepatitis B DNA and Hepatitis C and HIV-1 RNA in a medium sized University Hospital
2016 (English)In: Journal of Clinical Virology, ISSN 1386-6532, E-ISSN 1873-5967, Vol. 82, p. S27-S27Article in journal (Refereed) Published
Abstract [en]

Introduction: In the diagnosis and treatment of Hepatitis B (HBV), Hepatitis C (HCV) and HIV, it is crucial to detect and quantify viral nucleic acid. Patients on therapy are monitored continuously to out-rule relapses or reinfections (HCV) while for patients with HIV these tests are important to early on detect potential break-throughs due to resistance development. Quantification methods are today more standardized and fast but still with no opportunity to analyze the samples with full random access. Recently the VERIS MDxTMplatform from Beckman Coulter with this possibility was launched.

Objectives: To evaluate a new, random access laboratory instrument for the simultaneous detection and quantification of HBV, HCV and HIV-1.

Methods: WHO standards for HBV-DNA, HCV-RNA and HIV-1-RNA provided from the National Institute for Biological Standards and Control (NIBSC) were diluted down to the designated lowest level of detection and analyzed in triplicates on the Veris MDxTM(Beckman Coulter Inc. 250 S. Kraemer Blvd. Brea, CA U.S.A.) instrument. Plasma samples from routine laboratory testing were analyzed and compared to the routine methods used at our hospital or the referral hospital, for HBV; COBAS®AmpliPrep/COBAS® TaqMan®HBV Test, v2.0 (Roche Molecular Diagnostics, 4300 Hacienda Drive, Pleasanton, CA, USA) (Karolinska University Hospital Huddinge), for HCV; COBAS® TaqMan®HCV Test v2.0 for use with the High Pure System (Roche) (Örebro) and for HIV; Aptima HIV-1 Quant Dx Assay (Hologic Inc. 250 Campus Drive Marlborough, MA, USA) (Örebro). 55 samples for HBV, 120 samples for HCV and 60 samples for HIV have been analyzed so far. The absolute majority of samples for HCV and HIV analysis were from patients on treatment. All viral load data were analyzed as log10-transformed values.

Results: The Veris MDxTMshowed good compatibility to the designated quantities of the WHO standards (except for HIV-1 where a slight over-quantification could be observed for dilutions in the higher range, i.e. >1000 copies/mL). The limits of detection assigned by the manufacturer could be confirmed. In clinical samples the Veris MDxTM showed similar results to the comparators with a correlation for quantifiable samples of 0.94 (HBV), 0.98 (HCV) and 0.98 (HIV). The Veris MDxTMshowed a slightly higher sensitivity though as DNA/RNA was detected in 4 samples for HBV, 8 for HCV and 7 for HIV when the comparator method did not. The opposite was seen in 0, 0 and 6 samples respectively.

Conclusion: The Veris MDxTMfor quantitative analysis of HBV, HCV and HIV nucleic acids showed good correlation to the comparator methods used in this study with a tendency of higher sensitivity for the detection of HBV and HCV. The Instrument provides an easy, fast and flexible method for quantification of RNA and DNA in plasma samples.

Place, publisher, year, edition, pages
Elsevier, 2016
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:oru:diva-54824 (URN)10.1016/j.jcv.2016.08.052 (DOI)000390584800052 ()
Available from: 2017-01-19 Created: 2017-01-19 Last updated: 2019-03-01Bibliographically approved
Hansson, C., Schön, K., Kalbina, I., Strid, Å., Andersson, S., Bokarewa, M. I. & Lycke, N. Y. (2016). Feeding transgenic plants that express a tolerogenic fusion protein effectively protects against arthritis. Plant Biotechnology Journal, 14(4), 1106-1115
Open this publication in new window or tab >>Feeding transgenic plants that express a tolerogenic fusion protein effectively protects against arthritis
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2016 (English)In: Plant Biotechnology Journal, ISSN 1467-7644, E-ISSN 1467-7652, Vol. 14, no 4, p. 1106-1115Article in journal (Refereed) Published
Abstract [en]

Although much explored, oral tolerance for treatment of autoimmune diseases still awaits the establishment of novel and effective vectors. We investigated if the tolerogenic CTA1(R7K)-COL-DD fusion protein can be expressed in edible plants and in this way induce oral tolerance and protect against arthritis. The fusion protein was recombinantly expressed in Arabidopsis thaliana plants, which were fed to H-2q restricted DBA/1 mice to assess the preventive effect on collagen-induced arthritis (CIA). The treatment resulted in fewer mice exhibiting disease and arthritis scores were significantly reduced. Immune suppression was evident in treated mice and serum biomarkers for inflammation as well as anti-collagen IgG responses were reduced. In spleen draining and lymph nodes, CD4+ T cell responses were reduced. Concomitant with a reduced effector T cell activity with lower IFNg, IL-13 and IL-17A production we observed an increase in IL-10 production to recall antigen stimulation in vitro, suggesting reduced Th1, Th2 and Th17 activity subsequent to upregulated IL-10 and regulatory T cell (Treg) functions. The present study shows that edible plants expressing a tolerogen were effective at stimulating CD4 T cell tolerance and in protecting against CIA disease. Our study conveys optimism as to the potential of using edible plants for oral treatment of rheumatoid arthritis.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2016
Keywords
autoimmunity; transgenic plants; edible plants; CIA; IL-10; FoxP3
National Category
Immunology in the medical area Plant Biotechnology Biochemistry and Molecular Biology
Research subject
Biochemistry; Immunology; Molecular Biology
Identifiers
urn:nbn:se:oru:diva-45625 (URN)10.1111/pbi.12479 (DOI)000373069400006 ()26403330 (PubMedID)2-s2.0-84961215734 (Scopus ID)
Funder
Swedish Cancer SocietySwedish Research CouncilKnut and Alice Wallenberg FoundationAFA InsuranceEU, FP7, Seventh Framework ProgrammeSwedish Foundation for Strategic Research
Note

Funding Agency:

UNISEC

Available from: 2015-08-22 Created: 2015-08-22 Last updated: 2018-08-31Bibliographically approved
Hadad, R., Marks, E., Kalbina, I., Schön, K., Unemo, M., Lycke, N., . . . Andersson, S. (2016). Protection against genital tract Chlamydia trachomatis infection following intranasal immunization with a novel recombinant MOMP VS2/4 antigen. Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), 124, 1078-1086
Open this publication in new window or tab >>Protection against genital tract Chlamydia trachomatis infection following intranasal immunization with a novel recombinant MOMP VS2/4 antigen
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2016 (English)In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 124, p. 1078-1086Article in journal (Refereed) Published
Abstract [en]

The asymptomatic nature of most Chlamydia trachomatis infections and the lack of appropriate effects by current prevention and management call for vaccine development. We evaluated a recombinant subunit vaccine candidate based on the major outer membrane protein variable segments 2 and 4 (MOMP VS2/4). To achieve maximal immunogenicity and ease of production and purification, MOMP VS2/4 was constructed by using highly immunogenic sequences of MOMP only, thereby minimizing the presence of hydrophobic regions, and spacing the immunogenic epitopes with a flexible amino acid sequence. A purification tag was also added. The MOMP VS2/4 was given intranasally, with or without intravaginal boost, with cholera toxin (CT) adjuvant to C57BL/6 mice, which were screened for immunogenicity and protection against a live challenge infection with C. trachomatis serovar D. Bacterial shedding, cell-mediated responses, and antibody responses were monitored. Immunized mice exhibited significantly less bacterial shedding and were better protected against infertility as compared to unimmunized control mice. Immunizations stimulated both systemic and local specific antibody (IgG1, IgG2c, and IgA) responses, and primed T cells that produced interferon-c and interleukins 13 and 17 upon challenge with recall antigen. Thus, MOMP VS2/4, in combination with CT adjuvant, stimulated Th1, Th2, and Th17 effector cells, and generated protective immunity associated with less pathology. We regard MOMP VS2/4 as a promising candidate for further development into a mucosal chlamydial vaccine.

Place, publisher, year, edition, pages
Hoboken, USA: Wiley-Blackwell, 2016
Keywords
Chlamydia trachomatis, vaccine, major outer membrane protein, mice, antibody response, T cells
National Category
Immunology in the medical area Microbiology in the medical area
Research subject
Biochemistry; Immunology; Microbiology; Infectious Diseases
Identifiers
urn:nbn:se:oru:diva-53554 (URN)10.1111/apm.12605 (DOI)000388265700008 ()27859689 (PubMedID)2-s2.0-84995753108 (Scopus ID)
Projects
Utveckling av vacciner mot sexuellt överförbara sjukdomarMolecular farming
Funder
Stiftelsen Olle Engkvist Byggmästare
Note

Funding Agencies:

Sparbanksstiftelsen Nya

Örebro University's Faculty for Business, Science, and Technology

Foundation for Medical Research at Örebro University Hospital

Available from: 2016-11-18 Created: 2016-11-18 Last updated: 2019-03-06Bibliographically approved
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